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:

Local induction of bladder Th1 responses to combat urinary tract infections.

Given the high frequency of urinary tract infections (UTIs) and their recurrence, there is keen interest in developing effective UTI vaccines. Currently, most vaccine studies, including those in humans, involve parenteral vaccination aimed at evoking and sustaining elevated levels of systemic antibody directed at the uropathogens. In view of recent reports of aberrant Th2-biased bladder immune responses to infection, we hypothesized that immunizing mice intravesically with antigens from uropathogenic Escherichia coli (UPEC) combined with a Th1-skewing adjuvant could correct this defect and promote protection against UTIs. Here we report that compared with mice immunized subcutaneously with this vaccine combination, intravesically immunized mice were markedly more protected from UTIs because of their distinctive ability to recruit Th1 cells into the bladder. This mode of vaccination was effective even in mice that experienced multiple UTIs and displayed pronounced aberrant bladder immune responses. Thus, intravesical vaccination with one or more UPEC antigens to induce bladder Th1 responses represents a superior strategy to combat UTIs, especially in UTI-prone subjects.
Authors
Wu, J; Bao, C; Reinhardt, RL; Abraham, SN
MLA Citation
Wu, Jianxuan, et al. “Local induction of bladder Th1 responses to combat urinary tract infections.Proc Natl Acad Sci U S A, vol. 118, no. 10, Mar. 2021. Pubmed, doi:10.1073/pnas.2026461118.
URI
https://scholars.duke.edu/individual/pub1476152
PMID
33653961
Source
pubmed
Published In
Proc Natl Acad Sci U S A
Volume
118
Published Date
DOI
10.1073/pnas.2026461118

The Roles of T cells in Bladder Pathologies.

T lymphocytes play important roles in the skin and mucosal surfaces such as the gut and lung. Until recently the contributions of T cells to mammalian bladder immunity were largely unknown. With newer techniques, including single-cell RNA sequencing and reporter mice, an understanding is emerging of T cell roles in bladder diseases (bacterial infections, bladder cancer, chronic inflammation). In these pathologies, many bladder T cell responses can be harmful to the host through suboptimal clearance of bacteria or cancer cells, or by modulating autoinflammation. Recent findings suggest that T cell behavior might be influenced by resident T cell interactions with the bladder microbiota and other immunostimulants. Thus, regulating bladder T cell functions could emerge as a putative immunotherapy to treat some bladder diseases.
Authors
MLA Citation
Wu, Jianxuan, and Soman N. Abraham. “The Roles of T cells in Bladder Pathologies.Trends Immunol, vol. 42, no. 3, Mar. 2021, pp. 248–60. Pubmed, doi:10.1016/j.it.2021.01.003.
URI
https://scholars.duke.edu/individual/pub1473815
PMID
33536141
Source
pubmed
Published In
Trends Immunol
Volume
42
Published Date
Start Page
248
End Page
260
DOI
10.1016/j.it.2021.01.003

Th1-Polarized, Dengue Virus-Activated Human Mast Cells Induce Endothelial Transcriptional Activation and Permeability.

Dengue virus (DENV), an arbovirus, strongly activates mast cells (MCs), which are key immune cells for pathogen immune surveillance. In animal models, MCs promote clearance of local peripheral DENV infections but, conversely, also promote pathological vascular leakage when widely activated during systemic DENV infection. Since DENV is a human pathogen, we sought to ascertain whether a similar phenomenon could occur in humans by characterizing the products released by human MCs (huMCs) upon direct (antibody-independent) DENV exposure, using the phenotypically mature huMC line, ROSA. DENV did not productively infect huMCs but prompted huMC release of proteases and eicosanoids and induced a Th1-polarized transcriptional profile. In co-culture and trans-well systems, huMC products activated human microvascular endothelial cells, involving transcription of vasoactive mediators and increased monolayer permeability. This permeability was blocked by MC-stabilizing drugs, or limited by drugs targeting certain MC products. Thus, MC stabilizers are a viable strategy to limit MC-promoted vascular leakage during DENV infection in humans.
Authors
Syenina, A; Saron, WAA; Jagaraj, CJ; Bibi, S; Arock, M; Gubler, DJ; Rathore, APS; Abraham, SN; St John, AL
MLA Citation
Syenina, Ayesa, et al. “Th1-Polarized, Dengue Virus-Activated Human Mast Cells Induce Endothelial Transcriptional Activation and Permeability.Viruses, vol. 12, no. 12, Dec. 2020. Pubmed, doi:10.3390/v12121379.
URI
https://scholars.duke.edu/individual/pub1468732
PMID
33276578
Source
pubmed
Published In
Viruses
Volume
12
Published Date
DOI
10.3390/v12121379

Innate immune responses to bladder infection

The urinary tract (UT) consists of the kidneys, ureters, bladder, and urethra, all of which with the exception of the lower urethra are presumed to be sterile. Because of its close proximity to the gut, the lower UT is constantly exposed to a barrage of gut bacteria. However, the bladder remains for the most part free of infection. The resistance of the bladder to active microbial colonization is due to both anatomical design as well as secreted antimicrobial compounds of the urothelium. The apical face of the urothelium is covered by uroplakin plaques and is coated by mucus, which discourages adherence and invasion of most microorganisms (1, 2). Because of its role in storing urine for extended periods of time, the urothelium of the bladder has an additional role in protecting the underlying tissue from urine and its many toxic constituents. Since the bladder and urinary system as a whole need to constantly maintain the integrity of the urothelium, immune responses in the UT are often tightly regulated to minimize the extent of damage by quelling inflammation in a timely manner.
Authors
Hayes, BW; Abraham, SN
MLA Citation
Hayes, B. W., and S. N. Abraham. “Innate immune responses to bladder infection.” Urinary Tract Infections: Molecular Pathogenesis and Clinical Management, 2016, pp. 555–64. Scopus, doi:10.1128/9781555817404.ch22.
URI
https://scholars.duke.edu/individual/pub1476686
Source
scopus
Published Date
Start Page
555
End Page
564
DOI
10.1128/9781555817404.ch22

A highly polarized TH2 bladder response to infection promotes epithelial repair at the expense of preventing new infections.

Urinary tract infections (UTIs) typically evoke prompt and vigorous innate bladder immune responses, including extensive exfoliation of the epithelium. To explain the basis for the extraordinarily high recurrence rates of UTIs, we examined adaptive immune responses in mouse bladders. We found that, following each bladder infection, a highly T helper type 2 (TH2)-skewed immune response directed at bladder re-epithelialization is observed, with limited capacity to clear infection. This response is initiated by a distinct subset of CD301b+OX40L+ dendritic cells, which migrate into the bladder epithelium after infection before trafficking to lymph nodes to preferentially activate TH2 cells. The bladder epithelial repair response is cumulative and aberrant as, after multiple infections, the epithelium was markedly thickened and bladder capacity was reduced relative to controls. Thus, recurrence of UTIs and associated bladder dysfunction are the outcome of the preferential focus of the adaptive immune response on epithelial repair at the expense of bacterial clearance.
Authors
Wu, J; Hayes, BW; Phoenix, C; Macias, GS; Miao, Y; Choi, HW; Hughes, FM; Todd Purves, J; Lee Reinhardt, R; Abraham, SN
MLA Citation
Wu, Jianxuan, et al. “A highly polarized TH2 bladder response to infection promotes epithelial repair at the expense of preventing new infections.Nat Immunol, vol. 21, no. 6, June 2020, pp. 671–83. Pubmed, doi:10.1038/s41590-020-0688-3.
URI
https://scholars.duke.edu/individual/pub1441447
PMID
32424366
Source
pubmed
Published In
Nat Immunol
Volume
21
Published Date
Start Page
671
End Page
683
DOI
10.1038/s41590-020-0688-3