Key words: viral immunology, memory T cell differentiation, genetics of immune responses
My lab studies the underlying mechanisms that stimulate immune responses to virus infections. We characterize the molecular and host-genetic pathways that lead to antiviral T cell responses, as well as pathogenic outcomes to infection. We work with lymphocytic choriomeningitis virus (LCMV) and HAV infections in mouse models. We have several ongoing projects.
Histone demethylases and T cell responses to infection
Histone methylation regulates gene expression and affects antiviral T cell differentiation and function. We are examining the role of UTX, a histone demethylase, in immune defense against disseminated virus infection. We are currently characterizing specific genes and pathways that are regulated by UTX in T cells and extending our observations in mice to humans with chronic virus infection.
Host genetics and viral pathogenesis
Arenaviruses can cause hemorrhagic disease in humans though the outcome to infection varies by person. We identified a line of mice that undergoes severe immunopathological response to systemic LCMV infection that is associated with weight loss, elevated cytokines, thrombocytopenia, and lung edema, features resembling human arenavirus infection. We are using forward genetics to map the mutations responsible for this severe outcome and then investigate the underlying mechanistic basis of pathogenesis.
Obesity, T cell responses, and pathogenesis
Obesity is associated with worsened outcomes to virus infection in people. We identified a novel population of virus-specific T cells that is present in adipose tissue of infected mice. Obesity greatly increases the abundance of these cells, but results in an unusual form of pathogenesis upon re-infection, characterized by fat necrosis and pancreatitis. We are investigating how T cells are recruited to adipose, how obesity increases memory T cell numbers, and how T cells contribute to pathogenesis during infection.
Innate and adaptive immune defenses of a human hepatropic virus infection
n close collaboration with Stan Lemon’s lab (UNC), we have developed the first small vertebrate model of human hepatitis A virus infection. The infected mice replicate virus to high titers and develop lesions in the liver. We have identified several innate virus-sensing pathways that are critical for immune defense against this infection. With this new model in hand, we can now (1) dissect how HAV disarms immune defenses and (2) evaluate the cellular and molecular mechanisms associated with HAV-associated pathogenesis, which may be applicable to other picornavirus infections.
- Bias 101
- Faculty Mentoring Workshop for Biomedical Researchers
- Misumi, I., K.D. Cook, J.E. Mitchell, S.C. Vick, R.H. Lee, T. Uchimura, W. Bergmeier, P. Mieczkowski, F.P-M. de Villena, J.P.Y. Ting, and J.K. Whitmire . 2019. “Identification of a locus in mouse that regulates the collateral damage and lethality of virus infection”. Cell Reports. 27(5).
- Misumi, I. J. Starmer, M.A. Beck, T. Magnuson, and J.K. Whitmire . 2019. “Obesity expands a distinct population of adipose-resident T cells and increases vulnerability to infection”. Cell Reports 27: 514-524.
- Hirai-Yuki, Asuka, L. Hensley, A. Das, H. Feng, L. Sun, J.E. Wilson, F. Hu, Z. Feng, W. Lovell, I. Misumi, J. P-Y Ting, S. Montgomery, J. Cullen, J.K. Whitmire, and S.M. Lemon. 2016. “MAVS-dependent host species range and pathogenicity of a human hepatitis virus”. Science 353: 1541-1545.
- Cook, K.D., K.B. Shpargel, J. Starmer, F. Whitfield-Larry, B. Conley, D.E. Allard, J.E. Rager, R.C. Fry, M.L. Davenport, T. Magnuson, J.K. Whitmire , M.A. Su §. 2015. “Tfh-dependent clearance of a persistent virus infection requires T cell expression of the histone demethylase UTX”. Immunity 43: 703-714.
We seek a motivated postdoc to lead projects exploring the in vivo mechanisms of T cell differentiation following acute or chronic virus infections. Researchers have access to biocontainment facilities, flow cytometers, genomics core facilities, and other essential equipment for these studies. This position provides an opportunity to participate in collaborations with other laboratories and to train in viral immunology, genetics, epigenetics, and viral pathogenesis. This position requires a Ph.D. in a related field (immunology, virology, microbiology) with a strong background in immunology and experience in mouse models of infectious disease. Salary is dependent upon educational background and experience. Interested applicants should submit a curriculum vita, a brief statement of research interests and names & contact information for three references to Dr. Jason Whitmire at email@example.com.
Jason Whitmire in UNC Genetics News
March 20, 2021
Department of Genetics Publications for March 7-20, 2021
Department of Genetics faculty, postdocs, students and collaborators published ten papers during March 7-20, 2021.
November 2, 2020
Department of Genetics Publications for October 11-31, 2020
Department of Genetics faculty, postdocs, students and collaborators published 18 papers during October 11-31, 2020. Survival, Pathologic Response, and Genomics in CALGB 40601 (Alliance), a Neoadjuvant Phase III Trial of Paclitaxel-Trastuzumab With or Without Lapatinib in HER2-Positive Breast Cancer. Fernandez-Martinez A, Krop IE, Hillman DW, Polley MY, Parker JS, Huebner L, Hoadley KA, …
July 13, 2020
Department of Genetics Publications for June 28 – July 11, 2020
Department of Genetics faculty, postdocs, students and collaborators published five papers during June 28 – July 11, 2020.
June 1, 2020
Department of Genetics Publications for May 17-30, 2020
Department of Genetics faculty, postdocs, students and collaborators published eleven papers during May 17-30, 2020.
December 14, 2016
Genetics Faculty Publications for Nov 25 – Dec 9
Over the last few weeks, Department of Genetics faculty members, along with their colleagues, have published eight manuscripts on a wide variety of topics. Long-term exercise in mice has sex-dependent benefits on body composition and metabolism during aging. McMullan RC, Kelly SA, Hua K, Buckley BK, Faber JE, Pardo-Manuel de Villena F, Pomp D Physiol …
November 7, 2016
Genetics Faculty Publications for Oct 15 – Nov 4, 2016
During the last three weeks, Department of Genetics faculty members, along with their colleagues, have published 21 manuscripts on a wide variety of topics. A survey of current practices for genomic sequencing test interpretation and reporting processes in US laboratories. O’Daniel JM, McLaughlin HM, Amendola LM, Bale SJ, Berg JS, Bick D, Bowling KM, Chao …