{"id":11,"date":"2020-08-31T18:53:55","date_gmt":"2020-08-31T18:53:55","guid":{"rendered":"https:\/\/geiselmed.dartmouth.edu\/rosato\/?page_id=11"},"modified":"2025-07-21T14:49:18","modified_gmt":"2025-07-21T14:49:18","slug":"research","status":"publish","type":"page","link":"https:\/\/geiselmed.dartmouth.edu\/rosato\/about-us\/research\/","title":{"rendered":"Research"},"content":{"rendered":"

Tissue resident memory T cells (TRM<\/sub>) combine the exquisite specificity of adaptive immunity, with rapid frontline antiviral functions conventionally executed by innate immune cells.<\/p>\n

Our lab is interested in understanding the function and regulation of TRM<\/sub> in distinct tissue environments to be able to contextualize their role in cancer, infection and neurodegeneration.
\n<\/p>\n

Our current focuses<\/h2>\n

TRM<\/sub> in the brain<\/b><\/p>\n

\"\"<\/a>
Memory T cells (Red: Thy1.1+ P14) are found in the brain of mice at memory timepoints post intranasal LCMV infection. Scale bars 100um.<\/figcaption><\/figure>\n

T cell functions in the central nervous system (CNS) are critical for protection against neurotropic pathogens, are implicated in a range of neurologic disorders, and even participate in normal CNS homeostasis. Despite this, there remain significant gaps in knowledge about how T cells, specifically TRM<\/sub>, are regulated and function in the imunologically unique brain environment. We are particularly interested in the role of inhibitory receptors such as PD-1 (which are elevated on brain TRM<\/sub>) in regulating responses. Using mouse models, we take a reductionist approach to study brain TRM<\/sub> to then be able to then understand the role these cells play in protective and pathologic settings such as vaccination and cancer, and more recently in Alzheimer's disease.<\/p>\n

\n

TRM<\/sub> as a tumor immunotherapy<\/b><\/p>\n

\"\"<\/a>
In situ<\/i> tetramer stain of human Glioblastoma (GBM) tumor with influenza and EBV HLA-A*02 tetramers<\/figcaption><\/figure>\n

We found that tumors are populated by functional memory T cells specific for common viral infections (such as influenza, CMV and EBV). Remarkably, TRM<\/sub> with specificity for a single viral antigen can make up as much as 10% of the total CD8+ T cell population within a patient\u2019s tumor. We can trick these cells into thinking a reinfection has occurred by delivering viral-derived peptides. This leads to TRM<\/sub> reactivation within the tumor and in mouse models of melanoma, immune activation and tumor regression.<\/p>\n

Glioblastoma multiforme (GBM) is invariably fatal, notoriously immunosuppressive and novel therapies aimed at reversing the suppressive tumor environment are needed. Given this, we are interested in repurposing virus-specific TRM<\/sub> as a brain tumor immunotherapy.<\/p>\n

 <\/p>\n

 <\/p>\n","protected":false},"excerpt":{"rendered":"

Tissue resident memory T cells (TRM<\/sub>) combine the exquisite specificity of adaptive immunity, with rapid frontline antiviral functions conventionally executed by innate immune cells.<\/p>\n

Our lab is interested in understanding the function and regulation of TRM<\/sub> in distinct tissue environments to be able to contextualize their role in cancer, infection and autoimmunity.<\/p>\n

Our current focuses:<\/b><\/p>\n

• TRM<\/sub> in the brain
\n• TRM<\/sub> as a brain tumor immunotherapy
\n• TRM<\/sub> and oncolytic viral therapy<\/p>\n

 <\/p>\n

Learn more<\/a><\/p>\n","protected":false},"author":2,"featured_media":0,"parent":22,"menu_order":1,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-11","page","type-page","status-publish","hentry","author-2"],"_links":{"self":[{"href":"https:\/\/geiselmed.dartmouth.edu\/rosato\/wp-json\/wp\/v2\/pages\/11","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/geiselmed.dartmouth.edu\/rosato\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/geiselmed.dartmouth.edu\/rosato\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/geiselmed.dartmouth.edu\/rosato\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/geiselmed.dartmouth.edu\/rosato\/wp-json\/wp\/v2\/comments?post=11"}],"version-history":[{"count":20,"href":"https:\/\/geiselmed.dartmouth.edu\/rosato\/wp-json\/wp\/v2\/pages\/11\/revisions"}],"predecessor-version":[{"id":372,"href":"https:\/\/geiselmed.dartmouth.edu\/rosato\/wp-json\/wp\/v2\/pages\/11\/revisions\/372"}],"up":[{"embeddable":true,"href":"https:\/\/geiselmed.dartmouth.edu\/rosato\/wp-json\/wp\/v2\/pages\/22"}],"wp:attachment":[{"href":"https:\/\/geiselmed.dartmouth.edu\/rosato\/wp-json\/wp\/v2\/media?parent=11"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}