Lisa Ganley-Leal, Ph.D.

Ganley-LealAssistant Professor of Medicine

Ph.D. University of Connecticut Health Center
Postdoctoral training: Centers for Disease Control and Prevention, Boston University Medical Center

Our laboratory studies human schistosomiasis, which is caused tissue invasive parasitic trematodes, and currently affects over 207 million individuals in developing countries.  Vaccine development for this disease has been hindered by a poor understanding of the mechanisms involved in protective immunity in humans.  A relatively consistent finding in field-based studies is a correlation between high serum concentrations of parasite-specific IgE and resistance to reinfection following curative chemotherapy.  However, the function(s) of putatively protective IgE remains elusive and may include roles in direct killing of worms or in regulating immunity.  Furthermore, although B cells are the producers of IgE, remarkably little is known about human B cell function and the mechanisms involved in the initiation or maintenance of elevated antigen-specific IgE 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 induces cellular activation and increased IgE production.  However, the role of CD23 in human immunity is exceedingly complex and is virtually unstudied in human schistosomiasis.  Multiple specificities of the B cell receptor (BCR) and of CD23-bound IgE may affect how B cells respond to external antigens and ultimately to different outcomes for B cells. This may be especially evident in regions where several endemic pathogens induce high IgE production.  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, BCRe, CD21).  Microbial cysteine proteases, such as dust mite allergen, Der pI, also cleave CD23, which inhibits IgE synthesis.  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 an immune evasion technique targeted at CD23-mediated immunity.  Because the protease(s) that targets CD23 is likely a key molecule in parasitism and therefore a potential vaccine candidate, we are characterizing the role of CD23 in generating host protection and the schistosomal protease(s) that result in cleavage of CD23.   We are also characterizing the effects of schistosome-generated sCD23 on B cell function.  By understanding these complex host-parasite interactions in humans, we hope to hasten the pace of vaccine development for this disease.

Representative Publications:

PubMed Link

1. B cells from periodontal disease patients express surface Toll-like receptor 4.
Shin H, Zhang Y, Jagannathan M, Hasturk H, Kantarci A, Liu H, Van Dyke TE, Ganley-Leal LM, Nikolajczyk BS.
J Leukoc Biol. 2008 Dec 31. [Epub ahead of print]

2. Circulating CD23(+) B Cell Subset Correlates with the Development of Resistance to Schistosoma mansoni Reinfection in Occupationally Exposed Adults Who Have Undergone Multiple Treatments.
Mwinzi PN, Ganley-Leal L, Black CL, Secor WE, Karanja DM, Colley DG.
J Infect Dis. 2009 Jan 15;199(2):272-279.

3. YanMei Liang and L. Ganley-Leal.  A simple method for measuring cell-bound IgE in whole blood.  Accepted to the Journal of Immunological Methods.

4. Higher percentages of circulating mast cell precursors correlate with susceptibility to reinfection with Schistosoma mansoni.
Ganley-Leal LM, Mwinzi PN, Cetre-Sossah CB, Andove J, Hightower AW, Karanja DM, Colley DG, Secor WE.
Am J Trop Med Hyg. 2006 Dec;75(6):1053-7. PMID: 17172364 [PubMed - indexed for MEDLINE]

5. Correlation between eosinophils and protection against reinfection with Schistosoma mansoni and the effect of human immunodeficiency virus type 1 coinfection in humans.
Ganley-Leal LM, Mwinzi PN, Cetre-Sossah CB, Andove J, Hightower AW, Karanja DM, Colley DG, Secor WE.
Infect Immun. 2006 Apr;74(4):2169-76. PMID: 16552047 [PubMed - indexed for MEDLINE]

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Primary teaching affiliate
of BU School of Medicine