Radha Ananthakrishnan, PhD, Research Scientist

Radha Ananthakrishnan, PhDRecent findings have implicated the importance of enzymes of polyol pathway, RAGE and their involvement in ischemia-reperfusion injury. My current research interest is to investigate the underlying mechanism involved in cardiomyocyte stresses evoked by LAD occlusion and reperfusion injury in the myocardium using murine models, both in the absence and presence of diabetes.

Our studies demonstrated that cardiomyocyte RAGE is highly upregulated in the murine heart after ischemia reperfusion injury, signals devastating metabolic consequences in the healing myocardium, which trigger mitochondrial dysfunction, in part through GSK-3β and apoptotic events.  I have over 20 years of experience in designing and interpreting studies elucidating the impact of signal transduction events mediated by mitochondria. 

 

Publications
1. Zeng S, Zhang QY, Huang J, Vedantham S, Rosario R, Ananthakrishnan R, Yan SF, Ramasamy R, Dematteo RP, Emond JC, Friedman RA, Schmidt AM. Opposing roles of RAGE and Myd88 signaling in extensive liver resection. FASEB J. 2012 Feb;26(2):882-93. Epub 2011 Nov 10.

2. Juranek JK, Aleshin A, Rattigan EM, Johnson L, Qu W, Song F, Ananthakrishnan R, Quadri N, Yan SD, Ramasamy R, Schmidt AM, Geddis MS. Morphological Changes and Immunohistochemical Expression of RAGE and its Ligands in the Sciatic Nerve of Hyperglycemic Pig (Sus Scrofa). Biochem Insights. 2010 Sep 1;2010(3):47-59.

3. Vedantham S, Noh H, Ananthakrishnan R, Son N, Hallam K, Hu Y, Yu S, Shen X, Rosario R, Lu Y, Ravindranath T, Drosatos K, Huggins LA, Schmidt AM, Goldberg IJ, Ramasamy R. Human aldose reductase expression accelerates atherosclerosis in diabetic apolipoprotein E-/- mice. Arterioscler Thromb Vasc Biol. 2011 Aug;31(8):1805-13. Epub 2011 Jun 2.

4. Ananthakrishnan R, Li Q, Gomes T, Schmidt AM, Ramasamy R. Aldose reductase pathway contributes to vulnerability of aging myocardium to ischemic injury. Exp Gerontol. 2011 Sep;46(9):762-7. Epub 2011 May 10.

5. Hallam KM, Li Q, Ananthakrishnan R, Kalea A, Zou YS, Vedantham S, Schmidt AM, Yan SF, Ramasamy R. Aldose reductase and AGE-RAGE pathways: central roles in the pathogenesis of vascular dysfunction in aging rats. Aging Cell. 2010 Oct;9(5):776-84.  doi: 10.1111/j.1474-9726.2010.00606.x. Epub 2010 Aug 15.

6. Reiniger N, Lau K, McCalla D, Eby B, Cheng B, Lu Y, Qu W, Quadri N, Ananthakrishnan R, Furmansky M, Rosario R, Song F, Rai V, Weinberg A, Friedman R, Ramasamy R, D'Agati V, Schmidt AM. Deletion of the receptor for advanced glycation end products reduces glomerulosclerosis and preserves renal function in the diabetic OVE26 mouse. Diabetes. 2010 Aug;59(8):2043-54. Epub 2010 Jul 13.

7. Shang L, Ananthakrishnan R, Li Q, Quadri N, Abdillahi M, Zhu Z, Qu W, Rosario R, Touré F, Yan SF, Schmidt AM, Ramasamy R. RAGE modulates hypoxia/reoxygenation injury in adult murine cardiomyocytes via JNK and GSK-3beta signaling pathways.  PLoS One. 2010 Apr 9;5(4):e10092.

8. Ravindranath TM, Mong PY, Ananthakrishnan R, Li Q, Quadri N, Schmidt AM, Ramasamy R, Wang Q. Novel role for aldose reductase in mediating acute inflammatory responses in the lung. J Immunol. 2009 Dec 15;183(12):8128-37.

9. Ananthakrishnan R, Kaneko M, Hwang YC, Quadri N, Gomez T, Li Q, Caspersen C, Ramasamy R. Aldose reductase mediates myocardial ischemia-reperfusion injury in part by opening mitochondrial permeability transition pore. Am J Physiol Heart Circ Physiol. 2009 Feb;296(2):H333-41. Epub 2008 Dec 5.

10. Li Q, Hwang YC, Ananthakrishnan R, Oates PJ, Guberski D, Ramasamy R. Polyol pathway and modulation of ischemia-reperfusion injury in Type 2 diabetic BBZ rat hearts. Cardiovasc Diabetol. 2008 Oct 28; 7:33.

11. Bucciarelli LG, Ananthakrishnan R, Hwang YC, Kaneko M, Song F, Sell DR, Strauch C, Monnier VM, Yan SF, Schmidt AM, Ramasamy R. RAGE and modulation of ischemic injury in the diabetic myocardium. Diabetes. 2008 Jul;57(7):1941-51.  Epub 2008 Apr 16.

12. Guo J, Ananthakrishnan R, Qu W, Lu Y, Reiniger N, Zeng S, Ma W, Rosario R, Yan SF, Ramasamy R, D'Agati V, Schmidt AM. RAGE mediates podocyte injury in adriamycin-induced glomerulosclerosis. J Am Soc Nephrol. 2008 May;19(5):961-72.  Epub 2008 Feb 6.

13. Aleshin A, Ananthakrishnan R, Li Q, Rosario R, Lu Y, Qu W, Song F, Bakr S, Szabolcs M, D'Agati V, Liu R, Homma S, Schmidt AM, Yan SF, Ramasamy R. RAGE modulates myocardial injury consequent to LAD infarction via impact on JNK and STAT signaling in a murine model. Am J Physiol Heart Circ Physiol. 2008 Apr;294(4):H1823-32. Epub 2008 Feb 1.

14. Bucciarelli LG, Kaneko M, Ananthakrishnan R, Harja E, Lee LK, Hwang YC, Lerner S, Bakr S, Li Q, Lu Y, Song F, Qu W, Gomez T, Zou YS, Yan SF, Schmidt AM, Ramasamy R. Receptor for advanced-glycation end products: key modulator of myocardial ischemic injury. Circulation. 2006 Mar 7;113(9):1226-34. Epub 2006 Feb 27.

15. Goldenthal MJ, Ananthakrishnan R, Marín-García J. Nuclear-mitochondrial cross-talk in cardiomyocyte T3 signaling: a time-course analysis. J Mol Cell Cardiol. 2005 Aug;39(2):319-26.

16. Ananthakrishnan R, Moe GW, Goldenthal MJ, Marín-García J. Akt signaling pathway in pacing-induced heart failure. Mol Cell Biochem. 2005 Jan;268(1-2):103-10.

17. Marin-Garcia J, Goldenthal MJ, Ananthakrishnan R, Pierpont ME. The complete sequence of mtDNA genes in idiopathic dilated cardiomyopathy shows novel missense and tRNA mutations. J Card Fail. 2000 Dec;6(4):321-9.

18. Marin-Garcia J, Ananthakrishnan R, Goldenthal MJ, Pierpont ME. Biochemical and molecular basis for mitochondrial cardiomyopathy in neonates and children. J Inherit Metab Dis. 2000 Sep;23(6):625-33.

19. Marin-Garcia J, Ananthakrishnan R, Goldenthal MJ. Heart mitochondrial DNA and enzyme changes during early human development. Mol Cell Biochem. 2000 Jul;210(1-2):47-52.

20. Marin-Garcia J, Goldenthal MJ, Pierpont EM, Ananthakrishnan R, Perez-Atayde A.  Is age a contributory factor of mitochondrial bioenergetic decline and DNA defects in idiopathic dilated cardiomyopathy? Cardiovasc Pathol. 1999 Jul-Aug;8(4):217-22.

21. Marin-Garcia J, Ananthakrishnan R, Goldenthal MJ, Filiano JJ, Sarnat HB. Skeletal muscle mitochondrial defects in nonspecific neurologic disorders.  Pediatr Neurol. 1999 Aug;21(2):538-42.

22. Marin-Garcia J, Ananthakrishnan R, Goldenthal MJ, Filiano JJ, Perez-Atayde A. Mitochondrial dysfunction in skeletal muscle of children with cardiomyopathy.  Pediatrics. 1999 Feb;103(2):456-9.

23. Goldenthal MJ, Marin-Garcia J, Ananthakrishnan R. Cloning and molecular analysis of the human citrate synthase gene.  Genome. 1998 Oct;41(5):733-8.

24. Marin-Garcia J, Ananthakrishnan R, Goldenthal MJ. Human mitochondrial function during cardiac growth and development.  Mol Cell Biochem. 1998 Feb;179(1-2):21-6.

25. Marin-Garcia J, Ananthakrishnan R, Goldenthal MJ. Hypertrophic cardiomyopathy with mitochondrial DNA depletion and respiratory enzyme defects. Pediatr Cardiol.  1998 May-Jun;19(3):266-8.

26. Marin-Garcia J, Ananthakrishnan R, Goldenthal MJ, Filiano JJ, Perez-Atayde A.  Cardiac mitochondrial dysfunction and DNA depletion in children with hypertrophic cardiomyopathy. J Inherit Metab Dis. 1997 Sep;20(5):674-80.

27. Marin-Garcia J, Ananthakrishnan R, Goldenthal MJ. Mitochondrial gene expression in rat heart and liver during growth and development. Biochem Cell Biol. 1997;75(2):137-42.

28. Marin-Garcia J, Goldenthal MJ, Ananthakrishnan R, Mirvis D. Specific mitochondrial DNA deletions in canine myocardial ischemia. Biochem Mol Biol Int. 1996 Nov;40(5):1057-65.

29. Marin-Garcia J, Ananthakrishnan R, Korson M, Goldenthal MJ, Perez-Atayde A.  Cardiac mitochondrial dysfunction in Leigh syndrome. Pediatr Cardiol. 1996 Nov-Dec;17(6):387-9.

30. Marin-Garcia J, Hu Y, Ananthakrishnan R, Pierpont ME, Pierpont GL, Goldenthal MJ. A point mutation in the cytb gene of cardiac mtDNA associated with complex III deficiency in ischemic cardiomyopathy. Biochem Mol Biol Int. 1996 Oct;40(3):487-95.

31. Marin-Garcia J, Ananthakrishnan R, Goldenthal MJ. Mitochondrial dysfunction after fetal alcohol exposure. Alcohol Clin Exp Res. 1996 Sep;20(6):1029-32.

32. Marin-Garcia J, Ananthakrishnan R, Pierpont ME, Goldenthal MJ. Mitochondrial dysfunction in spontaneous inbred turkey cardiomyopathy. Biochem Mol Biol Int. 1996 May;38(6):1087-93.

33. Marin-Garcia J, Goldenthal MJ, Ananthakrishnan R, Pierpont ME, Fricker FJ, Lipshultz SE, Perez-Atayde A. Specific mitochondrial DNA deletions in idiopathic dilated cardiomyopathy. Cardiovasc Res. 1996 Feb;31(2):306-13.

34. Marin-Garcia J, Goldenthal MJ, Ananthakrishnan R, Pierpont ME, Fricker FJ, Lipshultz SE, Perez-Atayde A. Mitochondrial function in children with idiopathic dilated cardiomyopathy. J Inherit Metab Dis. 1996;19(3):309-12.

35. Marin-Garcia J, Ananthakrishnan R, Goldenthal MJ. Heart mitochondria response to alcohol is different than brain and liver. Alcohol Clin Exp Res. 1995 Dec;19(6):1463-6.

36. Marin-Garcia J, Goldenthal MJ, Pierpont ME, Ananthakrishnan R. Impaired mitochondrial function in idiopathic dilated cardiomyopathy: biochemical and molecular analysis. J Card Fail. 1995 Sep;1(4):285-91.

37. Marin-Garcia J, Goldenthal MJ, Ananthakrishnan R, Mirvis D. Localized mitochondrial dysfunction in canine myocardial ischemia. Biochem Mol Biol Int. 1995 Mar;35(3):651-9.

38. Marin-Garcia J, Ananthakrishnan R, Gonzalvo A, Goldenthal MJ. Novel mutations in mitochondrial cytochrome b in fatal post partum cardiomyopathy. J Inherit Metab Dis. 1995;18(1):77-8.

39. Marin-Garcia J, Ananthakrishnan R, Goldenthal MJ. Presence of a mitochondrial DNA deletion in fetal and adult bovine cardiac tissue. Biochem Mol Biol Int. 1994 Aug;33(5):817-25.

40. Marin-Garcia J, Ananthakrishnan R, Agrawal N, Goldenthal MJ. Mitochondrial gene expression during bovine cardiac growth and development. J Mol Cell Cardiol. 1994 Aug;26(8):1029-36.

41. Marin-Garcia J, Ananthakrishnan R, Carta M, Dubois R, Gu J, Goldenthal MJ. Mitochondrial dysfunction in a case of fatal infantile cardiomyopathy. J Inherit Metab Dis. 1994;17(6):756-7.