Boston University Medical Campus
Microbiology

Lisa Ganley-Leal, Ph.D.

Assistant Professor of Medicine and Microbiology

B.A.     Springfield College
Ph.D.   University of Connecticut Health Center

Human schistosomiasis, caused by parasitic trematodes, currently affects over 207 million people. A poor understanding of the mechanisms involved in protective immunity has hindered vaccine development. High serum concentrations of parasite-specific IgE are correlated with resistance to schistosomiasis, but the function(s) of IgE remain elusive. Although B cells are the producers of IgE, remarkably little is known about human B cell function in schistosomiasis. We recently reported that CD23 expression, the low affinity IgE receptor, on B cells is correlated with the development of resistance to schistosome infection in male, occupationally-exposed adult Kenyans. Cross-linking of CD23-bound IgE by antigen may induce cellular activation and increased IgE production. However, the role of CD23 in human immunity is exceedingly complex and is virtually unstudied in human schistosomiasis. CD23 has multiple ligands, including CD21, and may also affect IgE synthesis in its soluble form (sCD23).  The extracellular portion of membrane-CD23 is a 45kDa protein composed of the head with a C-terminal tail and the N-terminal stalk. The stalk region contains a “leucine zipper” that allows CD23 molecules to cross-link and polymerize into oligmers.  Endogenous host proteases cleave the cell-surface protein near the base of the stalk and at multiple sites closer to the head to release several sized sCD23 molecules.  The function of sCD23 on subsequent IgE synthesis is dependent upon whether sCD23 is an oligmer, large or small fragment and which ligands it binds (CD23-bound IgE, BCR epsilon, CD21). Our new data indicate that crude schistosomal antigen preparations cleave B cell surface CD23 with a parallel increase of sCD23 in cell culture supernatants providing evidence for a specific immune evasion tactic directly targeted at CD23-mediated immunity.  Our lab focuses on understanding the role of CD23-bound IgE and schistosome-generated sCD23 in generating protective immunity as well as the host-parasite interactions between CD23 and schistosomes.

Our second focus is to understand how Toll-like receptors (TLR) and systemic TLR ligands mediate or regulate inherent inflammatory responses by B cells in chronic inflammatory diseases, including inflammatory bowel disease, type 2 diabetes, and schistosomiasis.  This work involves collaboration with several clinicians on campus including Dr. Frank Farraye in Gastroenterology and Dr. Marie McDonnell in Endocrinology and involves patient-based research approaches.

Representative Publications

1. Noronha AM, Y Liang, JT Hetzel, H Hasturk, A Kantarci, A Stucchi, Y Zhang, BS Nikolajczyk, FA Farraye, and LM Ganley-Leal. 2009. Hyperactivated B cells in human inflammatory bowel disease. J. Leukoc. Biol. 86: 1007-1016. 
2. Liang Y, LM Ganley-Leal.  2009.  A simple method for measuring human cell-bound IgE levels in whole blood.  J. Immunol. Methods 343(2):134-139.
3. Shin H, Y Zhang, M Jagannathan, H Hasturk, A Kantarci, H Liu, TE Van Dyke, LM Ganley-Leal, and BS Nikolajczyk.  2009.  B cells from periodontal disease patients express surface Toll-like receptor 4.  J. Leukoc. Biol. 85(4):648-655.
4. Mwinzi PN, L Ganley-Leal, CL Black, WE Secor, DM Karanja,  and DG Colley.  2009.  Circulating CD23+ B cell subset correlates with the development of resistance to Schistosoma mansoni reinfection in occupationally exposed adults who have undergone multiple treatments.  J. Infect. Dis. 199(2):272-279.