Sergei Koralov, Ph.D.

Assistant Professor of Pathology
Ph.D., Harvard University 2007

New York University School of Medicine
550 First Ave, MSB 531
New York, NY 10016
Office Tel: (212) 263-1843
Lab Tel: (212) 263-6153

Research Theme(s): Immunology and molecular biology; Lymphomagenesis, cancer stem cells.
Keywords: Immunology, cancer, JAK/STAT, lymphomagenesis, B cell, T cell, miRNA, RNAi

Research Summary:

We are taking advantage of conditional gene targeting and a strong foundation in immunology to pursue two different biological questions.

The goal of the first project is to explore the role of chronic inflammation in lymphomagenesis. In order to elucidate the role of STAT3 as a transforming factor in T cell malignancies I generated a mouse model wherein expression of a hyper-active STAT3 mutant protein (STAT3C) can be induced in a conditional, tissue-specific manner through Cre-mediated deletion of an upstream stop cassette. These mice display two distinct forms of T cell-driven pathology: expression of a single copy of STAT3C in T cells (CD4-Cre R26STAT3Cstopfl/+) results in a disease closely resembling mycosis fungoides (MF), a common type of cutaneous T cell lymphoma, whereas mice expressing two copies of STAT3C (CD4-Cre R26STAT3Cstopfl/fl) develop fulminant autoimmunity driven by Th17 cell expansion. Interestingly, CD4-Cre R26STAT3Cstopfl/+ mice that succumb to CTCL exhibit low grade chronic Th17 inflammation prior to developing the pathology associated with the lymphoma.

The central premise of this project is to understand whether sustained chronic inflammation driven by Th17 cells can play a primary role in the transformation of T lymphocytes. We are continuing to take advantage of conditional gene targeting in order to examine the role of other suspected oncogenes in lymphocyte malignancies.

The aim of the second project is to understand the role of RNAi in B cell development and function. The emphasis of this project is to both explore the role of individual miRNAs in B cell survival and proliferation as well as to understand the contribution of RNAi to Ig locus accessibility during V(D)J recombination, somatic hypermutation and class switch recombination. We again are taking advantage of conditional gene targeting to ablate enzymes necessary for miRNA biogenesis (Dicer, Drosha and DGCR8), or to either induce expression of or shut down individual miRNA to examine the role of RNAi at different stages of B cell development.

Selected publications: