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Main and Health Science CampusesWolfe Hall 1227 (MC)
Frederic and Mary Wolfe Center 155 (HSC)
Phone: 419.383.1904 firstname.lastname@example.org
Medicinal and Biological Chemistry
Associate Dean for Research and Graduate Programs
Frederic and Mary Wolfe Center 145F, MS1013
Distinguished University Professor
Medicinal & Biological Chemistry
Adjunct Professor of Internal Medicine (Diabetes, Metabolism and Endocrinology) –
University of Michigan
Member - Center for Diabetes and Endocrine Research
Joint Professor of Pathology
Adjunct Professor of Biological Sciences
Voluntary Faculty- Biochemistry and Cancer Biology
EDUCATION AND TRAINING:
|U.of Connecticut||B.A.||Biology (with honors)|
|Case Western Reserve U||M.S.||Microbiology/Immunology|
|U. of Michigan||Ph.D. (1989)||Microbiology/Immunology|
|Yale U. Sch of Med||Postdoc (89-91)||Immunobiology|
|Joslin Diabetes Center/ Harvard U. / 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)
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
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.
1997 - 2004 Associate Professor, University of Toledo, College of Pharmacy,
Medicinal and Biological Chemistry Department and Adjunct Associate
Professor, Biology Department
Adjunct Associate Professor of Pathology, Medical College of Ohio.
2000- 2004 Associate Professor and Interim Chair, Medicinal and Biological Chemistry Dept., 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 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- Adjunct Professor of Internal Medicine (Division of Diabetes, Metabolism and Endocrinology) University of Michigan
2010- Distinguished University Professor, University of Toledo
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 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 is a collaborative USDA-funded research project with Dr. Sonia Najjar (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.
As a translational offshoot of the basic science work we have recently submitted an application to the USDA on Prevention of Childhood Obesity with a focus on 7th and 8th grade students. We wish to translate some of our basic research findings into the classroom and nurture positive peer to peer communication for prevention of obesity in adolescents.
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 also 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.
A final major aspect of my research is focused 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 flag tagged, T cell specific, IR transgenic mouse on a background that does not spontaneously become diabetic to determine if movement of T cells into an islet can be based on IR expression. We have been successful with one of the transgenic models and are pursuing this line of research in the hopes of targeting regulatory cells to the pancreas to prevent the development of T1D in animal models of the disease.
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 from the 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
EDITORIAL POSITIONS, BOARDS, AND PEER-REVIEW SERVICE
2010 The United Arab Emirates University external promotion/tenure
Al-Ain UAE reviewer
2009 Illinois State University external promotion to professor
2009 NIH/NIAMSD ad hoc reviewer – ZAR1 EHB-D M2 1
Program Project Review
2009- Editorial team Journal of Infectious Diseases and Immunology
2008 NIH/NIDCR ad hoc reviewer R01 osteoimmunology (ZDE1 RW 32)
(Crosstalk between Immune System and Bone)
2007-2011 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)
Meets three times per year
2007 NIH/NIDDK Ad Hoc Grant Reviewer
Diabetes, Endocrinology, and Metabolic Diseases B SubCommittee
2007-2010 Journal of Immunology Ad Hoc Reviewer
2007 Journal of Molecular Histology Ad Hoc Reviewer
2006, 2009 Diabetes Ad Hoc Journal Reviewer
2006 Ohio University Grant Reviewer
2006, 2008, 2010 Diabetes UK (England) Grant Reviewer
2006 Wright State University Grant Reviewer
2004- Diabetes Action Research Medical Advisory Board
and Education Foundation Grant Reviewer every summer
2003 American Journal of Pathology Ad Hoc Journal Reviewer
1998 Bioorganic and Medicinal Chemistry Ad Hoc Journal Reviewer
1998 Michigan Diabetes Research Grant Reviewer
and Training Center
1997 Pharmaceutical Research Ad Hoc Journal Reviewer
A. PEER REVIEWED JOURNAL ARTICLES
1. Rasche SS, Phillips M, McInerney MF, Sercarz, EE and Quinn A. IL-13Ra1 Expression on Beta Cell-specific T cells in NOD Mice. Diabetes 2011; June 60 (6): 1716-25
2. 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 nonalcholic steatohepatitis. Hepatic Medicine: Research and Evidence 2010; 2: 69–78.
3. 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]
4. 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
5. 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.
6. 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.
7. 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
8. Morran, M, M.F. McInerney, M. Pietropaolo. Innate and Adaptive Autoimmunity in Type 1 Diabetes. Pediatr Diabetes. 2008 Jan 25; [Epub ahead of print]
9. 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.
10. 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.
11. 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.
12. 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. Diabetes Res. 2004;5:177-185.
13. 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.
14. *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)
15. 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.
16. 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.
17. 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.
18. 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.
19. 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 Interleukin-1ß Inhibitors and Antioxidants on Interleukin 1ß - induced Reduction of Glucose-stimulated Insulin Release in Cultured Mouse Pancreatic Islets. Res. Comm. in Mol. Path. & Pharmacol.,1996;94(2):115-128.
20. 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.
21. 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.
22. 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.
23. 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.
24. 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
25. 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.
B. PUBLISHED ABSTRACTS
26. Ghosh S, Patel PR, Kaw M., Fernstrom MA, Bourey RE, Erickson SK, McInerney MF, Najjar SM. Loss of CEACAM1 Leads to the Development of Non-Alcholic Steatohepatitis. Endocrine Reviews, Supplement 1, June 2010; 31(3): S2173 (P3-452)
27. Lindsey A Alexander, Brandon D Slotterbeck, Sonia M Najjar, and Marcia F McInerney. The Role of Inflammation in Diet-Induced Obesity J. Immunol., Apr 2009; 182: 93.4.
28. Nirdesh K Gupta, James D Bretz, and Marcia F McInerney. Elucidating The Role Of Insulin Receptor In Type-I Diabetes By Developing An IR Transgenic Mouse Model. J. Immunol. 2007;178 (MeetingAbstracts):p. S235
29. A. Quinn, M.F.McInerney and E.E.Sercarz. GAD-Specific CD8+ T Cells in NOD Mice. FASEB J. 12(5) Part II:6314, A1091,1998.
30. Marcia F. McInerney and J.C. Flynn. "High Density Insulin Receptor -Positive Diabetogenic Lymphocytes in Nonobese Diabetic Mice are Memory Cells". Diabetes 46(1): 0750, 195A, 1997.
31. McInerney, M.F., Flynn, J.C., Goldblatt, P.J., Najjar, S.M., Sherwin, R.S. and Janeway, Jr., C.A. "High Density Insulin Receptor (IRHigh) Expression Defines Aggressively Diabetogenic T Cells in NOD Mice". Autoimmunity, 24(1): A064.
32. McInerney, M.F., Guan, L., Flynn, J.C, Oravecz, K.I. Burkey, J. and Janeway, Jr., C.A..Defining Autoantigen Recognition by Islet-Specific CD8+ T Cell Hybridomas Generated from Nonobese Diabetic (NOD) Mice.1996. FASEB J. 10(6): A1312(1802).
33. McInerney, M.F., B. Al-Ramadi, and C.A. Janeway Jr. Nitric Oxide Production in the Islets of NOD Mice.1992. J. Cell. Biochem. 16B: 290 (310).
34. McInerney, M.F., S. Pek, and D.W. Thomas. 1989. Cellular Defects in Nonobese Diabetic (NOD) mice. FASEB J. 3: A1120 (5193).
35. McInerney, M.F., S. Pek, and D.W. Thomas. 1988. Detection of a Lymphoproliferative Abnormality in NOD Mice. Diabetes. 37, 5: 16A (61).
36. McInerney, M.F., M.M. Dustoor, M.K. Cathcart, and R.S. Krakauer. 1983. Functional Activity of Purified T cells Subpopulations in PSS. Fed. Proc. 42,4 : 951 (3859).
37. McInerney, M.F., M. Caulfield, and R.S. Krakauer. 1982. Functional Activity of T4 (helper/inducer) and T8 (suppressor) Plate Purified T cells in SLE, PSS, and the Sezary Syndrome. Arth. and Rheum. 25, 4: S29 (157).