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Department of Medicinal and Biological Chemistry

Marcia F. McInerney

Marcia

Emeritus Faculty


E-Mail: marcia.mcinerney@utoledo.edu

PRIMARY ACADEMIC APPOINTMENTS

  • Distinguished University Professor
  • Medicinal & Biological Chemistry

SECONDARY APPOINTMENTS

  • Adjunct Professor of Internal Medicine (Diabetes, Metabolism and Endocrinology) – University of Michigan (2008-2013)
  • Member - Center for Diabetes and Endocrine Research
  • Joint Professor of Pathology
  • Adjunct Professor of Biological Sciences

EDUCATION AND TRAINING

University of Connecticut B.A. Biology (with honors) 
Case Western Reserve University M.S.  Microbiology/Immunology
University of Michigan Ph.D. (1989) Microbiology/Immunology
Yale University School of Medicine Postdoc (89-91)  Immunobiology
Joslin Diabetes Center/ Harvard University / Senior Iacocca Fellow Sabbatical (98-99) Immunogenetics
University of Michigan   Sabbatical (2008) Diabetes Metabolism and Endocrinology

CERTIFICATIONS AND LICENSURES

American Society of Clinical Pathologists
Clinical Certification - Immunology (1982)

APPOINTMENTS/PROFESSIONAL POSITIONS

1975-1978 Teaching Assistant, Case Western Reserve University
1978-1983 Research Associate, Cleveland Clinic Foundation
1984 –1988 Microbiology and Immunology PhD Teaching Assistantship, University of Michigan Medical School
1988 -1989 Predoctoral Fellowship, American Diabetes Association, University of Michigan
1989- 1990 Postdoctoral Fellowship, National Institutes of Health Training Grant, Yale University School of Medicine, Charles A. Janeway, Jr. laboratory
1990- 1991

Postdoctoral Fellowship, Juvenile Diabetes Foundation, Yale University School of Medicine, Charles A. Janeway Jr. laboratory
1991 -1997 Assistant Professor, University of Toledo, College of Pharmacy. Medicinal and Biological Chemistry Department; Adjunct Assistant Professor of Pathology, Medical College of Ohio
1997 - 2004

Professor, Biology Department; Adjunct Associate Professor of Pathology, Medical College of Ohio; Associate Professor, University of Toledo, College of Pharmacy, Medicinal and Biological Chemistry Department and Adjunct Associate
1998 -1999

Senior Mary K. Iacocca Fellow, Joslin Diabetes Center/ Harvard Medical School. (sabbatical leave); Visiting Associate Professor of Medicine, Harvard University and Visiting Scientist, Joslin Diabetes Center.
2000- 2004

Associate Professor and Interim Chair, Medicinal and Biological Chemistry Deptartment, College of Pharmacy, University of Toledo
2004-

Professor and Chair, Medicinal and Biological Chemistry, College of Pharmacy, and Adjunct Professor of Biological Sciences, University of Toledo;                            Adjunct Adjunct Professor of Pathology, Medical University of Ohio at Toledo
2006 Adjunct Professor of Biochemistry and Cancer Biology, The University of Toledo, College of Medicine. Member, Center for Diabetes and                            Endocrine Research (CeDER), The University of Toledo, College of Medicine
2008 Visiting Professor of Internal Medicine (Division of Diabetes, Metabolism and Endocrinology) University of Michigan Sabbatical with Dr.Massimo                               Pietropaolo
2008-2013 Adjunct Professor of Internal Medicine (Division of Diabetes, Metabolism and Endocrinology) University of Michigan
2010 Distinguished University Professor, University of Toledo (permanent title)

RESEARCH INTERESTS

My major research interest is in elucidating the underlying immunopathological mechanisms in diabetes, with the hope that a better understanding of the molecular and cellular basis for the disease will lead to better diagnostic, preventative and therapeutic strategies.

A major focus of my research is on the autoimmune aspects of Type 1 or insulin-dependent diabetes, using the nonobese diabetic (NOD) mouse as a primary model. In humans and the NOD mouse, insulin-dependent diabetes is inherited. Autoantibodies to insulin and islet cells are produced, and T lymphocytes invade the islets in the pancreas. T-cell invasion or insulitis is associated with destruction of the insulin-secreting beta cells. In the NOD mouse, insulitis begins at 4-6 weeks of age; however, the mice do not spontaneously become diabetic until 3 to 6 months of age, at which time sufficient beta cells have been destroyed to result in the loss of insulin secretion. Other investigators have shown that the insulin receptor (IR) can function as a chemotactic receptor capable of directing cell movement in response to a gradient of insulin. Published data from my laboratory has shown that flow cytometry-sorted T lymphocytes, from diabetic NOD mice expressing a high density of insulin receptors (IR+ T cells), aggressively transfer insulitis and diabetes, while T cells with low to negative IR expression (IR- T cells) are capable of neither. An association of IR+ T cells with an increased risk for diabetes would provide a new target for drug therapy. Furthermore, chemotactic signaling and metabolic signaling are mediated by distinct parts of the insulin receptor and could, therefore, be selectively targeted for therapeutic intervention prior to diabetes onset. Current research in my laboratory involves the development of a flag-tagged, T cell-specific, IR transgenic mouse on a background that does not spontaneously become diabetic to determine whether movement of T cells into an islet can be based on IR expression.  We have been successful in two of the transgenic models and now wish to make a transgenic mouse that has IR expression on the surface of Tregs to prevent the development of type 1 diabetes. We will be using Cre-Lox transgenic mice systems to reach this goal. There are areas of translational research associated with this work on high density IR expression using peripheral blood from human diabetic patients. The recent NIH/NIDDK grant (2014-18) supports this research.

A prime interest of my laboratory is in identifying dietary and genetic risk factors in Obesity and Insulin Resistant, or Type 2, Diabetes. The work on obesity and type 2 diabetes was a collaborative USDA-funded research project for 6 years with Dr. Sonia Najjar, who was at the time at The University of Toledo, College of Medicine. Type 2 Diabetes is a complex disease usually involving abnormal metabolism resulting from both genetic predisposition and environmental factors. Diet and lack of exercise play critical roles in obesity, which may progress to diabetes and its complications.  By identifying dietary and other environmental factors that act upon genetic predisposition, strategies may be developed and implemented to prevent obesity, diabetes and its associated diseases.  As of November 2005, 20.8 million Americans have diabetes, and the cost to society has increased to $150 billion a year, making the impact of diabetes highly significant in the United States. Recently, the American Diabetes Association indicated that of the live births in 2000, 1 out of every 3 will be diabetic in their lifetime, and for minorities, this is 1 in 2. These are horrendous statistics, making the work on diabetes highly significant. The USDA work has resulted in numerous publications and meeting presentations/seminars. 

Another major basic science focus involves assessment of innate immune responses to oral pathogens in diabetes. Diabetes is a risk factor for severe periodontal disease caused by gram negative anaerobes. Previous studies suggest that both innate and adaptive immunity are involved in protection against periodontal infection. Innate immune responses are the first line of defense against infection. Innate immune system cells, such as macrophages, react to common microbial surface molecules through newly discovered receptors on the macrophage cell surface called Toll-like receptors (TLRs). Our purpose is to determine the role of TLRs in the initiation of host immune responses against oral pathogens in periodontal infection, using the nonobese diabetic (NOD) mouse model of type 1 diabetes as well as animal models for type 2 diabetes. Macrophages respond to live bacteria and/or lipolysaccharide (LPS), derived from gram negative bacteria, by producing cytokines, expressing costimulatory molecule(s), fluctuating the TLR mRNA and protein levels and promoting TLR signal transduction. These events are essential for macrophage activation and initiation of specific adaptive immune responses for the generation of antigen specific cells. Macrophage activation in response to bacteria or LPS from oral pathogens will be compared in diabetic and nondiabetic mice. The working hypothesis is that a defect in innate immunity in diabetes contributes to the susceptibility to periodontal infection, since it is likely that the interaction between the TLR and the oral pathogen initiates immune responses.  

Innate immunity was the focus of my 2008 sabbatical at the University of Michigan in the Department of Internal Medicine, the Division of Metabolism, Endocrinology and Diabetes. Two review papers on innate immunity and diabetes were generated associated with this sabbatical.

Work continues with collaborators Drs. Quinn, Wall, and Sucheck on bioconjugates for delivery to present altered peptide ligands to prevent diabetes development in animal models. 

HONORS AND AWARDS

1988-89 Predoctoral Fellowship. American Diabetes Association."Immuno-regulatory Defects in the Nonobese Diabetic (NOD) Mouse."
1989-1990 Postdoctoral Fellowship. National Institutes of Health Training Grant. Yale University School of Medicine, Laboratory of Dr. Charles Janeway, Jr.
1990-91 Postdoctoral Fellowship. Juvenile Diabetes Foundation. "Regulatory T Cells in Diabetes." Yale University School of Medicine. Laboratory of Dr. Charles Janeway, Jr.
1993-96 Career Development Award. American Diabetes Association. "Autoantigen Recognition by CD8 T Lymphocytes in Type 1 Diabetes."
1996-97 CODA Children's Research Award. Central Ohio Diabetes Association. "Upregulated Insulin Receptor Expression on Peripheral T Cells : A Potential Predictor of Diabetes Onset?"
1998-99 Senior Mary K. Iacocca Fellow. Joslin Diabetes Center/Harvard Medical School
2005 Outstanding University Woman   University of Toledo, University Women's Commission
2006 Outstanding Research Award, University of Toledo
2006 Dean's Award for Outstanding Research, College of Pharmacy, University of Toledo (Nominated by graduate students in Medicinal and Biological Chemistry for this award)
2010 Distinguished University Professor (permanent title)
2012 Presidential Research Scholarship Award
2007-2012

NIH/NIDDK Committee Member  (DDK-B) Diabetes, Endocrinology, and.Metabolic Diseases B Subcommittee of the Diabetes and Digestive and Kidney Diseases Initial Review Group; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) awards and Training Grants met three times a year
 2014  NIH/NIDDK Chairman- SBIR/STTR 11/6
 2016  NIH SBIR Co-Chairman – Endocrinology, Metabolism, Nutrition and Reproductive Sciences 11/15-16
 2017  NIH SBIR Co-Chairman- Endocrinology, Metabolism, Nutrition and Reproductive Sciences 11/13-14

Grant Support

Current Grant Support

NIH/NIDDK R15 2014-2018

Past Grant Support

NIH/NIDDK, NIH/NIDCR, USDA/NIFA, ADA, JDFI, JDRFI, DAREF, CODA

EDITORIAL POSITIONS, BOARDS, AND PEER-REVIEW SERVICE

Dr. McInerney has served on over 30 grant review panels for NIH for NIDDK, NCI, NIAID, NIDCR-ODCS, NIDCR, NIAMSD, SEP in IMM. She has also reviewed grants for Diabetes UK, Diabetes Action Research and Education Foundation, where she is on the Medical Advisory Board; USDA/NIFA; Wright State University; Michigan Diabetes Research and Training Center; and Ohio University.

Dr. McInerney is on the editorial board of the Journal of Infectious Diseases and Immunology and has reviewed for the following journals:

  • J Immunology
  • Diabetes
  • PLOS ONE
  • Journal of Molecular Histology
  • Journal of Leukocyte Biology
  • Cellular Microbiology
  • Inflammation
  • American Journal of Physiology- Endocrinology and Metabolism
  • American Journal of Pathology
  • Pharmaceutical Research 

BIBLIOGRAPHY

PEER-REVIEWED JOURNAL ARTICLES

According to Research Gate, there are 704 citations of published work.

  1. Michael P Morran , Ali G Al-Dieri, Andrea L. Nestor-Kalinoski, Richard K Jordan, Nirdesh K. Gupta, Marcia F McInerney Insulin receptor lymphocyte trafficking in the progression of type 1 diabetes. Accepted for publication in Journal of Biological Methods October 29th, 2017 for publication in 2018.
  2. Russo L, Ghadieh HE, Ghanem SS, Al-Share QY, Smiley ZN, Gatto-Weis C, Esakov EL, McInerney MF, Heinrich G, Tong X, Yin L, Najjar SM. Role for hepatic CEACAM1 in regulating fatty acid metabolism along the adipocyte-hepatocyte axis. J Lipid Res. 2016 Dec; 57(12):2163-2175. PMID: 27777319.
  3. Heinrich G, Russo L, Castaneda TR, Pfeiffer V, Ghadieh HE, Ghanem SS, Wu J, Faulkner LD, Ergün S, McInerney MF, Hill JW, Najjar SM. Leptin Resistance Contributes to Obesity in Mice with Null Mutation of Carcinoembryonic Antigen-related Cell Adhesion Molecule 1. J Biol Chem. 2016 May 20;291(21):11124-32. doi: 10.1074/jbc.M116.716431. Epub 2016 Mar 21. PMID: 27002145 PMCID: PMC4900262. 
  4. Tulsulkar J, Nada SE, Slotterbeck BD, McInerney MF, Shah ZA. Obesity and hyperglycemia lead to impaired post-ischemic recovery after permanent ischemia in mice. Obesity (Silver Spring). 2015 Dec 23. doi: 10.1002/oby.21388. [Epub ahead of print NIHMSID: NIHMS733570;PMID:26694743; PMCID: PMC4731242.
  5. Lester SG, Russo L, Ghanem SS, Khuder SS, DeAngelis AM, Esakov EL, Bowman TA, Heinrich G, Al-Share QY, McInerney MF, Philbrick WM, Najjar SM.
  6. Hepatic CEACAM1 Over-Expression Protects Against Diet-Induced Fibrosis and Inflammation in White Adipose Tissue. Front Endocrinol (Lausanne). 2015 Aug 3;6:116. doi: 10.3389/fendo.2015.00116. eCollection 2015. PMID: 26284027 PMCID: PMC4522571.  
  7. Ebke LA, Nestor-Kalinoski AL, Slotterbeck BD, Al-Dieri AG, Ghosh-Lester S, Russo L, Najjar SM, von Grafenstein H, McInerney MF. Tight association between macrophages and adipocytes in obesity: Implications for adipocyte preparation. Obesity (Silver Spring). 2014 May; 22 (5):1246-55. doi: 10.1002/oby.20634. Epub 2013 Dec 4.  NIHMSID: NIHMS527968; PMID: 24376179; PMCID: PMC3980195. 
  8. Angevine KR, Wuescher LM, Andrews K, Alexander LA, McInerney MF, Kieffer TJ, Mensah-Osman EJ Menin and GIP are inversely regulated by food intake and diet via PI3/AKT signaling in the proximal duodenum. Nutr Diabetes. 2012 Dec 3;2:e55. doi: 10.1038/nutd.2012.30. PMID:23208416; PMCID: PMC3542434.
  9. Rasche SS, Phillips M, McInerney MF, Sercarz, EE and Quinn A. IL-13Ra Expression on Beta Cell-specific T cells in NOD Mice.  Diabetes  2011 Jun;60(6):1716-25. Accompanied by a commentary Wong, FS. Stimulating IL-13 receptors on T cells: a new pathway for tolerance induction in diabetes? pg 1657.   PMID:21617187; PMCID: PMC3114389.
  10. Ghosh S, Kaw M., Patel PR, Ledford KJ, Bowman TA, McInerney MF, Erickson SK, Bourey RE, Najjar SM. Mice with null mutation of CEACAM1 develop nonalcoholic steatohepatitis. Hepatic Medicine: Research and Evidence 2010; 2: 69–78.  NIHMSID: NIHMS318540; PMID:21949477; PMCID: PMC3177946 
  11. Dudley RW, Slotterbeck BD, McInerney MF, Peseckis SM. Fatty acylation enhances cellular localization of dansylated phenylalanines. Mol Cell Biochem. Molecular and Cellular Biochemistry: Volume 346, Issue 1 (2011), Page 81.2010 Oct 8. [Epub ahead of print] PMID: 20931354
  12. Huang S, Kaw M, Harris MT, Ebraheim N, McInerney MF, Najjar SM, Lecka-Czernik B. Decreased osteoclastogenesis and high bone mass in mice with impaired insulin clearance due to liver-specific inactivation to CEACAM1. Bone. 2010 Apr;46(4):1138-45. Epub 2010 Jan 4  NIHMSID: NIHMS171349; PMID:20044046 PMCID: PMC2862391. 
  13. Marcia F. McInerney, Lindsey A. Alexander, Michael P. Morran, Massimo Pietropaolo. Innate Immunity, Toll-like Receptors, and Diabetes. Current Immunology Reviews 2009; 5(2): 111-121.  
  14. Michael P. Morran, Lindsey A. Alexander, Brandon Slotterbeck, Marcia F. McInerney. Dysfunctional Innate Immune Responsiveness to P. gingivalis in Diabetes. Oral Microbiology and Immunology 2009; 24(4): 331-339.  PMID: 19572897
  15. Lee SJ, Heinrich G, Fedorova L, Al-Share QY, Ledford KJ, Fernstrom MA, McInerney MF, Erickson SK, Gatto-Weis C, Najjar SM. Development of nonalcoholic steatohepatitis in insulin-resistant liver-specific S503A carcinoembryonic antigen-related cell adhesion molecule 1 mutant mice. Gastroenterology. 2008 Dec;135(6):2084-95. Epub 2008 Aug 20 NIHMSID: NIHMS83433
  16. Morran, M, M.F. McInerney, M. Pietropaolo. Innate and Adaptive Autoimmunity in Type 1 Diabetes. Pediatr Diabetes. 2008 Jan 25; [Epub ahead of print]
  17. Quinn, A., McInerney, M.F. Huffman, D., McInerney, B.E., Mayo, S., Haskins, K., and Sercarz, E. T Cells to a Dominant Epitope of GAD65 Express a Public CDR3 Motif. Internat. Immunol. 2006; 18 (6): 967-979.  PMID:16641112
  18. Mohammad, M., Morran, M. Slotterbeck, B., Leaman, D.W., Sun, Y. vonGrafenstein, H., Hong, S.C., and M.F. McInerney. Dysregulated Toll-like Receptor Expression and Signaling in Bone Marrow-Derived Macrophages at the onset of Diabetes in the Nonobese Diabetic Mouse. Internat. Immunol. 2006; 18 (7): 1101-1113.  PMID:16728431
  19. Schroeder, M.M., Belloto, R.J. Jr., Hudson, R.A. and McInerney, M.F. Effects of antioxidants Coenzyme Q10 and Lipoic Acid on Interleukin-1- Mediated Inhibition of Glucose -Stimulated Insulin Release from cultured Mouse Pancreatic Islets. Immunopharmacol. and Immunotoxicol. 2005; 27: 1-14. PMID: 15803864
  20. McInerney, M.F., Najjar, S.M., Brickley, D., Abou Rjaily, G.A., Lutzke, M., Haskell, B.D., Flurkey, K., Zhang Y-J, Pietropaolo,S.L., Pietropaolo, M., Byers, J.P. and Leiter, E.H.  Anti-Insulin Receptor Autoantibodies are Not Required for Type 2 Diabetes Pathogenesis in NZL/Lt Mice, a New Zealand Obese (NZO)- Derived Mouse Strain.  Exper. Diabesity Res. 2004;5:177-185. PMID: 15512785 PMCID: PMC2478629
  21. Havari, E., Lennon-Dumenil, A.M., Taylor, J.A., Turley, S.J., Klein, L., Neely, D., McInerney, M.F., Wucherpfennig, K.W., and Lipes, M.A. Expression of the B7.1 Costimulatory Moleucle on Pancreatic  Cells Abrogates the Requirement for CD4 T Cells in the Development of Type 1 Diabetes  J. Immunol. 2004; 173:787-796. PMID: 15240665
  22. *Taylor, J.A., *Havari E, McInerney, M.F. Bronson, R.T., Wucherpfennig, K.W. and Lipes, M.A.  A Spontaneous Model for Autoimmune Myocarditis Using the Human MHC Molecule HLA-DQ8. J. Immunol. 2004, 172: 2651-2658. (* equivalent first authors) PMID: 14764740
  23. Quinn, A., M.F. McInerney and E.E. Sercarz. MHC class I- Restricted Determinants on the GAD65 Molecule Induce Spontaneous CTL Activity. J. Immunol. 2001;167:1748-57. PMID: 11466400
  24. McInerney, M. F., J. Burkey, L. Guan, J. C. Flynn and C. A. Janeway, Jr.  An Islet- Specific CD8+ T Cell Hybridoma Generated From Nonobese Diabetic Mice Recognizes Insulin as an Autoantigen. Diabetes Res. & Clin. Prac., 2000;47(3):151-168. PMID: 10741564.
  25. Flynn, J.C. and M. F. McInerney. High Density Insulin Receptor Positive Diabetogenic T Lymphocytes in Nonobese Diabetic Mice Are Memory Cells. Immunopharmacol. & Immunotoxicol., 2000;22(2): 387-400. PMID: 10952038
  26. McInerney, M.F.,  J.C. Flynn, P.J. Goldblatt, S. Najjar, R.S. Sherwin and C.A. Janeway, Jr. High Density Insulin Receptor Positive T Lymphocytes From NOD Mice Transfer Insulitis and Diabetes. J. Immunol., 1996; 157: 3716-3726. PMID: 8871675
  27. McInerney, M.F. M. Seidel, J.M.D. Nguyen, J.C. Flynn, N. Sturm, H. Lee, Z. Zhang, L.M.V. Tillekeratne and R.A. Hudson. Effects of a 33 residue interleukin-1 beta peptide and the antioxidant PQQ on interleukin-1 beta-mediated inhibition of glucose-stimulated insulin release from cultured mouse pancreatic islets. Res. Comm. in Mol. Path. & Pharmacol.,1996;94(2):115-128. PMID: 8987109
  28. McInerney, M.F., S. Rath and C.A. Janeway, Jr.  Exclusive Expression of MHC Class II Proteins on CD45-positive Cells in Pancreatic Islets of NOD Mice.  Diabetes 1991; 40: 648-651.  PMID: 1827081
  29. McInerney, M.F., S.B. Pek, and D.W. Thomas.  Prevention of Insulitis and Diabetes Onset by Treatment with Freund's Adjuvant in NOD mice.  Diabetes 1991; 40: 715-725. PMID: 2040388
  30. McInerney, M.F., J. Clough, D. Senitzer, and M. Cathcart.  Two Distinct Subsets of Patients with SLE.  Clin. Immunol. and Immunopathol. 1988; 49; 116-132.  PMID: 2970355
  31. Dustoor, M., M.F. McInerney, W. Mazanec, and M. Cathcart.  Abnormal lymphocyte function in scleroderma:  A study on identical twins.  Clin. Immunol. and Immunopathol. 1987; 44: 20-30. PMID: 2954728
  32. Tanzer, J.M., A.T. Brown, M.F. McInerney, F.N. Woodiel. Comparative study of invertases of Streptococcus mutans. Infect. & Immun.  1977;16(1):318-327 PMID: 873612; PMCID PMC421524
  33. Tanzer, J.M., A.T. Brown and M.F. McInerney. Identification, preliminary characterization, and evidence for regulation of invertase in Streptococcus mutans. J. Bacteriol. 1973; 116(1):192-202.  PMID: 4745413; PMCID: PMC246407
Last Updated: 7/15/24