Eric M. Verdin, M.D.
Areas of Investigation
Our laboratory explores different aspects of the biology of reversible protein acetylation, a posttranslational modification that is gaining increasing recognition as an important biological regulatory mechanism. Our laboratory is focused on the enzymes that remove acetyl groups from proteins, the histone/protein deacetylases (HDACs). We are exploring the role of protein acetylation in three different biological systems:
1. Transcriptional regulation of HIV expression. We have established that the chromatin organization of the HIV genome and the level of acetylation of its histones play a critical role in its transcriptional activity. We are currently focusing our effort on the Brg-1 and Brd4 proteins. Both factors contain bromodomains, an acetyl recognition motif, and are part of distinct multiprotein complexes that regulate HIV transcription. We have also established a new in vitromodel for HIV latency and are identifying the cellular factors that contribute to the establishment of latency (transcriptional silencing) and to the reactivation of latency.
2. Mechanism of of positive and negative selection during thymocyte development. We are studying the role of histone deacetylase 7, which is highly expressed and regulated in double positive (CD4 and CD8) developing T cells. We found that HDAC7 regulates the expression of a cassette of genes that play a critical role in the process of positive and negative selection. We are studying the regulation of HDAC7 nucleo-cytoplasmic shuttling in response to TCR activation, We are currently developing knockout mice for HDAC7 and will be exploring its biological role in the mouse immune system.
3. Role of mitochondrial protein deacetylases. We have identified a mitochondrial protein deacetylase, SIRT3 and its first target, acetylcoenzyme A synthetase. We are currently identifying mitochondrial proteins that are acetylated, studying their regulation by SIRT3 and defining the role of protein acetylation in mitochondrial function.
For more information about our lab, please visit the lab website at: http://www.gladstone.ucsf.edu/gladstone/files/verdin/lab/