The main focus of our research efforts is to understand the metabolic and inflammatory mechanisms underlying diabetic cardiovascular complications. In this context, our work has led to several novel findings that (a) the glucose metabolizing enzyme, aldose reductase (AR) plays critical role in the pathogenesis of myocardial ischemic injury, (b) advanced glycation end products (AGEs) modulates cardiomyocyte injury during ischemia-reperfusion injury in diabetics and non-diabetics via RAGE pathway driven signaling mechanisms, and (c) AR-driven mechanisms, in part, mediate acceleration and progression of atherosclerosis in diabetics. .
Specific areas of investigations are:
1) Elucidating mechanisms by which flux via AR drives acetylation of metabolic, transcriptional, and antioxidant enzymes in ischemic, diabetic, and aging heart.
2) Mechanisms by which RAGE tail binding partner Diaph1, in part, mediates cardiac aging and myocardial ischemic injury. Specifically, studies will address how Diaph1-driven changes in actin cytoskeleton dynamics mediate cardiac aging and increased vulnerability of the heart to ischemic stress.
3) Dissection of the RAGE/Diaph1 driven mechanisms mediating macrophage recruitment, retention, and inflammatory actions in impaired regression of diabetic atherosclerosis.
Driven by the complexities of mechanisms that underlie myocardial ischemic injury and heart failure, the goal of my laboratory is to elucidate the importance of AR and AGE-RAGE pathways in mediating ischemic injury, metabolic imbalances, heart failure and diabetic atherosclerosis. It is my hope and expectation that interventions that block AR and/ AGE-RAGE pathways will be employed in the near future to treat patients with evolving myocardial infarction and diabetic cardiovascular complications.
Professor, Department of Medicine
Professor, Department of Biochemistry and Molecular Pharmacology
PhD from Loyola University
BMC public health. 2018 Jan 05; 18(1):101-101
EBioMedicine. 2017 Dec; 26:165-174
PLoS one. 2017 Nov 30; 12(11):e0188981-e0188981
Journal of clinical & translational endocrinology. 2017 Aug 14; 10:1-8
PROFILING SRF and MODULATION OF SRF TARGET GENES IN A MOUSE MODEL OF CARDIAC AGING [Meeting Abstract]
Journal of the American Geriatrics Society. 2017 MAY; 65:S231-S232
Investigating RAGE Ectodomain Shedding (sRAGE) and Splice Variant (esRAGE) in Diabetic and Inflammatory Conditions [Meeting Abstract]
FASEB journal. 2017 APR; 31:?-?
Expert review of proteomics. 2016 Dec 22; 14(2):147-156
Biochimica & biophysica acta. 2016 Dec; 1862(12):2244-2252