Dr. Linda Baum is interested in the role of cell surface carbohydrates and endogenous lectins in the maturation and function of cells of the immune system.
T-cells mature in the thymus and then migrate to organs such as spleen and lymph nodes, where they participate in the immune response to foreign invaders. Baum and her colleagues have found that a carbohydrate binding protein termed galectin-1 is expressed in human and murine thymus, lymph nodes and spleen. This endogenous lectin participates in the trafficking of T-lymphocytes from the circulation into these tissues and also mediates adhesion of T-cells to stromal cells within the organs. In addition, galectin-1 induces programmed cell death of specific populations of T-cells at unique points in development, identifying a role for galectin-1 in modulating the immune response. Baum's lab has recently found novel immune system functions for other members of the galectin family, including galectins-3 and -9, such as regulating B-cell survival and dendritic cell function.
Baum's current work focuses on identifying the cell surface counter-receptors which bind various galectins and participate in galectin-mediated cell adhesion, activation and apoptosis; and dissecting the structural features of these molecules essential to these distinct functions. She and her associates use a combination of cellular and biochemical assays to understand the mechanism of galectin functions.
Selected Cancer-Related Publications:
Bi S, Hong PW, Lee B, Baum LG. Galectin-9 binding to cell surface protein disulfide isomerase regulates the redox environment to enhance T-cell migration and HIV entry. Proc Natl Acad Sci U S A. 2011 Jun 28;108(26):10650-5. Epub 2011 Jun 13.
Earl LA, Bi S, Baum LG. N- and O-glycans modulate galectin-1 binding, CD45 signaling, and T cell death. J Biol Chem. 2010 Jan 22;285(4):2232-44. Epub 2009 Nov 17
Fulcher JA, Chang MH, Wang S, Almazan T, Hashimi ST, Eriksson AU, Wen X, Pang M, Baum LG, Singh RR, Lee B. Galectin-1 co-clusters CD43/CD45 on dendritic cells and induces cell activation and migration through Syk and protein kinase C signaling. J Biol Chem. 2009 Sep 25;284(39):26860-70. Epub 2009 Jul 27
Pang M, He J, Johnson P, Baum LG. CD45-mediated fodrin cleavage during galectin-1 T cell death promotes phagocytic clearance of dying cells. J Immunol. 2009 Jun 1;182(11):7001-8.
Toscano MA, Bianco GA, Ilarregui JM, Croci DO, Correale J, Hernandez JD, Zwirner NW, Poirier F, Riley EM, Baum LG, Rabinovich GA. Differential glycosylation of TH1, TH2 and TH-17 effector cells selectively regulates susceptibility to cell death. Nat Immunol. 2007 Aug;8(8):825-34. Epub 2007 Jun 24