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URMC / Labs / Rangel-Moreno Lab / Projects

Projects

Role of Bronchus Associated Lymphoid Tissue in Pulmonary Immunity

Germinal center in the lung of mice infected with Pneumocystis murina. PCNA in red, PNA in green and B220 in whiteIn a collaborative project with Dr. Shabaana Abdul Khader at Washington University in Saint Louis and with support from the NIH, we are defining the contribution of inducible bronchus associated lymphoid tissue (iBALT) in the control of experimental pulmonary tuberculosis. Additionally, in a recent collaboration with Dr. Taylor Edens and Dr. Jay Kolls, we defined how IL17 and type 2 cytokines support IBALT formation during Pneumocystis murina infection (Cell Rep 18(13): 3078-3090:2017).

Impact of Radiation on Immunity

Immunofluorescence of lymph node after exposure to neonatal irradiation. PNAd in red, Lyve 1 in green and B220 in whitePreliminary data in our lab have shown a long-lasting impact of neonatal irradiation on the CD4 T cell response against influenza viruses. Although defective CD4 T cells response did not compromise immunity to influenza viruses, it is possible that CD4 T cell-mediated protection against other extracellular pulmonary pathogens can be compromised by exposure to radiation in neonatal life (Radiat Res 184(4): 352-366: 2015). Thus, we are currently focused to investigate the effect of neonatal irradiation in the control of clinically relevant pulmonary pathogens.

Tertiary Lymphoid Organs in Cancer

100x picture showing an ectopic lymphoid structure in prostate of individual with prostate intraepithelial neoplasiaIn a recent collaboration with researchers from University of Washington in Saint Louis (Shabaana Abdul Khader), University of Southern California in los Angeles (Martin W. Kast) and colleagues from the National Institute of Medical Sciences and Nutrition in Mexico City (Norma Ofelia Uribe Uribe, Ricardo Espinosa-Gonzalez), we demonstrated the existence of a unique microenvironment that is associated with the spontaneous regression of prostate cancer. Picture from TLO in evanescent prostate carcinoma (Front Immunol 8: 563: 2017).

Evaluation of Experimental Therapies in a Preclinical Model of Lupus

Spleen of mice treated with SINE drugs (PCNA in red and IgG in green)In collaboration with Dr. Allan Smrcka, we previously demonstrated that inhibition of G protein signaling prevents lupus nephritis by targeting the migration of immune cells and impairing auto-reactive germinal centers (Arthritis Rheumatol 68(9): 2244-2256: 2016). In a similar fashion, experimental treatment with inhibitors of nuclear disrupts splenic germinal centers and the niche for auto-reactive and inflammatory cells in the inflamed kidney of lupus prone mice. Picture from plasma cells after treatment with selective inhibitors of nuclear export.

Use of Laser-capture Microdissection to Decipher RNA Signatures in Target Tissues

Synovium with inflammatory cells (CD3 in red and CD20 in green)In a project supported by the AMP and NIH, we are dissecting the molecular signatures of infiltrating lymphocytes in the inflamed synovium of patients with rheumatoid arthritis by using immunofluorescence and laser capture microdissection. The purpose is to reveal molecules that can be used as markers of disease progression/severity and identify novel targets to increase the therapeutic armamentarium for rheumatoid arthritis.