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 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

Postdoctoral Fellowship

University of Tennessee at Knoxville

Assistant Professor, Medicine

University of Tennessee at Knoxville

Assistant Professor of Pathology, Microbiology And Immunology

University of Tennessee at 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
Co Investigator
Start Date
End Date

Immunotherapy to combat skin infections

Administered By
Pathology
Awarded By
National Institutes of Health
Role
Co 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

Publications:

Optimized Mucosal Modified Vaccinia Virus Ankara Prime/Soluble gp120 Boost HIV Vaccination Regimen Induces Antibody Responses Similar to Those of an Intramuscular Regimen.

The benefits of mucosal vaccines over injected vaccines are difficult to ascertain, since mucosally administered vaccines often induce serum antibody responses of lower magnitude than those induced by injected vaccines. This study aimed to determine if mucosal vaccination using a modified vaccinia virus Ankara expressing human immunodeficiency virus type 1 (HIV-1) gp120 (MVAgp120) prime and a HIV-1 gp120 protein boost could be optimized to induce serum antibody responses similar to those induced by an intramuscularly (i.m.) administered MVAgp120 prime/gp120 boost to allow comparison of an i.m. immunization regimen to a mucosal vaccination regimen for the ability to protect against a low-dose rectal simian-human immunodeficiency virus (SHIV) challenge. A 3-fold higher antigen dose was required for intranasal (i.n.) immunization with gp120 to induce serum anti-gp120 IgG responses not significantly different than those induced by i.m. immunization. gp120 fused to the adenovirus type 2 fiber binding domain (gp120-Ad2F), a mucosal targeting ligand, exhibited enhanced i.n. immunogenicity compared to gp120. MVAgp120 was more immunogenic after i.n. delivery than after gastric or rectal delivery. Using these optimized vaccines, an i.n. MVAgp120 prime/combined i.m. (gp120) and i.n. (gp120-Ad2F) boost regimen (i.n./i.m.-plus-i.n.) induced serum anti-gp120 antibody titers similar to those induced by the intramuscular prime/boost regimen (i.m./i.m.) in rabbits and nonhuman primates. Despite the induction of similar systemic anti-HIV-1 antibody responses, neither the i.m./i.m. nor the i.n./i.m.-plus-i.n. regimen protected against a repeated low-dose rectal SHIV challenge. These results demonstrate that immunization regimens utilizing the i.n. route are able to induce serum antigen-specific antibody responses similar to those induced by systemic immunization.IMPORTANCE Mucosal vaccination is proposed as a method of immunization able to induce protection against mucosal pathogens that is superior to protection provided by parenteral immunization. However, mucosal vaccination often induces serum antigen-specific immune responses of lower magnitude than those induced by parenteral immunization, making the comparison of mucosal and parenteral immunization difficult. We identified vaccine parameters that allowed an immunization regimen consisting of an i.n. prime followed by boosters administered by both i.n. and i.m. routes to induce serum antibody responses similar to those induced by i.m. prime/boost vaccination. Additional studies are needed to determine the potential benefit of mucosal immunization for HIV-1 and other mucosally transmitted pathogens.
Authors
Jones, DI; Pollara, JJ; Johnson-Weaver, BT; LaBranche, CC; Montefiori, DC; Pickup, DJ; Permar, SR; Abraham, SN; Maddaloni, M; Pascual, DW; Staats, HF
MLA Citation
URI
https://scholars.duke.edu/individual/pub1383210
PMID
31068425
Source
pubmed
Published In
J Virol
Volume
93
Published Date
DOI
10.1128/JVI.00475-19

Loss of Bladder Epithelium Induced by Cytolytic Mast Cell Granules.

Programmed death and shedding of epithelial cells is a powerful defense mechanism to reduce bacterial burden during infection but this activity cannot be indiscriminate because of the critical barrier function of the epithelium. We report that during cystitis, shedding of infected bladder epithelial cells (BECs) was preceded by the recruitment of mast cells (MCs) directly underneath the superficial epithelium where they docked and extruded their granules. MCs were responding to interleukin-1β (IL-1β) secreted by BECs after inflammasome and caspase-1 signaling. Upon uptake of granule-associated chymase (mouse MC protease 4 [mMCPT4]), BECs underwent caspase-1-associated cytolysis and exfoliation. Thus, infected epithelial cells require a specific cue for cytolysis from recruited sentinel inflammatory cells before shedding.
Authors
Choi, HW; Bowen, SE; Miao, Y; Chan, CY; Miao, EA; Abrink, M; Moeser, AJ; Abraham, SN
MLA Citation
Choi, Hae Woong, et al. “Loss of Bladder Epithelium Induced by Cytolytic Mast Cell Granules..” Immunity, vol. 45, no. 6, Dec. 2016, pp. 1258–69. Pubmed, doi:10.1016/j.immuni.2016.11.003.
URI
https://scholars.duke.edu/individual/pub1162302
PMID
27939674
Source
pubmed
Published In
Immunity
Volume
45
Published Date
Start Page
1258
End Page
1269
DOI
10.1016/j.immuni.2016.11.003

S1P-Dependent trafficking of intracellular yersinia pestis through lymph nodes establishes Buboes and systemic infection.

Pathologically swollen lymph nodes (LNs), or buboes, characterize Yersinia pestis infection, yet how they form and function is unknown. We report that colonization of the draining LN (dLN) occurred due to trafficking of infected dendritic cells and monocytes in temporally distinct waves in response to redundant chemotactic signals, including through CCR7, CCR2, and sphingosine-1-phospate (S1P) receptors. Retention of multiple subsets of phagocytes within peripheral LNs using the S1P receptor agonist FTY720 or S1P1-specific agonist SEW2871 increased survival, reduced colonization of downstream LNs, and limited progression to transmission-associated septicemic or pneumonic disease states. Conditional deletion of S1P1 in mononuclear phagocytes abolished node-to-node trafficking of infected cells. Thus, Y. pestis-orchestrated LN remodeling promoted its dissemination via host cells through the lymphatic system but can be blocked by prevention of leukocyte egress from DLNs. These findings define a novel trafficking route of mononuclear phagocytes and identify S1P as a therapeutic target during infection.
Authors
St John, AL; Ang, WXG; Huang, M-N; Kunder, CA; Chan, EW; Gunn, MD; Abraham, SN
MLA Citation
St John, Ashley L., et al. “S1P-Dependent trafficking of intracellular yersinia pestis through lymph nodes establishes Buboes and systemic infection..” Immunity, vol. 41, no. 3, Sept. 2014, pp. 440–50. Epmc, doi:10.1016/j.immuni.2014.07.013.
URI
https://scholars.duke.edu/individual/pub1045253
PMID
25238098
Source
epmc
Published In
Immunity
Volume
41
Published Date
Start Page
440
End Page
450
DOI
10.1016/j.immuni.2014.07.013

Contributions of mast cells and vasoactive products, leukotrienes and chymase, to dengue virus-induced vascular leakage

Dengue Virus (DENV), a flavivirus spread by mosquito vectors, can cause vascular leakage and hemorrhaging. However, the processes that underlie increased vascular permeability and pathological plasma leakage during viral hemorrhagic fevers are largely unknown. Mast cells (MCs) are activated in vivo during DENV infection, and we show that this elevates systemic levels of their vasoactive products, including chymase, and promotes vascular leakage. Treatment of infected animals with MC-stabilizing drugs or a leukotriene receptor antagonist restores vascular integrity during experimental DENV infection. Validation of these findings using human clinical samples revealed a direct correlation between MC activation and DENV disease severity. In humans, the MC-specific product, chymase, is a predictive biomarker distinguishing dengue fever (DF) and dengue hemorrhagic fever (DHF). Additionally, our findings reveal MCs as potential therapeutic targets to prevent DENV-induced vasculopathy, suggesting MC-stabilizing drugs should be evaluated for their effectiveness in improving disease outcomes during viral hemorrhagic fevers. Copyright St John et al.
Authors
John, ALS; Rathore, APS; Raghavan, B; Ng, ML; Abraham, SN
MLA Citation
John, A. L. S., et al. “Contributions of mast cells and vasoactive products, leukotrienes and chymase, to dengue virus-induced vascular leakage.” Elife, vol. 2013, no. 2, 2013. Scival, doi:10.7554/eLife.00481.001.
URI
https://scholars.duke.edu/individual/pub954302
Source
scival
Published In
Elife
Volume
2013
Published Date
DOI
10.7554/eLife.00481.001

New roles for mast cells in pathogen defense and allergic disease.

Mast cells (MC) are specialized exocytic cells that lie beneath the external surfaces of the body. For many decades, MCs were thought to primarily function as effector cells for IgE mediated allergic diseases. However, recent evidence indicates that MCs also function as important cells in immune surveillance. When activated by pathogens, MCs initiate innate and adaptive immune responses thereby resulting in protection against pathogens. The question remains if MC activation may also function in establishing immune responses against allergens and hence allergic disease. New studies suggest that MCs are not only the effector cell of allergy but may also be the initiator of allergy.
Authors
Hofmann, AM; Abraham, SN
MLA Citation
Hofmann, Alison M., and Soman N. Abraham. “New roles for mast cells in pathogen defense and allergic disease..” Discov Med, vol. 9, no. 45, Feb. 2010, pp. 79–83.
URI
https://scholars.duke.edu/individual/pub722215
PMID
20193631
Source
pubmed
Published In
Discov Med
Volume
9
Published Date
Start Page
79
End Page
83