Lakshman Segar, Ph.D

Clinical and Administrative Pharmacy, Augusta
Associate Professor

Clinical and Administrative Pharmacy, Augusta

Education

Associate Professor, University of Georgia 2011-Present

Research Pharmacologist, VA Medical Center 2011-Present

Core Lab Director, GCRC, Heart and Vascular Institute, Penn State University 2008-2010

Assistant Professor, Penn State University 2000-2011

Research Associate, Penn State University 1998-2000

Postdoctoral Fellow, University of British Columbia 1996-1998

Postdoctoral Fellow, University of Saskatchewan 1994-1996

Graduate Teaching Assistant, University of Saskatchewan 1992-1993

Ph.D. Pharmacology, University of Saskatchewan 1990-1994

Honors, Awards, and Achievements

Postdoctoral Fellowship award, Health Services Utilization and Research Commission, Saskatoon, Saskatchewan, Canada

Graduate Scholarship, College of Graduate Studies and Research, University of Saskatchewan, Saskatoon, Saskatchewan, Canada (1990-1994)

Member, Editorial Board of the Journal of Pharmacology and Clinical Toxicology

Research Interests

Diabetic vascular complications: Atherosclerosis, restenosis after angioplasty, vascular injury, dyslipidemia, smooth muscle cell phenotype, cell proliferation, cell differentiation, signal transduction mechanisms, platelet-derived growth factor receptor signaling, insulin receptor signaling, and glucose transporters.

Diabetic retinopathy: Neurovascular complications, retinal ganglion cells, retinal endothelial cells, cell survival, apoptosis, signal transduction mechanisms, platelet-derived growth factor receptor signaling, and insulin receptor signaling.

Fatty liver disease: dysregulated fatty acid metabolism / mitochondrial oxidative metabolism in metabolically compromised conditions such as alcoholic liver disease, obesity, and diabetes.

Selected Publications

Fairaq, A., Shawky, N. M., Osman, I., Pichavaram, P. and Segar, L.  AdipoRon, an adiponectin receptor agonist, attenuates PDGF-induced VSMC proliferation through inhibition of mTOR signaling independent of AMPK: implications toward suppression of neointimal hyperplasia.  Pharmacol Res. 119: 289-302; 2017.

Shawky, N. M. and Segar, L.  Sulforaphane inhibits platelet-derived growth factor-induced vascular smooth muscle cell proliferation by targeting mTOR/p70S6kinase signaling independent of Nrf2 activation.  Pharmacol Res. 119: 251-264; 2017.

Osman, I., Poulose, N., Ganapathy, V. and Segar, L.  High fructose-mediated attenuation of insulin receptor signaling does not affect PDGF-induced proliferative signaling in vascular smooth muscle cells.  Eur J Pharmacol. 791: 703-710; 2016.

Shawky, N.M., Pichavaram, P., Shehatou, G.S.G., Suddek, G.M., Gameil, N.M., Jun, J.Y. and Segar L.  Sulforaphane improves dysregulated metabolic profile and inhibits leptin-induced VSMC proliferation: implications toward suppression of neointima formation after arterial injury in western diet-fed obese mice.  J Nutr Biochem. 32: 73-84; 2016.

Segar, L.  Letter to the Editor: Comment on “SGLT2 Inhibitors May Predispose to Ketoacidosis” by Taylor S.I., et al.  J Clin Endocrinol Metab. 101: L27-L28; 2016.

Osman, I. and Segar, L.  Pioglitazone, a PPARγ agonist, attenuates PDGF-induced vascular smooth muscle cell proliferation through AMPK-dependent and AMPK-independent inhibition of mTOR/p70S6K and ERK signaling.  Biochem Pharmacol. 101: 54-70; 2016.

Pyla, R., Pichavaram, P., Fairaq, A., Park, M.A., Kozak, M., Kamath, V., Patel, V.S. and Segar L.  Altered energy state reversibly controls smooth muscle contractile function in human saphenous vein during acute hypoxia-reoxygenation: Role of glycogen, AMP-activated protein kinase, and insulin-independent glucose uptake.  Biochem Pharmacol. 97: 77-88; 2015.

Pyla, R, Osman, I., Pichavaram, P., Hansen, P. and Segar, L.  Metformin exaggerates phenylephrine -induced AMPK phosphorylation independent of CaMKKbeta and attenuates contractile response in endothelium-denuded rat aorta.  Biochem Pharmacol. 92: 266-279; 2014.

Pyla, R, Poulose, N., Jun, J.Y. and Segar, L.  Expression of conventional and novel glucose transporters, GLUT1, -9, -10, -12, in vascular smooth muscle cells.  Am J Physiol:Cell Physiol. 304: C574-C589; 2013.

Jun, J.Y., Ma, Z., Pyla, R. and Segar, L.  Leptin treatment inhibits the progression of atherosclerosis by attenuating hypercholesterolemia in type 1 diabetic Ins2+/Akita:apoE-/- mice.  Atherosclerosis 225: 341-347; 2012.

Jun, J.Y., Ma, Z. and Segar, L.  Spontaneously diabetic Ins2+/Akita:ApoE-deficient mice exhibit exaggerated hypercholesterolemia and atherosclerosis.  Am J Physiol:Endocrinol Metab. 301: E145-E154; 2011.

Zhao, Y., Biswas, S.K., McNulty, P.H., Kozak, M., Jun, J.Y. and Segar, L.  PDGF-induced vascular smooth muscle cell proliferation is associated with dysregulation of insulin receptor substrates.  Am J Physiol:Cell Physiol. 300: C1375-C1385; 2011.

Biswas, S.K., Zhao, Y., Nagalingam, A., Gardner, T.W. and Sandirasegarane, L.  PDGF- and Insulin/IGF-1-specific distinct modes of Class IA PI 3-kinase activation in normal rat retinas & RGC-5 retinal ganglion Cells.  Invest Ophthal Vis Sci. 49: 3687-3698; 2008.

Antonetti, D.A., Barber, A.J., Bronson, S.K., Freeman, W.M., Gardner, T.W., Jefferson, L.S., Kester, M., Kimball, S.R., Krady, J.K., LaNoue, K.F., Norbury, C.C., Quinn, P.G., Sandirasegarane, L. and Simpson, I.A..  Diabetic retinopathy: Seeing beyond glucose-induced microvascular disease.  Diabetes 55: 2401-2411; 2006.

Reiter, C.E.N., Wu, X., Sandirasegarane, L., Nakamura, M., Gilbert, K.A., Singh, R.S.J., Fort, P.E., Antonetti, D.A. and Gardner, T.W.  Diabetes reduces basal retinal insulin receptor signaling:  Reversal with systemic and local insulin.  Diabetes 55: 1148-1156; 2006.

Stahl, J.M., Sharma, A., Cheung, M., Zimmerman, M., Cheng, J.Q., Bosenberg, M.W., Kester, M., Sandirasegarane, L. and Robertson, G.P.  Deregulated Akt3 activity promotes development of malignant melanoma.  Cancer Res. 64: 7002-7010; 2004.

Reiter, C.E.N., Sandirasegarane, L., Wolpert, E.B., Klinger, M., Simpson, I.A., Barber, A.J., Antonetti, D.A., Kester, M. and Gardner, T.W.  Characterization of insulin signaling in rat retina in vivo and ex vivo.  Am J Physiol:Endocrinol Metab. 285: E763-E774; 2003.

Bourbon, N., Sandirasegarane, L. and Kester, M.  Ceramide-induced inhibition of Akt is mediated through PKCzeta: implications for growth arrest.  J Biol Chem. 277: 3286-3292; 2002.

Charles, R., Sandirasegarane, L., Yun, J., Bourbon, N., Wilson, R., Rothstein, R.P., Levison, S. and Kester, M.  Ceramide-coated balloon catheters limit neointimal hyperplasia following stretch injury in carotid arteries.  Circ Res. 87: 282-288; 2000.

Sandirasegarane, L., Charles, R., Bourbon, N. and Kester, M.  NO regulates PDGF-induced activation of PKB but not ERK in A7r5 cells: implications for vascular growth arrest.  Am J Physiol:Cell Physiol. 279: C225-C235; 2000.

Grant Support

R.C. Wilson Pharmacy Fund – UGA College of Pharmacy Foundation Fund
(01/2018-12/2018)

Grant-In-Aid award from NIH/NHLBI (R01 Grant, 08/2010-11/2017)

Grant-In-Aid awards from National Diabetes Research funding agencies (NIH/NIDDK-R21 Grant, 09/2005-06/2008; JDRF-Regular Research Grant, 08/2005-07/2009; and ADA-Innovation Award)

Beginning Grant-In-Aid awards from American Heart Association, Pennsylvania-Delaware Affiliate (07/1999-06/2002; 07/2002-12/2004)