{"id":164610,"date":"2025-11-05T17:45:12","date_gmt":"2025-11-05T17:45:12","guid":{"rendered":"https:\/\/www.europesays.com\/ie\/164610\/"},"modified":"2025-11-05T17:45:12","modified_gmt":"2025-11-05T17:45:12","slug":"viral-immunologist-taps-incredible-potential-of-immune-system","status":"publish","type":"post","link":"https:\/\/www.europesays.com\/ie\/164610\/","title":{"rendered":"Viral immunologist taps \u2018incredible potential\u2019 of immune system"},"content":{"rendered":"

Viral immunologist Paul Thomas, PhD<\/a>, is working to turn the \u201cincredible potential\u201d of the immune system into real-life diagnostic and therapeutic applications that will improve vaccination strategies and cancer treatments. Thomas, who recently joined Fred Hutch Cancer Center\u2019s Vaccine and Infectious Disease Division<\/a>, studies how our immune system responds to (and evolves with) the pathogen exposures that leave an imprint in our genes and shape how we will respond to the next infection.<\/p>\n

\u201cQuantitative human immunology is a unifying theme of my program,\u201d said Thomas, Bezos Family Distinguished Scholar in Viruses and Vaccines. Thomas comes to Fred Hutch from St. Jude\u2019s Children\u2019s Research Hospital and the University of Tennessee, where he was a member of St. Jude\u2019s Center of Excellence for Influenza Research and Response. \u201cThe approach we take is a mix of quantitative methods, computational methods and experimental approaches to try to really understand human immunology.\u201d<\/p>\n

Using these methods and cohorts of adult and pediatric patients, Thomas seeks to define important immunological patterns and understand what they mean for our health and susceptibility to disease.<\/p>\n

\u201cPaul is an internationally renowned T-cell immunologist and leader in the influenza field,\u201d said VIDD Senior Vice President and Director Julie McElrath, MD, PhD<\/a>, who holds the Joel D. Meyers Endowed Chair. \u201cHe brings new cutting-edge technologies to Fred Hutch for both infectious disease and cancer research, as well as skilled lab team members who are arriving now and over the next few months.\u00a0We are so excited to have Paul join us in VIDD, and overall, he is a giant win for all of us!\u201d\u00a0<\/p>\n

In particular, Thomas studies critical immune cells called T cells and their T-cell receptors (or TCRs), specialized molecules T cells use to recognize immunological threats. T cells\u2019 duties range from big-picture orchestration of immune responses to boots-on-the ground elimination of infected cells. TCRs help them zero in on targets by detecting changes in the proteins our cells produce, which may signal infection or cancer. We are constantly churning out new T cells, and each new T cell carries a one-of-a-kind TCR.<\/p>\n

\u201cTCRs have this vast potential diversity,\u201d Thomas said. \u201cAnd you can see your risk or protection level encoded in your T-cell receptor repertoire.\u201d<\/p>\n

\u201cVast\u201d is an understatement.<\/p>\n

Scientists estimate that there are over a novemdecillion<\/a> (i.e., more than 1060) potential TCR gene sequences. Your T-cell repertoire (huge, but still a mere sliver of that novemdecillion) is your personal collection of T cells and their TCRs. When we fight off infections, the T cells involved transform into long-lived \u201cmemory\u201d T cells that serve as a living record of our immunological history. These memory T cells, plus newly generated \u201cna\u00efve\u201d T cells that have yet to meet a microbe, make up our T-cell repertoire.<\/p>\n

We need a diverse range of TCRs to combat microbial diversity. An individual\u2019s unique TCR repertoire influences how well their immune system can protect them against a particular infection and or tumor, as well as their responses to vaccines.<\/p>\n

\u201cThe potential of the T-cell repertoire, and the immune repertoire more broadly, is incredible in terms of both diagnostic and therapeutic applications,\u201d Thomas said.<\/p>\n

Diagnostic and therapeutic potential<\/p>\n

Thomas hopes to use the knowledge he gains to improve diagnostic and therapeutic tools. He and collaborators like Fred Hutch computational and structural biologist Phil Bradley, PhD<\/a>, who holds the Bob and Pat Herbold Computational Biology Endowed Chair, are working to understand the complex relationship between TCR gene sequences, TCR protein structures and their targets.<\/p>\n

\u201cIf we can learn how that code works between the T cell and its antigens [TCR targets], we can then also use it as this backward-looking lens of everything that\u2019s happened to you immunologically over the course of your life, and a forward-looking lens to your potential response to an infection,\u201d Thomas said.<\/p>\n

Accurately interpreting the TCR code could help us design better vaccines, improve T cell-based immunotherapies<\/a> and possibly lead to new diagnostic tools for infections or tumors.<\/p>\n

Cracking the TCR code<\/p>\n

Decoding what TCRs mean for our health is not simple.<\/p>\n

A TCR is made up of two molecules, each encoded by a different gene \u2014 on separate chromosomes. A full picture only comes into view when scientists can match the two correct genes; identifying one or the other gives only spotty insight. Even though technologies have improved the picture, there\u2019s still much to be done to define TCR signatures and decode their meaning.<\/p>\n

Thomas and his collaborators have developed several computational approaches, including single-cell<\/a> and bulk-cell methods, to tackle the problem. One of their recent innovations, called TIRTL-seq<\/a>, uses computational strategies, rather than single-cell technologies, to extract single-cell resolution of the TCR repertoire\u2019s gene pairings at high depth. TIRTL-seq provides scientists a low-cost way to glean highly specific information from millions of cells, Thomas said.<\/p>\n

His computational work is buttressed by real-life TCR, T-cell and immune data collected from real people. This information is essential to interpreting what a TCR repertoire means for a person\u2019s health. With his collaborators, Thomas has assembled multiple cohorts of patients (adult and pediatric) to track their immune responses to influenza infection and vaccination over time.<\/p>\n

As part of these efforts, he co-leads the\u00a0DIVINCI consortium<\/a>, a flu research collaboration across 12 institutions that draws on a cohort of children enrolled at birth and followed as infants. The cohort is providing insights into how the early immune system develops. Thomas is extending these studies to the immune response against cancer.<\/p>\n

\u201cThe idea is to use these approaches to both build up our understanding of the human immune repertoire in actual humans, and try to understand empirically what these receptors are and what they target,\u201d Thomas said. \u201cAnd then also to build up enough data to potentially solve this problem synthetically and computationally in collaboration with the structural biologists here.\u201d<\/p>\n

Synthetic TCRs would be scientist-designed TCRs that, ideally, improve on nature, and enable the development of more selective and effective cancer immunotherapies.<\/p>\n

Thomas is looking forward to taking advantage of the scientific milieu of Fred Hutch and Seattle, deepening long-standing collaborations and initiating new connections.<\/p>\n

\u201cFred Hutch is just incredibly well-situated for human immunology. They’ve been leaders in this for years,\u201d he said, pointing to Fred Hutch\u2019s leadership role in the HIV Vaccine Trials Network and the computational work from Fred Hutch biostatistician Peter Gilbert, PhD<\/a>, which has helped define immunological signatures that predict protection for vaccines to a variety of infections, including HIV and COVID-19.<\/p>\n

\u201cFred Hutch is this perfect mix of infectious disease, cancer, computation, and immunology that I think is very unique in the world,\u201d Thomas said.<\/p>\n","protected":false},"excerpt":{"rendered":"Viral immunologist Paul Thomas, PhD, is working to turn the \u201cincredible potential\u201d of the immune system into real-life…\n","protected":false},"author":2,"featured_media":164611,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[74],"tags":[94945,94946,13544,18,94943,19,94948,24622,17,94944,85056,94949,82,87424,94947],"class_list":{"0":"post-164610","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-technology","8":"tag-bezos-family","9":"tag-cancer-immunotherapy","10":"tag-computational-biology","11":"tag-eire","12":"tag-genetically-engineered-t-cells","13":"tag-ie","14":"tag-immunology-vaccine-development","15":"tag-influenza","16":"tag-ireland","17":"tag-paul-thomas","18":"tag-t-cell","19":"tag-tcr","20":"tag-technology","21":"tag-vaccine-and-infectious-disease","22":"tag-vaccine-development"},"share_on_mastodon":{"url":"https:\/\/pubeurope.com\/@ie\/115498341030921724","error":""},"_links":{"self":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/posts\/164610","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/comments?post=164610"}],"version-history":[{"count":0,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/posts\/164610\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/media\/164611"}],"wp:attachment":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/media?parent=164610"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/categories?post=164610"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/tags?post=164610"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}