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Ashay Bhatwadekar, Ph.D.

Assistant Professor, Department of Ophthalmology;
Department of Pharmacology and Toxicology


 

Our research is focused on understanding the molecular basis of diabetic retinopathy and developing cell-based and pharmacological treatments. We undertake a comprehensive approach to study pathogenesis of diabetic retinopathy by examining the bone marrow microenvironment, endothelial precursor cell function, and circadian dysregulation.

In the past we used a phosphorodiamidate morpholino oligo (PMO) to silence hyperactive transforming growth factor beta 1 (TGF-β1) in diabetic CD34+ cells and showed that inhibition of TGF-β 1 improves incorporation of diabetic CD34+ cells to ischemic injured areas of retina. Continuing with this work we are ascertaining newer molecular targets dysregulated in diabetic CD34+ cells. Now, we have identified key miRNAs altered specifically in diabetic CD34+ cells; ongoing experiments attempt to explore ways to restore normal miRNA levels and correct defects in diabetic CD34+ cells.  Our research is increasingly focused towards identifying important molecular regulators of bone marrow which help in maintaining long-term repopulating stem cells and understanding their contribution in vascular repair of the retina. In the future, we are planning to develop bone marrow specific drug delivery to counteract diabetes induced oxidative stress to sustain repair by stem cells during the vasodegenerative stage of diabetic retinopathy.

We previously highlighted a novel paradigm of diabetes research by correlating diabetic neuropathy with retinopathy and by recognizing an unexplored area of circadian dysfunction in endothelial precursor cells. Consecutively, we showed that clock gene (Per2) mutant mice recapitulate the vascular phenotype similar to that observed in diabetic retinopathy as indicated by an increase in retinal permeability, dissociation of tight junctions and accelerated development of acellular capillaries. While our studies suggested that retinal phenotype in Per2 mutant mice was associated with an increase connective tissue growth factor (CTGF), the precise mechanism remains unknown. We speculate that upregulation of β-catenin is a key intermediate in CTGF induced retinal vascular dysfunction in Per2 mutant mice. Interestingly, β-catenin is known to be increased both in diabetic retinopathy and in our studies using Per2 siRNA-treated human retinal endothelial cells. Ongoing experiments will ascertain this pathway in detail and determine the potential role of post-translational modification of PER2 on retinal CTGF expression.

 

  • International Retinal Research Fund (to suppot diabetic retinopathy research)
  • Ralph W. and Grace M. Showalter Research Trust Fund


Dr. Bhatwadekar's publications as indexed in
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  1. Yan Y, Salazar TE, Dominguez JM 2nd, Nguyen DV, Li Calzi S, Bhatwadekar AD, Qi X, Busik JV, Boulton ME, Grant MB. Dicer Expression Exhibits a Tissue-Specific Diurnal Pattern That Is Lost during Aging and in Diabetes. PLoS One. 2013 Nov 7;8(11):e80029.
  2. Hazra S, Stepps V, Bhatwadekar AD, Caballero S, Boulton ME, Higgins PJ, Nikonova EV, Pepine CJ, Thut C, Finney EM, Stone DJ, Bartelmez SH, Grant MB. Enhancing the Function of CD34(+) Cells by Targeting Plasminogen Activator Inhibitor-1. PLoS One. 2013 Nov 1;8(11):e79067.
  3. Hu P, Thinschmidt JS, Yan Y, Hazra S, Bhatwadekar AD, Caballero S, Salazar T, Miyan JA, Li W, Derbenev A, Zsombok A, Tikhonenko M, Dominguez JM 2nd, McGorray SP, Saban DR, Boulton ME, Busik JV, Raizada MK, Chan-Ling T, Grant MB. CNS inflammation and bone marrow neuropathy in type 1 diabetes. Am J Pathol. 2013 Nov;183(5):1608-20.
  4. Caballero S, Hazra S, Bhatwadekar AD, Li Calzi S, Paradiso LJ, Miller LP, Chang LJ, Kern TS, Grant MB. Circulating mononuclear progenitor cells: differential roles for subpopulations in repair of retinal vascular injury. Invest Ophthalmol Vis Sci. 2013 Apr 26;54(4):3000-9
  5. Bhatwadekar AD, Yan Y, Qi X, Thinschmidt JS, Neu MB, Li Calzi S,  Shaw LC,   Dominguez JM,  Busik JV, Lee C,  Boulton ME, Grant MB. Per2 mutation recapitulates the vascular phenotype of diabetes in the retina and bone marrow. Diabetes 2013; 62(1):273-82.
  6. Jarajapu YP, Bhatwadekar AD, Caballero S, Shenoy V, Nikinova E, Li Q, Tanis K, Stone D, Kent D, Medina RJ, Stitt AW,  Thut C, Finney E, Katovich MJ, Raizada MK, Grant MB. Activation of the protective arm of Renin Angiotensin System (RAS) corrects the reparative dysfunction of diabetic CD34+ cells. Diabetes 2013 Apr;62(4):1258-69
  7. Hazra S, Rasheed A, Bhatwadekar AD, Wang X, Shaw LC, Patel M, Caballero S, Magomedova L, Solis N, Yan Y, Wang W, Thinschmidt JS, Verma A, Li Q, Levi M, Cummins CL and Grant MB. Liver x receptor modulates diabetic retinopathy outcome in a mouse model of streptozotocin-induced diabetes. Diabetes 2012 Dec;61(12):3270-9
  8. Douglas YJ, Bhatwadekar AD, Shaw LC, Carnegie D, Caballero S, Li Q, Li Calzi S, Raizada MK,  Stitt AW,  Grant MB,. Bone marrow-CNS connections: Implications in the pathogenesis of diabetic retinopathy. Progress in Retina Eye Research  2012 Sep;31(5):481-94
  9. Jadhao CS, Bhatwadekar AD, Boulton ME, Steinle JJ, Grant MB. Nerve growth factor promotes endothelial progenitor cell-mediated angiogenic responses. Invest Ophthalmol Vis Sci 2012; 18;53(4):2030-7
  10. Bhatwadekar AD, Guerin EP, Jarajapu YP, Caballero S, Sheridan C, Kent D, Kennedy L, Lansang MC, Ruscetti FW, Pepine CJ, Higgins PJ, Bartelmez SH, Grant MB. Transient inhibition of transforming growth factor ß1 in human diabetic CD 34+ cells enhances vascular reparative functions. Diabetes 2010 Aug;59(8):2010-9
  11. Bhatwadekar AD, Shaw LC, Grant MB: Promise of endothelial progenitor cell for treatment of diabetic retinopathy. Exp Rev Endocrin & Metab; 2010, (5) 1: 29-37.
  12. Busik JV*, Tikhonenko M*Bhatwadekar AD*, Opreanu M, Yakubova N, Caballero S, Player D, Nakagawa T, Afzal A, Kielczewski J, Sochacki A, Hasty S, Li Calzi S, Kim S, Duclas SK, Segal MS, Guberski DL, Esselman WJ, Boulton ME, Grant MB. Diabetic retinopathy is associated with bone marrow neuropathy and a depressed peripheral clock J Exp Med. 2009; 206(13):2897-906. * equal contribution
  13. Bhatwadekar AD, Glenn JV, Curtis TM, Grant MB, Stitt AW, Gardiner TA. Retinal endothelial cell apoptosis stimulates recruitment of endothelial progenitor cells. Invest Ophthalmol Vis Sci. 2009 Oct;50(10):4967-73.
  14. McDonald DM, Coleman G, Bhatwadekar AD, Gardiner TA, Stitt AW. Advanced glycation of the Arg-Gly-Asp (RGD) tripeptide motif modulates retinal microvascular endothelial cell dysfunction. Mol Vis. 2009 Aug 5;15:1509-20
  15. Bhatwadekar AD, Glenn JV, Figarola JL, Scott S, Rahbar S, Gardiner TA, Stitt AW. A new advanced glycation inhibitor LR-90 prevents experimental diabetic retinopathy in rats. Br J Ophthalmol: 2008; (4):545-7. 
  16. Bhatwadekar AD, Glenn JV, Curtis TM, Gardiner TA, Stitt AW. Advanced glycation of fibronectin impairs vascular repair by endothelial progenitor cells: implications for vasodegeneration in diabetic retinopathy. Invest Ophthalmol Vis Sci 2008; 49 (3):1232-41
  17. Bhatwadekar AD and Stitt AW. AGE and RAGE inhibitors in the treatment of diabetic retinopathy. Expert Rev Ophthalmol 2007 2 (1):105-20
  18. Bhatwadekar AD and Ghole VS. Rapid method for the preparation of an AGE-BSA standard calibrator using thermal glycation. J Clin Lab Anal 2005;19:11-15
  19. Bhatwadekar AD, Logade NA, Shirsat AM, Kasture VS, Kasture SB. Effects of nicotine on behavior mediated via monoamine neurotransmitters. Ind J Pharmacol 1999; 31:410-15
  20. Bhatwadekar AD, Chintawar SD, Logade NA, Somani RS, Kasture VS, Kasture SB Anti-stress activity ofButea monosperma flowers. Ind J Pharmacol 1999; 31: 153-55
INSTITUTION AND LOCATION DEGREE
(if applicable)
YEAR FIELD OF STUDY
Amravati University      
India Tata Pharma
India University of Pune
Queen’s University Belfast
University of Florida

B. Pharm
Intern
M. Pharm
Ph.D.
Post-Doctoral Training

1997
1997
1999
2007
2011
Pharmacy
Industrial Training
Pharmacology
Pharmacy
Stem Cells and Diabetic Retinopathy

Ashay Bhatwadekar, Ph.D. 

Assistant Professor of Ophthalmology
Eugene & Marilyn Glick Eye Institute
Department of Ophthalmology

Assistant Professor of Pharmacology &
Toxicology

 

 

 





Office phone: (317) 278-5075
Lab Phone: (317) 274-3565 
Fax: (317) 274-2277

 

Lab Address:

Eugene and Marilyn Glick Eye Institute 
1160 W. Michigan St., Room 318 GK 318
Indianapolis, IN  46202       

Email: abhatwad@iupui.edu
Website: http://glick.iu.edu/bhatwadekar


Lab staff
 

 

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Iraj Hassan

B.S. Biology, IUPUI

 

 

   

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Vaishnavi Jadhav

B.Sc. Biotechnology, University of Pune
M.Sc. Biotechnology, University of Pune

 

   

 

Honors & Awards

2011                       Thomas H Maren Junior Investigator, University of Florida

2009                       American Heart Association Post-Doctoral Fellow

 

Professional Memberships

  • Association for Research In Vision And Ophthalmology

  • American Heart Association

  • International Maillard Reaction Society

 

Academic Editor and Reviewer

Academic Editor

  • Journal of Pharmacology and Clinical Toxicology

  • Frontiers of Endocrinology

Reviewer

  • Investigative Ophthalmology and Vision Science

  • Brain Research Bulletin

  • Expert Opinion on Emerging Drugs

  • Pediatric Research

  • Ophthalmic Research

  • Anti-oxidant and Redox signaling

  • PLoS ONE

1160 W. Michigan St. | Indianapolis, IN 46202 | Ph: (317) 944-2020