McLachlan, JB, Hart, JP, Pizzo, SV, Shelburne, CP, Staats, HF, Gunn, MD, and Abraham, SN. "Mast cell-derived tumor necrosis factor induces hypertrophy of draining lymph nodes during infection." Nat Immunol 4, no. 12 (December 2003): 1199-1205.
Soman Ninan Abraham, PhD
The Abraham 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.
There are two major research areas being pursued in this laboratory. The first involves elucidating the role of mast cells in modulating immune responses to microbes. Our studies have revealed that mast cells play a key sentinel role and upon bacterial or viral infection, modulate both innate and adaptive immune responses through the release of immunomodulatory molecules borne in granules. Our current investigations are centered on elucidating the molecular and cellular aspects of how mast cells mediate their immunomodulatory role. We are also examining several mast cell-targeted strategies to boost immunity to infections as well as reduce any pathological consequences of infection.
The second area of research investigates cross-talk between distinct infectious agents such as Uropathogenic E. coli, Salmonella typhimurium and Yersinia pestis and the immune system. We have recognized that different pathogens possess distinct mechanisms to evade or coopt one or more immune cells to establish infection. We have also unraveled novel intracellular innate host defense activities including expulsion of whole bacteria from infected epithelial cells, a feat mediated by immune recognition molecules and the cellular trafficking system.
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.
Education and Training
- Clinical Director, Serology, Washington University, 1993 - 1997
- Assistant Professor, Molecular Microbiology, Washington University, 1990 - 1997
- Associate Clinical Director, Microbiology/Serology, Washington University, 1990 - 1993
- Assistant Professor Of Pathology, Microbiology And Immunology, University of Tennessee at Knoxville, 1990 - 1990
- Assistant Professor, Medicine, University of Tennessee at Knoxville, 1986 - 1990
- Postdoctoral Fellowship, University of Tennessee at Knoxville, 1982 - 1986
- Ph.D., Newcastle University, 1981
- M.S., Ahmadu Bello University (Nigeria), 1978
- B.S., Ahmadu Bello University (Nigeria), 1976
Selected Grants and Awards
- Organization and Function of Cellular Structure
- Interdisciplinary Training Program in Lung Disease
- Basic Immunology Training Program
- Duke KURe Program
- Platelets as regulators of inflammation and tissue injury after cardiac surgery
- Immune mediated exocytosis of intravesicular UPEC from bladder cells
- Platelet/Mast Cell Interactions as Determinants of End-Organ Injury in Cardiac Surgery
- Mast Cells in Dengue Pathology and Prevention
- Institutional Training Grant in Pediatric Infectious Disease
- The role of SP-A in Mp-induced exacerbations during allergic airway disease
- Mechanism of Bacterial Expulsion from Infected Bladder Cells.
- The role of SP-A in Mp-induced exacerbations during allergic airway disease.
- Targeting EGFRvIII in Brain Tumors with Bispecific Antibodies
- Modulation of Bladder cAMP to combat UTI's
- Caveolae Mediated Bacterial Uptake in the Urinary Tract
- Role Of Surfactant In Innate and Adaptive Immunity
- Ligand Receptor Interactions in UTIs
- Mast Cells and IBD Pathogenesis
- Pseudomonas invasion and the role of caveolin-2
- Proteome Mining in Caveolae of the Bladder Epithelium
- Mast Cells in Pulmonary Inflammation
Shin, JS, and Abraham, SN. "Cell biology. Caveolae--not just craters in the cellular landscape." Science 293, no. 5534 (August 24, 2001): 1447-1448.
McLachlan, JB, and Abraham, SN. "Studies of the multifaceted mast cell response to bacteria." Curr Opin Microbiol 4, no. 3 (June 2001): 260-266. (Review)
Shin, JS, and Abraham, SN. "Co-option of endocytic functions of cellular caveolae by pathogens." Immunology 102, no. 1 (January 2001): 2-7. (Review)
Shin, JS, Gao, Z, and Abraham, SN. "Involvement of cellular caveolae in bacterial entry into mast cells." Science 289, no. 5480 (August 4, 2000): 785-788.
Malaviya, R, Gao, Z, Thankavel, K, van der Merwe, PA, and 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 96, no. 14 (July 6, 1999): 8110-8115.
Thankavel, K, Shah, AH, Cohen, MS, Ikeda, T, Lorenz, RG, Curtiss, R, and Abraham, SN. "Molecular basis for the enterocyte tropism exhibited by Salmonella typhimurium type 1 fimbriae." J Biol Chem 274, no. 9 (February 26, 1999): 5797-5809.
Belaaouaj, A, McCarthy, R, Baumann, M, Gao, Z, Ley, TJ, Abraham, SN, and Shapiro, SD. "Mice lacking neutrophil elastase reveal impaired host defense against gram negative bacterial sepsis." Nat Med 4, no. 5 (May 1998): 615-618.
Baorto, DM, Gao, Z, Malaviya, R, Dustin, ML, van der Merwe, A, Lublin, DM, and Abraham, SN. "Survival of FimH-expressing enterobacteria in macrophages relies on glycolipid traffic." Nature 389, no. 6651 (October 9, 1997): 636-639.
Thankavel, K, Madison, B, Ikeda, T, Malaviya, R, Shah, AH, Arumugam, PM, and 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 100, no. 5 (September 1, 1997): 1123-1136.
Malaviya, R, Ikeda, T, Ross, E, and Abraham, SN. "Mast cell modulation of neutrophil influx and bacterial clearance at sites of infection through TNF-alpha." Nature 381, no. 6577 (May 2, 1996): 77-80.
Jones, CH, Pinkner, JS, Roth, R, Heuser, J, Nicholes, AV, Abraham, SN, and 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 92, no. 6 (March 14, 1995): 2081-2085.
Malaviya, R, Ross, E, Jakschik, BA, and Abraham, SN. "Mast cell degranulation induced by type 1 fimbriated Escherichia coli in mice." J Clin Invest 93, no. 4 (April 1994): 1645-1653.
Jones, CH, Pinkner, JS, Nicholes, AV, Slonim, LN, Abraham, SN, and 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 90, no. 18 (September 15, 1993): 8397-8401.
Abraham, SN, Sun, D, Dale, JB, and Beachey, EH. "Conservation of the D-mannose-adhesion protein among type 1 fimbriated members of the family Enterobacteriaceae." Nature 336, no. 6200 (December 15, 1988): 682-684.