Kumar Sambamurti PhD

Biography

I am a tenured Professor at the Medical University of South Carolina and have extensive experience in the biochemistry, cellular and molecular biology of Alzheimer’s disease (AD). I also Co-Directed of the Carroll A. Campbell, Jr. neuropathology laboratory. where, we have collected over 120 human brain samples to date including African American and Early onset AD. My citation impact (H-index is 46). My laboratory has worked extensively on the biology of APP and Aβ and has contributed several key discoveries on the regulation and cell biology of the pathway. These studies include identification of the intracellular fragment of APP generated after γ-secretase cleavage and developing a novel in vitro assay for the enzyme, identifying regulatory pathways for β-secretase and determining the role of glycosylation in APP processing. Our most recent studies have discovered a novel mechanism for the paradoxical increase in Aβ obtained at low doses of several γ-secretase inhibitors. We have also collaborated with Dr. Nigel Greig and Debomoy Lahiri in understanding the regulation of APP synthesis and turnover by an acetylcholinesterase inhibitor. As a part of these studies, we developed rigorous methods to measure biomarkers in AD plasma and CSF.  More recently, we have expanded our interest by including multiple biomarkers for AD and are examining the relationship between the extracellular Aβ deposition and cell-associated deposition of Tau.

We have also been intimately involved in studying molecules that modify metabolism such as exenetide and ones that affect inflammation such as thalidomide derivatives. After joining MUSC, I have teamed with Dr. Granholm to gain considerable experience in the breeding and management of mice and in addressing specific questions in mouse models, including behavior. Over the last 10 years, I have been interested in the environmental and physiological regulators of APP processing that phenocopy familial Alzheimer’s disease mutation with the ultimate goal of reducing AD risk. I was part of a discovery that a homocystinuria mouse model shows increases in Aβ levels. I also co-mentored a PhD student; Javier Pacheco-Quinto, who has extended the discovery to understand the mechanisms by which homocysteine increases Aβ. I have successfully graduated one Ph.D. student (Chitra Venugopal) and three Masters students (Christina Demos, Liu Fang, Robert Baranello) and co-mentored two Ph.D. students (Brice Williams and Javier Pacheco-Quinto) who have all secured excellent post-doctoral fellowships. I have also trained nine post- doctoral fellows who are all well situated in their careers. In addition, I am currently mentoring one graduate student and one post-doctoral fellow. I have developed all the tools required for this study in my laboratory and have excellent collaborators for providing cutting edge help on behavior and neuropathology. I have also developed high quality analytical methods for key biomarkers. Training in my laboratory is geared towards development of detail-oriented scientists who can combine molecular biology, protein biochemistry, cell biology and anatomy to address key biomedical problems.