Heads of Laboratories
Professor
Laboratory of Lymphocyte Signaling
tarakho@rockefeller.edu
In cells, information is transmitted through complex protein networks that are assembled with the help of various posttranslational protein modifications. Dr. Tarakhovsky investigates the broad design principles and logic underlying signal transduction and how these principles are integrated and applied to specific biological problems.
The Tarakhovsky laboratory studies cell signaling and epigenetic mechanisms involved in immune cell responses to pathogens. Dr. Tarakhovsky’s research on cell signaling focuses on the role of protein lysine methylation in the formation of multiprotein signaling networks in the cytosol of immune cells. Several years ago the Tarakhovsky lab identified a novel signaling mechanism that utilizes protein lysine methylation to transmit signals from the T lymphocyte membrane to the nucleus. They found that a histone methyltransferase called Ezh2, a well-known histone-modifying enzyme in the nucleus, plays an important role in ligandinduced actin polymerization in the cytosol. The finding has suggested a more general role for protein lysine methylation in the regulation of cell signaling and function and has also extended the potential usage of lysine methylation beyond the nucleusspecific modification of chromatin.
In support of this model, the Tarakhovsky lab has also found that many nonhistone proteins share a consensus lysine methylation sequence with histone H3. This sequence has been defined as a histone mimic that contributes to the methylation of histone methyltransferase G9a, a potent regulator of gene expression in cells of various types. The physiological significance of the “histone mimics” that are present in various proteins is the subject of the current research program in the lab. Dr. Tarakhovsky and his colleagues are now testing the hypothesis that lysine methylation contributes to the formation of the long-lasting signaling networks in immune cells as well as in cells of other types.
A second focus of the Tarakhovsky lab lies in the area of the epigenetic control of antiviral responses. Infection with pathogenic viruses, such as influenza, is associated with substantial transcriptional reprogramming of the infected cells. This reprogramming reflects an effort of the virus to conquer the cell as well as the cell’s attempt to suppress the virus and mount an efficient immune response. The virus-host conflict involves hundreds of host genes and numerous signaling processes that must act in concert to suppress viral infection. Recent studies in the Tarakhovsky lab have shown that distinct histone-modifying enzymes play selective roles in antiviral responses. The laboratory is currently focusing on identifying viral and host regulatory proteins, including microRNA processing enzymes, that govern epigenetic cell reprogramming in a course of viral infection.
Prior work by Dr. Tarakhovsky focused on analyzing the role of cytosolic kinases in lymphocyte signaling and function. In this
work, the Tarakhovsky lab found that the protein kinases C 
and C 
are key regulators of B cell immune responses to nonselfand
self-antigens. The Tarakhovsky lab also identified a unique role for Csk, a negative regulator of Src tyrosine kinases, in support
of antigen dependence of T cell development and maintenance.
CAREER
Dr. Tarakhovsky received his medical degree from the Kiev Medical Institute in Ukraine in 1978 and his Ph.D. from the Institute
for Oncology at the Academy of Science in Kiev in 1982. He has worked as a research associate at the Institute for Oncology, the
All-Union Cancer Research Center in Moscow and the Institute for Molecular Genetics in Tallinn, Estonia. In 1990 he joined as a
postdoc the Institute of Genetics at the University of Cologne; he was promoted to group leader in 1993 and tenured professor and
head of the Laboratory of Lymphocyte Signaling in 1995. He moved that lab to Rockefeller in 2000, when he was appointed Irene
Diamond Associate Professor. He was named full professor in 2003. Dr. Tarakhovsky was awarded the Alexander von Humboldt
Fellowship in 1990.
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