Department of Physiology and Pharmacology

Ritu Chakravarti, Ph.D.

Assistant Professor
Office: 419.383.4468
Laboratory: 419.383.4212
Fax: 419.383.2871
Email: Ritu.Chakravarti@utoledo.edu 

 Listen to BBC interview with Dr. Chakravarti

Watch Dr. Chakravarti's work featured on UT's discovery site

Research Interest

Autoimmune diseases are associated with substantial socioeconomic costs. Primarily cytokines and autoantigens lead to dysregulation and chronic illness, which remain mostly incurable. About 80 clinically distinct autoimmune diseases affect approximately 4-8% American population and cost more than $100 billion per year. Rheumatoid arthritis, vasculitis, and lupus are some of the examples of autoimmune diseases. Our research is focused on promoting the understanding of autoantigen's role in autoimmune diseases. We have reported that 14-3-3 proteins are autoantigen in large vessel vasculitis. The 14-3-3 proteins play an essential role in the cell cycle, metabolism, autophagy, and signal transduction. The 14-3-3 proteins play very important immune functions in other species,  including plants and insects, but their role in human immune disease is yet emerging. The 14-3-3ζ, a family member, is an active antigen that promotes proinflammatory cytokine production in humans. Autoantigens are presumed to play a pathogenic role in autoimmune diseases; however, recent literature suggests that they can be useful tools to target autoimmunity. We use biochemical, bioinformatics, and genetic techniques to dissect the mechanism of autoantigenicity and understand its translational significance. We study the role of 14-3-3 proteins in rheumatoid arthritis, vasculitis, fungal infections, and several other diseases related to autoimmunity. Our work has generated two patents and several publications in the last few years. Additionally, we discovered that 14-3-3 proteins are not restricted to eukaryotes, but are present in certain bacteria and also shows significant sequence and structure similarity with human 14-3-3ζ, structure shown in the figure here. Serendipity!!

Publications

Complete List of Publications  

 R. Chakravarti. 2021. Immune Regulations by 14-3-3: A Misty Terrain. Immunobiology (in press)

 A. Glanz, S. Chakravarty, S. Fan, K. Chawla, G.S. Subramnaian, T. Rahman, D. Walters, R. Chakravarti & S. Chattopadhyay.  2021. Autophagic Degradation of IRF3 induced by the small molecule auranofin inhibits transcriptional and pro-apoptotic activities. Journal of Biological Chemistry, (in press).

Kim, K. Chun, J. McGowan, Y. Zhang, P.J. Czernik, B. Mell, B. Joe, S. Chattopadhyay, J. Holoshitz & R. Chakravarti*. 2021. 14-3-3z: A novel suppressor of inflammatory arthritis. Proceedings of National Academy of Science, 118(34): e2025257118.

A. Glanz, S. Chakravarty, M. Varghese, A. Kottapalli, S. Fan, R. Chakravarti & S. Chattopadhyay.  2021. Transcriptional and non-transcriptional activation, post-translational modifications, and anti-viral functions of Interferon regulatory factor-3 and viral antagonism by the SARS-Coronavirus. Viruses, 13(4): 575.

U.M. Ashraf, A.A. Abokor, J.M. Edwards, E.W. Waigi, R.S. Royfman, S.M. Hasan, K.B. Smedlund, A.M.G. Hardy, R. Chakravarti & L.G. Koch. 2021. SARS-Cov2, ACE2 expression, and systemic organ invasion. Physiological Genomics, 53(2):51-60.

J. McGowan,  C. Peter, J. Kim, S. Popli, B. Veerman, J. Saul-Beth, H. Conti, S. Pruett-Miller, S. Chattopadhyay, & R. Chakravarti*. 2020. 14-3-3z-TRAF5 axis governs Interleukin-17A signaling. Proc Natl Acad Sci USA. 10.1073/pnas.2008214117.

 G.S. Subramanian, S. Popli., S. Chakraborty, R.T. Taylor, R. Chakravarti, &S.Chattopadhyay. 2020. Interferon-Inducible Protein TDRD7 Inhibits AMPK to Restrict Autophagy-Independent Virus Replication. Journal of Biological Chemistry. 295(20): 6811-6822.

 A. Glanz, K. Chawla, S. Fabry, G.S. Subramanian, J. Garcia, B. Jay, J. Ciricillo, R.Chakravarti, R.T. Taylor, & S. Chattopadhyay. 2020. High throughput screening of FDA-approved drug library reveals the compounds that promote IRF3-mediated pro-apoptotic pathway inhibit virus replication. Viruses, 12(4): E442.

B. Benhuri, A. ElJack, B. Kahaleh, & R. Chakravarti*. 2019. Mechanisms and Biomarkers in Aortitis- A Review. Journal of Molecular Medicine (Berl), 10.1007/s00109-019-01838-1.

J. McGowan, C. Peter, S. Chattopadhyay, & R. Chakravarti*. 2019. 14-3-3ζ: A Novel Immunogen promotes inflammatory cytokine production. Frontiers in Immunology, 10: 1553. 

G.S. Subramanian, R. Chakravarti, & S. Chattopadhyay. 2018. Ifi204/p204, a new piece in the sepsis puzzle. Annals of Translational Medicine, 6(1): S12. 

E.A. Sweeny, A.B. Singh, R. Chakravarti, O. Martinez-Guzman, A. Saini, M. Haque, G. Garee, P.D. Dans, L. Hannibal, A.R. Reddi & D.J. Stuehr. 2018. Journal of Biological Chemistry, 293(37):14557-14568. 

A.K. Majors, R. Chakravarti, L.M. Ruple, R. Leahy, D.J. Stuehr, M. Lauer, S.C. Erzurum, A. Janocha & M.A. Aronica. 2018. PLoS One, 13(7): e0200074.

G.S. Subramanian, T. Kuzmanovic, Y. Zhang, C.B. Peter, M. Veleeparambil, R. Chakravarti, G.C. Sen & S. Chattopadhyay. 2018. A New Mechanism of Interferon’s Antiviral Action: Induction of Autophagy, Essential for Paramyxovirus Replication, is Inhibited by the Interfereon Stimulated Gene, TDRD7. PLoS Pathogens, 14(1): e1006877.

J. McGowan, J. Kratch, S. Chattopadhyay, B. Joe, H. Conti & R. Chakravarti* 2017. Bioinformatic Analysis Reveals New Determinants of Antigenic 14-3-3 Proteins and A Novel Antifungal Strategy. PLoS One, 12(12): e0189503.

B. Veerman & R. Chakravarti*. 2017. Qualitative and Quantitative assay of circulating autoantibodies against human tissue antigen. Bio-Protocol, 7(13).

M.  Swain, A. Bosali, G.S. Hoffman & R. Chakravarti*. 2017. 14-3-3: A glue for medial inflammation. Journal of Investigative Medicine, 65(4):874-875.

G.S. Subrammanian, K. Pan, R. Chakravarti, & S. Chattopadhyay. 2016. Biochemical Analysis of Caspase-8-dependent Proteolysis of IRF-3 in Virus-infected Cells. Bio-protocol, 6(22).

 R. Chakravarti*, K. Gupta, M. Swain, B. Willard, J. Scholtz, L. Svensson, E. Roselli, G. Pettersson, D. Johnston, E. Soltesz, M. Yamashita, D. Stuehr, T.M. Daly & G.S. Hoffman. 2015. 14-3-3 in Aortic Aneurysms: Identification of a Novel Auto-antigen in Large Vessel Vasculitis. Arthritis & Rheumatology, 67(7):1913-1921.

R. Chakravarti, K. Gupta, A. Majors, L. Ruple, M. Aronica & D. J. Stuehr. 2015.  Novel insights in mammalian catalase heme maturation: Effect of NO and thioredoxin-1.Free Radical Biology & Medicine, 82: 105-113.

H. Zhang, J. Amick, R. Chakravarti, S. Santarriaga, S. Schlanger, C. McGlone, M. Dare, J.C. Nix, K.M. Scagline, D.J. Stuehr, S. Misra & R.C. Page. 2015. A bipartite interaction between Hsp70 and CHIP regulates ubiquitination of chaperoned client proteins. Structure, 23(3): 472-482.

G. Revsbech, X. Shen, R. Chakravarti, F.B. Jensen, B. Thiel, A.L. Evans, J. Kindberg, O. Fröbert, D.J. Stuehr, C.G. Kevil and A. Fago. 2014. Hydrogen sulfide and nitric oxide metabolites in the blood of free-ranging brown bears and their potential roles in hibernation. Free Radical Biology & Medicine, 73: 349-357.

R. Chakravarti & D.J. Stuehr. 2012. Thioredoxin regulates cellular heme insertion via denitrosylation of Glyceraldehye-3-phosphate dehydrogenase. Journal of Biological Chemistry, 287(20): 16179-16186.

L. Hannibal, D. Collins, J. Brassard, R. Chakravarti, R. Vempati, P. Dorlet, J. Santolini, J.H. Dawson & D.J. Stuehr. 2012. Heme binding properties of Glyceraldehyde-3-phosphate Dehydrogenase. Biochemistry, 51(43): 8514-8529.

M. Aytekin, K.S Aulak, Haserodt S, R. Chakravarti, J. Cody, O.A. Minai & R.A. Dweik. 2012. Abnormal platelet aggregation in idiopathic pulmonary arterial hypertension: Role of nitric oxide. American Journal of Physiology- Lung Cellular & Molecular Physiology, 302(6): L512-520.

R. Chakravarti, K.S. Aulak, P.L. Fox& D.J. Stuehr. 2010. GAPDH Regulates Cellular Heme Insertion into Inducible Nitric Oxide Synthase. Proceedings of National Academy of Science, 107(42): 18004-18009.  This article has been chosen by Faculty of 1000 in the exceptional category.

S.M. Waheed, A. Ghosh, R. Chakravarti, A. Biswas, M.M. Haque, K. Panda & D.J. Stuehr. 2010. Nitric oxide blocks cellular heme insertion into a broad range of heme proteins. Free Radical Biology & Medicine, 48: 1548-1558.

M. Valiyaveettil, A. Bentley, P. Gurusahaney, R. Hussien, R. Chakravarti, N. Kureishy, S. Prag & J.C. Adams. 2008. Novel Role of Muskelin/RanBP9 Complex as a Nucleocytoplasmic Mediator of Cell Morphology Regulation. Journal of Cell Biology, 182(4):727-739.

R. Chakravarti & J.C. Adams. 2006. Comparative Genomics of the Syndecans Defines an Ancestral Genomic Context Associated with Matrilins in Vertebrates. BMC Genomics, 7(1): 83.

R. Chakravarti, V. Sapountzi & J.C. Adams. 2005. Functional Role of Syndecan-1 Cytoplasmic V Region in Lamellipodial Spreading, Actin Bundling, and Cell Migration. Molecular Biology of the Cell, 16(8): 3678-3691.

R. Chakravarti & V. Sahai. 2004. Compactin - A Review. Applied Microbiology & Biotechnology, 64(5): 618-624.

R. Chakravarti & V. Sahai. 2002. Optimization of Compactin Production in Chemically Defined Production Medium by Penicillium citrinum Using Statistical Methods. Process Biochemistry, 38(4): 481-486.

R. Chakravarti & V. Sahai. 2002. A New Medium for Production of Compactin by Penicillium citrinum. Biotechnology Letters, 24: 527-530.

Patents

Novel role of 14-3-3 inhibitor as an anti-fungal agent.
Treatment of Rheumatoid Arthritis by Therapeutic Administration of 14-3-3zeta.

Academic Appointments

• Assistant Professor, Department of Physiology and Pharmacology, University of Toledo, College of Medicine and Life Sciences, Toledo, OH. 2018-present
• Assistant Professor, Department of Surgery, University of Toledo, College of Medicine and Life Sciences, Toledo, OH. 2016-2018
• Assistant Professor, Cleveland Clinic Lerner College of Medicine, Cleveland, OH. 2014-2016
• Joint Staff, Rheumatic and Immunological Disease, Cleveland Clinic, Cleveland, OH. 2014-2016
• Project Staff, Lerner Research Institute, Cleveland Clinic, Cleveland, OH. 2013- 2016
• Research Associate, Lerner Research Institute, Cleveland, OH. 2006-2013
• Post-Doctoral Fellow, Lerner Research Institute, Cleveland Clinic, Cleveland, OH. 2002-2012

Awards and honors

• Early Career Faculty Travel Award 2019, Immunology 2019, San Diego, CA, USA.
• CSCTR Travel Award 2017, Central Society of Clinical & Translational Research, Chicago, USA.
• Travel Award 2011, Gordon Research Conference ‘Nitric Oxide’, Ventura, California, USA.
• Travel Award 2010, The 6^th International Conference on the Biology, Chemistry and Therapeutic Applications of Nitric Oxide’, Kyoto, Japan.
• Moran Fellowship in Cardiovascular Research, Department of Cell Biology, Lerner Research Institute (15 Mar 2006 - Dec 2006)
• Elsa Albrecht Fellow Award 2005, Department of Cell Biology, Lerner Research Institute, USA
• Young Histochemist Award 2004, International Federation of Societies for Histochemistry and Cytochemistry, USA
• National Educational Talent Fellowship, Council of Scientific and Industrial Research, India (1998-2002)
• Common Entrance Test Fellowship, Department of Biotechnology, India (1995-1997)

Education

Ph.D., Indian Institute of Technology-Delhi, India