Associate Investigator, Center for Experimental Biology
Professor, Elmezzi Graduate School for Molecular Medicine
Research Associate Professor, Department of Pathology, NYU School of Medicine
350 Community Drive, Manhasset, NY  11030

Tel:  (516) 562-3442
Fax: (516) 562-1011
Email:  pmongini@nshs.edu

Education:
B.S., Northern Arizona University (1972)
Ph.D, Stanford University (1976)
Post-doctoral fellow:  Tufts University School of Medicine (1976-1978)
NIAID, NIH (1978-1981)

Research:
While most of the body’s B lymphocytes express highly unique receptors that recognize and help eliminate microbes, a subset expresses receptors specific for body components (self-antigens).  The outgrowth (clonal expansion) of these self-reactive B cells is highly regulated to prevent disease.  Nevertheless, in some pathologic situations, i.e. chronic lymphocytic leukemia (CLL) and B cell autoimmunity, the regulatory processes are circumvented and self-reactive B cell clones gain prominence.

One goal of the Mongini laboratory is to unravel how stimuli within certain inflamed body tissues may predispose self-reactive B lymphocytes to survival, rather than death, after a burst of proliferation.   Ongoing studies indicate that p53, a molecule known as “the guardian of the genome” has an important role in eliminating human B cell clones stimulated by molecules characteristic of many inflammatory sites.

Importantly, we have found that signals from two inflammation-associated proteins, i.e. BAFF and APRIL, reduce vulnerability to p53-mediated death by apoptosis. Both of the above have been significantly linked to B cell autoimmunity and B cell malignancy.   The protective effects of BAFF and APRIL in part reflect the upregulation of COX-2 and downstream prostaglandin E2 (PGE2) during B lymphocyte clonal expansion.    The lab is evaluating the receptors and biochemical pathways responsible for COX-2/PGE2-mediated pro-survival signals, with a goal of better targeting this newly identified B cell survival pathway in patients with B cell autoimmunity, and possibly B-CLL .  Additional efforts are being placed in identifying whether certain human genetic backgrounds are better able to utilize the PGE-mediated pro-survival pathway.

As another major goal, the lab is investigating the role of B cell-expressed COX-2/PGE2 in promoting the expression/activation of a mutation-inducing enzyme, i.e. activation-induced cytosine deaminase (AID).   During the course of a normal immune response to microbes, AID functions to generate mutant daughter B cells whose antibodies are more effective than the parent B cell at eliminating the invader.  More rarely, AID induces unwanted mutations in genes that control cell growth, e.g. p53.   The laboratory is examining whether COX-2/PGE2 contributes to heightened AID activity and heightened numbers of B cells with mutations.

As a final goal, the lab is investigating the functional importance of COX-2 expression within CLL B cells that have undergone malignant transformation.  COX-2 is expressed in elevated levels in CLL clones with a worse prognosis, but its role in promoting CLL growth/mutation remains unclear.   Present studies are investigating whether downstream PGE2, or another lipid molecule downstream of COX-2, is of functional relevance in promoting the extended growth or survival of these transformed B lymphocytes.   The greater insights may lead to novel, more targeted therapies in patients with CLL.

		Name:  Shabirul Haque, Ph.D. Position: Post-doctoral fellow, 2009- Education: B.Sc. Chemistry, Aligarh Muslim University, India, 2001 M.Sc. Biotechnology, Aligarh Muslim University, India, 2003 Ph.D. Laboratory Medicine, All India Institute of Medical Sciences (AIIMS), 2008 Research: Illuminating how B cell expressed COX-2/PGE2 influences the expression/function of activation-induced cytosine deaminase (AID) mRNA and protein within both normal human B lymphocytes and B-CLL E-mail: shaque@nshs.edu
		Name: Joshua Trott Position: Research Assistant, 2008- Education: B.S., College of the Holy Cross 2007 Research: Regulation of p53 and COX-2 function within activated normal human B cells and B-CLL E-mail: jtrott@nshs.edu
		Name: Hyunjoo Lee Position: Research Assistant, 2009- Education: B.S., Swarthmore College 2009 Research: Analysis of p53 and COX-2 function within human B lymphocytes through SNP and gene signature analyses

Selected Publications:

Mongini, P.K.A., S. Friedman, and H.H. Wortis:  Accessory cell requirement for anti-IgM induced proliferation of B lymphocytes.  Nature 276:709 (1978).

Mongini, P.K.A., W.E. Paul, and E.S. Metcalf:  Analysis of IgG subclass, IgE and IgA antibody production by TNP-Ficoll responsive B cells:  Evidence in support of three distinct switching pathways.  J. Exp. Med. 157:69 (1983).

Rudich, S.M., R.J. Winchester, and P.K.A. Mongini: Human B cell activation: Evidence for diverse signals provided by various monoclonal anti-IgM antibodies. J. Exp. Med. 162:1236 (1985).

Rudich, S.M., D. Mihaesco, R. Winchester, and P.K.A. Mongini:  Analysis of the domain specificity of various murine anti-human IgM monoclonal antibodies differing in human B lymphocyte signaling activity.  Mol. Immunol. 24:809 (1987).

Mongini, P., C. Blessinger, S. Seremetis, R. Winchester, and S.M. Rudich:  Human leukemic B cell activation:  Functional consequence of membrane IgM interaction with anti-IgM is an alterable cell characteristic. Blood, 70:1193 (1987).

Rudich, S.M., K.H. Roux, R.J. Winchester, and P.K.A. Mongini:  Anti-IgM-mediated B cell signaling:  Molecular analysis of ligand binding requisites for human B cell activation and tolerance.  J. Exp. Med., 168:247 (1988).

Mongini, P.K.A., C. Blessinger, S.M. Rudich, and M.J. Brunda:  Diversity in inhibitory effects of IFN-γ and IFN-αA on the induced DNA synthesis of a hairy cell leukemia B lymphocyte clone reflects nature of the activating ligand.  Blood, 72:1553 (1988).

Mongini, P.K.A., C. Blessinger, and S.M. Rudich:  Membrane IgD and membrane IgM differ in capacity to transduce inhibitory signals within the same human B cell clonal populations.  J. Immunol., 143:1565 (1989).

Mongini, P.K.A. and S.M. Rudich:  Membrane Ig-mediated triggering of B cell tolerance and B cell clonal expansion:  Implications for rheumatoid factor production in rheumatoid synovitis.  Springer Seminars in Immunopathology, 11:93 (1989).

Mongini, P.K.A., C.A. Blessinger, and J.P. Dalton:  Affinity requirements for induction of sequential phases of human B cell activation by mIgM-crosslinking ligands.  J. Immunol., 146:1791 (1991).

Mongini, P.K.A., C.A. Blessinger, J.P. Dalton, and T. Seki:  Differential effects of cyclosporin A on diverse B cell activation phenomena triggered by crosslinking of membrane IgM.  Cell. Immunol.  140:478 (1992).

Mongini, P.K.A., C.A. Blessinger, P.F. Highet, and J.K. Inman:  Membrane IgM-mediated signaling of human B cells:  effect of increased ligand binding site valency on the affinity and concentration requirements for inducing diverse stages of activation.  J. Immunol. 148:3892 (1992).

Mongini, P.K.A., Blessinger, C.A., and Rudich, S.M.:  A monovalent C 4-specific ligand enhances the activation of human B cells by mIgM-crosslinking ligands.  International Immunology 7: 317 (1995).

Mongini, P.K.A., C.A. Blessinger, P.F. Highet, and J.K. Inman:  Human B cell activation:  Effect of T cell cytokines on the physicochemical binding requirements for achieving cell cycle progression via the membrane IgM signaling pathway.  J. Immunol. 155: 3385 (1995).

Marches, R., E. Racila, T. F. Tucker, L. Picker, P. Mongini, R. Hsueh, R. H. Scheuermann, and J. W. Uhr:  Tumor dormancy and cell signaling.  III: Role of hypercrosslinking of IgM and CD40 on the induction of cell cycle arrest and apoptosis in B lymphoma cells.  Ther. Immunol. 2: 125 (1995).

Wu, C. -Y., R. R. Warrier, D. M. Carvajal, A. O. Chua, L. J. Minetti, R. Chizzonite, P. K. A. Mongini, A. S. Stern, U. Gubler, D. H. Presky, and M. K. Gately:  Biological function and distribution of human interleukin-12 receptor β chain.  Eur. J. Immunol. 26: 345 (1996).

Mongini, P.K.A, M. A. Vilensky, P. F. Highet, and J. K. Inman.  The affinity threshold for human B cell activation via the antigen receptor complex is reduced upon co-ligation of the antigen receptor with CD21 (CR2).  J. Immunol. 159:3782 (1997).

Rudich, S.M., P.K.A. Mongini, R.V. Perez, and S. Katznelson.  HMG-CoA reductase inhibitors pravastatin and simvastatin inhibit human B-lymphocyte activation.  Transpl. Proc. 30:992 (1998).

Mongini, P.K.A, Q. Liu, M.A.Vilensky, P.F. Highet, and J.K. Inman:   Evidence for an upper affinity threshold for anti-IgM-induced apoptosis in a human B cell lymphoma.  Blood, 92:3756 (1998).

Mongini, P.K.A., M.A.Vilensky, P.F. Highet, and J.K. Inman:  Membrane IgM stimulated human B lymphocytes succumb to activation-related apoptosis at a G1  S transition: influence of ligand affinity and valency.  Cell. Immunol., 188:137 (1998).

Mongini, P.K.A. and J.K. Inman:  Cytokine dependency of human B cell cycle progression elicited by ligands which coengage BCR and the CD21/CD19/CD81 costimulatory complex.  Cell. Immunol. 207:127 (2001).

Mongini, P.K.A., S. Tolani, R.J. Fattah, and J.K. Inman:  Antigen receptor triggered upregulation of CD86 and CD80 in human B cells:  augmenting role of the CD21/CD19 co-stimulatory complex and IL-4.  Cell. Immunol. 216:50 (2002).

Mongini, P.K.A., A.E. Jackson, S. Tolani, R.J. Fattah, and J.K. Inman:  Role of complement-binding CD21/CD19/CD81 in enhancing human B cell protection from Fas-mediated apoptosis.  J. Immunol. 171:5244 (2003).

Mongini, P.K.A., J.K. Inman, H. Han, S.L. Kalled, R.J. Fattah, and S. McCormick:  Innate immunity and human B cell clonal expansion:  Effects on the recirculating B2 subpopulation.  J. Immunol. 175:6143 (2005).

Mongini, P.K.A., J.K. Inman, H. Han, R.J. Fattah, S. Abramson, and M. Attur: APRIL and BAFF promote increased viability of replicating human B2 cells via mechanism involving cyclooxygenase 2.   J. Immunol. 176:6736 (2006).

Mongini, P.K.A.:  COX-2 expression in B lymphocytes:  Links to vaccines, inflammation and malignancy.  Clinical Immunology, 125:117 (2007).

Ghumra A., Semblat J.P., McIntosh R.S., Raza A., Rasmussen I.B., Braathen R., Johansen F.E., Sandlie I., Mongini P.K., Rowe J.A., Pleass R.J.HHH  Identification of residues in the Cmu4 domain of polymeric IgM essential for interaction with Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1).   J Immunol.  181:1988-2000 (2008).

Suhail Rasool; B.L. Jailkhani; M. Irshad; Madhuri Behari; Shahnaz Suhail; H. Shabirul. Purification of Beta Bungarotoxin (β-Bgtx) Binding Protein from Human Cadaver Skeletal Muscle. Journal of Medical Sciences 2007, Vol.7, Issue 2,   Pages 195-202.

Naeem A, Haque Shabirul, Khan RH .Purification and Characterization of Novel β-D-Galactosides Specific Lectin from Clitoria ternatea seeds. The Protein Journal.  Vol. 26, No. 6 Sept. 2007. Pages: 403 - 413.

Patent:

Patent:  USPTO Application #: 20070082015, Class: 424258100 (USPTO). Inventors: B. L. Jailkhani, M. K. Bhan, R. Kumar, S. Sengupta, Shabirul Haque “Cloning and expression of outer membrane protein C of Salmonella typhi Ty2 and conjugation of the purified insoluble protein to Vi-polysaccharide for use as a vaccine for typhoid fever”.