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Charles R. Wira, PhD

Title(s):
Professor of Microbiology and Immunology

Department(s):
Microbiology and Immunology

Education:
Dartmouth College, PHD 1970
Delaware Valley College, BS 1962
Michigan State University, MS 1966

Programs:
Program in Experimental and Molecular Medicine

Contact Information:

Dartmouth Medical School
One Medical Center Drive, HB 7700
Lebanon NH 03756

Office: Borwell 708 West
Phone: 603 650-7733
Fax: 603 650-6130
Email: Charles.R.Wira@Dartmouth.EDU


Professional Interests:

Dr. Wira's research focuses on how female sex hormones influence immunity in the female reproductive tract using animal models and human tissues. Dr. Wira has been funded by NIH for the past 35 yrs, has published approximately 160 research papers, and serves as editor on several scientific journals. He has received numerous awards including a National Institutes of Health Merit Award, which is awarded to approximately 0.1% of scientists by NIH. He is also the recipient of the Distinguished Investigator Award in Reproductive Immunology by the American Society of reproductive Immunology (ASRI). As Principal Investigator of an NIH funded Program Project grants for the past 14 years, he heads a major collaborative effort at Dartmouth Medical School to characterize immune functions in the Fallopian tube, uterus, cervix and vagina and to define the roles of sex hormones in mucosal immune regulation.

Dr. Wira is actively involved in a Dartmouth Medical School Fogarty Grant that is working with colleagues at Dartmouth and the University of Muhimbili in Tanzania to bring scientists to Dartmouth for training in HIV-related Mucosal Immunology. He also sits on the board of directors of an NGO at the University of Nairobi, Kenya that focuses on improving women's health against a spectrum of diseases including AIDS. He is the past Secretary to American Society of Reproductive Immunology, has served as Councilor for ASRI from 1998-2006. Dr. Wira is presently the Secretary General of ISIR and the President Elect of ASRI (2008-2009). Most recently, he has received a 5-year NIH grant to understand the role that human FRT immune cells play in protection against the heterosexual transmission of HIV-1. The goal in this study is to test the hypothesis that immune cells, specifically the epithelial cells which line mucosa of the female reproductive tract, from White-American, African-American, and Tanzanian women exhibit intracellular and secreted antiviral activity that protects against heterosexual transmission of HIV-1. These studies will be carried out in the USA and with colleagues in Muhimbili College of Health Sciences (MUCHS) in Dar es Salaam, Tanzania. While there have been recent advances in our understanding of how innate immunity protects women, very few studies have been performed to define the mechanisms of FRT immunity that exist in African women and the extent to which innate immune function is compromised in HIV-1-infected women.

His research is at the interface of the endocrine and immune systems should increase the presently limited knowledge of immune protection in women and should provide basic information essential for prevention and control of cancers in the reproductive tract, of local infection in the genital mucosa, for management of sexually transmitted diseases including the heterosexual transmission of HIV-1 and for autoimmune diseases. Further, these studies relate to endogenous protective immunity and to the development and evaluation of candidate vaccines and microbicides and the role of mucosal immunity in natural and vaccine induced protection against HIV and tuberculosis.

Grant Information:

Ongoing Research Support

1 P01 AI/NS 51877 Wira (PI) 09/30/02 - 07/31/08
NIH/NIAID (currently in 1-year no-cost extension)
Sex Hormone Regulation of Innate Immunity in Women and Men - PROGRAM PROJECT
The overall objective of this Program Project is to define the role of sex hormones (androgens, estrogens and progestins) in regulating the innate immune system, as it functions systemically and at mucosal surfaces.
Role: PI

R01 AI 13541 Wira (PI) 04/01/07 - 03/31/12
NIH/NIAID
Sex Hormone Regulation of the Mucosal Immune System
The overall objective of this research proposal is to define the role of sex hormones, cytokines and chemokines in the regulation of the innate and adaptive immune systems in the female reproductive tract.
Role: PI

R01 AI071761 08/01/07 - 07/31/12
NIH/NIAID
Innate immune protection against HIV-1 by reproductive tract epithelial cells
The overall objective of this research is to understand the role that human female reproductive tract (FRT) epithelial cells play in innate immune protection against HIV-1. As sentinels of innate immune defense, epithelial cells throughout the reproductive tract are the first line of protection against sexually transmitted infections and are crucial for orchestrating a rapid response to potential viral pathogens. Our goal in this proposal is to test the hypothesis that epithelial cells from White-American, African-American, and Tanzanian women exhibit intracellular and secreted antiviral activity that protects the reproductive tract against HIV-1.
Role: PI

Courses Taught:

Lecturer: Immunotherapy (Graduate studies)
Lecturer: Advanced Endocrinology (Graduate studies)
Lecturer: Medical Physiology
Lecturer: Medical Immunology
Course Director: Advanced Immunology: Mucosal Immunology (Graduate studies)

Biography:

Dr. Wira received his B.S. in 1962 in Animal Husbandry from Delaware Valley College, Doylestown, PA and his M.S. in Physiology from Michigan State University in 1966. Dr. Wira came to Dartmouth in 1966 where he received his Ph.D. in 1970. From 1970 to 1972 he did his postdoctoral training at the University of Paris, France, studying molecular mechanism of estrogen action in the uterus. He returned to Dartmouth as an Assistant Professor in the Department of Physiology and was promoted to Professor in 1985.


Selected Publications:

 

Estradiol-regulated innate antiviral responses of human endometrial stromal fibroblasts.
Patel MV, Shen Z, Rossoll RM, Wira CR
Am J Reprod Immunol. 2018 Nov;80(5):e13042. doi: 10.1111/aji.13042. Epub 2018 Sep 17.
PMID: 30295964

Neutrophil extracellular traps prevent HIV infection in the female genital tract.
Barr FD, Ochsenbauer C, Wira CR, Rodriguez-Garcia M
Mucosal Immunol. 2018 Sep;11(5):1420-1428. doi: 10.1038/s41385-018-0045-0. Epub 2018 Jun 6.
PMID: 29875403

Poly (I:C) and LPS induce distinct immune responses by ovarian stromal fibroblasts.
Patel MV, Shen Z, Wira CR
J Reprod Immunol. 2018 Jun;127:36-42. doi: 10.1016/j.jri.2018.05.001. Epub 2018 May 9.
PMID: 29758486

Isolation of Dendritic Cells from the Human Female Reproductive Tract for Phenotypical and Functional Studies.
Rodriguez-Garcia M, Fortier JM, Barr FD, Wira CR
J Vis Exp. 2018 Mar 13;(133) doi: 10.3791/57100. Epub 2018 Mar 13.
PMID: 29608161

IL-27 Expression and Responsiveness in Human Uterine Epithelial Cells and Fibroblasts In Vitro and the Role of Estradiol.
Patel MV, Shen Z, Rossoll RM, Wira CR
J Interferon Cytokine Res. 2018 Mar;38(3):101-110. doi: 10.1089/jir.2017.0038.
PMID: 29565744

Aging impacts CD103<sup>+</sup> CD8<sup>+</sup> T cell presence and induction by dendritic cells in the genital tract.
Rodriguez-Garcia M, Fortier JM, Barr FD, Wira CR
Aging Cell. 2018 Jun;17(3):e12733. doi: 10.1111/acel.12733. Epub 2018 Feb 18.
PMID: 29455474

Hormonal Contraceptives Differentially Suppress TFV and TAF Inhibition of HIV Infection and TFV-DP in Blood and Genital Tract CD4+ T cells.
Shen Z, Rodriguez-Garcia M, Patel MV, Bodwell J, Kashuba ADM, Wira CR
Sci Rep. 2017 Dec 18;7(1):17697. doi: 10.1038/s41598-017-18078-3. Epub 2017 Dec 18.
PMID: 29255206

Chlamydia trachomatis regulates innate immune barrier integrity and mediates cytokine and antimicrobial responses in human uterine ECC-1 epithelial cells.
Mukura LR, Hickey DK, Rodriguez-Garcia M, Fahey JV, Wira CR
Am J Reprod Immunol. 2017 Dec;78(6) doi: 10.1111/aji.12764. Epub 2017 Sep 16.
PMID: 28921726

Characterization of immune cells and infection by HIV in human ovarian tissues.
Shen Z, Rodriguez-Garcia M, Ochsenbauer C, Wira CR
Am J Reprod Immunol. 2017 Jul;78(1) doi: 10.1111/aji.12687. Epub 2017 Apr 11.
PMID: 28397318

Tenofovir Inhibits Wound Healing of Epithelial Cells and Fibroblasts from the Upper and Lower Human Female Reproductive Tract.
Rodriguez-Garcia M, Patel MV, Shen Z, Bodwell J, Rossoll RM, Wira CR
Sci Rep. 2017 Apr 3;8:45725. doi: 10.1038/srep45725. Epub 2017 Apr 3.
PMID: 28368028