Michael S Kuhns, PhD
Biography
Michael Kuhns did his PhD training with James Allison at UC Berkeley studying the role that CTLA-4 plays in regulating CD4 T cell responses. He then went on to Stanford University for his postdoctoral studies with Mark Davis, studying the architecture and function of the TCR-CD3 complex, and joined the Department of Immunobiology at the University of Arizona in 2010. When in search of a mental diversion, he enjoys mountain biking and hiking in the local desert and sky islands.
Cancer Focus
His research program is focused on (i) increasing our basic understanding of how T cell fate decisions are made (e.g. development, activation, differentiation, effector functions), and (ii) increasing their working knowledge of how to manipulate these decisions to direct T cells towards a desired outcome, such as increasing responses to vaccines or tumors, preventing transplant rejection, or attenuating autoimmunity.
To this end they are pursuing three lines of investigation.
- The first involves identifying and characterizing the molecular mechanisms that transfer information from the outside to the inside of a T cell.
- The second involves characterizing how these unique mechanisms each influence T cell fate decisions in vivo while developing reagents to manipulate these mechanisms to assess their suitability as targets for translational immune-modulating reagents in humans.
- The third involves determining if and how aging impacts T cell receptor proximal signaling events during T cell APC interactions in order to better understand how aging diminishes immune capacity and, conversely, increases susceptibility to infections.
In pursuit of these efforts, they have gained a broad working knowledge of the molecular and cellular components of the vertebrate immune system and experimental expertise in in vitro and in vivo experiments. Importantly, they have established a variety of reductionist systems that allow them to interrogate the molecular mechanisms by which key molecular machines relay information from the outside to the inside of a T cell function to instruct T cell fate decisions.
Selected Publications
Kobayashi, S., M. A. Thelin, H. L. Parrish, N. R. Deshpande, M. S. Lee, A. Karimzadeh, M. A. Niewczas, T. Serwold, and M. S. Kuhns, "A biomimetic five-module chimeric antigen receptor (CAR) designed to target and eliminate antigen-specific T cells.", Proc Natl Acad Sci U S A, vol. 117, issue 46, pp. 28950-28959, 2020 Nov 17. PMCID: PMC7682351 PMID: 33139567
Krummel, M., C. Blish, M. Kuhns, K. Cadwell, A. Oberst, A. Goldrath, M. K Ansel, H. Chi, R. O'Connell, J. E Wherry, et al., "Universal Principled Review: A Community-Driven Method to Improve Peer Review.", Cell, vol. 179, issue 7, pp. 1441-1445, 2019 Dec 12. PMID: 31835023
Glassman, C. R., H. L. Parrish, M. S. Lee, and M. S. Kuhns, "Reciprocal TCR-CD3 and CD4 Engagement of a Nucleating pMHCII Stabilizes a Functional Receptor Macrocomplex.", Cell Rep, vol. 22, issue 5, pp. 1263-1275, 2018 01 30. PMCID: PMC5813697 PMID: 29386113
Deshpande, N. R., J. L. Uhrlaub, S. Sing Way, J. Nikolich-Žugich, and M. S. Kuhns, "A disconnect between precursor frequency, expansion potential, and site-specific CD4+ T cell responses in aged mice.", PLoS One, vol. 13, issue 6, pp. e0198354, 2018. PMCID: PMC5986155 PMID: 29864157
Lichauco, K., M. S. Lee, and M. S. Kuhns, "Bonds Voyage! A Dissociative Model of TCR-CD3 Triggering Is Proposed.", Immunity, vol. 49, issue 5, pp. 786-788, 2018 11 20. PMID: 30462991