Charlene S. Dezzutti, PhD

Associate Professor, Department of Obstetrics, Gynecology & Reproductive Sciences, Department of Infectious Diseases & Microbiology, Graduate School of Public Health, University of Pittsburgh

Research

Description

Sexual transmission of HIV is the primary route of viral spread. Yet, decades into the HIV epidemic, the fundamentals of HIV transmission remain poorly understood. Dr. Dezzutti’s laboratory strives to elucidate the early events and potential co-factors involved in HIV transmission. Even though oral drugs have been approved for HIV prevention, not everyone will want to be on daily medication. Therefore, defining prevention options continues. Her laboratory also conducts side-by-side comparative assessments of microbicide candidates – products used topically to prevent the sexual acquisition of HIV – that will be used in clinical trials. The majority of the work done in her lab relies upon the use of polarized mucosal tissue explants.

dezzutti-explant

Polarized explant cultures using human mucosal tissue developed in Dezzutti Laboratory.

The Dezzutti laboratory focuses on:

Mechanism(s) of transmission:

  • Attempting to determine the first HIV-infected cells, the lab has developed cervical and colorectal tissue explant systems to study HIV transmission ex vivo. One goal is to evaluate the role of cell-free and cell-associated HIV for infection of mucosal tissue.
  • Host innate immunity may modulate HIV transmission and this lab is utilizing new techniques to characterize mucosal immunity such as anti-microbial testing and proteomic approaches.

Factors that influence transmission:

  • The lab has an active program studying the interaction(s) between sexually transmitted infections (for example, herpes simplex virus and Trichomonas vaginalis) and HIV in acute in vitro and tissue explant systems.
  • The lab also studies the influence of hormones such as progesterone on HIV infection.

Prevention of HIV transmission:

  • The lab is evaluating topical microbicides that may be utilized in human clinical trials to prevent sexually acquired HIV. The polarized mucosal tissue models are used to evaluate safety and efficacy of the products being developed.
  • Another point of interest is to define pharmacokinetic and pharmacodynamic models to predict a biomarker of efficacy for early phase clinical trials of microbicide products.
  • Currently the lab is working on the development of the ex vivo challenge assay for female genital tract tissue to characterize host factors that may affect drug efficacy and HIV infection.

 

Selected Publications

  • Dezzutti, C.S., Richardson, B.A., Marrazzo, J.M., Tugetman, J., Ramjee, G., Taha, T., Chirenje, Z.M., Abdool Karim, S.S., Hillier, S.L., Herold, B.C. Mucosal E. coli bactericidal activity and immune mediators are associated with HIV-1 seroconversion in women participating in the HPTN 035 trial. J. Inf. Dis. 206:1931-5, 2012. PMC3502373
  • Dezzutti, C.S., Brown, E.R., Moncla, B., Russo, J., Cost, M., Wang, L., Uranker, K., Kunjara Na Ayudhya, R.P., Pryke, K., Pickett, J., LeBlanc, M.A., Rohan, L.C. Is Wetter Better? An Evaluation of Over-the-Counter Personal Lubricants for Safety and Anti-HIV-1 Activity. PLOS ONE 2012;7(11):e48328. doi: 10.1371/journal.pone.0048328. PMC3492332
  • Dezzutti, C.S., Uranker, K., Bunge, K., Richardson-Harman, N., Macio, I., and Hillier, S.L. HIV-1 infection of female genital tract tissue for use in prevention studies. J Acquir Immune Defic Syndr 63:548-554, 2013. PMC3760971
  • Chappell, C.A., Isaacs, C.E., Weimin, X., Meyn, L.A., Uranker, K., Dezzutti, C.S., Moncla, B.J., Hillier, S.L. The effect of menopause on the innate anti-viral activity of cervicovaginal lavage. Am J Obst Gyn. 213(2):204.e1-6. doi: 10.1016/j.ajog.2015.03.0452015. PMC4519412
  • Dezzutti, C.S. Animal and human mucosal tissue models to study HIV biomedical interventions: can we predict success? J. IAS 2015, 18:20301. PMC4631705 http://dx.doi.org/10.7448/IAS.18.1.20301
  • Scott, Y. M., Park, S.Y., Dezzutti, C.S. Broadly neutralizing anti-HIV antibodies prevent HIV infection of mucosal tissue ex vivo. Antimicrob. Agents Chemother. 2015 Nov 23. [Epub ahead of print].

For additional publications, see: http://www.ncbi.nlm.nih.gov/pubmed?term=dezzutti c%5BAuthor%5D&cmd=DetailsSearch&log%24=details

 

Clinical Trials

  • Optimization of the ex vivo challenge assay – collection of female genital tract tissue and mucosal secretions to better understand how HIV infects tissue in the laboratory.
  • The impact of semen on HIV infection in the laboratory – a collaboration with the Pittsburgh Men’s Study where we are collecting semen from HIV infected men prior to their start on therapy. Our interest is to define specific factors in semen that may increase HIV infection ex vivo.
  • Evaluation of Tissue Specific Parameters Important In Microbicide Product Development – acquisition of tissue remainders from surgeries performed at UPMC hospitals. We evaluate microbicide products using polarized ectocervical and colonic tissues for safety and efficacy.

 

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