Soman Abraham

Overview:

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.

Positions:

Grace Kerby Distinguished Professor of Pathology

Pathology
School of Medicine

Professor in Pathology

Pathology
School of Medicine

Professor in Molecular Genetics and Microbiology

Molecular Genetics and Microbiology
School of Medicine

Professor in Immunology

Immunology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

B.S. 1976

Ahmadu Bello University (Nigeria)

M.S. 1978

Ahmadu Bello University (Nigeria)

Ph.D. 1981

Newcastle University (United Kingdom)

Postdoctoral Fellowship

University of Tennessee, Knoxville

Assistant Professor, Medicine

University of Tennessee, Knoxville

Assistant Professor of Pathology, Microbiology And Immunology

University of Tennessee, Knoxville

Associate Clinical Director, Microbiology/Serology

Washington University in St. Louis

Assistant Professor, Molecular Microbiology

Washington University in St. Louis

Clinical Director, Serology

Washington University in St. Louis

Grants:

Aberrant remodeling of bladder following infection

Administered By
Pathology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Combatting Bladder Cancer by Inducing Epithelial Turnover

Administered By
Pathology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Novel Adjuvants and Carriers for Opiod Vaccines

Administered By
Pathology
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

Adjuvant Discovery Program (Option #2)

Administered By
Pathology
Awarded By
National Institutes of Health
Role
Co-Principal Investigator
Start Date
End Date

Adjuvant Discovery Program (Option #3)

Administered By
Pathology
Awarded By
National Institutes of Health
Role
Co-Principal Investigator
Start Date
End Date

Publications:

Platelets trigger perivascular mast cell degranulation to cause inflammatory responses and tissue injury.

Platelet responses have been associated with end-organ injury and mortality following complex insults such as cardiac surgery, but how platelets contribute to these pathologies remains unclear. Our studies originated from the observation of microvascular platelet retention in a rat cardiac surgery model. Ensuing work supported the proximity of platelet aggregates with perivascular mast cells (MCs) and demonstrated that platelet activation triggered systemic MC activation. We then identified platelet activating factor (PAF) as the platelet-derived mediator stimulating MCs and, using chimeric animals with platelets defective in PAF generation or MCs lacking PAF receptor, defined the role of this platelet-MC interaction for vascular leakage, shock, and tissue inflammation. In application of these findings, we demonstrated that inhibition of platelet activation in modeled cardiac surgery blunted MC-dependent inflammation and tissue injury. Together, our work identifies a previously undefined mechanism of inflammatory augmentation, in which platelets trigger local and systemic responses through activation of perivascular MCs.
Authors
Karhausen, J; Choi, HW; Maddipati, KR; Mathew, JP; Ma, Q; Boulaftali, Y; Lee, RH; Bergmeier, W; Abraham, SN
MLA Citation
Karhausen, Jörn, et al. “Platelets trigger perivascular mast cell degranulation to cause inflammatory responses and tissue injury.Sci Adv, vol. 6, no. 12, Mar. 2020, p. eaay6314. Pubmed, doi:10.1126/sciadv.aay6314.
URI
https://scholars.duke.edu/individual/pub1435663
PMID
32206714
Source
pubmed
Published In
Science Advances
Volume
6
Published Date
Start Page
eaay6314
DOI
10.1126/sciadv.aay6314

Novel mucosal adjuvant, mastoparan-7, improves cocaine vaccine efficacy.

Cocaine is one of the most potent and addictive psychostimulants known and there are no available pharmacotherapies to treat cocaine addiction. Here we describe a novel cocaine vaccine employing the mucosal adjuvant and mast cell-activating oligopeptide, mastoparan-7 (M7), to achieve optimal IgA antibody responses in mucosal secretions and effective induction of humoral immunity using a short immunization protocol. This formulation, using a hapten-carrier system to deliver cocaine as antigen, also reduced cocaine penetration of the blood brain barrier and protected mice from its psychoactive effects by reducing cocaine-induced locomotion. Surprisingly, the magnitude of cocaine-specific antibody titers induced by each adjuvant was not the major determinant of functional protection from cocaine challenge. A side-by-side comparison of the two haptens, cocaine and its analog GNC demonstrated that cocaine haptenation resulted in superior functional protection when used in combination with the novel mucosal adjuvant, M7. These results provide a new potential strategy for combatting cocaine addiction through mucosal vaccination.
Authors
St John, AL; Choi, HW; Walker, QD; Blough, B; Kuhn, CM; Abraham, SN; Staats, HF
MLA Citation
St John, Ashley L., et al. “Novel mucosal adjuvant, mastoparan-7, improves cocaine vaccine efficacy.Npj Vaccines, vol. 5, 2020, p. 12. Pubmed, doi:10.1038/s41541-020-0161-1.
URI
https://scholars.duke.edu/individual/pub1429605
PMID
32047657
Source
pubmed
Published In
Npj Vaccines
Volume
5
Published Date
Start Page
12
DOI
10.1038/s41541-020-0161-1

Mucosal Vaccines

MLA Citation
Mucosal Vaccines. Elsevier, 2020. Crossref, doi:10.1016/c2016-0-00017-7.
URI
https://scholars.duke.edu/individual/pub1429606
Source
crossref
Published Date
DOI
10.1016/c2016-0-00017-7

C-KIT Is Necessary For Protection From Emphysema-Like Disease In Mice

Authors
Lindsey, JY; Ganguly, K; Brass, DM; Li, Z; Potts, EN; Degan, S; Chen, H; Brockway, B; Abraham, SN; Berndt, A; Stripp, BR; Foster, WM; Leikauf, G; Schulz, H; Hollingsworth, JW
MLA Citation
Lindsey, J. Y., et al. “C-KIT Is Necessary For Protection From Emphysema-Like Disease In Mice.” American Journal of Respiratory and Critical Care Medicine, vol. 183, AMER THORACIC SOC, 2011.
URI
https://scholars.duke.edu/individual/pub974159
Source
wos
Published In
American Journal of Respiratory and Critical Care Medicine
Volume
183
Published Date

Innate immunity-based mucosal modulators and adjuvants

© 2020 Elsevier Inc. All rights reserved. The development of mucosally administered vaccines remains a goal of many researchers who desire to develop a needle-free method of immunization that can induce antigen-specific immune responses in both systemic and mucosal tissues. The coadministration of adjuvants is often required to maximize the induction of protective immunity following mucosal vaccination, especially when subunit immunogens are used. A major class of mucosal vaccine adjuvants and modulators includes substances that can activate the innate immune system. Innate immune system activators that exhibit mucosal vaccine adjuvant and modulator activity will be discussed, including proinflammatory cytokines, nanoemulsions, mast cell activators, and toll-like receptor ligands.
Authors
Johnson-Weaver, BT; Abraham, SN; Staats, HF
MLA Citation
Johnson-Weaver, B. T., et al. “Innate immunity-based mucosal modulators and adjuvants.” Mucosal Vaccines: Innovation for Preventing Infectious Diseases, 2019, pp. 167–83. Scopus, doi:10.1016/B978-0-12-811924-2.00010-9.
URI
https://scholars.duke.edu/individual/pub1429607
Source
scopus
Published Date
Start Page
167
End Page
183
DOI
10.1016/B978-0-12-811924-2.00010-9