Dr. Koralov is a cellular and molecular immunologist with experience in studying the molecular and cellular etiology of autoimmune and malignant 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 a strong foundation in immunology and expertise in conditional gene targeting and molecular biology 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 asthma and psoriatic arthritis. For this purpose we are taking advantage of biospecimens from patients as well as novel mouse models of disease. We are 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 and microbial metabolites in these inflammatory diseases.
We are also interested in furthering our understanding of malignant transformation of T lymphocytes and in particular have been focused on understanding the pathogenesis of an enigmatic hematologic malignancy, Cutaneous T Cell Lymphoma (CTCL). This cancer is characterized by accumulation of malignant cells in the skin, where they are exposed to bacterial and environmental antigens. We have been studying the contribution of antigen receptor signaling and bacterial antigens and super antigens in the malignant transformation of T cells using a unique mouse model of this disease as well as through analysis of patient biospecimens.
Another project in the lab focuses on 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.
A relatively new area of research for our group leverages our expertise in studying tissue specific inflammation to understand the mechanisms of immune suppression and evasion in the context of lung cancer and melanoma. We aim to understand how tumor metabolism subverts immune responses and our goal is to take advantage of our insight to improve current immunotherapy modalities in a patient specific manner.
Herrera A, Cheng A, Mimitou EP, Seffens A, George D, Bar-Natan M, Heguy A, Ruggles KV, Scher J, Hymes K, Latkowski A, Ødum N, Kadin ME, Ouyang Z, Geskin LJ, Smibert P, Buus TB, Koralov SB. Multimodal single-cell analysis of cutaneous T cell lymphoma reveals distinct malignant sub-clones and tissue dependent signatures. Blood 2021 Oct 21;138(16):1456-1464. PMID: 34232982.
Hines MJ, Coffre M, Panduro M, Wigton EJ, Tegla C, Osario-Vasquez V, Kageyama R, Benhamou D, Perez O, Bajwa S, McManus MT, Ansel KM, Melamed D, Koralov SB. miR-29 sustains B cell survival and controls terminal differentiation via regulation of PI3K signaling. Cell Reports 2020 Dec 1;33(9):108436.
Mimitou E, Cheng A, Montalbano A, Hao S, Stoeckius M, Herrera A, Papalexi E, Ouyang Z, Satija R, Sanjana N, Koralov SB, Smibert P. Expanding the CITE-seq tool-kit: Detection of proteins, transcriptomes, clonotypes and perturbations with multiplexing, in a single assay. Nature Methods 2019, May; 16(5): 409-412.
Yang L, Fanok MH, Mediero-Munoz A, Fogli LK, Abdollahi S, Cronstein BN, Scher JU, Koralov SB. Augmented Th17 differentiation leads to cutaneous and musculoskeletal inflammation in a novel model of psoriatic arthritis. Arthritis and Rheum. 2018 Feb 13; Epub ahead of print
Fanok MH, Sun A, Fogli LK, Narendran V, Eckstein M, Kannan K, Dolgalev I, Lazaris C, Heguy A, Laird ME, Sundrud MS, Liu C, Kutok J, Lacruz RS, Latkowski JA, Aifantis I, Ødum N, Hymes KB, Goel S, Koralov SB. Role of dysregulated cytokine signaling and bacterial triggers in the pathogenesis of Cutaneous T Cell Lymphoma. J Invest Dermatol. 2017 Nov 8. pii: S0022-202X(17)33144-5.
Coffre M, Benhamou D, Rieß D, Blumenberg L, Snetkova V, Hines MJ, Chakraborty T, Bajwa S, Jensen K, Chong MMW, Getu L, Silverman GJ, Blelloch R, Littman DR, Calado D, Melamed D, Skok JA, 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.
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.
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
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
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.
Yang L, Lejeune A, Chang G, Scher JU, Koralov SB. Microbial-derived antigens and metabolites in spondyloarthritis. Seminars in Immunopathology. 2021 Apr;43(2):163-172.
Borbet TC, Hines MJ, Koralov SB. MicroRNA regulation of B cell receptor signaling. Immunol Rev. 2021 Sep 14 Nov;304(1):111-125.
Seffens A, Herrera A, Tegla C, Buus TB, Hymes KB, Ødum N, Geskin LJ, Koralov SB. STAT3 Dysregulation in Mature T and NK Cell Lymphomas. Cancers, 2019 Nov 2; 11(11) E1711.
Coffre M, Koralov SB. miRNAs in B Cell Development and Lymphomagenesis. Trends Mol Med. 2017 Aug;23(8):721-736.
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.
