Postdoctoral Profile: Institute Proved to be 'Heart' of Research for Postdoctoral Fellow

Anushree Bhatnagar, Ph.D., a National Research Service Award Fellow (NRSA), has been a postdoctoral fellow at the Institute since January 2005. She received her Ph.D. from the Department of Biochemistry at Case Western Reserve University in Cleveland. The focus of Dr. Bhatnagar’s research is to understand the role of angiotensin receptor (ATR) mediated signaling in the molecular mechanisms that lead to heart failure. In almost all forms of heart failure the heart begins to express genes that are normally only expressed in the fetal heart. Researchers have known for years that this fetal-gene reactivation occurs, but do not know what regulates it. Her research is focused on understanding the phenomenon of plasma membrane (PM)-to-chromatin retrograde signaling, which coordinates gene expression with cardiomyocyte functions. PM receptor coupled activation of protein kinases and transcription factors has been described as retrograde signals for nuclear events, but little is known of signaling pathways that change epigenetic regulation. By using a high-throughput mass spectrometric approach to analyze the nuclear proteome of angiotensin-activated cells, Dr. Bhatnagar and her colleagues have been able to develop a model in which multiple signals are integrated upstream of a responsive gene by the G-protein subunits dissociating from activated G-protein-coupled receptors (GPCR). This event may lead to agonist-mediated transcription of genes. Her Faculty mentor is Sadashiva Karnik, Ph.D., in Molecular Cardiology.

Why should a graduate student or postdoctoral fellow consider the Lerner Research Institute to continue their education?

 The fact that the Institute is an integrated research community with 11 different research Departments plus centers of excellence, spanning a broad range of biomedical research interests, makes it an attractive launching pad for graduate students and postdoctoral fellows. There is also a great deal of interdisciplinary interaction among the basic and clinical scientists. This is especially helpful for the budding scientist who wishes to pursue translational research. The Institute and Cleveland Clinic certainly have the edge over many institutes worldwide.

Sadashiva Karnik, Ph.D. (left) and Anushree Bhatnagar, Ph.D.

What have you liked the best about your experience at the Lerner Research Institute?

The most invigorating experience for me, as a postdoctoral fellow, has been the ease and pace of conducting my research. Interacting and collaborating with the Mass Spectrometry core, the Imaging core and other laboratories in the Department of Molecular Cardiology has been a positive experience. Most of the credit goes to my mentor. His constant support has instilled confidence in me as a scientist. My interactions with him help crystallize my thoughts and ideas and constantly push our work forward. Earning the NIH Individual NRSA award for my postdoctoral training for three years, starting 2007, is a testament to that.

Why did you select the Institute?

 I wanted to continue G-protein-coupled receptor research, but in the cardiovascular system. GPCRs are the major targets of therapeutic intervention for various diseases, including cardiac hypertrophy and heart failure. What better place than the Cleveland Clinic? I visited Dr. Karnik’s laboratory. His angiotensin receptor research is a broad program. It includes structure-function analysis, design of agonists for selective signaling, AT1R transgenic mouse models of heart failure and hypertension, and analysis of variation in angiotensin receptor genes in the human population. Dr. Karnik had recently developed considerable interest in linking AT1R signal transduction to global changes in proteome and genome regulation. I wanted to contribute to this endeavor and simultaneously gain insight into cardiovascular disease models of GPCR, an experience I needed to incorporate.

What has been some of the surprises about coming to the Lerner Research Institute?

The strength of the support staff in the laboratory and Department has been a positively pleasant surprise. Overall, I must say it has been an excellent learning experience.