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Charles R. Wira, Ph.D.

Title(s):
Professor of Physiology

Department(s):
Physiology

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:

 

Wira CR, Fahey JV, Rodriguez-Garcia M, Shen Z, Patel MV
Regulation of Mucosal Immunity in the Female Reproductive Tract: The Role of Sex Hormones in Immune Protection Against Sexually Transmitted Pathogens.
Am J Reprod Immunol 2014 Apr 16;
PMID: 24734774

Wira CR, Rodriguez-Garcia M, Shen Z, Patel M, Fahey JV
The Role of Sex Hormones and the Tissue Environment in Immune Protection Against HIV in the Female Reproductive Tract.
Am J Reprod Immunol 2014 Mar 24;
PMID: 24661500

Biswas N, Rodriguez-Garcia M, Crist SG, Shen Z, Bodwell JE, Fahey JV, Wira CR
Effect of tenofovir on nucleotidases and cytokines in HIV-1 target cells.
PLoS One 2013; 8(10):e78814
PMID: 24205323

Boesch AW, Zhao Y, Landman AS, Garcia MR, Fahey JV, Wira CR, Ackerman ME
A multiplexed assay to detect antimicrobial peptides in biological fluids and cell secretions.
J Immunol Methods 2013 Nov 29; 397(1-2):71-6
PMID: 24035708

Shen Z, Fahey JV, Bodwell JE, Rodriguez-Garcia M, Rossoll RM, Crist SG, Patel MV, Wira CR
Estradiol regulation of nucleotidases in female reproductive tract epithelial cells and fibroblasts.
PLoS One 2013; 8(7):e69854
PMID: 23936114

Rodriguez-Garcia M, Biswas N, Patel MV, Barr FD, Crist SG, Ochsenbauer C, Fahey JV, Wira CR
Estradiol reduces susceptibility of CD4+ T cells and macrophages to HIV-infection.
PLoS One 2013; 8(4):e62069
PMID: 23614015

Rodriguez-Garcia M, Patel MV, Wira CR
Innate and adaptive anti-HIV immune responses in the female reproductive tract.
J Reprod Immunol 2013 Mar; 97(1):74-84
PMID: 23432874

Patel MV, Fahey JV, Rossoll RM, Wira CR
Innate immunity in the vagina (part I): estradiol inhibits HBD2 and elafin secretion by human vaginal epithelial cells.
Am J Reprod Immunol 2013 May; 69(5):463-74
PMID: 23398087

Hickey DK, Fahey JV, Wira CR
Estrogen receptor α antagonists mediate changes in CCL20 and CXCL1 secretions in the murine female reproductive tract.
Am J Reprod Immunol 2013 Feb; 69(2):159-67
PMID: 23025258

Jensen AL, Collins J, Shipman EP, Wira CR, Guyre PM, Pioli PA
A subset of human uterine endometrial macrophages is alternatively activated.
Am J Reprod Immunol 2012 Nov; 68(5):374-86
PMID: 22882270