2020 News Archive

Congratulations to Dr. Tao Yang, Dr. Saroj Chakraborty and graduate students, Ms. Mandal and Ms. Mei from the Joe Lab! Their latest invited review was accepted in Comprehensive Physiology, which is an exclusively invited review journal of the American Heart Association.

Title: "Microbiota and metabolites as factors influencing blood pressure regulation."

Authors: Yang, T, Chakraborty, S, Mandal, J, Mei, X, Joe, B

Abstract: The study of microbes has rapidly expanded in recent years due to a surge in our understanding that humans host a plethora of commensal microbes, which reside in their bodies and depending upon their composition, contribute to either normal physiology or pathophysiology. This article provides a general foundation for learning about host-commensal microbial interactions as an emerging area of research. The article is divided into two sections. The first section is dedicated to introducing commensal microbiota and its known effects on the host. The second section is on metabolites, which are biochemicals that the host and the microbes use for bi-directional communication with each other. Together, the sections review what is known about how microbes interact with the host to impact cardiovascular physiology, especially blood pressure regulation.

Dr. Stephanie Watts from the Michigan State University, who is the 2020 Harriet Dustan Awardee, wrote an article associated with her award which is accepted and scheduled for publication in the Feb 2021 issue of Hypertension. In this article she showcased someof her predecessors of this award from the AHA, for their advice to the next generation of hypertension researchers.

Title: "Connecting generations of scientists in the Council on
Hypertension through Harriet Dustan."

Authors: Stephanie W.Watts, Barbara Alexander, ChrisBaylis, Nancy Brown, Lisa Cassis, Kate Denton, Bina Joe, Lilach Lerman, Suzanne Oparil, Jane Reckelhoff, Kathryn Sandberg and Rhian M. Touyz.

Congratulations to Dr. Lauren G. Koch and her collaborator, Dr. Colleen Novak, from Kent State University! They published a paper in Physiology & Behavior.

Title: “Enhanced weight and fat loss from long-term intermittent fasting in obesity-prone, low-fitness rats”.

Physiol Behav. 2020 Dec 4:113280. doi: 10.1016/j.physbeh.2020.113280. Online ahead of print.

Authors: Smyers ME, Koch LG, Britton SL, Wagner JG, Novak CM.

Highlights:

• Alternate-day fasting induced weight and fat loss in female rats
• Obesity-prone, low-aerobic-fitness rats lost weight & fat with intermittent fasting
• Intermittent fasting suppressed physical activity more in lean, high-fitness rats
• Activity fluctuated between fed and fasted days, especially in aerobically fit rats
• The weight-loss effects of intermittent fasting are modulated by aerobic capacity

Welcome, Ms. Rebecca Rashleigh! She is a new Research Associate in Dr. Jennifer Hill's Lab.

Congratulations to Ishan Manandhar from the Joe lab! His abstract was selected for a poster presentation at the American Society for Human Genetics (ASHG) Virtual Meeting 2020 held in October. The title of his abstract is, "Application of Artificial Intelligence for Microbiome-Based Detection of Inflammatory Bowel Disease."

Vaish Aradhyula, medical student and trainee of Dr. Camilla Ferreira Wenceslau, received a American Physiological Society Poster Award at the Integrative Physiology of Exercise Meeting which took place during the week of November 9-13, on her abstract titled “Female Rats Selected for High Intrinsic Aerobic Capacity Switch Inflammatory Cascade to Maintain Vascular Physiology.” Authors on the research include Dr. Cameron G. McCarthy, Emily Waigi, Nicole R. Bearss, Jonnelle Edwards, Dr. Bina Joe, Dr. Lauren G. Koch, and Dr. Camilla F. Wenceslau. The award was chosen from pre- and post-doctoral presenters, and will include a certificate of recognition and cash prize.

Shaunak Roy, a medical student and trainee of Dr. Camillia Ferreira Wenceslau, recently had a manuscript accepted for publication in the journal Function.

Title: Intrinsic exercise capacity and mitochondrial DNA lead to opposing vascular-associated risks. https://academic.oup.com/functi
on/advance-article/doi/10.1093/function/zqaa029/5952679#.X6GoE1nflC8 .

The American Physiological Society also wrote a press release about the research which can be found here: https://www.newswise.com/articles/intrinsic-exercise-capacity-and-mitochondrial-dna-lead-to-opposing-vascular-associated-risks.

Congratulations to a Physiology and Pharmacology team effort of graduate student, post-docs and faculty co-authors on publishing a Review paper!

Title: “SARS-CoV-2, ACE2 expression, and systemic organ invasion” in the journal Physiological Genomics (Physiol Genomics. 2020 Dec 4. doi: 10.1152/physiolgenomics.00087.2020. Online ahead of print.

Authors: Usman M Ashraf, Ahmed A Abokor, Jonnelle M Edwards, Emily W Waigi, Rachel S Royfman, Syed Abdul-Moiz Hasan, Kathryn B Smedlund, Ana Maria Gregio Hardy, Ritu Chakravarti, and Lauren G Koch

Abstract: A novel coronavirus disease, COVID-19, has created a global pandemic in 2020, posing an enormous challenge to healthcare systems and affected communities. COVID-19 is caused by Severe Acute Respiratory Syndrome (SARS)-CoronaVirus-2 (CoV-2) that manifests as bronchitis, pneumonia, or a severe respiratory illness. SARS-CoV-2 infects human cells via binding a "spike" protein on its surface to angiotensin-converting enzyme 2 (ACE2) within the host. ACE2 is crucial for maintaining tissue homeostasis and negatively regulates the renin-angiotensin-aldosterone system (RAAS) in the humans. The RAAS is paramount for normal function in multiple organ systems including the lungs, heart, kidney, and vasculature. Given that SARS-CoV-2 internalizes via ACE2, the resultant disruption in ACE2 expression can lead to altered tissue function and exacerbate chronic diseases. The widespread distribution and expression of ACE2 across multiple organs is critical to our understanding of the varied clinical outcomes of COVID-19. This perspective review based on the current literature was prompted to show how disruption of ACE2 by SARS-CoV-2 can affect different organ systems.

Congratulations to Dr. Camilla Ferreira Wenceslau! She has been invited as a reviewer on the AHA-Hypertension Committee. This committee is responsible for the review of Postdoctoral and Predoctoral Fellowship applications in the Hypertension area.

Congratulations to Dr. Saroj Chakraborty! He successfully defended his dissertation, December 1, 2020.

Congratulations to Dr. Bina Joe, she is now an International Society of Hypertension Fellow (ISHF)!

Congratulations to Dr. Matam Vijay-Kumar and his trainee, Rachel Golonka on the publication of their book chapter!

Title: Atypical immunometabolism and metabolic reprogramming in liver cancer: Deciphering the role of gut microbiome
Authors: Rachel M. Golonka, Matam Vijay-Kumar
Journal: Advances in Cancer Research

Congratulations to Dr. Tao Yang on his recent publications!

Title: Pulmonary arterial hypertension-associated changes in gut pathology and microbiota.
Authors: Sharma RK, Oliveira AC, Yang T, Kim S, Zubcevic J, Aquino V, Lobaton GO, Goel R, Richards EM, Raizada MK.
Journal: ERJ Open Res.

Title: Probiotic Bifidobacterium breve prevents DOCA-salt hypertension.
Authors: Robles-Vera I, de la Visitación N, Toral M, Sánchez M, Romero M, Gómez-Guzmán M, Yang T, Izquierdo-García JL, Guerra-Hernández E, Ruiz-Cabello J, Raizada MK, Pérez-Vizcaíno F, Jiménez R, Duarte J.
Journal: FASEB J.

Title: Antihypertensive effects of exercise involve reshaping of gut microbiota and improvement of gut-brain axis in spontaneously hypertensive rat.
Authors: Wen-Jie Xia, Meng-Lu Xu, Xiao-Jing Yu, Meng-Meng Du, Xu-Hui Li, Tao Yang, Lu Li, Ying Li, Kai B. Kang, Qing Su, Jia-Xi Xu, Xiao-Lian Shi, Xiao-Min Wang, Hong-Bao Li, Yu-Ming Kang.
Journal: Gut Microbes.

Congratulations to Rachel Golonka from Dr. Matam Vijay Kumar's lab for her article with a special video feature published in AJP – Gastrointestinal and Liver Physiology (AJP-GIL)! The video link is below. It is a testimony to the creativity of our budding researchers.

Authors:
Rachel M Golonka , Beng San Yeoh , Yaqi Li , Piu Saha , Ahmed A Abokor , Xi Cheng , Xia Xiao , Darshan Shimoga Chandrashekar , Sooryanarayana Varambally, David J Gonzalez , A Catharine Ross , Matam Vijay-Kumar

Video Abstract

Congratulations to Dr. Piu Saha from Dr. Matam Vijay Kumar's lab on her recently accepted first authored a paper to be published in the journal, Gut Microbes!

Authors: Piu Saha, Beng San Yeoh, Xia Xiao, Rachel M. Golonka, Ahmed A. Abokor, Camilla F. Wenceslau, Yatrik M. Shah, Bina Joe and Matam Vijay-Kumar

Congratulations to Emily Waigi! She is a trainee of Dr. Camilla Ferreira Wenceslau and passed her Master's qualifying exam. Well done!

Congratulations to Dr. Camilla Ferreira Wenceslau's trainee, Jonnelle Edwards! Her research article was published today in The Blade.

See Her Article Here

Congratulations to Dr. Cameron McCarthy and team for their publication being accepted to Comprehensive Physiology! "Innate immune cells and hypertension: Neutrophils and neutrophil extracellular traps (NETs)"

Authors
Cameron G. McCarthy, Piu Saha, Rachel M. Golonka, Camilla F. Wenceslau, Bina Joe, & Matam Vijay-Kumar

Congratulations to Dr. Lauren Koch and team! Their publication was published in PLOS ONE in October. “Differences in intrinsic aerobic capacity alters sensitivity to ischemia-reperfusion injury but not cardioprotective capacity by ischemic preconditioning in rats.”

Authors
Marie Vognstoft Hjortbak ,Thomas Skjærlund Grønnebæk,Nichlas Riise Jespersen,Thomas Ravn Lassen,Jacob Marthinsen Seefeldt,Pernille Tilma Tonnesen,Rebekka Vibjerg Jensen,Lauren Gerard Koch,Steven L. Britton,Michael Pedersen,Niels Jessen,Hans Erik Bøtker

Congratulations to Dr. Camilla Ferreira Wenceslau and team! Their manuscript, "Intrinsic exercise capacity and mitochondrial DNA lead to opposing vascular-associated risks" has been accepted for publication in FUNCTION.

Authors
Shaunak Roy, Jonnelle M Edwards, Jeremy C Tomcho, Zachary Schreckenberger, Nicole R Bearss, Youjie Zhang, Eric E Morgan, Xi Cheng, Adam C Spegele, Matam Vijay-5 Kumar, Cameron G McCarthy, Lauren G Koch, Bina Joe and Camilla Ferreira Wenceslau

Last week, Women & Philanthropy held a virtual webinar presentation regarding COVID-19 and Hypertension, featuring Dr. Bina Joe and Dr. Cameron McCarthy. With the College of Medicine and Life Sciences Alumni Affiliate as a co-sponsor, there were 79 attendees for this event. The webinar was recorded and is now online for those who were unable to attend or wish to view it.

Watch The Webinar

Dr. Xi Cheng was invited by Takara Bio USA, Inc (Ann Arbor) to give a virtual seminar about the application of artificial intelligence into next-generation sequencing and metagenomics in cardiovascular medicine, which will be followed by a group discussion with their R&D Scientists. The meeting takes place on November 17, 2020.

The Machine Learning Lab was recently featured in an article in the UT News. The article is about the potential of artificial intelligence screening for cardiovascular disease. They are also currently featured in a UT postcard campaign for U.S. News and World Report featuring COVID-19 research. http://news.utoledo.edu/index.php/10_08_2020/utoledo-research-shows-potential-of-artificial-intelligence-to-screen-for-cardiovascular-disease

Congratulations to Dr. Koch and her collaborators at Karolinska Institute, Mayo Clinic, and University of Michigan! Their paper titled “Comparative analysis of skeletal muscle transcriptional signatures associated with aerobic exercise capacity or response to training in humans and rats” was accepted for publication in Frontiers in Endocrinology, section Diabetes: Molecular Mechanisms; Research Topic: Exercise Factors in Organ Cross-talk: Novel Players and Therapeutic Options.
Authors: Yildiz Kelahmetoglu, Paulo R. Jannig, Igor Cervenka, Lauren G. Koch, Steven Britton, Matthew M. Robinson, K Sreekumaran Nair, Jorge Lira Ruas.

Welcome to the Department!

Seungyong Lee, Ph.D., is our newest Dean's Postdoctoral to Faculty Fellow. He is a native of South Korea and a researcher whose career in Exercise and Applied Physiology extends over ten years.
Dr. Lee received a bachelor's degree in Physical Education from Dankook University, Korea in 2006; a MS degree in Exercise Physiology from University of Kentucky in 2013; a Ph.D. in Kinesiology from the University of Texas at Arlington in 2018; and and finished his post-doctoral fellowship from the Department of Pathology at Johns Hopkins University School of Medicine. His research interests focus on exercise and neuro-vascular interactions targeting skeletal health. Understanding and manipulating the complex physiological interactions that occur during exercise implants for tissue regeneration and bone disease application.

Janara Furtado, M.D. is a new postdoctoral fellow in Dr. Camila Ferreira Wenceslau’s lab and was previously a volunteer in the same lab. She came from Brazil, where she earned her degree as an Endocrinologist M.D. She has been living in the U.S. for the last 4 years and says, "I’m very excited to be part of this great team."

Dr. Marziyeh Salehi Jahromi is a Molecular Medicine Ph.D. graduate from SBMU, Tehran, Iran. Her Ph.D. thesis and following research projects were focusing on Gene Expression Profiling and Epigenetics of PCOS. Among her published papers, she has two papers collaborating with Dr. Jennifer Hill's lab where she worked for 7 months in 2015. She recently joined Dr. Edwin Sanchez's lab, as a Research Associate, working on his grant projects and also collaborating with Dr. Hill's lab and Dr. Lecka-Czernik's lab.

Congratulations to Dr. Jennifer Hill!TheEndocrine Society selected her paper, ‘Delayed Puberty but Normal Fertility in Mice With Selective Deletion of Insulin Receptors From Kiss1 Cells,’ in Endocrinology for their Thematic Issue, Contributions by Flare Fellows. They stated that her research, "with 209 downloads, is being recognized due to its high Altmetric Attention Score and Featured Article designations. We appreciate your cutting-edge, influential contributions to the endocrine community and are delighted to promote it in our thematic collection. We trust that your work will continue to gain recognition and serve as a ground-breaking addition to the field. The society is committed to expanding its reach globally."

Dr. Hill's previous students, Xiao Qui was the first author and Latrice Faulkner was the Flare Fellow in question. Both were PhD students at the time.

Congratulations to Dr. Cameron McCarthy! He has been selected as one of the top 3 best performing Star Reviewers for 2019 from the American Physiological Society.

Congratulations to Dr. Ritu Chakravarti, whose manuscript was accepted for publication in PNAS!

Title: 14-3-3z-TRAF5 Axis Governs Interleukin-17A Signaling
Authors: Jenna McGowan, Cara Peter, Joshua Kim, Sonam Popli, Brent Veerman, Jessica Saul-McBeth, Heather Conti, Shondra M. Pruett-Miller, Saurabh Chattopadhyay, Ritu Chakravarti#

Abstract
Interleukin-17A (IL-17A) is a therapeutic target in many autoimmune diseases. Most non-hematopoietic cells express IL-17A receptors and respond to extracellular IL-17A by inducing pro-inflammatory cytokines. The IL-17A signal transduction triggers two broad, TRAF6- and TRAF5-dependent, intracellular signaling pathways to produce representative cytokines (IL-6) and chemokines (CXCL-1), respectively. Our limited understanding of the crosstalk between these two branches has generated a crucial gap of knowledge leading to therapeutics indiscriminately blocking IL-17A and global inhibition of its target genes. In previous work, we discovered an elevated expression of 14-3-3 proteins in inflammatory aortic disease, a rare human autoimmune disorder with increased levels of IL-17A. Here we report that 14-3-3z is essential for IL-17 signaling by differentially regulating the signal-induced IL-6 and CXCL-1. Using genetically manipulated human and mouse cells, and ex vivo and in vivo rat models, we uncovered a new function of 14-3-3z. As a part of the molecular mechanism, we show that 14-3-3z interacts with several TRAF proteins; in particular, its interaction with TRAF5 and TRAF6 is increased in the presence of IL-17A. Contrary to TRAF6, we found TRAF5 to be an endogenous suppressor of IL-17A-induced IL-6 production, an effect countered by 14-3-3z. Furthermore, we observed that 14-3-3z interaction with TRAF proteins is required for the IL-17A-induced IL-6 levels. Together, our results show that 14-3-3z is an essential component of IL-17A signaling and IL-6 production, an effect that is suppressed by TRAF5. To the best of our knowledge, this is the first report of the 14-3-3z-TRAF5 axis, which differentially regulates IL-17A-induced IL-6 and CXCL-1 production.

Dr. Lauren Koch was invited to author for News & Views for Nature Reviews Endocrinology entitled "Aerobics — decades of data for future hypothesis-testing research".

https://www.nature.com/articles/s41574-020-00415-8
Sept 7. 2020

Also, her manuscript, "Rats Genetically Selected for High Aerobic Exercise Capacity Have Elevated Plasma Bilirubin by Upregulation of Hepatic Biliverdin Reductase-A (BVRA) and Suppression of UGT1A1", has been published in Antioxidants as part of the Special Issue Pharmacological and Clinical Significance of Heme Oxygenase-1:
PDF Version: https://urldefense.com/v3/__https://www.mdpi.com/2076-3921/9/9/889/pdf__;!!LoBwcKfm!yDDM2BCOXovgzIKCf6n6-9sSwBODJPLwAGFpdtV2B7RJ9dPlVECkm1sJhNn4Mvkej6OUAA$

Sept 19, 2020.

Congratulations to Dr. Camilla Ferreira Wenceslau and the Germ-Free Rat Research Team of the UT Microbiome Consortium! Their manuscript, "Microbiota introduced to germ-free rats restores vascular contractility and blood pressure", was accepted for publication in Hypertension.

Authors: Bina Joe, Cameron G. McCarthy, Jonnelle M. Edwards, Xi Cheng, Saroj Chakraborty, Tao Yang, Rachel M. Golonka, Blair Mell, Ji-Youn Yeo, Nicole Bearss, Janara Furtado, Piu Saha, Beng San Yeoh, Matam Vijay-Kumar, Camilla F. Wenceslau.

Abstract
Commensal gut microbiota are strongly correlated with host hemodynamic homeostasis, but only broadly associated with cardiovascular health. This includes a general correspondence of quantitative and qualitative shifts in intestinal microbial communities found in hypertensive rat models and human patients. However, the mechanisms by which gut microbes contribute to the function of organs important for blood pressure control remain unanswered. To examine the direct effects of microbiota on blood pressure, we conventionalized germ-free (GF) rats with specific pathogen free rats for a short-term period of 10 days, which served as a model system to observe the dynamic responses when reconstituting the holobiome. The absence of microbiota in GF rats resulted with relative hypotension compared to their conventionalized counterparts, suggesting an obligatory role of microbiota in blood pressure homeostasis. Hypotension observed in GF rats was accompanied by a marked reduction in vascular contractility. Both blood pressure and vascular contractility were restored by the introduction of microbiota to GF rats, indicating that microbiota could be impacting blood pressure through a vascular-dependent mechanism. This is further supported by the decrease in actin polymerization in arteries from GF rats. Improved vascular contractility in conventionalized GF rats, as indicated through stabilized actin filaments, was associated with an increase in cofilin phosphorylation. These data indicate that the vascular system senses the presence (or lack of) microbiota to maintain vascular tone via actin polymerization. Taken together, these results constitute a fundamental discovery of the essential nature of microbiota in blood pressure regulation.

Dr. Camilla Ferreira Wenceslau recently participated in an AJP-Heart Podcast about the potential detrimental effects of prolonged sitting in healthy individuals. Listen to the podcast by clicking the link. https://ajpheart.podbean.com/e/vascular-response-to-prolonged-sitting-in-hypercapnia/

Congratulations to Dr. Tao Yang! He has been selected as one of the top 3 best performing Star Reviewers for 2019 from the American Physiology Society. The criteria for being chosen for this honor is: timeliness, number of MMS reviewed and consistent willingness to review invites.

We are pleased to announce that Dr. Bina Joe was accepted to the editorial board of Genes.

Congratulations to Dr. Piu Saha! Her abstract has been selected to present at the Crohn's & Colitis Foundation's Research Investigators Symposium 2020. The even will be held virtually on September 30th & October 1st. Her abstract was chosen for an Environmental Triggers presentation. The title is, "Enterobactin, a catecholate-type of siderophore induces pro-inﬂammatory signature in intestinal epithelial cells."

Authors: Piu Sah, Beng San Yeoh, Xia Xiao, Rachel M Golonka and Matam Vijay-Kumar.

Dr. Saha is a postdoctoral fellow in Dr. Vijay-Kumar's lab.

2020 NV graduate Avinash Singh has been selected as a Melvin Scholar for the Ohio Academy of Science (OAS) for his scientific presentation at the Academy's Annual Meeting in April 2020.

Avi completed the AP Capstone Diploma Program at Sylvania Northview. During Avi's senior year, he landed a premier AP research opportunity developed by his teacher, Ms. Kathryn Nelson, and Dr. Bina Joe, Chair of the Department of Physiology and Pharmacology at the University of Toledo, College of Medicine. As part of his AP Research experience, Avi worked for approximately 16 hours per week in Dr. Joe's lab at the Center for Hypertension and Precision Medicine. His investigations resulted in his original research paper titled 'A Novel Ex Vivo Procedure for Monitoring B-Hydroxybutyrate (BOHB) Production Isolated from Whole Livers.' Avi will have the opportunity to present his outstanding scientific contribution at the National meeting of the American Academy for the Advancement of Science meeting (AJAS; February 2021). Avi will also interact with top student scientists and professional researchers, as well as world-renowned scientists and engineers from around the globe.

We are very proud of Avi, Northview's first Melvin Scholar. We look forward to more exciting things from him as he continues his education at the University of Pennsylvania (an ivy league institution). More information is available at www.ohiosci.org/ajas, and the abstract of his work is on page 20 of the OAS journal https://www.ohiosci.org/s/OJS-AM-Program-Vol-120-No-1.pdf.

The Department was highlighted by a press release from the American Heart Association. Congrats to the Machine Learning Lab on their work being in the spot light! See the list of highlights below:

AHA: https://newsroom.heart.org/news/gut-microbiome-data-may-be-helpful-in-routine-screening-of-cardiovascular-disease

Drug Topics: Study: Gut Microbiome Data May Be Useful in Screening for Heart Disease
Health IT Analytics: Machine Learning Could Improve Cardiovascular Disease Screening
UPI: AI tool screens for heart disease using gut bacteria, study shows
Science Daily: Gut microbiome data may be helpful in routine screening of cardiovascular disease
Home Health Choices: Gut microbiome knowledge could also be useful in routine screening of cardiovascular disease
Medpage Today: Can Machine Learning Make Fecal Testing Part of CVD Screening?

Congratulations to Dr. Vijay Kumar! His article, "Lipocalin 2 deficiency-induced gut microbiota dysbiosis evokes metabolic syndrome in aged mice" has been selected for APSselect, a collection from the APS that showcases some of the best recently published articles in physiological research. Dr. Vijay Kumar received a certificate for this honor. https://journals.physiology.org/journal/apsselect

Congrats to Dr. Camilla Ferriera Wenceslau! She has been elected as a Fellow of the American Heart Association (FAHA).

Dr. Wenceslau has also been invited to join the Journal of Applied Physiology Editorial Board. Members are selected based on scientific enterprise, commitment as reviewers and stature in the field.

Well done!

Congratulations to Dr. Cameron McCarthy! He has been elected as a Fellow of the American Heart Association (FAHA).

Well done!

Congratulations, Dr. Piu Saha! Her application application to the National Cancer Institute NOSI (NOT-CA-20-082) entitled, “NCI Emergency Administrative Supplements for Research and Training Continuity of Postdoctoral Fellows during Coronavirus Disease 2019 (COVID-19)” has been approved for funding.

Congrats to Dr. Camilla Ferriera Wenceslau! She has been invited to speak during the (NAVBO) North American Vascular Biology Organization's Vascular Biology 2020 meeting. The meeting will take place virtually October 26-29, 2020.

Dr. Wenceslau has also been invited as a reviewer for (HM) Hypertension and Microcirculation Study Section Meeting, October 19-20, 2020 via Zoom Video Conference.

Congratulations to Sachin Aryal and colleagues! Their manuscript has been accepted for publication in the November 2020 edition of Hypertension.

A machine learning strategy for gut microbiome-based diagnostic screening of cardiovascular disease
Sachin Aryal, Ahmad Alimadadi, Ishan Manandhar, Bina Joe* and Xi Cheng*
Bioinformatics & Artificial Intelligence Laboratory, Center for Hypertension and Precision Medicine, Program in Physiological Genomics, Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA

Abstract
Cardiovascular disease (CVD) is the number one leading cause for human mortality. Besides genetics and environmental factors, in recent years, gut microbiota has emerged as a new factor influencing CVD. Although cause-effect relationships are not clearly established, the reported associations between alterations in gut microbiota and CVD are prominent. Therefore, we hypothesized that machine learning (ML) could be used for gut microbiome-based diagnostic screening of CVD. To test our hypothesis, fecal 16S rRNA sequencing data of 478 CVD and 473 non-CVD human subjects collected through the American Gut Project were analyzed using 5 supervised ML algorithms including random forest (RF), support vector machine, decision tree, elastic net and neural networks (NN). Thirty-nine differential bacterial taxa were identified between the CVD and non-CVD groups. ML modeling using these taxonomic features achieved a testing AUC (area under the receiver operating characteristic curves; 0.0: perfect anti-discrimination; 0.5: random guessing; 1.0: perfect discrimination) of ~0.58 (RF and NN). Next, the ML models were trained with the top 500 high-variance features of operational taxonomic units (OTUs), instead of bacterial taxa, and an improved testing AUC of ~0.65 (RF) was achieved. Further, by limiting the selection to only the top 25 highly contributing OTU features, the AUC was further significantly enhanced to ~0.70. Overall, our study is the first to identify dysbiosis of gut microbiota in CVD patients as a group and apply this knowledge to develop a gut microbiome-based ML approach for diagnostic screening of CVD.

Congratulations to Dr. Ahmad Alimadadi and colleagues! Their manuscript was accepted to Physiological Genomics.

Title: Machine learning based classification and diagnosis of clinical cardiomyopathies
Authors: Ahmad Alimadadi, Ishan Manandhar, Sachin Aryal, Patricia B. Munroe, Bina Joe, Xi Cheng
Abstract:
Dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM) are two common types of cardiomyopathies leading to heart failure. Accurate diagnostic classification of different types of cardiomyopathies is critical for precision medicine in clinical practice. In this study, we hypothesized that machine learning (ML) can be used as a novel diagnostic approach to analyze cardiac transcriptomic data for classifying clinical cardiomyopathies.RNA-seq data of human left ventricle tissues were collected from 41 DCM patients, 47 ICM patients and 49 non-failure controls (NF) and tested using five ML algorithms: support vector machine with radial kernel (svmRadial), neural networks with principal component analysis (pcaNNet), decision tree (DT), elastic net (ENet) and random forest (RF).Initial ML classifications achieved ~93% accuracy (svmRadial) for NF vs DCM, ~82% accuracy (RF) for NF vs ICM, and ~80% accuracy (ENet and svmRadial) for DCM vs ICM. Next, 50 highly contributing genes (HCGs) for classifying NF and DCM, 68 HCGs for classifying NF and ICM, and 59 HCGs for classifying DCM and ICM were selected for re-training ML models. Impressively, the re-trained models achieved ~90% accuracy (RF) for NF vs DCM, ~90% accuracy (pcaNNet) for NF vs ICM, and ~85% accuracy (pcaNNet and RF) for DCM vs ICM. Pathway analyses further confirmed the involvement of those selected HCGs in cardiac dysfunctions such as cardiomyopathies, cardiac hypertrophies and fibrosis. Overall, our study demonstrates the promising potential of using artificial intelligence via ML modeling as a novel approach to achieve a greater level of precision in diagnosing different types of cardiomyopathies.

Congratulations to Dr. Katye Smedlund and Dr. Jennifer Hill! Their manuscript has been accepted for publication in the journal Molecular and Cellular Endocrinology.

Title: The Role of Non-neuronal Cells in Hypogonadotropic Hypogonadism
Authors: Kathryn B. Smedlund, PhD and Jennifer W. Hill, PhD
Abstract:
The hypothalamic-pituitary-gonadal axis is controlled by gonadotropin-releasing hormone (GnRH) released by the hypothalamus. Disruption of this system leads to impaired reproductive maturation and function, a condition known as hypogonadotropic hypogonadism (HH). Most studies to date have focused on genetic causes of HH that impact neuronal development and function. However, variants may also impact the functioning of non-neuronal cells known as glia. Glial cells make up 50% of brain cells of humans, primates, and rodents. They include radial glial cells, microglia, astrocytes, tanycytes, oligodendrocytes, and oligodendrocyte precursor cells. Many of these cells influence the hypothalamic neuroendocrine system controlling fertility. Indeed, glia regulate GnRH neuronal activity and secretion, acting both at their cell bodies and their nerve endings. Recent work has also made clear that these interactions are an essential aspect of how the HPG axis integrates endocrine, metabolic, and environmental signals to control fertility. Recognition of the clinical importance of interactions between glia and the GnRH network may pave the way for the development of new treatment strategies for dysfunctions of puberty and adult fertility

A hearty congratulations to Ahmed Abokor, a trainee of Dr. Matam Vijay-Kumar, whose grant application was recommended for funding! He applied for a Diversity Supplement, which is part of the Continuing Umbrella of Research Experiences (CURE) program. Well done!

A warm welcome to Emily Crowe and Benjamin French! They are the newest incoming MOME students. Emily was accepted as a MS MOME Track student and comes to us from Heidelberg University in Tiffin, Ohio with a Bachelor of Science in Biology. Benjamin hales from Rose-Hulman Institute of Technology in Terre Haute, Indiana with a Bachelor of Science in Biochemistry. He was accepted as a PhD Mome Track student. We are pleased to welcome them both to our program!

Dr. Ritu Chakravarti has replaced Dr. Andrew Beavis as the new MOME Track Director; her term began August 1, 2020. I am confident that she will do well in this new endeavor. Congratulations!

Jonnelle Edwards, trainee of Dr. Camilla F. Wenceslau, was recently featured in UT's Diversity, Equity and Inclusion Newletter. Please see link for full spotlight. Read Full Spotlight

Congratulations to Dr. Matam Vijay-Kumar, Rachel Golonka, and Ahmed Abokor! They had a book chapter published recently.

Textbook: Lipid Signaling and Metabolism (1st Eds)

Chapter Title: Gut Microbiota in Host Lipid Metabolism

Citation: Golonka RM, Abokor A, Vijay-Kumar M. 2020. Gut Microbiota Interaction in Host Lipid Metabolism. Ntambi JM (1st Eds), Lipid Signaling and Metabolism. Elsevier Publications. ISBN: 9780128194041

Congrats to Saroj Chakravarti, trainee of Dr. Bina Joe, his manuscript has been selected for publication in Hypertension!

Title: A single nucleotide polymorphism of Secreted phosphoprotein 2
confers sex-specific effects on blood pressure and bone health

Authors: Saroj Chakraborty, Blair Mell, Ying Nie, Xi Cheng, Sarah Galla, Piotr Czernik2, Beata Lecka-Czernik and Bina Joe

Abstract:
Hypertension is a complex polygenic disease caused by a combination of genetic and environmental factors. Rat models serve as tools to dissect and prioritize genetic factors as candidate genes causing hypertension. One such candidate gene prioritized through systematic linkage and substitution mapping is Secreted Phosphoprotein 2 (Spp2). A non-synonymous G/T single nucleotide polymorphism (SNP) between the Dahl Salt-Sensitive (S) rats and Spontaneously Hypertensive Rats (SHR) at the Spp2 locus was prioritized as a candidate quantitative trait nucleotide (QTN) responsible for the reduction in blood pressure (BP) and bone mineral density (BMD) observed in the S.SHR congenic strain spanning the Spp2 locus. We hypothesized that CRISPR/Cas9 precision-engineering guided replacement of the ‘G’ allele at the Spp2 locus with a ‘T’ allele would lower BP and BMD of the S rat. Radiotelemetry and micro-CT was performed with Spp2 knock-in rats using S rat as control. Systolic BP of the Spp2 knock-in male rats was significantly lower compared to that of the non-founder S rats. However, there was no change in systolic BP of the Spp2 knock-in female rats compared to that of the non-founder S rats. In addition, there was a significant reduction in bone size and bone mass resulting in lower bone volume by total volume (BV/TV) in female Spp2 knock-in rats compared to S. These data provide conclusive evidence for a single nucleotide polymorphism within the Spp2 gene as a quantitative trait nucleotide (QTN) responsible for the sex-dependent inheritance of blood pressure and bone health.

An abstract from research first authored by Dr. Piotr Czernik and lead by Drs. Vijay-Kumar, Joe and Lecka-Czernik has been selected by the BMA2020 Organizing Committee to be presented as a Plenary Oral presentation at a virtual meeting of the 6th International Meeting on Bone Marrow Adiposity (BMA2020, Marrow Adiposity: Bone, Aging and Beyond). The meeting will be held September 9-10, 2020.

Abstract Title: Reconstitution of the host holobiont acutely increases bone growth and marrow adiposity of the gnotobiotic rat

Our friend and colleague, Dr. Andrew Beavis, retires this week! (7-31-2020) We wish him a happy retirement and hope this next chapter brings him endless time to do the things he enjoys!

Dr. Beavis, you will be greatly missed! Thank you for the hard work and dedication that you've put into teaching over these many years. Your kindness and generosity will always be remembered. We wish you much happiness!

Ms. Xue Mei, a PhD trainee of Dr. Bina Joe, and Dr. Xi Cheng, a post doc to faculty fellow of Dr. Bina Joe were both selected to receive the HTN New Investigator Travel Award.

Since the meeting is virtual this year, they will both receive complimentary registration, be listed on the conference website and receive award certificates.

Well done, Mei and Dr. Cheng!

Congratulations Dr. Lecka-Czernik, Dr. Czernik and team for their recent publication on bioRxiv: Reconstitution of the host holobiont acutely increases bone growth of the gnotobiotic rat. Authors:PJ Czernik, RM Golonka, S Chakraborty, BS Yeoh, P Saha, B Mell, Y Tian, AD Patterson, B Joe, M Vijay-Kumar, B Lecka-Czernik

https://www.biorxiv.org/content/10.1101/2020.07.15.201657v1

Dr. Koch and her collaborator, Dr. Sarah Lessard at Joslin Diabetes Center, Harvard Medical School published a paper July 20, 2020 in Nature Metabolism titled, “Hyperglycaemia is associated with impaired muscle signalling and aerobic adaptation to exercise.”

The article was highlighted in nature metabolism news and views: “Sugar not so sweet for training-enhanced fitness”. https://www.nature.com/articles/s42255-020-0240-7

Soyoung Cheon, who completed her MSBS-MS research work in Dr. Camilla F. Wenceslau's laboratory, was recently invited to present at the High Blood Pressure Research Council of Australia (HBPRCA) Winter School Blitz, being held virtually on July 16th & 17th. The title of her talk is, "Opioids Cause Sex-Specific Vascular Remodeling via Cofilin-ERK Signaling: Female Mice Present Higher Risk of Developing Morphine-Induced Vascular Dysfunction than Male Mice."

Additionally, she had this abstract accepted to the Association of Women Surgeons (AWS) Research Madness. This is a medical student and/or resident research competition where students, residents and fellow members of AWS are able to showcase their work to a large, international audience. It features multiple rounds of abstracts and presentations. Good luck, Soyoung!

An editorial that Dr. Bina Joe contributed to has been published by the American Journal of Physiology-Lung Cellular and Molecular Physiology.

Title
"An American Physiological Society cross-journal Call for Papers on "Deconstructing organs: Single-cell analyses, decellularized organs, organoids, and organ-on-a-chip models". https://journals.physiology.org/doi/abs/10.1152/ajplung.00311.2020

Authors
Josephine C. Adams, P. Darwin Bell, Sue C. Bodine, Heddwen L. Brooks, Nigel Bunnett, Bina Joe, Kara Hansell Keehan, Thomas R. Kleyman, Andre Marette, Rory E. Morty, Jan-Marino Ramirez, Morten B. Thomsen, Bill J. Yates, Irving H. Zucker.

Two MSBS students from Dr. Camilla Wenceslau's lab have been selected as oral presenters at the North American Vascular Biology Organization's Summer Camp (VAVBO). The titles of their presentations are listed below.

Vaishnavi Aradhyula:
Female rats artificially selected for low and high intrinsic aerobic capacity swap inflammatory cascade in resistance arteries: Mechanisms of cyclooxygenase-derived prostanoids
Aradhyula, Vaishnavi; Bearss, Nicole; McCarthy, Cameron; Edwards, Jonnelle; Joe, Bina; Koch, Lauren; Wenceslau, Camilla
University of Toledo College of Medicine and Life Sciences, Toledo, OH
Vaishnavi will be presenting on July 1st at 2:50PM.

Soyoung Cheon:
Opioids cause sex-specific vascular remodeling via Cofilin-ERK signaling: Female mice present higher risk of developing morphine-induced vascular dysfunction than male mice
Cheon, Soyoung; Edwards, Jonnelle; Tomcho, Jeremy; Bearss, Nicole; Joe, Bina; McCarthy, Cameron; Wenceslau, Camilla
University of Toledo College of Medicine and Life Sciences, Toledo, OH
Soyoung presented on June 24th, at 3:30PM.

Our Department has remained highly productive during the lockdown phase as evidenced by the following publications. Some of these publications, especially related to COVID-19 have been downloaded over 8,000 times just within the short period of a few months. This is an impressive performance by our students and faculty, one that speaks to our high level of productivity despite the pandemic.

Harnessing innate immunity to eliminate SARS-CoV-2 and ameliorate COVID-19 disease. Golonka RM, Saha P, Yeoh BS, Chattopadhyay S, Gewirtz AT, Joe B, Vijay-Kumar M. Physiol Genomics. 2020 May 1;52(5):217-221. doi: 10.1152/physiolgenomics.00033.2020. Epub 2020 Apr 10. PMID: 32275178
Artificial intelligence and machine learning to fight COVID-19. Alimadadi A, Aryal S, Manandhar I, Munroe PB, Joe B, Cheng X. Physiol Genomics. 2020 Apr 1;52(4):200-202.doi:10.1152/physiolgenomics.00029.2020. Epub 2020 Mar 27. PMID: 32216577
Microbiota are critical for vascular physiology: Germ-free status weakens contractility and induces sex-specific vascular remodeling in mice. Edwards JM, Roy S, Tomcho JC, Schreckenberger ZJ, Chakraborty S, Bearss NR, Saha P, McCarthy CG, Vijay-Kumar M, Joe B, Wenceslau CF. Vascul Pharmacol. 2020 Feb-Mar;125-126:106633. doi: 10.1016/j.vph.2019.106633. Epub 2019 Dec 13. PMID: 31843471
Vancomycin prevents fermentable fiber-induced liver cancer in mice with dysbiotic gut microbiota. Singh V, Yeoh BS, Abokor AA, Golonka RM, Tian Y, Patterson AD, Joe B, Heikenwalder M, Vijay-Kumar M. Gut Microbes. 2020 Mar 30:1-15. doi: 10.1080/19490976.2020.1743492. Online ahead of print. PMID: 32223398
Genetic predisposition for increased red blood cell distribution width is an early risk factor for cardiovascular and renal comorbidities. Cheng X, Mell B, Alimadadi A, Galla S, McCarthy CG, Chakraborty S, Basrur V, Joe B. Dis Model Mech. 2020 Apr 3:dmm.044081. doi: 10.1242/dmm.044081. Online ahead of print. PMID: 32238420
Metabolites and Hypertension: Insights into Hypertension as a Metabolic Disorder: 2019 Harriet Dustan Award. Chakraborty S, Mandal J, Yang T, Cheng X, Yeo JY, McCarthy CG, Wenceslau CF, Koch LG, Hill JW, Vijay-Kumar M, Joe B.Hypertension. 2020 Apr 27:HYPERTENSIONAHA12013896. doi: 10.1161/HYPERTENSIONAHA.120.13896. Online ahead of print. PMID: 32336227
Probiotics Prevent Dysbiosis and the Rise in Blood Pressure in Genetic Hypertension: Role of Short-Chain Fatty Acids. Robles-Vera I, Toral M, de la Visitación N, Sánchez M, Gómez-Guzmán M, Romero M, Yang T, Izquierdo-Garcia JL, Jiménez R, Ruiz-Cabello J, Guerra-Hernández E, Raizada MK, Pérez-Vizcaíno F, Duarte J. Mol Nutr Food Res. 2020 Mar;64(6):e1900616. doi: 10.1002/mnfr.201900616. Epub 2020 Feb 6. PMID: 31953983
The obligatory role of the acetylcholine-induced endothelium-dependent contraction in hypertension: Can arachidonic acid resolve this inflammation? Edwards JM, McCarthy CG, Wenceslau CF. Curr Pharm Des. 2020 Apr 17. doi: 10.2174/1381612826666200417150121. Online ahead of print. PMID: 32303165
Mitophagy in Hypertension-Associated Premature Vascular Aging. Schreckenberger ZJ, Wenceslau CF, Joe B, McCarthy CG. Am J Hypertens. 2020 Apr 6:hpaa058. doi: 10.1093/ajh/hpaa058. Online ahead of print.PMID: 32533696
Renal Fibrosis Is Significantly Attenuated Following Targeted Disruption of Cd40 in Experimental Renal Ischemia. Zhang S, Breidenbach JD, Khalaf FK, Dube PR, Mohammed CJ, Lad A, Stepkowski S, Hinds TD, Kumarasamy S, Kleinhenz A, Tian J, Malhotra D, Kennedy DJ, Cooper CJ, Haller ST. J Am Heart Assoc. 2020 Apr 7;9(7):e014072. doi: 10.1161/JAHA.119.014072. Epub 2020 Mar 21. PMID: 32200719
The interferon-inducible protein TDRD7 inhibits AMP-activated protein kinase and thereby restricts autophagy-independent virus replication. Subramanian G, Popli S, Chakravarty S, Taylor RT, Chakravarti R, Chattopadhyay S.J Biol Chem. 2020 Apr 9:jbc.RA120.013533. doi: 10.1074/jbc.RA120.013533. Online ahead of print. PMID: 32273341
High Throughput Screening of FDA-Approved Drug Library Reveals the Compounds that Promote IRF3-Mediated Pro-Apoptotic Pathway Inhibit Virus Replication. Glanz A, Chawla K, Fabry S, Subramanian G, Garcia J, Jay B, Ciricillo J, Chakravarti R, Taylor RT, Chattopadhyay S. Viruses. 2020 Apr 14;12(4):E442. doi: 10.3390/v12040442. PMID: 32295140
Kirkpatrick JF and Turner JWJr (2020), Wildlife Contraception and Political Cuisinarts (Chapt. 19), In ( Allen DM and Howell JW, eds.) Title: Groupthink in Science, (subtitle; Greed, Pathological Altruism, Ideology, Competition and Culture), Springer Int’l Publ., New York , 278 pp. [ ISBN 978-3-030-36822-7 ].
Gnotobiotic Rats Reveal That Gut Microbiota Regulates Colonic mRNA of Ace2, the Receptor for SARS-CoV-2 Infectivity.Yang T, Chakraborty S, Saha P, Mell B, Cheng X, Yeo JY, Mei X, Zhou G, Mandal J, Golonka R, Yeoh BS, Putluri V, Piyarathna DWB, Putluri N, McCarthy CG, Wenceslau CF, Sreekumar A, Gewirtz AT, Vijay-Kumar M, Joe B.Hypertension. 2020 Jul;76(1):e1-e3. doi: 10.1161/HYPERTENSIONAHA.120.15360. Epub 2020 May 19.PMID: 32426999
Diurnal Timing Dependent Alterations in Gut Microbial Composition Are Synchronously Linked to Salt-Sensitive Hypertension and Renal Damage. Chakraborty S, Mandal J, Cheng X, Galla S, Hindupur A, Saha P, Yeoh BS, Mell B, Yeo JY, Vijay-Kumar M, Yang T, Joe B.Hypertension. 2020 Jul;76(1):59-72. doi: 10.1161/HYPERTENSIONAHA.120.14830. Epub 2020 May 26.PMID: 32450738
Altered nutrient status reprograms host inflammation and metabolic health via gut microbiota. Golonka RM, Xiao X, Abokor AA, Joe B, Vijay-Kumar M.J Nutr Biochem. 2020 Jun;80:108360. doi: 10.1016/j.jnutbio.2020.108360. Epub 2020 Feb 22. PMID: 32163821 Review.

Soyoung Cheon and Vaishnavi (Vaish) Aradhyula were accepted to UT's Medical School Program. We are so proud of you both and wish you all the best.

Dr. Shermel Sherman from Dr. Jennifer Hill's Lab successfully defended her thesis on June 19, 2020. Well done, Shermel!

The high school students who spent their fall with us obtaining college credit for research presented their work virtually at the State Science Day and won Ohio Academy of Science placements. Shrey Gupta, who worked with Dr. Ritu Chakravarti won an 'Excellent' rating. Daven Serakonda, who worked under Dr. Matam Vijay-Kumar, Avinash Singh who worked closely with Dr. Cameron McCarthy and Evangelina Louis who worked closely with Saroj Chakraborty, all obtained a superior rating. Ms. Louis also won first prize for statistical analysis. We are proud of these talented students.

Congratulations to Dr. Ritu Chakravarti and Dr. Bina Joe! Their patent, "Materials and Methods for the Prevention of Rheumatoid Arthritis", was published on May 22, 2020.

Dr. Usman Ashraf from Dr. Sivarajan Kumarasamy's Lab successfully defended his thesis on May 29, 2020. Well done, Usman! Usman has accepted a Post-Doc Fellowship at the University of Mississippi Medical Center.

Congratulations to Dr. Beng San Yeoh, Postdoc who was selected by the American Physiological Society to submit a full application for the 2020-2021 Postdoctoral Fellowship program. Good Luck Beng!

Congratulations to Rachel Golonka for her first-authored publication with her colleagues, Dr. Beng San Yeoh, her mentor Dr. Matam Vijay Kumar and their collaborators from the University of Alabama. Their manuscript, "Fermentable fiber-induced hepatocellular carcinoma in mice recapitulates gene signatures found in human liver cancer" was accepted for publication in PLoSOne.

Congratulations to Dr. Camilla Wenceslau! She was selected as the winner of the 2020 John Laragh Research Award of the American Journal of Hypertension (AJH).

The editors have judged her work to be exemplary in the field of hypertension. She has been invited to submit a manuscript to the AJH and the award also consists of a plaque and $5,000.

https://academic.oup.com/ajh/pages/john_laragh_research_award

Congrats to Saroj Chakroborty, mentee of Dr. Bina Joe! His first authored manuscript was accepted for publication in the journal, Hypertension.

Title: Diurnal Timing Dependent Alterations in Gut Microbial Composition Are Synchronously Linked to Salt-Sensitive Hypertension and Renal Damage
Authors: Saroj Chakraborty, Juthika Mandal, Xi Cheng, Sarah Galla, Anay Hindupur, Piu Saha, Beng San Yeoh, Blair Mell, Ji-Youn Yeo, Matam Vijay-Kumar, Tao Yang, Bina Joe

Congratulations to Ms. Jonnelle Edwards and Colleagues in the Wenceslau Lab for their review article taking a closer look at a lipid, arachidonic acid, for its effect on vascular tone.
"The Obligatory Role of the Acetylcholine-Induced Endothelium-Dependent Contraction in Hypertension: Can Arachidonic Acid Resolve This Inflammation?"
Authors: Jonnelle M Edwards, Cameron G McCarthy, Camilla F Wenceslau

Congratulations to our May 2020 Graduates!

Master of Science in Biomedical Sciences
Ahmad Alimadadi
Bioinformatics and Proteomics/Genomics
Advisor: Bina Joe, Ph.D.

Doctor of Philosopy in Biomedical Science
Usman Ashraf
Molecular Medicine
Advisor: Sivarajan Kumarasamy, Ph.D.

Doctor of Philosopy in Biomedical Science
Shermel Borwluedae Sherman
Molecular Medicine
Advisor: Jennifer W. Hill, Ph.D.

During the months of May and December scholarships are awarded to graduating students in the College of Medicine and Life Sciences who have demonstrated excellence in Pharmacology and Physiology. These awards are named after one of the founding chairs of our department, Dr. Edward J. Cafruny. They are presented to the recipients by the MOME track director during the graduation awards ceremony held the evening before graduation. The current recipients are: DJ Kleppel - recipient of the Edward J. Cafruny Award for Excellence in Pharmacology and Jonathan Clement Henricks- recipient of the Outstanding Student Award in Physiology. Congrats to you both!

Congratulations to Dr. Tao Yang, et al! Their manuscript was recently accepted for publication in Hypertension!

Gnotobiotic Rats Reveal that Gut Microbiota Regulates Colonic mRNA of Ace2, the Receptor for SARS-CoV-2 Infectivity

Tao Yang1, Saroj Chakraborty1, Piu Saha1, Blair Mell1, Xi Cheng1, Ji-Youn Yeo1, Xue Mei1, Guannan Zhou1, Juthika Mandal1, Rachel Golonka1, Beng San Yeoh1, Vasanta Putluri2, Danthasinghe Waduge Badrajee Piyarathna3, Nagireddy Putluri2, Cameron G. McCarthy1, Camilla Wenceslau1, Arun Sreekumar2, Andrew T. Gewirtz4, Matam Vijay-Kumar1, Bina Joe1

1Microbiome Consortium, Center for Hypertension and Precision Medicine and the Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA

2Dan L. Duncan Cancer Center, Advanced Technology Core, Alkek Center for Molecular Discovery, Baylor College of Medicine, Houston, TX, USA

3Department of Molecular and Cell Biology, Baylor College of Medicine, Houston, TX, USA

4Center for Inflammation, Immunity, and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA

This study clearly showed that gut microbiota represents a critical factor for the regulation of colonic Ace2 expression and associated colonic and systemic factors that likely contribute to the pathology of the gut-lung axis during COVID-19. Therefore, further studies are necessary to examine the gut microbial composition and its role in ACE2 expression in the COVID-19 susceptible and resistant populations, which would importantly inform on better clinical management of COVID-19.

Shermel Sherman, graduate student of Dr. Jennifer Hill, was highlighted in the Toledo Blade for her article entitled, "UT researchers explore the possibilities of spexin". Read the full article in the link below.

https://www.toledoblade.com/a-e/culture/2020/05/04/ut-researchers-explore-the-possibilities-of-spexin/stories/20200406137

Congratulations on two new manuscripts published by Dr. John Turner!

The first one is a journal paper covering an 8-year study of contraception in wild horses in New Mexico by his research team. It was published in December.

Carey KA, Oritz A, Grams K, Elkins D, Turner JWJr, Rutberg AT (2019) , Efficacy of dart-delivered PZP-22 immunocontraceptive vaccine in wild horses (Equus caballus) in baited traps in New Mexico, USA. Wildlife Research, 46:713-718. [ https://doi.org/10.1071/WR18112 ]

The second one is a book chapter addressing more than 40 years of the political aspects of wildlife contraception. It was published April 24th.

Kirkpatrick JF and Turner JWJr (2020), Wildlife Contraception and Political Cuisinarts (Chapt. 19), In ( Allen DM and Howell JW, eds.) Title: Groupthink in Science, (subtitle; Greed, Pathological Altruism, Ideology, Competition and Culture), Springer Int’l Publ., New York , 278 pp. [ ISBN 978-3-030-36822-7 ].Kudos to Dr. Bina Joe's trainee, Dr. Ahmad Alimadadi! Ahmad is a Masters student in Bioinformatics and has accepted an intership at Scripps Research Institute in San Diego. He is highly skilled in machine learning and recently completed a project on cardiomyopathies.

Dr. Matam Vijay-Kumar was among three researchers at the University to receive Medical Research Society funding for COVID-19 research. As noted in the Dean's Update: "Dr. Vijay-Kumar is investigating flagellin — a bacterial component previously shown to eliminate viral infection — as a possible way to harness innate immune responses to fight the novel coronavirus that causes COVID-19. His project is also aimed at identifying biomarkers that can help clinicians diagnose the early and late stage biomarkers." Also, a hearty congratulations to Dr. Vijay-Kumar on his promotion to full Professor in the Department of Physiology and Pharmacology!

A publication emanating from Dr. Youjie Zhang's graduate work in Dr. Joe's laboratory has been selected as the cover for the April issue of Physiological Genomics. The art developed by the journal reflects the content of the publication to indicate that the microbiome is vertically co-inherited depending on the selection of the nuclear and mitochondrial genomes.

Congratulations to Dr. Cameron McCarthy, a Postdoctoral to Faculty Fellow from Dr. Bina Joe's lab! He has secured 5 year K99/R00 funding. This is no small feat. Your hard work and dedication have paid off!

The purpose of the NIH Pathway to Independence Award (K99/R00) program is to increase and maintain a strong cohort of new and talented, NIH-supported, independent investigators. This program is designed to facilitate a timely transition of outstanding postdoctoral researchers with a research and/or clinical doctorate degree from mentored, postdoctoral research positions to independent, tenure-track or equivalent faculty positions. The program will provide independent NIH research support during this transition in order to help awardees to launch competitive, independent research careers.

Project Title: Autophagy regulates β-hydroxybutyrate synthesis to prevent hypertension-associated premature vascular aging Grant Number: 1K99HL151889-01 Project Period: 07/01/2020 – 06/30/2022 (K99); 07/01/2022 - 06/30/2025 (R00)

Project Narrative
Hypertension is a condition of premature vascular aging, where the normal decline in vascular function as we age is accelerated and exacerbated. It is well established that upregulation of autophagy can ameliorate this “aged” phenotype; however, underlying mechanisms are yet to be determined. Given that autophagy also serves to mobilize macro- and micronutrients in times of stress, we hypothesize that upregulation of autophagy in the liver, stimulates the production of ketone body, β-hydroxybutyrate, which induces vasodilation, and decreases phenotypes of premature vascular aging associated with hypertension.

Congratulations to Dr. Matam Vijay Kumar and team! Their manuscript was accepted for publication by Physiological Reports.

Title:Distinct Iron Homeostasis in C57BL/6 and Balb/c Mouse Strains

Piu Saha#, Xia Xiao#, Yaqi Li, Rachel M. Golonka, Ahmed A. Abokor, Beng San Yeoh, and Matam Vijay-Kumar

# These authors contributed equally

Abstract
C57BL/6 (BL6) and Balb/c mice exhibit prototypical Th1- and Th2-dominant immune predispositions, respectively. Iron is a pro-inflammatory metal ion; however, limited information is documented on the differences in iron homeostasis between BL6 and Balb/c strains. The objective of this study was to investigate the extent to which strain-level differences in these mice dictates the regulation of iron homeostasis during physiologic and inflammatory conditions. At basal levels, Balb/c mice displayed significantly higher levels of iron in systemic circulation and tissue compared to BL6 mice. Moreover, Balb/c mice had greater iron absorption as indicated by higher gene expressions of duodenal DcytB, DMT1, Fpn, SFT, and Heph. Similarly, hepatic Tf, TfR1, TfR2, and DMT1 expressions were augmented in Balb/c mice. Interestingly, there was no change in hepatic Hamp expression between the two strains, suggesting that the disparity in their maintenance of iron is independent of hepcidin. Additionally, the basal levels of intracellular labile iron pool in Balb/c intestinal epithelial cells, and bone marrow-derived macrophages and neutrophils, were higher compared to BL6 mice. When mice were challenged with lipopolysaccharide, the acute inflammatory response in BL6 mice was more pronounced than in Balb/c mice, as indicated by the more rapid development of hypoferremia and upregulation of serum IL-6 and TNF-a levels in BL6 mice. In conclusion, this study underscores that iron homeostasis is distinct between BL6 and Balb/c strains under both physiologic and inflammatory conditions.

Congratulations to Dr. Ritu Chakravarti! The Research Council approved her proposal, entitled “14-3-3zeta- A Novel Supressor of Rheumatoid Arthritis” for funding under the deArce-Koch Memorial Endowment Program. The award is in the amount of $20,800.
Well done!

Congratulations to Dr. Vijay Matam Kumar! He was awarded funding for his URFO Biomedical Research Innovation Program application, “Dissecting hypcholesterolemia as a novel risk factor underlying the predisposition toward diet-induced liver cancer”, has been awardedat the amount of $42,000. Well done!

Congratulations to Dr. Ritu Chakravarti on two manuscripts recently accepted from on-going collaborative work with Dr. Saurabh Chattopadhyay!

The interferon-inducible protein TDRD7 inhibits AMP-activated protein kinase and thereby restricts autophagy-independent virus replication.

Subramanian G, Popli S, Chakravarty S, Taylor RT, Chakravarti R, Chattopadhyay S.
J Biol Chem. 2020 Apr 9. pii: jbc.RA120.013533. doi: 10.1074/jbc.RA120.013533. [Epub ahead of print]
Abstract
Interferon (IFN) regulatory factor 3 (IRF3) is the key transcription factor for the induction of IFN and antiviral genes. The absence of antiviral genes in IRF3 deficiency leads to susceptibility to a wide range of viral infections. Previously, we uncovered a function for nontranscriptional IRF3 (nt-IRF3), RLR (RIG-I-like receptor)-induced IRF3-mediated pathway of apoptosis (RIPA), which triggers apoptotic killing of virus-infected cells. Using knock-in mice expressing a transcriptionally inactive, but RIPA-active, IRF3 mutant, we demonstrated the relative contribution of RIPA to host antiviral defense. Given that RIPA is a cellular antiviral pathway, we hypothesized that small molecules that promote RIPA in virus-infected cells would act as antiviral agents. To test this, we conducted a high throughput screen of a library of FDA-approved drugs to identify novel RIPA activators. Our screen identified doxorubicin as a potent RIPA-activating agent. In support of our hypothesis, doxorubicin inhibited the replication of vesicular stomatitis virus, a model rhabdovirus, and its antiviral activity depended on its ability to activate IRF3 in RIPA. Surprisingly, doxorubicin inhibited the transcriptional activity of IRF3. The antiviral activity of doxorubicin was expanded to flavivirus and herpesvirus that also activate IRF3. Mechanistically, doxorubicin promoted RIPA by activating the extracellular signal-regulated kinase (ERK) signaling pathway. Finally, we validated these results using another RIPA-activating compound, pyrvinium pamoate, which showed a similar antiviral effect without affecting the transcriptional activity of IRF3. Therefore, we demonstrate that the RIPA branch of IRF3 can be targeted therapeutically to prevent virus infection.

High throughput screening of FDA-approved drug library reveals the compounds that promote IRF3-mediated pro-apoptotic pathway inhibit virus replication.

Glanz A, Chawla K, Fabry S, Subramanian G, Garcia J, Jay B, Ciricillo J, Chakravarti R, Taylor RT, Chattopadhyay S.
Viruses (accepted)
Abstract
The interferon (IFN) system is the first line of defense against virus infection. Recently, using a high-throughput genetic screen of a human IFN-stimulated gene (ISG) shRNA library, we identified a viral restriction factor, Tudor domain containing 7 (TDRD7). TDRD7 inhibits the paramyxo/pneumo viruses (e.g. Sendai virus and respiratory syncytial virus) by interfering with the virus-induced cellular autophagy pathway, which these viruses use for their replication. Here, we report that TDRD7 is a viral restriction factor against herpes simplex virus (HSV-1). Using knockdown, knockout, and ectopic expression systems, we demonstrate the anti-HSV-1 activity of TDRD7 in multiple human and mouse cell types. TDRD7 inhibited the virus-activated AMP-activated protein kinase (AMPK), which was essential for HSV-1 replication. Genetic ablation or chemical inhibition of AMPK activity suppressed HSV-1 replication in multiple human and mouse cells. Mechanistically, HSV-1 replication after viral entry was dependent on AMPK, but not on its function in autophagy. The antiviral activity of TDRD7 was dependent on its ability to inhibit virus-activated AMPK. In summary, our results indicate that the newly identified viral restriction factor TDRD7 inhibits AMPK and thereby blocks HSV-1 replication independently of the autophagy pathway. These findings suggest that AMPK inhibition represents a potential strategy to manage HSV-1 infections.
Kudos to Vaishnavi Aradhyula from Dr. Camilla Wenceslau's lab! She received an honorable mention for her presentation during the Three Minute Thesis Competition.

Congratulations to Dr. Matam Vijay Kumar and team who published an editorial on COVID-19! The following editorial was accepted for publication to AJP-Physiological Genomics.
Harnessing Innate Immunity to Eliminate SARS-CoV-2 and Ameliorate COVID-19 Disease
Authors: Rachel M. Golonka, Piu Saha, Beng San Yeoh, Saurabh Chattopadhay, Andrew T. Gewirtz, Bina Joe, Matam Vijay-Kumar
Abstract:
The newest coronavirus disease, COVID-19, has become the cause of a worldwide pandemic. Along with social distancing to minimize the COVID-19 wildfire-like spread, clinicians and research teams around the globe are working toward developing effective vaccines and repurposing anti-viral drugs to fight against COVID-19. Besides these conventional methods, we suggest that immunomodulation of innate immunity could present a novel, non-conventional approach to combat COVID-19.

Congratulations to Dr. Andrew Beavis!

He has been selected as the recipient of the Golden Apple Award for Basic Sciences by the COMLS Graduating Class of 2020! This is the third time he has received the Golden Apple Award.

Kudos to Ms. Rachel Golonka from Dr. Vijay-Kumar’s laboratory! She has won the first prize in the University-wide 3-minute thesis competition!

She will be heading to the State-level competition. Congrats Rachel and Vijay!! Also proud that Ahmed Abokor from the same lab competed and represented our Department.

A hearty congratulations to Dr. Bina Joe's trainee, Dr. Ahmad Alimadadi, who is pursuing his MS in Bioinformatics! He has been selected as the recipient of the COMLS Class of 2020 Graduate Student Award. Even though UT will not be having the in-person pre-commencement awards ceremony, award recipients will still be receiving an award plaque and check for their excellent achievements. Well done, Ahmad, you make us proud!

Ji-Youn Yeo was recently highlighted in the Toledo Blade on her work in helping bring Coronavirus testing to UTMC. Read the full article here: http://www4.toledoblade.com/local/Coronavirus/2020/04/01/how-university-toledo-medical-center-specialists-brought-coronavirus-testing-lucas-county/stories/20200401137

She was also highlighted in the UT news: http://news.utoledo.edu/index.php/04_08_2020/early-interest-in-covid-19-testing-helped-utmc-launch-lab-services

Congratulations to Dr. Tao Yang who recently had 3 manuscripts accepted for publication!
1. Maternal Treatment With Captopril Persistently Alters Gut-Brain Communication and Attenuates Hypertension of Male Offspring. Hypertension (Accepted).
Hong-Bao Li, Tao Yang, Elaine M. Richards, Carl J. Pepine, Mohan K. Raizada
Abstract: Maternal-fetal crosstalk has been implicated in long-term control of the health of offspring, including transgenerational hypertension. However, current knowledge is limited regarding maternal influences on the gut and its microbiome in blood pressure control in offspring. Therefore, the current study was designed to test the hypothesis that maternal factors influence the gut-brain axis impacting hypertension in offspring. We elected to use captopril, an antihypertensive angiotensin-converting enzyme inhibitor that possesses antibacterial properties, for the study. Pregnant female spontaneously hypertensive rats and normotensive Wistar Kyoto rats were treated with captopril water (100 mg/[kg·day]) or sterile water throughout pregnancy and lactation. At weaning, the pups from dams drinking sterile water were continued with sterile water until 12 weeks of age. The male pups from dams drinking captopril water were divided at weaning into 2 groups: offspring drinking captopril water and offspring withdrawn from captopril water, then drinking sterile water until 12 weeks of age. Captopril changed gut microbiota of spontaneously hypertensive rat dams, and some of these changes were reflected in their 12-week-old male offspring. These 12-week-old spontaneously hypertensive rat male offspring exposed to captopril via dams demonstrated persistently decreased systolic blood pressure, decreased number of activated microglia and neuroinflammation, as well as improvement of gut inflammation and permeability. Therefore, maternal captopril treatment improves the dysregulated gut-brain axis in spontaneously hypertensive rat male offspring, providing conceptual support that targeting the gut-brain axis via the mother may be a viable strategy for control of hypertension in the offspring.

2. Gut Pathology and Its Rescue by ACE2 in Hypoxia-Induced Pulmonary Hypertension. Hypertension (Accepted).
Ravindra Sharma , Aline Oliveira , Tao Yang , Marianthi Karas , Jing Li , Gilberto Lobaton , Victor Aquino , Inaki Robles-Vera , Annette de Kloet , Eric Krause , Andrew Bryant , Amrisha Verma , Qiuhong Li , Elaine Richards, Mohan Raizada
Abstract: Therapeutic advances for pulmonary hypertension (PH) have been incremental because of the focus on the pulmonary vasculature in PH pathology. Here, we evaluate the concept that PH is, rather, a systemic disorder involving interplay among multi-organ systems including brain, gut and lungs. Therefore, the objective of this study was to evaluate the hypothesis that PH is associated with a dysfunctional brain-gut-lung axis and that global overexpression of angiotensin-converting enzyme 2 (ACE2) rebalances this axis and protects against PH. ACE2 knock-in (ACE2KI) and wild-type (WT; C57BL/6) mice were subjected to chronic hypoxia (10% FIO2) or room air for 4 weeks. Cardio-pulmonary hemodynamics, histology, immunohistochemistry and fecal 16S rRNA microbial gene analyses were evaluated. Hypoxia significantly increased right ventricular systolic pressure, sympathetic activity as well as the number and activation of microglia in the paraventricular nucleus of the hypothalamus (PVN) in WT mice. This was associated with a significant increase in muscularis layer thickening, and decreases in both villi length and goblet cells and altered gut microbiota. Global overexpression of ACE2 prevented changes in hypoxia-induced pulmonary and gut pathophysiology and established distinct microbial communities from WT hypoxia mice. Further, WT mice subjected to fecal matter transfer (FMT) from ACE2KI mice were resistant to hypoxia-induced PH compared with their controls receiving WT FMT. These observations demonstrate that ACE2 ameliorates these hypoxia-induced pathologies and attenuates PH. The data implicate dysfunctional brain-gut-lung communication in PH and provide novel avenues for therapeutic interventions.

3. Gastrointestinal dysbiosis following diethylhexyl phthalate exposure in zebrafish (Danio rerio): altered microbial diversity, functionality, and network connectivity. Environmental Pollution (Accepted).
Amanda N Buerger, David T Dillon, Jordan Schmidt, Tao Yang, Jasenka Zubcevic, Christopher J Martyniuk, Joseph H Bisesi
Abstract: Microbiome community structure is intimately involved in key biological functions in the gastrointestinal (GI) system including nutrient absorption and lipid metabolism. Recent evidence suggests that disruption of the GI microbiome is a contributing factor to metabolic disorders and obesity. Poor diet and chemical exposure have been independently shown to cause disruption of the GI microbiome community structure and function. We hypothesized that the addition a chemical exposure to overfeeding exacerbates adverse effects on the GI microbiome community structure and function. To test this hypothesis, adult zebrafish were fed a normal feeding regime (Control), an overfeeding regime (OF), or an overfeeding regime contaminated with diethylhexyl phthalate (OF+DEHP), a suspected obesogen-inducing chemical. After 60 days, fecal matter was collected for sequencing, identification, and quantification of the GI microbiome using the 16s rRNA hypervariable region. Analysis of beta diversity indicated distinct microbial profiles between treatments with the largest divergence between Control and OF+DEHP groups. Based upon functional predictions, OF+DEHP treatment altered carbohydrate metabolism, while both OF and OF+DEHP affected biosynthesis of fatty acids and lipid metabolism. Co-occurrence network analysis revealed decreases in cluster size and a fracturing of the microbial community network into unconnected components and a loss of keystone species in the OF + DEHP treatment when compared to Control and OF treatments. Data suggest that the addition of DEHP in the diet may exacerbate microbial dysbiosis, a consequence that may explain in part its role as an obesogenic chemical.

Congratulations to Dr. Matam Vijay Kumar! His proposal to the University Research Funding Opportunity (URFO) Biomedical Research Innovation Program, “Dissecting hypcholesterolemia as a novel risk factor underlying the predisposition toward diet-induced liver cancer”, has been awarded. Well done!

Congratulations to Dr. Bina Joe and team on their manuscript being accepted for publication to Disease Models & Mechanisms!

TITLE: Genetic predisposition for increased red blood cell distribution width is an early risk factor for cardiovascular and renal comorbidities

AUTHORS: Xi Cheng, Blair Mell, Ahmad Alimadadi, Sarah Lynn Galla, Cameron G McCarthy, Saroj Chakraborty, Basrur Venkatesha, and Bina Joe

Abstract

Red blood cell distribution width (RDW) is a measurement of the variation in size and volume of red blood cells (RBCs). Increased RDW, indicating a high heterogeneity of RBCs, is prominently associated with a variety of illnesses, especially cardiovascular diseases. However, the significance of this association to the onset and progression of cardiovascular and renal diseases is unknown. We hypothesized that a genetic predisposition for increased RDW is an early risk factor for cardiovascular and renal comorbidities. Since there is no known animal model of increased RDW, we examined a CRISPR/Cas9 gene-edited rat model (RfflTD) which presented with features of hematologic abnormalities as well as severe cardiac and renal comorbidities. A mass-spectrometry based quantitative proteomic analysis indicated anemia of these rats presented with significant downregulation of hemoglobin and haptoglobin. Decreased hemoglobin and increased RDW were further observed in RfflTD through complete blood count. Next, a systematic temporal assessment detected an early increased RDW in RfflTD, which was prior to the development of other comorbidities. The primary mutation of RfflTD is a 50bp deletion in a non-coding region, whereby, our study has serendipitously identified this locus as a novel quantitative trait locus (QTL) for RDW.To our knowledge, our study is the first to experimentally pinpoint a QTL for RDW and provides a novel genetic rat model mimicking the clinical association of increased RDW with poor cardio-renal outcomes.

Congratulations to the Artificial Intelligence and Machine learning laboratory in our Department for their latest publication focused on COVID-19. Dr. Xi Cheng, who directs this laboratory along with Dr. Joe and 3 of her students who are pursuing their bioinformatics degrees: Ahmad Alimadadi, Ishan Manandhar and Sachin Aryal, authored this timely publication on artificial intelligence and machine learning applications to combat COVID-19. Read the article here: https://journals.physiology.org/doi/full/10.1152/physiolgenomics.00029.2020

Well done to Dr. Vijay Kumar and team! Their manuscript was accepted for publication.

Journal: AJP - Gastrointestinal and Liver Physiology

Title: Fermentable Fibers Induce Rapid Macro and Micronutrient Depletion in Toll-like Receptor 5 Deficient Mice

Authors: Rachel M. Golonka, Beng San Yeoh, Yaqi Li, Piu Saha, Ahmed Abokor, Xi Cheng, Xia Xiao, Darshan Shimoga Chandrashekar, Sooryanarayana Varambally, David J. Gonzalez, A. Catharine Ross, Matam Vijay-Kumar

Abstract: Functional fermentable fibers are considered essential for a healthy diet. Recently, we demonstrated that gut microbiota dysbiotic mice fed an inulin-containing diet (ICD) developed hepatocellular carcinoma (HCC) within 6 months. In particular, a subset of toll-like receptor 5-deficient (T5KO) mice prone to HCC exhibited rapid onset of hyperbilirubinemia (HB) and cholemia; these symptoms provide rationale that ICD induces cholestasis. Our objective in the current study was to determine whether inulin-fed T5KO-HB mice exhibit other known consequences of cholestasis, including essential fatty acid and fat-soluble vitamin deficiencies. Here, we measured hepatic fatty acids and serum vitamin A and D levels from WT, T5KO low bilirubin (LB) and T5KO-HB mice fed ICD for 4 weeks. Additionally, hepatic RNAseq and proteomics were performed to ascertain other metabolic alterations. Compared to WT and T5KO-LB, T5KO-HB mice exhibited steatorrhea, i.e. ~50% increase in fecal lipids. This could contribute to the significant reduction of linoleate in hepatic neutral lipids in T5KO-HB mice. Alongside, serum vitamins A and D were ~50% reduced in T5KO-HB mice, which was associated with metabolic compromises. Overall, our study highlights that fermentable fiber-induced cholestasis is further characterized by depletion of macro and micronutrients.

Dr. Anita Easterly was invited to serve as a judge for the qualifying rounds at the 3rd annual 3MT® (Three Minute Thesis®) competition, which is an exercise that develops academic, presentation and research communication skills. Students have 3 minutes to explain their research from a single PowerPoint slide. Anita judged 3 qualifying rounds. There will be 8 finalists chosen from UT to proceed in the final competition.

Four high schoolers in the department's college credit program participated in the Northwest Ohio District 2 Science Day that was held at the Thompson Student Union on Main Campus this past Saturday.

Daven Sarikonda, mentee of Dr. Matam Vijay Kumar, won one of the top two awards at the fair. He is the recipient of the Tillotson University of Toledo District Science Day Scholarship which is a $1000 award that is renewable for three years. Daven will be moving on to the Ohio Academy of Science's 72nd Annual State Science Day which will take place on Saturday, May 9, 2020, and is hosted by Ohio State University.

Shrey Gupta, a mentee of Dr. Ritu Chakravarti, won the "Achievement Rating of Superior In Recognition of a Science Project Presented at District Science Day at the University of Toledo” and qualified to present at State Science Day at Ohio State University and the Buckeye Science and Engineering Fair 2020 (BSEF) at Ohio State University.

Evangelina "Angie" Louis, a mentee of Dr. Bina Joe, won the first prize in the entire competition and the SciFood, Nutrition & Health Diatetic Association Special (cash) award. Angie qualifies to move on to the Ohio Academy of Science's 72nd Annual State Science Day and the Buckeye Science and Engineering Fair. Angie will also be presenting at the 57th Ohio Junior Science and Humanities Symposium to be held at BGSU this week.

Avinash Singh, a mentee of Dr. Bina Joe, earned a perfect score on his presentation at the fair and also qualifies to move on to the Ohio Academy of Science's 72nd Annual State Science Day. These are hard working and talented young people that have raised the research profile of our department. Congratulations to their mentors for guiding them and please join me in wishing these students the best of luck in the upcoming fairs and competitions.

Mitchell Harberson, a trainee of Dr. Jennifer Hill, has been invited to present a poster at the University of Michigan Diabetes Research Center's Annual Diabetes Symposium 2020. The meeting will be held Saturday, March 14. The title of Mitchell's poster is "Dopamine Neurons Mediate Bremelanotide Action in Female Hypoactive Sexual Desire Disorder" and the authors are: Mitchell T. Harberson, Jessica Brockert, Jennifer W. Hill.

Good luck on your presentation, Mitchell!

Congratulations to Ahmed Abokor, Vaishnavi Aradhyul, Rachel Golonka and Sudipta Baroi for being selected as four of the eight finalists of the 3MT® (Three Minute Thesis®) competition!

Dr. Matam Vijay-Kumar was invited to lecture at the University of Michigan's Mucosal Immunology Pathology Symposium held last Friday. His team also presented oral and poster presentations. Well done, each of you!

Congrats to Dr. Ritu Chakravarti!

Her abstract, “Novel Mechanism of Regulating IL-17 Signaling by 14-3-3zeta”, has been selected for podium presentation at IMMUNOLOGY2020T in Honolulu, HI at the Hawaii Convention Center. The meeting will be held May 8-12, 2020.

Additionally, she has been selected by the American Association of Immunologists as a recipient of a 2020 AAI Early Career Faculty Travel Grant.

March 8th we celebrated International Women’s Day. Over the years, we have grown significantly in the number of women faculty and staff in our department. We are especially proud of both the academic and cultural vibrancy that women faculty, staff and students bring to our everyday work-life. Also, as an invited speaker in a Toledo Community organized event celebrating this day, Dr. Bina Joe had the opportunity to share some of our academic accomplishments as women scientists in Toledo. NBC24 coverage of this event can be viewed below.

The 2020 HSC Artist Showcase at the Mulford Library features many wonderul exhibits, including pieces from Phys/Pharm faculty members, Drs. Andrew Beavis and John Turner. The exhibits are on display through April.

Hearty congratulations to both Dr. Beng San Yeoh and MOME Trainee, Rachel Golonka! They will both present at the Society for Mucosal Immunology - Local Chapter Meeting in Ann Arbor, MI. Dr. Yeoh's research entitled 'Persistent IL-1β Signaling Aggravates Murine Enteropathogen, Citrobacter rodentium infection in mice' was accepted for a poster presentation. Rachel's research was accepted for an oral presentation. Her presentation is titled, "Aggravated colitis in Farnesoid X Receptor deficient mice is associated with altered immunological responses and a reshaped gut microbiota". Rachel is a trainee of Dr. Matam Vijay Kumar. SMI brings together researchers from the University of Michigan, Michigan State University, Wayne State University, and the University of Toledo to discuss current topics in immunology at mucosal surfaces.

This symposium is sponsored by the Society for Mucosal Immunology and invites all investigators to share their work, but specifically aims to promote the work of junior investigators.

Dr. Tao Yang has been invited to serve on the Editorial Board of Hypertension, a prestigious international journal of the American Heart Association.

Dr. Yang is a member of the UT Microbiome Consortium (UT MiCo). He has considerable experience in studying the gut-brain axis in hypertension and was recently recruited from the University of Florida to develop his independent research in this area under Dr. Bina Joe's mentorship.

Congratulations to Dr. Matam Vijay Kumar and team! Their manuscript entitled, "Vancomycin prevents fermentable fiber-induced liver cancer in mice with dysbiotic gut microbiota" was accepted for publication in Gut Microbes.

Authors: Vishal Singh#, Beng San Yeoh#, Ahmed A. Abokor, Rachel M. Golonka, Yuan Tian, Andrew D. Patterson, Bina Joe, Mathias Heikenwalderand Matam Vijay-Kumar
#These authors contributed equally

Dr. Bina Joe has been invited by the Toledo Opera Guild to speak at the International Women's Day celebration to be held at the Pinnacle, Sunday, March 8th from 10 a.m to 3 p.m. Please see the announcement in the Toledo City Newspaper.

There will be educational booths, activities and entertainment throughout the day and Dr. Joe's classical dance troupe will be performing at 10:30 a.m. and the speakers begin at 12:15 p.m.

https://toledocitypaper.com/feature/international-womens-day-2020/

Dr. Bina Joe's research was highlighted in the UT Alumni eMagazine. See the link for the whole article. https://alumninews.utoledo.edu/2020/02/17/utoledo-faculty-break-new-ground-in-research-attract-project-funding/

Dr. Matam Vijay-Kumar was invited to speak at the 2020 Microbiome, Viruses, and Cancer Meeting of the American Association for Cancer Research (AACR) in Orlando, FL this past weekend.

He presented his work during the Microbiota and Gastrointestinal Cancer session and his talk was titled, "Gut microbiota dysbiosis and dietary fermentable fibers in a pickle: a brew for liver cancer".

An abstract of Usman Ashraf, a trainee of Dr. Sivarajan Kumarasamy, has been selected for a poster presentation during the Midwest Clinical and Translational Research Meeting of CSCTR and MWAFMR at the Holiday Inn Chicago Mart Plaza in Chicago in April. Well done!

The title of Usman's abstract is: Transcriptomic Analysis of Resp18mutant Rat Kidneys Reveals Up-Regulation of Renin-Angiotensin System.

Dr. Jennifer Hill served as a reviewer of The Integrative Physiology of Obesity and Diabetes (IPOD) Study Section this past week.

This study section reviews applications dealing with etiology and treatment of metabolic disturbances associated with obesity and diabetes, involving endocrinology, molecular/genetic, biochemical, neuroanatomical, systems biology, dietary, metabolic and integrative physiological approaches. Emphasis is on integrative systems approaches to elucidating peripheral and central regulatory pathways of carbohydrate, lipid and energy homeostasis in animals and cellular models.

Dr. Bina Joe has been invited to lecture at the Joint Meeting of the European Society of Hypertension (ESH) and the International Society of Hypertension (ISH) that will be held in Glasgow, UK, from 29th May 2020 to 1st June 2020.

The lecture will be part of an oral session titled, "Experimental Hypertension".

Congratulations to the trainees from our department who have been selected for oral presentations at the 2020 Graduate Research Forum. Below are the topics each will be presenting on. In addition to attending the poster sessions at the forum, I hope that we can all attend our departmental students' oral presentations.

Ahmad Alimadadi (Joe Lab) - "Application of Artificial Intelligence via Machine Learning to Classify Clinical Cardiomyopathies Using RNA-Seq Data"

Saroj Chakraborty (Joe Lab) - "Bile acid metabolites modulate Hypertension"

Jonnelle Edwards (Wenceslau Lab) - "Formyl Peptide Receptor-1 Activation is Crucial for Spontaneous Hypertension in Dahl Salt Sensitive Rats"

Good luck to all!

Our faculty and students are adding to community outreach, which is one of the important activities of the University of Toledo. On Thursday of last week, several of our department's faculty and students participated as judges for the 2020 Science Fair at Ottawa Hills High School. Mr. Jeremy Nixon, one of the school's science teachers, organized the event.

Congratulations to Dr. Kumar and team! Their manuscript, "Altered Nutrient Status Reprograms Host Inflammation and Metabolic Health via Gut Microbiota" was accepted to Journal of Nutritional Biochemistry. (Impact Factor: 4.518)

The authors are: Rachel M. Golonka, Xia Xiao, Ahmed Abokor, Bina Joe, Matam Vijay-Kumar

Kudos to Juthika Mandal! Juthika, a trainee from Dr. Bina Joe's lab, has been invited for oral presentation not only at EB 2020 but also at the Hypertension 2020 Meeting in Scotland. The title of her abstract is, "Concerted diurnal rhythms of gut microbiota with salt-sensitive hypertension and renal inflammation".

A hearty congratulations to Saroj Chakraborty! Saroj is a trainee from Dr. Bina Joe's lab and has been selected to participate in the March 2020 Cell Modeling Hackathon.

The hackathon is funded through the National Science Foundation (NSF). Saroj and a team of other selected participants will work as a group to generate a model of any particular cell system of their choice.

Congratulations to the Wenceslau and Joe Labs for two of their trainees, Soyoung Cheon and Juthika Mandal who are invited for oral presentations at the upcoming Experimental Biology Meeting!

Abstract Title: Opioids Cause Vascular Remodeling via Changes in Cofilin-ERK Signaling: Female Mice Present Higher Risk of Developing Morphine-induced Cardiovascular Disease than Male Mice
Presenting Author: Soyoung Cheon (Trainee of Dr. Camilla Wenceslau)
Poster Presentation:
Session Title: Vascular Pharmacology I
Session Day: Tuesday, April 7, 2020
Oral Presentation:
Session Title: Symposium - ASPET Daily Datablitz - Tuesday
Session Day: Tuesday, April 7, 2020
Programming Society: American Society for Pharmacology and Experimental Therapeutics

Abstract Title: Concerted diurnal rhythms of gut microbiota with salt-sensitive hypertension and renal inflammation
Presenting Author: Juthika Mandal (Trainee of Dr. Bina Joe)
Poster Presentation:
Session Title: Diet, Nutrients and the Microbiome in Blood Pressure and Electrolyte Regulation
Session Day: Tuesday, April 7, 2020
Oral Presentation:
Session Title: Featured Topic - Diet, Nutrients and the Microbiome in Blood Pressure and Electrolyte Homeostasis and Allostasis
Session Day: Tuesday, April 7, 2020
Programming Society: The American Physiological Society

Also congratulations to the following high school through postdoctoral trainees who will be representing the department at the annual EB 2020 meeting. Congratulations to all!

Wenceslau Lab:

Abstract 1:
Title: Formyl Peptide Receptor-1 Activation is Crucial for Spontaneous and Salt-Induced Hypertension in Dahl Salt Sensitive Rats: Mitochondria vs. Microbiota
Presenting Author: Jonnelle Edwards
Poster Presentation:
Session Title: CV Section Young Investigators I
Session Day: Sunday, April 5, 2020
Programming Society: The American Physiological Society

Abstract 2:
Title: Female Rats Artificially Selected for Low and High Intrinsic Aerobic Capacity Swap Inflammatory Cascade in Resistance Arteries: Mechanisms of Cyclooxygenase-Derived Prostanoids
Presenting Author: Vaishnavi Aradhyula
Poster Presentation:
Session Title: Exercise, Health and Disease
Session Day: Sunday, April 5, 2020
Programming Society: The American Physiological Society

Abstract 3:
Title: Commensal microbiota are essential for vascular contractility mediated by actin polymerization
Presenting Author: Janara Furtado
Poster Presentation:
Session Title: Cardiovascular Disease and Metabolic Disorders II
Session Day: Tuesday, April 7, 2020
Programming Society: The American Physiological Society

Joe Lab:

Abstract 1:
Title: Gnotobiotic rats reveal an obligatory role of microbiota in blood pressure
Presenting Author: Saroj Chakraborty
Poster Presentation:
Session Title: CV Section Young Investigators II
Session Day: Tuesday, April 7, 2020
Programming Society: The American Physiological Society

Abstract 2:
Title: Sex differences in salt-responsive modulation of bile acids by microbiota regulates Hypertension
Presenting Author: Saroj Chakraborty
Poster Presentation:
Session Title: CV Section Young Investigators II
Session Day: Tuesday, April 7, 2020
Programming Society: The American Physiological Society

Abstract 3:
Title: &[beta]-Hydroxybutyrate (&[beta]OHB) Activates Gpr109a to Contribute to the Anti-vascular Aging Effect of Autophagy
Presenting Author: Cameron McCarthy
Poster Presentation:
Session Title: Heterocellular Communication in the Heart and Vasculature
Session Day: Tuesday, April 7, 2020
Programming Society: The American Physiological Society

Abstract 4:
Title: Reshaping commensal gut microbiota in early life lowers blood pressure potentially via a succinate mediated mechanism
Presenting Author: Saroj Chakraborty
Poster Presentation:
Session Title: Hypertension
Session Day: Tuesday, April 7, 2020
Programming Society: American Society for Pharmacology and Experimental Therapeutics

Abstract 5:
Title: A novel ex-vivo procedure for monitoring &[beta]-hydroxybutyrate (&[beta]OHB) production from isolated whole livers
Presenting Author: Avinash Singh
Poster Presentation:
Session Title: Liver Physiology and Pathophysiology
Session Day: Sunday, April 5, 2020
Programming Society: The American Physiological Society

Congratulations to Usman Ashraf, trainee of Dr. Sivarajan Kumarasamy, for his article that was published in the Toledo Blade today! The article is about salt sensitivity and blood pressure and can be viewed here:

https://www.toledoblade.com/culture/2020/02/03/ut-ressearch-explores-salt-and-blood-pressure

A hearty congratulations to two of Dr. Camilla Wenceslau's trainees!

Jonnelle Edwards and Vaish Aradhyula are both recipients of the 2020 Caroline tum Suden/Frances Hellebrandt Professional Opportunity Award.

This award helps trainees to attend the annual APS Experimental Biology Meeting. This year the meeting is held in April in San Diego.

Congratulations to Dr. Tao Yang! He has been selected to serve on the editorial board of Hypertension. His term will last three years.

Congrats to Dr. Matam Vijay-Kumar and Dr. Piu Saha who co-authored a manuscript, "Functional MAIT Cells Are Associated With Reduced Simian-Human Immunodeficiency Viru Infection" was accepted in Frontiers in Immunology!

Authors: Amudhan Murugesan, Chris Ibegbu, Tiffany M. Styles, Andrew T. Jones, Uma Shanmugasundaram, Pradeep B. J. Reddy, Sadia J. Rahman, Piu Saha, Matam Vijay-Kumar, Esaki Muthu Shankar, Rama Rao Amara, and Vijaykumar Velu

Drs. Camilla Wenceslau and Cameron McCarthy were featured in a debut podcast from theAmerican Physiological Society depicting the social life of scientists. Here is the link to the ‘Cam-squared’ episode featuring the two.

https://ajpheart.podbean.com/e/behind-the-bench-episode-one-cam-squared/

Kudos to Dr. Tao Yang for two recent manuscripts being accepted for publication!

"Transcriptomic signature of gut microbiome-contacting cells in colon of spontaneously hypertensive rats"
Journal: Physiological Genomics.
Authors: Tao Yang, Hongbao Li, Aline C. Oliveira, Ruby Goel, Elaine M. Richards, Carl J. Pepine and Mohan K. Raizada

"Probiotics prevent dysbiosis and the rise in blood pressure in genetic hypertension: role of short-chain fatty acids"
Journal: Molecular Nutrition & Food Research
Authors: Iñaki Robles-Vera, , Marta Toral, Néstor de la Visitación , Manuel Sánchez, Manuel Gómez-Guzmán, Miguel Romero, Tao Yang , José L. Izquierdo-Garcia , Rosario Jiménez, Jesús Ruiz-Cabello , Eduardo Guerra-Hernández , Mohan K Raizada , Francisco Pérez-Vizcaíno , Juan Duarte

Congratulations to Dr. Bina Joe and Blair Mell and collaborators in Australia! Their manuscript was accepted for publication to Journal of Pediatric Surgery.
Title: Interplay between collagenase and undescended testes in Adamts16 knockout rats
Authors: Gulcan Sarila, Tuya Bao, Sanduni Amaya Abeydeera, Ruili Li, Blair Mell, Bina Joe, Angelique Catubig, John

HutsonCongratulations to Dr. Jennifer Hill and team - their manuscript was accepted to Endocrinology!
Title: Microbial reconstitution reverses early female puberty induced by maternal high-fat diet during lactation
Authors: Mengjie Wang, Youjie Zhang, David Miller, Naveen O. Rehman, Xi Cheng, Ji-Youn Yeo, Bina Joe, Jennifer W. Hill

Congratulations to Masters student, Ahmad Alimadadi (Dr. Bina Joe's Lab) for his first publication and Dr. Xi Cheng, corresponding author! Our manuscript was accepted for publication in Genes.
Title: Meta-analysis of Dilated Cardiomyopathy Using Cardiac RNA-Seq
Transcriptomic Datasets
Authors: Ahmad Alimadadi, Patricia Munroe, Bina Joe, Xi Cheng

Congratulations to Dr. Bina Joe, students and colleagues who recently had a manuscript accepted for publication to JAHA: Journal of the American Heart Association! Title: Exposure to amoxicillin in early life is associated with changes in gut microbiota and reduction in blood pressure: Findings from a study on rat dams and offspring. Authors: Sarah Galla, PhD, Saroj Chakraborty, MS, Xi Cheng, PhD, Ji-Youn Yeo, PhD, Blair Mell, BS, Nathaline Chiu, BS, Camilla F. Wenceslau, PhD, Matam Vijay-Kumar, PhD, Bina Joe, PhD.

Congratulations to Jonnelle Edwards, mentee of Dr. Camilla Wenceslau, and team! Their manuscript, "Microbiota are critical for vascular physiology: Germ-free status weakens contractility and induces sex-specific vascular remondeling in mice", was accepted for publication in Vascular Pharmacology!

Several students and faculty of the Department are engaged in providing research training to honors high school students of Ottawa Hill High School. Dr. Joe was recently featured on WTOL News featuring this UT- Ottawa Hills partnership, which is also supported with funds for a research class at the school by ProMedica. https://www.wtol.com/article/life/family-focus/local-high-school-students-work-with-researchers-on-cancer-dna/512-b98e6325-d366-4467-849d-e5bb766f408e

Dr. Bina Joe has been selected as the 2020 Distinguished Mayerson-DiLuzio Visting Professor of the Department of Physiology at Tulane University in New Orleans. This award is presented to an outstanding physiologist who is also recognized for their unique relationships with the Tulane Physiology department and faculty. She will deliver a lecture and accept this award in late March. Congratulations!