Heads of Laboratories

Alexander Tarakhovsky, M.D., Ph.D.

Professor
Laboratory of Immune Cell Epigenetics and Signaling
Alexander.Tarakhovsky@rockefeller.edu

Lab Members Publications In the News

Faculty Bio

Alexander Tarakhovsky

The interaction of immune cells with their environment leads to changes in the function of genes that contribute to effective immune response. These changes in gene expression, controlled by various signaling pathways, including those that converge at the chromatin level, are responsible for forming immune and nonimmune cell phenotypes that may persist for significant time periods. The Tarakhovsky lab studies the mechanisms by which pathogens affect chromatin function and how they affect long-lasting immune and nonimmune cell responses to the environment.

Organism response to environmental stresses has both a predetermined, as well as an adaptive, nature. The predetermined response reflects the cell type-specific differences in signaling pathways and gene expression programs. In turn, adaptive responses reflect the ability of individual cells within a given lineage to integrate distinct environmental cues and to respond to them in a well-calibrated fashion. The predetermined and adaptive responses depend largely on tightly controlled gene expression programs that operate within limits imposed by a gene-specific chromatin environment. In the immune system, changes in chromatin are associated with, and contribute to, differentiation of hematopoietic stem cells into highly diverse immune cell subpopulations. Cell type-specific programs that drive responses of differentiated immune cells to pathogens differ significantly between B and T lineage cells as well as between cells of the adaptive and innate immune systems. The Tarakhovsky laboratory studies the mechanisms by which pathogens affect the function of chromatin, as well as how they affect long-lasting immune and nonimmune cell responses to the environment.

Several years ago, the Tarakhovsky laboratory proposed the “histone mimicry” paradigm as a novel mechanism for regulation of gene expression. According to this paradigm, regulation of gene expression could be controlled by histone-like entities present in nonhistone proteins that can compete with histones for the regulators of gene expression. The foundation of this model originates from identification of the histone mimic within the histone methyltransferase G9a, which plays the important role of gene silencing. Further studies show the presence of histone mimics in a large number of human and mouse proteins. Furthermore, the laboratory found that pathogenic microorganisms carry histone mimics in the proteins that critically contribute to pathogen-mediated suppression of the host immune response. This finding led them to propose a mechanism according to which histone mimics in bacterial and viral proteins may serve as histone surrogates, thus hijacking chromatin-based pathways of immune response. The histone mimics concept led the Tarakhovsky laboratory to develop synthetic histone mimics that regulate inflammatory gene expression by interfering with association between histones and transcription regulators. In the future, the laboratory plans to extend its research toward an understanding of the mechanism of epigenetic conditioning of host cells by pathogens. This research may help to elucidate the basis of chronic inflammatory disorders that are initiated by infection but can persist in the absence of infectious agents.

CAREER

Dr. Tarakhovsky received his medical degree from the Kiev Medical Institute in the 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 the Institute of Genetics at the University of Cologne as a postdoc; he was promoted to group leader in 1993 and tenured professor and head of the Laboratory of Lymphocyte Signaling in 1995. He moved to Rockefeller in 2000, when he was appointed Irene Diamond Associate Professor. He was named full professor in 2003.



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