Faculty

Raghu G. Mirmira, MD, PhD

Raghu G. Mirmira, MD, PhD

Eli Lilly Foundation Professor of Pediatric Diabetes
Professor of Pediatrics and Medicine
Adjunct Professor of Cellular & Integrative Physiology and Biochemistry & Molecular Biology

Phone: (317) 274-4145
Fax: (317) 274-4107
Email: rmirmira@iu.edu
Address:
635 Barnhill Drive, MS 2031B
Indianapolis, IN  46202

Bio

Specialty

Internal Medicine Endocrinology

Areas of Interest

Diabetes, islet biology,  insulin action, islet inflammation, islet autoimmunity, diabetes biomarkers, ? cell development, obesity, insulin resistance.

Dr. Raghu Mirmira received his bachelor’s, MD, and PhD degrees from the University of Chicago.  Dr. Mirmira subsequently completed his residency in Internal Medicine and subspecialty training in Diabetes and Endocrinology at the University of California at San Francisco.  During his fellowship, Dr. Mirmira did his research training in the laboratory of Michael German, where he studied how insulin-producing beta cells form during development in the embryo.  Dr. Mirmira then joined the faculty at the University of Virginia, where he studied transcription factors that direct the development and function of beta cells, including Nkx6.1 and Pdx1. His research has more recently focused on mechanisms by which inflammation affects the islet ? cell in type 1 diabetes mellitus. Dr. Mirmira is currently the Eli Lilly Professor in Pediatric Diabetes and Director of the Pediatric Diabetes Research Group at Indiana University in Indianapolis, and also Director of the MD/PhD (MSTP) program at IU School of Medicine.

Education

1986 BA, The University of Chicago
1991 PhD, The University of Chicago
1993 MD, The University of Chicago Pritzer School of Medicine

Honors & Awards

2011-2013 Indianapolis Monthly, Top Doctor, Endocrinology and Metabolism
2011-2013 US News and World Report, Top Doctor, Endocrinology and Metabolism
2010 Merck/Endocrine Society Visiting Professor in Endocrine Pancreas Preservation, University of Utah, Salt Lake City, UT.
2010 American Society for Clinical Investigation (ASCI)
2008 Eli Lilly Foundation Endowed Chair in Pediatric Diabetes at Indiana University
2007 UVA Department of Medicine Excellence in Mentoring Award
2006 Member, University of Virginia Academy of Distinguished Educators
2006 Selected by the Dean for participation in “Leadership in Academic Medicine” series, University of Virginia
2004-2009 American Diabetes Association Thomas R. Lee Career Development Award
2004 Discovery Health Channel American Medical Honors Award, Constitution Hall, Washington, DC. Aired on Discovery Networks July 8, 2004
1999-2003 National Institutes of Health, Research Career Award (K08)
1999 Juvenile Diabetes Foundation Career Development Award (years 2-4 declined)
1996-1999 Howard Hughes Medical Institute Physician Postdoctoral Fellowship
1993 The Harold Lamport Biomedical Research Award for the best dissertation in biomedical research
1993 Alpha Omega Alpha Medical Honor Society
1993 Medical Student Award, NIDDK
1991 Marc Perry Galler Prize for the most distinguished Ph.D. dissertation (Univ. of Chicago, Division of the Biological Sciences)
1986 Medical Scientist Training Program (University of Chicago)
1985 Phi Beta Kappa

Clinical

Riley Hospital Outpatient Center
MSA3
705 Riley Hospital Drive
Indianapolis, IN  46202 


Research & Grants

It is widely known now that the prevalence of diabetes has been rising to alarming rates in the United States. The American Diabetes Association reports that almost 21 million Americans (7% of the US population) have diabetes. The pathophysiology of diabetes is complex, but it is clear that defects at the level of the insulin-producing islets underlie the development of the disorder in nearly all forms of diabetes. Thus, my laboratory focuses on the regulation of gene transcription during pancreatic islet development, function, and survival.  The projects in my laboratory fall into three main categories:

(1) the role of homeodomain transcription factors, basic helix-loop-helix transcription factors, and PPAR-gamma during the development of islets and the pathogenesis of islet dysfunction in type 1 and type 2 diabetes,

(2) the interrelationships between chromatin structure and gene transcription in the mature islet, and

(3) the role of post-transcriptional mechanisms in cytokine-mediated islet dysfunction.

We believe that intervening at any of these three stages in the islet life-cycle (development, function, and survival) will allow for the development of new sources of islets for the treatment of diabetes.  Toward this effort, my lab has also engaged in translational work that would bring new therapies developed by us or our collaborators into the clinic to treat patients with diabetes.  These areas of research include bench and bedside testing of new inhibitors of the islet inflammatory intermediates (including 12-lipoxygenase, lisofylline, and eukaryotic translation initiation factor 5A).

Current Grants

“Transcriptional Mechanisms Governing B-Cell Differentiation”
NIH/NIDDK R01 DK60581               
Role: PI
03/01/02 – 05/31/15

"Chromatin Cofactors in Islet Development and Function"
NIH/NIDDK R01 DK083583
Role:  PI
4/1/10-3/31/14

“Deoxyhypusine synthase: a novel target for islet preservation”
Juvenile Diabetes Research Foundation Research Grant
Role: PI
11/01/10 – 10/31/12

"Unmethylation Index as a Biomarker for B Cell Death"
Eli Lilly & Co. Research Award
Role: PI
11/01/13 – 10/31/14

“B Cell Growth and Survival in Diabetes”
American Diabetes Association Mentored-Based Minority Fellowship
Role:  PI
07/01/11 – 6/30/15

“Indiana Medical Scientist/Engineer Training Program”
NIH/GM T32 GM077229
Role:  PI
7/01/08 – 6/30/18


Representative PublicationsView All Publications

1. Evans-Molina C, Garmey JC, Ketchum R, Brayman KL, Deng S, Mirmira RG. 2007. Glucose Regulation of Human Insulin Gene Transcription and Pre-mRNA Processing. Diabetes 56:827

2. Babu DA, Chakrabarti SK, Garmey JC, Mirmira RG. 2008. Pdx1 and BETA/NeuroD1 participate in a transcriptional complex that mediates short-range DNA looping at the insulin gene. J Biol Chem 283 :8164.

3. Chuang JC, Cha JY, Garmey JC, Mirmira RG, Repa JJ. 2008. Research resource: nuclear hormone receptor expression in the endocrine pancreas. Mol Endocrinol. 22:2353.

4. Deering TG, Ogihara T, Trace AP, Maier B, Mirmira RG. 2009. The methyltransferase Set7/9 maintains transcription and euchromatin structure at islet-enriched genes. Diabetes 58:185

5. Evans-Molina C, Robbins R, Kono, Tersey SA, Vestermark G, Nunemaker C, Garmey JC, Deering TG, Keller SR, Maier B, Mirmira RG. 2009. PPAR-gamma activation restores islet function in diabetic mice through reduction of ER stress and maintenance of euchromatin structure. Mol Cell Biol 29:2053.

6. Ogihara T, Vanderford N, Maier B, Stein, RW, Mirmira RG. 2009. Expression and function of Set7/9 in pancreatic islets. Islets 1:3, 1-4.

7. Sachdeva MM, Claiborn KC, Yang J, Groff DN, Mirmira RG, Stoffers DA. 2009. Pdx1 (MODY4) promotes islet compensation for insulin resistance by reducing ?-cell susceptibility to ER stress and apoptosis. Proc Natl Acad Sci USA 106:19090.

8. Robbins RD, Prasain N, Maier B, Yoder M, Mirmira RG. 2010. Inducible pluripotent stem cells: Not quite ready for prime time? Curr Opin Organ Transplant 15:61-67.

9. Maier B, Ogihara T, Trace AP, Tersey SA, Robbins RD, Chakrabarti SK, Nunemaker CS, Stull ND, Taylor CA, Thompson JE, Dondero RS, Lewis EC, Dinarello CA, Nadler JL, Mirmira RG. 2010. The Unique Hypusine Modification of eIF5A Promotes Islet ? Cell Inflammation and Dysfunction. J Clin Invest 120:2156-2170.

10. Robbins RD, Tersey SA, Ogihara T, Gupta D, Farb TB, Ficorilli J, Bokvist K, Maier B, Mirmira RG. 2010. Inhibition of deoxyhypusine synthase enhances islet beta cell function and survival in the setting of endoplasmic reticulum stress and type 2 diabetes. J Biol Chem 285:39943-39952.

11. Templin AT, Maier B, Nishiki Y, Tersey SA, Mirmira RG. 2011. Deoxyhypusine synthase haploinsufficiency attenuates acute cytokine signaling. Cell Cycle 10:1-7.

12. Tersey SA, Nishiki Y, Templin AT, Cabrera SM, Colvin SC, Evans-Molina C, Rickus JL, Maier B, Mirmira RG. 2012. Islet ? Cell Endoplasmic Reticulum Stress Precedes the Onset of Type 1 Diabetes in the Non-Obese Diabetic Mouse Model. Diabetes 61:818-827.

13. Cabrera SM, Rigby MR, Mirmira RG. 2012. Targeting Regulatory T Cells in the Treatment of Type 1 Diabetes. Curr Mol Med 12:1-2 .

14. Nishiki Y, Adewola A, Hatanaka M, Templin AT, Maier B, Mirmira RG. 2013. Translational Control of Inducible Nitric Oxide Synthase by p38 MAPK in Islet ? Cells. Mol Endocrinol 2:336-349.

15. Evans-Molina C, Mirmira RG. 2013. Achieving PeaK-A Insulin Secretion. Diabetes 62:1389-1390.

16. Chen YC, Colvin ES, Maier BF, Mirmira RG, Fueger PT. 2013. Mitogen-inducible Gene 6 Triggers Apoptosis and Exacerbates ER stress-Induced ? cell death. Mol Endocrinol 27:162-71.

17. Cabrera SM, Colvin SC, Tersey SA, Maier B, Nadler JL, Mirmira RG. 2013. Effects of combination therapy with dipeptidyl peptidase-IV and histone deacetylase inhibitors in the non-obese diabetic mouse model of type 1 diabetes. Clin Exp Immunol 172:375-382.

18. Fisher MM, Perez Chumbiauca CN, Mather KJ, Mirmira RG, Tersey SA. 2013. Detection of Islet ? Cell Death in vivo by Multiplex PCR Analysis of Differentially Methylated DNA. Endocrinology In Press.

19. Tersey SA, Colvin SC, Maier B, Mirmira RG. 2013. Protective effects of polyamine depletion in mouse models of type 1 diabetes: implications for therapy. Amino Acids In Press.

20. Colvin SC, Maier B, Morris DL, Tersey SA, Mirmira RG. 2013. Deoxyhypusine Synthase Promotes Differentiation and Proliferation of Th1 Cells in Autoimmune Diabetes. J Biol Chem In Press.