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

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
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:

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

Flavivirus serocomplex cross-reactive immunity is protective by activating heterologous memory CD4 T cells.

How previous immunity influences immune memory recall and protection against related flaviviruses is largely unknown, yet encounter with multiple flaviviruses in a lifetime is increasingly likely. Using sequential challenges with dengue virus (DENV), yellow fever virus (YFV), and Japanese encephalitis virus (JEV), we induced cross-reactive cellular and humoral immunity among flaviviruses from differing serocomplexes. Antibodies against JEV enhanced DENV replication; however, JEV immunity was protective in vivo during secondary DENV1 infection, promoting rapid gains in antibody avidity. Mechanistically, JEV immunity activated dendritic cells and effector memory T cells, which developed a T follicular helper cell phenotype in draining lymph nodes upon secondary DENV1 infection. We identified cross-reactive epitopes that promote recall from a pool of flavivirus serocomplex cross-reactive memory CD4 T cells and confirmed that a similar serocomplex cross-reactive immunity occurs in humans. These results show that sequential immunizations for flaviviruses sharing CD4 epitopes should promote protection during a subsequent heterologous infection.
Authors
Saron, WAA; Rathore, APS; Ting, L; Ooi, EE; Low, J; Abraham, SN; St John, AL
MLA Citation
Saron, Wilfried A. A., et al. “Flavivirus serocomplex cross-reactive immunity is protective by activating heterologous memory CD4 T cells..” Sci Adv, vol. 4, no. 7, July 2018. Pubmed, doi:10.1126/sciadv.aar4297.
URI
https://scholars.duke.edu/individual/pub1331001
PMID
29978039
Source
pubmed
Published In
Science Advances
Volume
4
Published Date
Start Page
eaar4297
DOI
10.1126/sciadv.aar4297

Correction notice for TNF-R on mast cells regulate airway responses to Mycoplasma pneumoniae.

Authors
Hsia, BJ; Ledford, JG; Potts-Kant, EN; Nikam, VS; Lugogo, NL; Foster, WM; Kraft, M; Abraham, SN; Wright, JR
MLA Citation
Hsia, Bethany J., et al. “Correction notice for TNF-R on mast cells regulate airway responses to Mycoplasma pneumoniae..” J Allergy Clin Immunol, vol. 137, no. 1, Jan. 2016. Pubmed, doi:10.1016/j.jaci.2015.09.049.
URI
https://scholars.duke.edu/individual/pub1105059
PMID
26611673
Source
pubmed
Published In
The Journal of Allergy and Clinical Immunology
Volume
137
Published Date
Start Page
336
DOI
10.1016/j.jaci.2015.09.049

Intestinal mast cells mediate gut injury and systemic inflammation in a rat model of deep hypothermic circulatory arrest.

OBJECTIVE: Cardiac surgery, especially when employing cardiopulmonary bypass and deep hypothermic circulatory arrest, is associated with systemic inflammatory responses that significantly affect morbidity and mortality. Intestinal perfusion abnormalities have been implicated in such responses, but the mechanisms linking local injury and systemic inflammation remain unclear. Intestinal mast cells are specialized immune cells that secrete various preformed effectors in response to cellular stress. We hypothesized that mast cells are activated in a microenvironment shaped by intestinal ischemia/reperfusion, and investigated local and systemic consequences. DESIGN: Rat model of deep hypothermic circulatory arrest. SETTING: University research laboratory. SUBJECTS: Twelve- to 14-week-old male Sprague-Dawley rats. INTERVENTIONS: Rats were anesthetized and cooled to 16°C to 18°C on cardiopulmonary bypass before instituting deep hypothermic circulatory arrest for 45 minutes. Specimens were harvested following rewarming and 2 hours of recovery. MEASUREMENTS AND MAIN RESULTS: Significant intestinal barrier disruption was found, together with macro- and microscopic evidence of ischemia/reperfusion injury in ileum and colon, but not in the lungs or kidneys. Immunofluorescence and toluidine blue staining revealed increased numbers of mast cells and their activation in the gut. In animals pretreated with the mast cell stabilizer, cromolyn sodium, mast cell degranulation was blocked, and intestinal morphology and barrier function were preserved following deep hypothermic circulatory arrest. Furthermore, cromolyn sodium treatment was associated with reduced intestinal neutrophil influx and blunted systemic release of proinflammatory cytokines. CONCLUSION: Our data provide primary evidence that intestinal ischemia/reperfusion is a leading pathophysiologic process in a rat model of deep hypothermic circulatory arrest, and that intestinal injury, and local and systemic inflammatory responses are critically dependent on mast cell activation. This identifies intestinal mast cells as central players in deep hypothermic circulatory arrest-associated responses, and opens novel therapeutic possibilities for patients undergoing this procedure.
Authors
Karhausen, J; Qing, M; Gibson, A; Moeser, AJ; Griefingholt, H; Hale, LP; Abraham, SN; Mackensen, GB
MLA Citation
Karhausen, Jörn, et al. “Intestinal mast cells mediate gut injury and systemic inflammation in a rat model of deep hypothermic circulatory arrest..” Crit Care Med, vol. 41, no. 9, Sept. 2013, pp. e200–10. Pubmed, doi:10.1097/CCM.0b013e31827cac7a.
URI
https://scholars.duke.edu/individual/pub932499
PMID
23478660
Source
pubmed
Published In
Crit Care Med
Volume
41
Published Date
Start Page
e200
End Page
e210
DOI
10.1097/CCM.0b013e31827cac7a

Mast cell modulation of the vascular and lymphatic endothelium.

Mast cells (MCs) promote a wide range of localized and systemic inflammatory responses. Their involvement in immediate as well as chronic inflammatory reactions at both local and distal sites points to an extraordinarily powerful immunoregulatory capacity with spatial and temporal versatility. MCs are preferentially found in close proximity to both vascular and lymphatic vessels. On activation, they undergo a biphasic secretory response involving the rapid release of prestored vasoactive mediators followed by de novo synthesized products. Many actions of MCs are related to their capacity to regulate vascular flow and permeability and to the recruitment of various inflammatory cells from the vasculature into inflammatory sites. These mediators often work in an additive fashion and achieve their inflammatory effects locally by directly acting on the vascular and lymphatic endothelia, but they also can affect distal sites. Along these lines, the lymphatic and endothelial vasculatures of the host act as a conduit for the dissemination of MC signals during inflammation. The central role of the MC-endothelial cell axis to immune homeostasis is emphasized by the fact that some of the most effective current treatments for inflammatory disorders are directed at interfering with this interaction.
Authors
Kunder, CA; St John, AL; Abraham, SN
MLA Citation
Kunder, Christian A., et al. “Mast cell modulation of the vascular and lymphatic endothelium..” Blood, vol. 118, no. 20, Nov. 2011, pp. 5383–93. Pubmed, doi:10.1182/blood-2011-07-358432.
URI
https://scholars.duke.edu/individual/pub756799
PMID
21908429
Source
pubmed
Published In
Blood
Volume
118
Published Date
Start Page
5383
End Page
5393
DOI
10.1182/blood-2011-07-358432