INDIVIDUAL RESEARCHERJonathan A. Harton , B.S. , Ph.D.
Phone: 518 262-4445
Education1995 - Ph.D. from University of Iowa
1987 - B.S. from Eastern College
The Harton lab is focused on molecular regulation of immune responses relevant to innate immunity, inflammation, and cancer. Two main projects are ongoing. The first project examines the transcriptional control of class II MHC genes as it relates to antigen presentation and tumor recognition. At the molecular level we are dissecting the ability of a transcriptional regulator, CIITA, to differentially regulate HLA-DR and its chaperones invariant chain and HLA-DM. CIITA's influence on MHC II transcription is highly regulated and involves CIITA's GTP-binding domain, leucine rich repeats, phosphorylation, ubiquitination, and interactions with a host of transcription factors. We hypothesize that differences in regulation of CIITA-responsive genes influences antigen presentation. This is important for clinical problems ranging from arthritis to multiple sclerosis and from transplant biology to cancer. While assessing the mechanisms of CIITA's transactivator function at the molecular level, at the level of disease, we are employing molecular tools towards understanding how class II MHC contributes to tumor elimination, equilibrium and escape in the mouse models of melanoma and breast cancer. The second project examines the role of intracellular pathogen receptor proteins of the NLR family involved in innate immunity and inflammation. These receptors are structurally related to CIITA and have the interesting property of regulating IL-1beta and IL-18 production as well as occasionally promoting cell death. This area of study has implications for infectious disease and inflammatory syndromes principally, but is likely relevant to cancer as well. We are currently interested in the molecular biology of host responses to the potential bioterrorism agents, Bacillus anthracis and Francisella tularensis, the causative agents of Anthrax and Tularemia. Our current focus is on the NLR proteins that mediate organism specific responses and how these are regulated at the molecular level. One of these proteins, POP2 prevents the interaction of essential players in the NLR-inflammatory pathway and inhibits other intracellular signals (NF-kB). This dual regulatory role is likely important in multiple inflammatory conditions. Since NF-kB is frequently constitutively active in tumors we are also exploring the mechanism and utility of inhibiting NF-kB in tumor cells.
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- Harton J.A., Linhoff M.W., Zhang J., Ting J.P. 2002 Cutting edge: CATERPILLER: a large family of mammalian genes containing CARD, pyrin, nucleotide-binding, and leucine-rich repeat domains. Journal of Immunology 169:4088.
- Bewry N.N., Bollick S., Wright K.L., Harton J.A. 2007 GTP-dependent recruitment of CIITA to the class II MHC promoter. Journal of Biological Chemistry 282:26178.
- Bedoya F., Sandler L.L., Harton J.A. 2007 Pyrin-only protein 2 modulates NF-kappaB and disrupts ASC:CLR interactions. Journal of Immunology 178:3837.
- Porter K.A., Kelley L.N., Nekorchuk M.D., Jones J.H., Hahn A.B., de Noronha C.M., Harton J.A., Duus K.M. 2010 CIITA enhances HIV-1 attachment to CD4+ T cells leading to enhanced infection and cell depletion. Journal of Immunology 185:6480.
- Atianand M.K., Fuchs T., Harton J.A. 2011 Recent evolution of the NF-?B and inflammasome regulating protein POP2 in primates. BMC Evolutionary Biology 11:56.
- Busman-Sahay K., Sargent E., Harton J.A., Drake J.R. 2011 The Ia.2 epitope defines a subset of lipid raft-resident MHC class II molecules crucial to effective antigen presentation. Journal of Immunology 186:6710.
- Atianand M.K., Duffy E.B., Shah A., Kar S., Malik M., Harton J.A. 2011 Francisella tularensis reveals a disparity between human and mouse NLRP3 inflammasome activation. Journal of Biological Chemistry 286:39033.
- Atianand M.K., Harton J.A. 2011 Uncoupling of Pyrin-only protein 2 (POP2)-mediated dual regulation of NF-kB and the inflammasome. Journal of Biological Chemistry 286:40536.