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

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

Platelets as regulators of inflammation and tissue injury after cardiac surgery

Administered By
Anesthesiology, Cardiothoracic
Awarded By
American Heart Association
Role
Significant Contributor
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

Particulate allergens potentiate allergic asthma in mice through sustained IgE-mediated mast cell activation.

Authors
Jin, C; Shelburne, CP; Li, G; Potts, EN; Riebe, KJ; Sempowski, GD; Foster, WM; Abraham, SN
MLA Citation
Jin, Cong, et al. “Particulate allergens potentiate allergic asthma in mice through sustained IgE-mediated mast cell activation..” J Clin Invest, vol. 127, no. 10, Oct. 2017. Pubmed, doi:10.1172/JCI97321.
URI
https://scholars.duke.edu/individual/pub1276541
PMID
28920926
Source
pubmed
Published In
J Clin Invest
Volume
127
Published Date
Start Page
3913
DOI
10.1172/JCI97321

A TRP Channel Senses Lysosome Neutralization by Pathogens to Trigger Their Expulsion.

Vertebrate cells have evolved elaborate cell-autonomous defense programs to monitor subcellular compartments for infection and to evoke counter-responses. These programs are activated by pathogen-associated pattern molecules and by various strategies intracellular pathogens employ to alter cellular microenvironments. Here, we show that, when uropathogenic E. coli (UPEC) infect bladder epithelial cells (BECs), they are targeted by autophagy but avoid degradation because of their capacity to neutralize lysosomal pH. This change is detected by mucolipin TRP channel 3 (TRPML3), a transient receptor potential cation channel localized to lysosomes. TRPML3 activation then spontaneously initiates lysosome exocytosis, resulting in expulsion of exosome-encased bacteria. These studies reveal a cellular default system for lysosome homeostasis that has been co-opted by the autonomous defense program to clear recalcitrant pathogens.
Authors
Miao, Y; Li, G; Zhang, X; Xu, H; Abraham, SN
MLA Citation
Miao, Yuxuan, et al. “A TRP Channel Senses Lysosome Neutralization by Pathogens to Trigger Their Expulsion..” Cell, vol. 161, no. 6, June 2015, pp. 1306–19. Pubmed, doi:10.1016/j.cell.2015.05.009.
URI
https://scholars.duke.edu/individual/pub1073763
PMID
26027738
Source
pubmed
Published In
Cell
Volume
161
Published Date
Start Page
1306
End Page
1319
DOI
10.1016/j.cell.2015.05.009

Innate immunity and its regulation by mast cells.

Mast cells (MCs), which are granulated tissue-resident cells of hematopoietic lineage, constitute a major sensory arm of the innate immune system. In this review we discuss the evidence supporting the dual role of MCs, both as sentinels for invading pathogens and as regulatory cells throughout the course of acute inflammation, from its initiation to resolution. This versatility is dependent on the ability of MCs to detect pathogens and danger signals and release a unique panel of mediators to promote pathogen-specific clearance mechanisms, such as through cellular recruitment or vascular permeability. It is increasingly understood that MCs also contribute to the regulated contraction of immune activation that occurs within tissues as inflammation resolves. This overarching regulatory control over innate immune processes has made MCs successful targets to purposefully enhance or, alternatively, suppress MC responses in multiple therapeutic contexts.
Authors
St John, AL; Abraham, SN
MLA Citation
St John, Ashley L., and Soman N. Abraham. “Innate immunity and its regulation by mast cells..” J Immunol, vol. 190, no. 9, May 2013, pp. 4458–63. Pubmed, doi:10.4049/jimmunol.1203420.
URI
https://scholars.duke.edu/individual/pub938252
PMID
23606723
Source
pubmed
Published In
J Immunol
Volume
190
Published Date
Start Page
4458
End Page
4463
DOI
10.4049/jimmunol.1203420

Particulate allergens potentiate allergic asthma in mice through sustained IgE-mediated mast cell activation.

Allergic asthma is characterized by airway hyperresponsiveness, inflammation, and a cellular infiltrate dominated by eosinophils. Numerous epidemiological studies have related the exacerbation of allergic asthma with an increase in ambient inhalable particulate matter from air pollutants. This is because inhalable particles efficiently deliver airborne allergens deep into the airways, where they can aggravate allergic asthma symptoms. However, the cellular mechanisms by which inhalable particulate allergens (pAgs) potentiate asthmatic symptoms remain unknown, in part because most in vivo and in vitro studies exploring the pathogenesis of allergic asthma use soluble allergens (sAgs). Using a mouse model of allergic asthma, we found that, compared with their sAg counterparts, pAgs triggered markedly heightened airway hyperresponsiveness and pulmonary eosinophilia in allergen-sensitized mice. Mast cells (MCs) were implicated in this divergent response, as the differences in airway inflammatory responses provoked by the physical nature of the allergens were attenuated in MC-deficient mice. The pAgs were found to mediate MC-dependent responses by enhancing retention of pAg/IgE/FcεRI complexes within lipid raft–enriched, CD63(+) endocytic compartments, which prolonged IgE/FcεRI-initiated signaling and resulted in heightened cytokine responses. These results reveal how the physical attributes of allergens can co-opt MC endocytic circuitry and signaling responses to aggravate pathological responses of allergic asthma in mice.
Authors
Jin, C; Shelburne, CP; Li, G; Potts, EN; Riebe, KJ; Sempowski, GD; Foster, WM; Abraham, SN
MLA Citation
Jin, Cong, et al. “Particulate allergens potentiate allergic asthma in mice through sustained IgE-mediated mast cell activation..” J Clin Invest, vol. 121, no. 3, Mar. 2011, pp. 941–55. Pubmed, doi:10.1172/JCI43584.
URI
https://scholars.duke.edu/individual/pub731004
PMID
21285515
Source
pubmed
Published In
J Clin Invest
Volume
121
Published Date
Start Page
941
End Page
955
DOI
10.1172/JCI43584