Sergei Koralov, Ph.D.
Assistant Professor of Pathology
Ph.D., Harvard University 2007
Cancer Stem Cells, Immunology and Molecular Biology; Lymphomagenesis
inflammation, Immunology, B cell, T cell, JAK/STAT signaling, lymphoma, miRNAs, non-coding RNAs
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
We are taking advantage of conditional gene targeting and a strong foundation in immunology to pursue projects related to autoimmunity, cancer and basic B and T cell development.
The goal of the first project is to explore the role of Th17 driven inflammation in lymphomagenesis and in asthma. For this purpose we are taking advantage of a mouse model we recently generated in which activation of the STAT3 signaling cascade selectively in T cells leads to the development of spontaneous Th17 driven inflammation. Depending on the level of STAT3 expression these mice either develop severe Th17 driven asthma or T cell lymphoma. We are using additional genetic tools to dissect the contribution of chronic Th17 inflammation to the lymphoma phenotype. In the context of this project we are also exploring the role of microbiota in asthma and lymphomagenesis and the role of antigen stimulation in Th17 driven diseases. In addition, because epigenetic therapy (HDAC inhibitors) is successfully used in the clinic to treat T cell lymphoma we are using our mouse model of this disease as well as biopsy samples from patients undergoing HDACi treatment to understand the nature of chromatin changes in T cells during lymhomagenesis and the consequences of this treatment of T cell differentiation program.
The aim of the second project is to understand the role of RNAi in B cell development, differentiation and function. The emphasis of this project is to both explore the role of individual miRNAs in maintaining lymphoid identity and to understand the contribution of RNAi to Ig locus accessibility during V(D)J recombination, somatic hypermutation and class switch recombination. Our aim is to gain better understanding of the regulation of these dangerous genetic events and to dissect the various ways in which non-coding RNAs contribute to normal B cell development and function as well as to lymphomagenesis.
Rotation projects are available in all of the topics listed above and there is ample opportunity for motivated, bright students to develop their own rotation project in the context of immunology/cancer biology focus of the lab
- Fogli LK, Sundrud MS, Goel S, Bajwa S, Jensen K, Derruder E, Sun A, Coffre M, Uyttenhove C, Van Snick J, Schmidt-Supprian M, Rao A, Grunig G, Durbin J, Casola SS, Rajewsky K and Koralov SB. (2013) T cell-derived IL-17 mediates epithelial changes in the airway and drives pulmonary neutrophilia. J. of Immunology Sep 15; 191(6)3100-11. PMID: 23966625
- Koa M, Bandukwala HS, Ana J, Lamperti ED, Thompson EC, Hastie R, Tsangaratou A, Rajewsky K, Koralov SB, and Rao A. (2011) Ten-eleven-translocation 2 (Tet2) negatively regulates homeostasis and differentiation of hematopoietic stem cells in mice. PNAS Aug 30; 108(35): 14566-71. PMID: 21873190
- Arnaout R, Lee W, Cahill P, Honan T, Sparrow T, Weiand M, Nusbaum C, Rajewsky K and Koralov SB (2011) High-resolution description of antibody heavy-chain repertoires in humans. PLOS One Aug 6(8):e22365. PMID: 21829618
- Ghosh S, Koralov SB, Stevanovic I, Sundrud MS, Sasaki Y, Rajewsky K, Rao A, Muller M. (2010) Hyperactivation of NFAT1 in T cells attenuates severity of murine autoimmune encephalomyelitis. PNAS Aug 24;107(34):15169-74. PMID: 20696888
- Sundrud MS, Koralov SB, Feuerer M, Calado DP, Kozhaya AE, Rhule-Smith A, Lefebvre RE, Unutmaz D, Mazitschek R, Waldner H, Whitman M, Keller T, Rao A. Halofuginone inhibits TH17 cell differentiation by activating the amino acid starvation response. Science. 2009 Jun 5;324(5932):1334-8. PMID: 19498172
- Koralov SB, Muljo SA, Galler GR, Krek A, Chakraborty T, Kanellopoulou C, Jensen K, Cobb BS, Merkenschlager M, Rajewsky N, Rajewsky K. Dicer ablation affects antibody diversity and cell survival in the B lymphocyte lineage. Cell. 2008 Mar 7;132(5):860-74. PMID: 18329371