Sara Hamilton Hart
Dr. Hamilton is a research immunologist and is focusing her research on CD8+ T cells with the goal of learning how to manipulate them to elicit the optimal protective immune response to pathogen infection. She is currently working in two different model systems: mice that have been naturally exposed to environmental microbes to gain a better understanding of T-cell function in these mice, and mice exposed to malaria to gain a better understanding of T-cell activity during severe cerebral complications of the disease.
For many years immunologists have experimented with genetically inbred mice housed in clean quarantined facilities. These facilities protect experimental mice from exposure to environmental pathogens, including viruses that humans are exposed to in daily life. Hamilton and co-investigators have conducted research in which they house pathogen-free inbred mice with mice from pet stores that carry environmental microbes, and then track CD8+ T cell behavior both in the pet store mice and in the inbred mice housed with them. In the pilot study, they characterized CD8+ T cell populations and distribution in various organs of environmentally exposed mice and found measurable differences compared to CD8+ T cells from environmentally protected inbred mice. The next step is to immunize the mice with different agents and compare CD8+ T cell responses. Preliminary data shows that environmentally exposed mice acquire increased levels of immune protection from some infectious microbes that inbred mice housed in clean facilities do not possess.In her malaria studies, Hamilton uses a mouse model that mimics the human experience in development of cerebral malaria, a condition caused by specific malarial strains to which certain individuals are vulnerable, particularly children. During this infection CD8+ T cell populations traffic to the brains of experimental mice. These cells recognize antigen presented by brain endothelial cells and mount an attack, which can cause brain hemorrhages. The goal of the study is to find ways to inhibit or control CD8+ T cell activity in the brain through immune system modulation to prevent cerebral hemorrhaging. Hamilton and her colleagues have found that stimulation by specific cytokine therapy can dampen the CD8+ T cell response to triggering antigens in the brain.Hamilton is also following up on earlier research that involved compartmentalizing CD8+ T cell memory cells into subset populations. She and her colleagues found a small subset that does not readily expand after antigen exposure, yet provides the most effective immune response to acute infection. She will delve deeper into how this specific subset of CD8+ memory T cells is created, how these cells can be more easily identified through specific cell-surface markers, how they function, and how they can be stimulated to expand, possibly through a vaccine strategy.
Fiege JK, Block KE, Pierson MJ, Nanda H, Shepherd FK, Mickelson CK, Stolley JM, Matchett WE, Wijeyesinghe S, Meyerholz DK, Vezys V, Shen SS, Hamilton SE, Masopust D, Langlois RA. Mice with diverse microbial exposure histories as a model for preclinical vaccine testing. Cell Host Microbe. 2021 Oct 27:S1931-3128(21)00463-7. doi: 10.1016/j.chom.2021.10.001.
Senolytics reduce coronavirus-related mortality in old mice. Christina D. Camell, Matthew J. Yousefzadeh, Yi Zhu, Larissa G. P. Langhi Prata, Matthew A. Huggins, Mark Pierson, Lei Zhang, Ryan D. O’Kelly, Tamar Pirtskhalava, Pengcheng Xun, Keisuke Ejima, Ailing Xue, Utkarsh Tripathi, Jair Machado Espindola-Netto, Nino Giorgadze, Elizabeth J. Atkinson, Christina L. Inman, Kurt O. Johnson, Stephanie H. Cholensky , Timothy W. Carlson, Nathan K. LeBrasseur, Sundeep Khosla, M. Gerard O’Sullivan, David B. Allison, Stephen C. Jameson, Alexander Meves, Ming Li, Y. S. Prakash, Sergio E. Chiarella, Sara E. Hamilton, Tamara Tchkonia, Laura J. Niedernhofer, James L. Kirkland, and Paul D. Robbins. Science, 08 Jun 2021.doi: 10.1126/science.abe4832
Generating mice with diverse microbial experience. Pierson M, Merley A, Hamilton SE. Curr Protoc. 2021 Feb;1(2):e53. doi: 10.1002/cpz1.53.
T cell economics: precursor cells predict inflation. Huggins MA, Hamilton SE. Nat Immunol. 2020 Dec;21(12):1482-1483. doi: 10.1038/s41590-020-00819-8.
KLRG1+memory CD8 T cells combine properties of short-lived effectors and long-lived memory. Renkema KR, Huggins MA, Borges da Silva H, Knutson TP, Henzler CM, Hamilton SE. J Immunol. 2020 Aug 15;205(4):1059-1069. doi: 10.4049/jimmunol.1901512. Epub 2020 Jul 1
New insights into the immune system using dirty mice. Hamilton SE, Badovinac VP, Beura LK, Pierson M, Jameson SC, Masopust D, Griffith TS. J Immunol. 2020 Jul 1;205(1):3-11. doi: 10.4049/jimmunol.2000171.
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