Dr. Koralov is a cellular and molecular immunologist with experience in generating and analyzing mouse models of human malignancies and autoimmune diseases. His past projects focused on V(D)J recombination, lymphomagenesis and the role of RNAi in lymphocyte biology. Dr. Koralov’s research has previously helped characterize the molecular mechanisms of secondary IgH recombination and defined the role of RNAi in B cell survival and proliferation.
We are now 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 biospecimens from patients as well as mouse models. Using conditional gene targeting we able to dissect the contribution of Th17 cells to chronic inflammation in the airways, skin and bone; determine the role of antigen receptor specificity and explore the role of microbiota in autoimmunity and cancer.
Because Cutaneous T cell lymphoma, one of the malignancies that the lab studies, is amenable to epigenetic therapy (HDAC inhibitors), we are also interested in understanding the nature of chromatin changes in T cells during lymhomagenesis and the consequences of this treatment of T cell differentiation program. We are exploring this using a hundred percent penetrant mouse model of CTCL that the lab developed as well as by analyzing patient biospecimens before and after HDACi treatment.
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.
In addition to these two projects the laboratory also has active projects in tumor immunology (in the context of melanoma), in basic B and T cell development and in the cancer stem cell field (in the context of myeloma and T cell lymphomas).
Coffre M, Benhamou D, Rieb D, Blumenberg L, Snetkova V, Hines M, Chakraborty T, Bajwa S, Jensen K, Chong MW, Getu L, Silverman GJ, Blelloch R, Litman DR, Melamed D, Skok J, Rajewsky K, Koralov SB. miRNAs are essential for the regulation of the PI3K/AKT/FOXO pathway and receptor editing during B cell maturation. Cell Rep. 2016 Nov 22;17(9):2271-2285.
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.
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. T cell-derived IL-17 mediates epithelial changes in the airway and drives pulmonary neutrophilia. J Immunol. 2013 Sep 15; 191(6):3100-11
Kaplinsky J, Li A, Sun A, Coffre M, Koralov SB* and Araout R*. Antibody repertoire deep-sequencing reveals antigen-independent selection in maturing B cells. PNAS 2014, Jun24;111(25): 2622-9. *equal contribution
Sun A, Novobrantseva TI, Coffre M, Hewitt SL, Jensen K, Skok JA, Rajewsky K and Koralov SB. VH replacement in primary immunoglobulin repertoire diversification. PNAS 2015, Feb 3; 112(5):E458-66.
Sundrud M and Koralov SB. Negative regulation of Th17 differentiation. Chapter for TH17 Cells in Health and Disease, Springer New York. July 2011
Willerslev-Olsen A, Krejsgaard T, Lindahl LM, Menne C, Wasik MA, Koralov SB, Geisler C, Kilian M, Iversen L, Woetmann A, Odum N. Bacterial toxins fuel disease progression in cutaneous T-cell lymphoma. Toxins 2013 Aug 14; 5(8):1402-21.
Member of NYU Cancer Institute
NYU Kimmel Center for Stem Cell Biology
American College of Rheumatology
The American Society of Hematology
Irma T. Hirschl Career Scientist Award
NYU Whitehead Junior Faculty Fellow
Cutaneous Lymphoma Foundation, CLARION Award