Marilia Cascalho, M.D., Ph.D
The impact of immune receptor diversity in the response to mutable pathogens and tumors
Immunological memory and transplantation
Our laboratory researches mutation and generation of diversity in health and disease. We investigate the molecular properties of cells undergoing somatic hypermutation of immunoglobulin genes to determine whether these mechanisms contribute to pathogen diversity and/or to tumorigenesis. Additional research is carried out into molecular and cellular mechanisms in the generation of diverse immune receptors in lymphocytes and how diversity imports to health.
Our laboratory also investigates mechanisms for the generation of B cell memory and the impact of memory responses in transplantation. We study the means by which B cell memory is generated from naïve B cells and the requirements for the maintenance of memory responses. We investigate the contributions of immunoglobulin somatic hypermutation, thymus and T cells for the generation of long-lived B cells. To elucidate the mechanisms of B cell memory, the laboratory studies human subjects and novel experimental gene-targeted and conditional mouse models.
Balin SJ, Cascalho M. The Rate of Mutation of a Single Gene. Nucleic Acids Research, doi: 10.1093/nar/gkp1119, 2009.
Platt JL, Cascalho M, West LJ. Lessons From Cardiac Transplantation in Infancy. Pediatric Transplantation, 13:814-819, 2009.
Balin SJ, Platt JL, Cascalho M. Non Cognate Function of B cells in Transplantation, Transplant International 22:593-598, 2009.
Cascalho M, Ogle BM, Razonable RR, West LJ, Platt JL. Cardiac transplantation in infancy: A model for dissecting immunological function. Journal of Paediatrics and Child Health 18 (Suppl 1):30-32, 2008.
Cascalho M, Platt JL. B cells diversify the T cell receptor repertoire. In: "Journal of Paediatrics and Child Health" in the Proceedings of the 3rd Joint Conference OPBG/Mayo. Journal of Paediatrics and Child Health 18 (Suppl 1):S14-S15, 2008.
Balin SJ, Platt JL, Cascalho M. New insights into the functions of B cells. Pediatr Transplant, 12:510-515, 2008.
Balin SJ, Ross TM, Platt JL, Cascalho M. HIV genes diversify in B cells. Curr HIV Res. 6:10-8.2008.
AbuAttieh M, Rebrovich M, Wettstein PJ, Vuk-Pavlovic Z, Limper AH, Platt JL, Cascalho M. Fitness of cell-mediated immunity independent of repertoire diversity. J Immunol 178:2950-2960, 2007.
Mantchev GT, Cortesão C, Rebrovich M, Cascalho M, Bram RJ. TACI is required for efficient plasma cell differentiation in response to T-independent type 2 antigens. J Immunol 179:1962-1967, 2007 (MC: Corresponding Author).
Geraldes P, Rebrovich M, Herrmann K, Wong J, Jäck H-M, Wabl M, Cascalho M. Ig heavy chain promotes mature B cell survival in the absence of light chain. J Immunol 179:1659-1668, 2007.
Cascalho M, Platt JL. Novel functions of B cells. Curr Rev Immunol 27:141-151, 2007.
Martin DA, Lu L, Cascalho M, Wu GE. Maintenance of surrogate light chain expression induces developmental delay in early B cell compartment. J Immunol 179:4996-5005, 2007.
Ogle, BM., West, LJ., Driscoll, DJ., Strome, SE., Razonable, RR., Paya, CV., Cascalho, M., Platt, JL. Effacing of the T cell compartment by cardiac transplantation in infancy. J Immunol 176(3):1962-1967, 2006.
Cascalho M, Platt JL. B cells and B cell products-helping to restore cellular immunity? Transfus Med Hemother 33(1):45-49, 2006.
Cascalho M, Platt JL. The immunologic barriers to replacing damaged organs. Curr Immunol Rev 2:65-72, 2006.
Wu X, Geraldes P, Platt JL, Cascalho M. The double-edged sword of activation-induced cytidine deaminase. J. Immunol 174:934-941, 2005.
Cascalho M. B cell tolerance: lessons from transplantation. Curr Drug Targets - Cardiovasc & Haematol Disord 5(3):271-5, 2005.
Cascalho M, Platt JL. Basic mechanisms of humoral rejection. Pediatr Transplantation 9:9-16, 2005.
Kanayama N, Cascalho M, Ohmori H. Analysis of marginal zone B cell development in the mouse with limited B cell diversity: role of the antigen receptor signals in the recruitment of B cells to the marginal zone. J Immunol 174:1438-1445, 2005.
Ogle BM, Cascalho M, Platt JL. Biological implications of cell fusion. Nat Rev Mol Cell Biol 6:567-575, 2005.
João CM, Ogle BM, Gay-Rabinstein C, Platt JL, Cascalho M. B cell-dependent TCR diversification. J Immunol 172(8):4709-4716, 2004.
Ogle BM, Butters KA, Plummer TB, Ring KR, Knudsen B, Litzow MR, Cascalho M, Platt JL. Spontaneous fusion of cells between disparate species yields transdifferentiation and retroviral DNA transfer in vivo. FASEB J 18:548-550, 2004.
Cascalho M. Advantages and disadvantages of cytidine deamination. J Immunol 172:6513-6518, 2004.
Keshavarzi S, Rietz C, Simões S, Wong J, Shih S, Platt JL, Wong J, Wabl M, Cascalho M. The possibility of B-cell-dependent T-cell development. Scand J Immunol 57:446-452, 2003.
Wu X, Platt JL, Cascalho M. Dimerization of MLH1 and PMS2 limits nuclear localization of MutLα. Mol Cell Biol 23: 3320-3328, 2003.
Kojima H, Sitkovsky MV, Cascalho M. HIF-1α deficiency perturbs T and B cell functions. Curr Pharm Des 9:1827-32, 2003.
Ogle BM, Cascalho M, Joao CM, Taylor W, West LJ, Platt JL. Direct measurement of lymphocyte receptor diversity. Nucleic Acids Res 31:e139, 2003.
O'Connor BP, Cascalho M, Noelle RJ. Short-lived and long-lived bone marrow plasma cells are derived from a novel precursor population. J Exp Med 195(6):737-45, 2002.
Erickson LD, Durell BG, Vogel LA, O'Connor BP, Cascalho M, Yasui T, Kikutani H, Noelle RJ. Short-circuiting long-lived humoral immunity by the heightened engagement of CD40. J Clin Invest 109(5):613-20, 2002.
Cascalho M, Platt JL. The immunological barrier to xenotransplantation. Immunity 14:437-446, 2001.
Cascalho M, Platt JL. Xenotransplantion and other means of organ replacement. Nature Reviews 1:154-160, 2001.
Vinuesa C, Cook M, Ball J, Drew M, Sunners Y, Cascalho M, Wabl M, Klaus G, MacLennan I. Germinal centres can form without T cells, but a failsafe mechanism prevents the emergence of autoreactive cells. J Exp Med 191:485-94, 2000.
Wabl M, Cascalho M, Steinberg C. Hypermutation in antibody affinity maturation. Curr Opin Immunol 11:186-189, 1999.
Lopez-Macías C, Kalinke U, Cascalho M, Wabl M, Hengartner H, Zinkernagel R M, Lamarre A. Secondary rearrangements and hypermutation generate sufficient B cell diversity to mount protective antiviral immunoglobulin responses. J Exp Med 189:1791-1798, 1999.
Cascalho M, Wong J, Steinberg C, Wabl M. Mismatch repair co-opted by hypermutation. Science 279:1207-1210, 1998.
Cascalho M, Wong J, Wabl M. VH gene replacement in hyperselected B cells of the quasi-monoclonal mouse. J Immunol 159:5795-5801, 1997.
Cascalho M, Ma A, Lee S, Masat L, Wabl M. A quasi-monoclonal mouse. Science 272:1649-1652, 1996.