Soman Ninan Abraham, Ph.D., M.S.

Professor in Pathology

Department:
Pathology

Division:
Pathology Research

Email:
somanabrahamdukeedu

Mailing Address:
Box 3712, DUMC
Durham, NC 27710

Telephone:
--

Training:
Ph.D., University of Newcastle upon TyneM.S., Ahmadu Bello University (Nigeria)

Last Updated:
February 19, 2009

Research Interests:
The last century is notable for the remarkable successes made in the area of antibiotic and vaccine development against infectious agents. However, as we begin this century, the singular most common cause of morbidity and mortality in man and animals is once again infectious diseases. With the anticipated growth in the aged and immunocompromised populations in our midst and the rapid emergence of multiresistant bacteria, there is an acute need for the development of alternate approaches to curb microbial infections and their harmful sequellae.

This laboratory is interested in developing innovative approaches for curbing microbial infections through the study of the molecular interactions occurring between pathogenic bacteria and prominent immune and epithelial cells. We believe that there is a significant amount of crosstalk occurring between bacteria and host cells during infection and that the outcome of this interaction dictates both how quickly the infection is cleared and the severity of the pathology associated with the infection. We also believe that through deciphering this crosstalk we should be able to selectively promote certain beneficial interactions while abrogating the harmful ones.  In so doing, we hope to minimize the severity of the infection and achieve more rapid clearance of the pathogen.
There are two major research areas being pursued in this laboratory. The first is centered around elucidating how mast cells, frequently overlooked players in initiating and maintaining host immune responses, mobilize key components of the immune system during bacterial infections.  Ultimately, the goal of these studies is to harness some of these activities attributed to mast cells for therapeutic or vaccine development purposes.

The second area of research within our laboratory focuses on understanding how uropathogenic Escherichia coli, the overwhelmingly predominate causative agent of urinary tract infections, successfully gains entryinto epithelial cells of the bladder to cause infection. This subject is especially intriguing because of the role the bladder plays as a reservoir for urine. Predictably the “water-tight” epithelial barrier of the bladder is especially difficult for bacteria to breech. Yet, E.coli, which compared to other pathogens have no specialized organelles for cell entry, appears to achieve this feat. We believe that by investigating the molecular events associated with the entry of E.coli into bladder epithelial cells and the resulting break down of the bladder barrier, we will be able to develop novel strategies to prevent these infections.

Other studies currently undertaken by one or more members of the laboratory include (i) examination of how particulate allergens interact with pulmonary mast cells to trigger air way hyperesponses and pulmonary inflammation. (ii)  investigation of how, during infection, highly virulent pathogens such asYersinia pestis, Salmonella typhimurium, etc., actively remodel the draining  lymph nodes, the epicenter of the adaptive immune response (iii) investigation of how Pseudomonas aeruginosa co-opts cellular entities generally known as lipid rafts to colonize the airways.

Our studies are located at the intersection of cell biology, molecular biology, immunology and bacterial pathogenesis. Cumulatively, our studies should facilitate the design of innovative strategies to combat pathogens that selectively potentiate the host’s immune response without evoking some of its harmful side effects.

Publications:
2009 -- Pubmed # 19211560 -- Zaas DW, Swan ZD, Brown BJ, Li G, Randell SH, Degan S, Sunday ME, Wright JR, Abraham SN. Counteracting signaling activities in lipid rafts associated with the invasion of lung epithelial cells by Pseudomonas aeruginosa. J Biol Chem. 2009 Feb 11.

2008 -- Pubmed # 18243043 -- Song J, Abraham SN. TLR-mediated immune responses in the urinary tract. Curr Opin Microbiol. 2008 Feb;11(1):66-73.

2008 -- Pubmed # 18425129 -- McLachlan JB, Shelburne CP, Hart JP, Pizzo SV, Goyal R, Brooking-Dixon R, Staats HF, Abraham SN. Mast cell activators: a new class of highly effective vaccine adjuvants. Nat Med. 2008 May;14(5):536-41.

2007 -- Pubmed # 17465679 -- Song J, Duncan MJ, Li G, Chan C, Grady R, Stapleton A, Abraham SN. A novel TLR4-mediated signaling pathway leading to IL-6 responses in human bladder epithelial cells. PLoS Pathog. 2007 Apr;3(4):e60.

2007 -- Pubmed # 17710226 -- Song J, Bishop BL, Li G, Duncan MJ, Abraham SN. TLR4-initiated and cAMP-mediated abrogation of bacterial invasion of the bladder. Cell Host Microbe. 2007 Jun 14;1(4):287-98.

2007 -- Pubmed # 17360489 -- Wang X, Ribeiro AA, Guan Z, Abraham SN, Raetz CR. Attenuated virulence of a Francisella mutant lacking the lipid A 4'-phosphatase. Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):4136-41.

2007 -- Pubmed # 17417648 -- Bishop BL, Duncan MJ, Song J, Li G, Zaas D, Abraham SN. Cyclic AMP-regulated exocytosis of Escherichia coli from infected bladder epithelial cells. Nat Med. 2007 May;13(5):625-30.

2006 -- Pubmed # 17056503 -- Shin JS, Shelburne CP, Jin C, LeFurgey EA, Abraham SN. Harboring of particulate allergens within secretory compartments by mast cells following IgE/FcepsilonRI-lipid raft-mediated phagocytosis. J Immunol. 2006 Nov 1;177(9):5791-800.

2005 -- Pubmed # 16118220 -- Duncan MJ, Mann EL, Cohen MS, Ofek I, Sharon N, Abraham SN. The distinct binding specificities exhibited by enterobacterial type 1 fimbriae are determined by their fimbrial shafts. J Biol Chem. 2005 Nov 11;280(45):37707-16.

2005 -- Pubmed # 16289370 -- Zaas DW, Duncan M, Rae Wright J, Abraham SN. The role of lipid rafts in the pathogenesis of bacterial infections. Biochim Biophys Acta. 2005 Dec 30;1746(3):305-13.

2004 -- Pubmed # 14976212 -- Duncan MJ, Li G, Shin JS, Carson JL, Abraham SN. Bacterial penetration of bladder epithelium through lipid rafts. J Biol Chem. 2004 Apr 30;279(18):18944-51.

2003 -- Pubmed # 12759438 -- Muñoz S, Hernández-Pando R, Abraham SN, Enciso JA. Mast cell activation by Mycobacterium tuberculosis: mediator release and role of CD48. J Immunol. 2003 Jun 1;170(11):5590-6.

2003 -- Pubmed # 14595438 -- McLachlan JB, Hart JP, Pizzo SV, Shelburne CP, Staats HF, Gunn MD, Abraham SN. Mast cell-derived tumor necrosis factor induces hypertrophy of draining lymph nodes during infection. Nat Immunol. 2003 Dec;4(12):1199-205.

2001 -- Pubmed # 11520975 -- Shin JS, Abraham SN. Cell biology. Caveolae--not just craters in the cellular landscape. Science. 2001 Aug 24;293(5534):1447-8.

2001 -- Pubmed # 11378476 -- McLachlan JB, Abraham SN. Studies of the multifaceted mast cell response to bacteria. Curr Opin Microbiol. 2001 Jun;4(3):260-6.

2001 -- Pubmed # 11168630 -- Shin JS, Abraham SN. Co-option of endocytic functions of cellular caveolae by pathogens. Immunology. 2001 Jan;102(1):2-7.

2000 -- Pubmed # 10926542 -- Shin JS, Gao Z, Abraham SN. Involvement of cellular caveolae in bacterial entry into mast cells. Science. 2000 Aug 4;289(5480):785-8.

1999 -- Pubmed # 10026202 -- Thankavel K, Shah AH, Cohen MS, Ikeda T, Lorenz RG, Curtiss R 3rd, Abraham SN. Molecular basis for the enterocyte tropism exhibited by Salmonella typhimurium type 1 fimbriae. J Biol Chem. 1999 Feb 26;274(9):5797-809.

1999 -- Pubmed # 10393956 -- Malaviya R, Gao Z, Thankavel K, van der Merwe PA, Abraham SN. The mast cell tumor necrosis factor alpha response to FimH-expressing Escherichia coli is mediated by the glycosylphosphatidylinositol-anchored molecule CD48. Proc Natl Acad Sci U S A. 1999 Jul 6;96(14):8110-5.

1998 -- Pubmed # 9585238 -- Belaaouaj A, McCarthy R, Baumann M, Gao Z, Ley TJ, Abraham SN, Shapiro SD. Mice lacking neutrophil elastase reveal impaired host defense against gram negative bacterial sepsis. Nat Med. 1998 May;4(5):615-8.

1997 -- Thankavel K, Madison B, Ikeda T, Malaviya R, Shah A, Abraham SN: Protection against experimental urinary tract infection by antibodies directed at the adhesive domain on the FimH adhesin of Escherichia coli type 1 fimbriae. J Clin Invest 1997; 100: 1123-1136.

1997 -- Pubmed # 9276729 -- Thankavel K, Madison B, Ikeda T, Malaviya R, Shah AH, Arumugam PM, Abraham SN. Localization of a domain in the FimH adhesin of Escherichia coli type 1 fimbriae capable of receptor recognition and use of a domain-specific antibody to confer protection against experimental urinary tract infection. J Clin Invest. 1997 Sep 1;100(5):1123-36.

1997 -- Pubmed # 9335508 -- Baorto DM, Gao Z, Malaviya R, Dustin ML, van der Merwe A, Lublin DM, Abraham SN. Survival of FimH-expressing enterobacteria in macrophages relies on glycolipid traffic. Nature. 1997 Oct 9;389(6651):636-9.

1996 -- Pubmed # 8609993 -- Malaviya R, Ikeda T, Ross E, Abraham SN. Mast cell modulation of neutrophil influx and bacterial clearance at sites of infection through TNF-alpha. Nature. 1996 May 2;381(6577):77-80.

1995 -- Pubmed # 7892228 -- Jones CH, Pinkner JS, Roth R, Heuser J, Nicholes AV, Abraham SN, Hultgren SJ. FimH adhesin of type 1 pili is assembled into a fibrillar tip structure in the Enterobacteriaceae. Proc Natl Acad Sci U S A. 1995 Mar 14;92(6):2081-5.

1994 -- Pubmed # 7512987 -- Malaviya R, Ross E, Jakschik BA, Abraham SN. Mast cell degranulation induced by type 1 fimbriated Escherichia coli in mice. J Clin Invest. 1994 Apr;93(4):1645-53.

1993 -- Pubmed # 8104335 -- Jones CH, Pinkner JS, Nicholes AV, Slonim LN, Abraham SN, Hultgren SJ. FimC is a periplasmic PapD-like chaperone that directs assembly of type 1 pili in bacteria. Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8397-401.

1988 -- Pubmed # 2904657 -- Abraham SN, Sun D, Dale JB, Beachey EH. Conservation of the D-mannose-adhesion protein among type 1 fimbriated members of the family Enterobacteriaceae. Nature. 1988 Dec 15;336(6200):682-4.