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Biography

Dr. Wilbert Derbigny joined ºÚÁÏÍø College of Osteopathic Medicine as an associate professor in the Department of Microbiology and Immunology in July 2020. After receiving his Bachelor of Science degree in 1990 from Xavier University of Louisiana, he served a four-year stint in the biotech sector before returning to academia in 1994 to pursue an advanced degree at Louisiana State University Health Sciences Center (LSUHSC) in Shreveport. In 2001, Dr. Derbigny completed his Ph.D. in Molecular Virology at LSUHSC, and his dissertation research focused on defining the role of the ICP22 homolog in the gene regulation of equine herpesvirus-1 replication.

Immediately after completing the Ph.D., Dr. Derbigny joined Eli Lilly and Company in Indianapolis, Indiana as a postdoctoral fellow in the pharmaceutical industry. During that time at Eli Lilly, he was part of a lab in drug discovery research where much of the research in the division was proprietary investigations into therapeutics to treat patients infected with hepatitis C virus (HCV). As a postdoctoral fellow in drug discovery, Dr. Derbigny was assigned a project investigating ways to exploit the various mechanisms utilized by the viral proteins NS5A and NS5B to initiate HCV viral replication. The unfortunate economic downturn post 9/11 caused premature termination of the postdoctoral fellowship at Eli Lilly, at which point Dr. Derbigny returned to academia in 2003 where he joined the Infectious Disease division as a postdoctoral fellow at Indiana University School of Medicine (IUSM).

As a postdoctoral fellow at IUSM, Dr. Derbigny switched gears from virology to bacteriology and joined a laboratory whose primary focus was the immunopathogenesis of genital tract Chlamydiainfections. Dr. Derbigny experienced a major shift in research direction with the switch from investigating viral gene regulation and its impact of viral replication to studying host-pathogen interactions and their impact on clinical disease. The two major projects during this second postdoctoral appointment included: (1) Delineating Toll-like receptor (TLR) dependent responses to Chlamydia infection of murine oviduct epithelium and (2) Investigating mechanisms of Chlamydia-induced T-cell anergy. The publications from this second postdoctoral appointment served as preliminary data for a successfully funded NIH K22 application, whereby he proposed to test the hypothesis that TLR3 plays a significant role in the chlamydial-induced synthesis of interferon beta (IFN-β) in genital tract epithelial cells.

The NIH K22 career development award was a critical part of Dr. Derbigny’s successful transition into the Microbiology and Immunology department at IUSM as a tenure-track assistant professor position in the fall of 2007. Dr. Derbigny established his lab with the primary goal of demonstrating a role for TLR3 in the immune response to Chlamydia in murine oviduct tissue. He then spent the subsequent 13 years establishing himself as a leader in the field of researchers investigating the chlamydial-induced innate immune response in the female upper genital tract. During his tenure at IUSM, Dr. Derbigny has published numerous abstracts, poster presentations, and manuscripts on the novel interactions between Chlamydia and TLR3, and he has recently expanded the scope of his studies to address the impact of TLR3 function in outcomes of human Chlamydia-human papillomavirus (HPV) co-infection. Towards this goal, Dr. Derbigny will test the hypothesis that pathogenesis of genital tract Chlamydia infection can enhance the infectivity of HPV and thereby can serve as a co-factor in HPV-induced cervical cancer.

Dr. Derbigny’s transition to ºÚÁÏÍø will include transferring over a robust research program developed during his tenure at IUSM—one funded by numerous agencies, including funding from an NIH R01 grant that is in the process of competitive renewal. While at ºÚÁÏÍø, Dr. Derbigny will continue teaching future medical professionals the basic principles of medical microbiology and help them better understand how host-pathogen interactions contribute to clinical disease. With a highly developed research understanding and extensive experience in teaching, training, and mentoring students in a research setting, Dr. Derbigny will continue his mission to contribute to student education by helping the future medical professionals attending ºÚÁÏÍø learn how to develop critical thinking skills and conduct high-quality, hypothesis-driven research.

Clinical/Research Interests

Chlamydia trachomatis is a gram-negative intracellular bacterium and the cause of the disease chlamydia, which is the most common sexually transmitted infection in the United States, with over 1.7 million cases reported in the US in 2017 alone. C. trachomatis infections can be effectively treated with antibiotics, but these infections are often asymptomatic and unrecognized in women. To effectively intervene in women where this chronic condition is often discovered late, we need to understand better the mechanisms that lead to pelvic inflammatory disease (PID) and infertility caused during prolonged Chlamydia infection. Our discovery of an unexpected and atypical activation of Toll-like receptor 3 (TLR3) provides exciting new opportunities to better understand chlamydia-related chronic inflammation.

My long-term goal is to understand further the pathophysiologic processes that contribute to Chlamydia-induced reproductive tract pathology. My lab focused on identifying the inflammatory mediators that induce scarring of the oviduct epithelium and identifying therapeutic countermeasures that can prevent this. We were the first to demonstrate (and others have now confirmed) that TLR3 is a key pattern recognition receptor (PRR) in the immune response to Chlamydia muridarum (Cm) infection in mice. We were the first to show that chlamydial induction of IFN-β is TLR3-dependent in oviduct tissue, TLR3-modulates inflammatory immune responses to Chlamydia in vitro, and TLR3-deficient mice develop significantly more chronic inflammatory uterine and oviduct pathology paralleling the human sequelae of untreated chlamydia infection. This set of observations is paradoxical because Cm lacks a known dsRNA agonist for the TLR3 receptor, suggesting that our understanding of TLR3 is incomplete.

The overall objectives of my continuing research program will be: (A) to investigate further the specific cellular pathways and mechanisms that are dysregulated during TLR3 deficiency that contributes to genital tract pathology during Chlamydia infection, (B) to ascertain the specific role (if any) that TLR3 and its effector pathways have on chronic inflammatory genital tract chlamydial disease and persistent infection, and (C) identifying the likely novel chlamydial pathogen-associated molecular pattern (PAMP) that binds to and triggers TLR3 signaling pathways. Because we recently reported that TLR3 deficiency leads to an increased rate of the ascension of Cm into the upper genital tracts of mice and a more rapid breakdown in epithelial barrier function, our data suggest that TLR3 has a role in limiting the chlamydial spread and that TLR3 modulates the chlamydial caused disruption in epithelial barrier function. The chlamydial caused breakdown in the protective epithelial barrier can make the host more vulnerable to co-infection by other sexually transmitted pathogens such as HIV and HPV. The finding that TLR3 can potentially have an impact on limiting the co-infectivity and disease progression of other genital tract pathogens that are commonly observed as a co-infection in patients allows us to expand the scope of our research and pursue other funding sources. In this regard, we hypothesize that Chlamydia causes a breakdown in epithelial barrier function that is partially modulated by TLR3, and the barrier disruption will allow better access to the underlying basal cell layers and thus increasing the infectivity of HPV. Testing this hypothesis will now enable us to pursue funding sources from institutes that fund cancer research as we propose (D) to examine the putative impact that TLR3 has on facilitating cervical carcinogenesis in Chlamydia-HPV co-infected patients.

Current Funding

NIH – National Institutes of Allergy and Infectious Disease: “Developing a mouse model to examine the specific impact of IFNα in the pathogenesis of genital tract Chlamydia infection (1R03AI154033; starts 8/1/2020).

Recent Publications

Xu, J. Z., Kumar, R., Gong, H., Liu, L., Ramos-Solis, N., Li, Y., and W. A. Derbigny. (2019). Toll-Like Receptor 3 Deficiency Leads to Altered Immune Responses to Chlamydia trachomatis Infection in Human Oviduct Epithelial Cells. Infect Immun. 87: e00483-19. https://doi.org/10.1128/IAI .00483-19. 

Kumar, R., Gong, H., Liu, L., Ramos-Solis, N., Seye, C., and W. A. Derbigny. (2019). TLR3 Deficiency Exacerbates the Loss of Epithelial Barrier Function during Genital Tract Chlamydia muridarum Infection. PLoS ONE 14(1): e0207422. .

Kumar, R. and W. A. Derbigny. (2018). Cellulose Acetate Electrophoresis of Hemoglobin. Methods Mol Biol. 2019;1855:81-85. doi: 10.1007/978-1-4939-8793-1_7.

Kumar, R. and W. A. Derbigny. (2018). TLR3 Deficiency Leads to a Dysregulation in the Global Gene-Expression Profile of Murine Oviduct Epithelial Cells Infected with Chlamydia muridarum. Madridge J Bioinform Syst Biol.2018; 1(1): 1-13.doi: 10.18689/ijmr-1000101

Carrasco, S, Hu, S., Imai, D. M., Kumar, R., Sandusky, G. E., Yang, X. F., and W.A. Derbigny. (2018). Toll-like receptor 3 (TLR3) Promotes the Resolution of Chlamydia muridarum Genital Tract Infection in Congenic C57BL/6N Mice. PLoS One. 2018 Apr 6;13(4):e0195165. doi: 10.1371/journal.pone.0195165. eCollection 2018. PMID:29624589.