Matthew A. Williams

Matthew A. Williams, PhD

Languages spoken: English

Academic Information

Departments Primary - Pathology

Academic Office Information

matthew.williams@path.utah.edu

Lab

Research Interests

  • Immunology
  • Immunologic Memory
  • T Cell Biology
  • Viral infections
  • Bacterial Infections
  • Vaccination
  • Immunotherapy
  • Cancer Vaccines

Matthew Williams, PhD, is an Associate Professor in the Department of Pathology, Division of Microbiology and Immunology at the University of Utah, and he is currently serving as the C. Scott and Dorothy E. Watkins Endowed Chair in Honor of Ernst J. Eichwald, MD (2018-2021). He is also a member of the Cell Response and Regulation program within the Huntsman Cancer Institute. The Williams laboratory studies T cell differentiation and function in response to infections and tumors. Dr. Williams recieved his PhD from Emory University in 2002. While there, he focused on the role of infectious history in disrupting the efficacy of costimulation blockade-induced transplant tolerance. He later moved on to post-doctoral work in the laboratory of Dr. Michael Bevan at the University of Washington, where he studied the role of Interleukin-2 in promoting the differentiation and function of long-lived T cell memory. Dr. Williams moved to the University of Utah in 2007.

Following viral or bacterial infection, numerous components of the immune response play a role in recognizing, engaging and eradicating the offending pathogen. T cells are particularly central to protection from a wide variety of infections. A key hallmark of protective T cell responses is the long-lived (in many cases life-long) persistence of memory T cells after the pathogen is cleared. Because memory T cells are present at elevated frequencies and recognize the pathogen quickly, they are able to provide rapid protection upon encountering the same pathogen a second time. While many successful vaccines of the past have relied on the development of antibody responses for their protective effect, future disease challenges will require the induction of cell-mediated protection provided by T cells. The research focus of the Williams laboratory is to understand the nature of T cell intrinsic signals, such as the T-cell receptor, and T cell extrinsic signals, such as inflammation, in promoting the ability of T cells to acquire the functions that allow them to eradicate pathogens and form long-lived immunological memory.

A major obstacle in harnessing the immune system to combat cancer is the ability of many tumors to inhibit T cell function. The Williams laboratory is engaged in basic and pre-clinical studies to understand the mechanisms that tumors use to suppress T-cell responses. The end goal is to improve upon existing immune-based therapies to induce long-lived, highly functional anti-tumor memory T cells that promote durable cancer remission.

Education History

Postdoctoral Fellowship University of Washington
 Postdoctoral Fellow
Emory University
 PhD
Undergraduate Brigham Young University
 BS

Selected Publications

Journal Article

  1. Burnett WJ, Burnett DM, Parkman G, Ramstead A, Contreras N, Gravley W, Holmen SL, Williams MA, VanBrocklin MW (2021). Prior Exposure to Coxsackievirus A21 Does Not Mitigate Oncolytic Therapeutic Efficacy. Cancers (Basel), 13(17). (Read full article)
  2. Snook JP, Soedel AJ, Ekiz HA, OConnell RM, Williams MA (2020). Inhibition of SHP-1 expands the repertoire of antitumor T cells available to respond to immune checkpoint blockade. Cancer Immunol Res, 8(4), 506-517.
  3. Ekiz HA, Huffaker TB, Grossmann AH, Stephens WZ, Williams MA, Round JL, OConnell RM (2019). MicroRNA-155 coordinates the immunological landscape within murine melanoma and correlates with immunity in human cancers. JCI Insight, 4(6). (Read full article)
  4. Snook JP, Kim C, Williams MA (2018). TCR signal strength controls the differentiation of CD4+ effector and memory T cells. Sci Immunol, 3(25). (Read full article)
  5. Ekiz HA, Lai SA, Gundlapalli H, Haroun F, Williams MA, Welm AL (2018). Inhibition of RON kinase potentiates anti-CTLA-4 immunotherapy to shrink breast tumors and prevent metastatic outgrowth. Oncoimmunology, 7(9), e1480286. (Read full article)
  6. Whiteside SK, Snook JP, Ma Y, Sonderegger FL, Fisher C, Petersen C, Zachary JF, Round JL, Williams MA, Weis JJ (2018). IL-10 Deficiency Reveals a Role for TLR2-Dependent Bystander Activation of T Cells in Lyme Arthritis. J Immunol, 200(4), 1457-1470. (Read full article)
  7. Meek SM, Williams MA (2018). IFN-Gamma-Dependent and Independent Mechanisms of CD4⁺ Memory T Cell-Mediated Protection from Listeria Infection. Pathogens, 7(1). (Read full article)
  8. Huffaker TB, Lee SH, Tang WW, Wallace JA, Alexander M, Runtsch MC, Larsen DK, Thompson J, Ramstead AG, Voth WP, Hu R, Round JL, Williams MA, OConnell RM (2017). Antitumor immunity is defective in T cell-specific microRNA-155-deficient mice and is rescued by immune checkpoint blockade. J Biol Chem, 292(45), 18530-18541. (Read full article)
  9. Ray A, Williams MA, Meek SM, Bowen RC, Grossmann KF, Andtbacka RH, Bowles TL, Hyngstrom JR, Leachman SA, Grossman D, Bowen GM, Holmen SL, VanBrocklin MW, Suneja G, Khong HT (2016). A phase I study of intratumoral ipilimumab and interleukin-2 in patients with advanced melanoma. Oncotarget, 7(39), 64390-64399. (Read full article)
  10. Shakya A, Goren A, Shalek A, German CN, Snook J, Kuchroo VK, Yosef N, Chan RC, Regev A, Williams MA, Tantin D (2015). Oct1 and OCA-B are selectively required for CD4 memory T cell function. J Exp Med, 212(12), 2115-31. (Read full article)
  11. Hu R, Kagele DA, Huffaker TB, Runtsch MC, Alexander M, Liu J, Bake E, Su W, Williams MA, Rao DS, Mller T, Garden GA, Round JL, OConnell RM (2014). miR-155 promotes T follicular helper cell accumulation during chronic, low-grade inflammation. Immunity, 41(4), 605-19. (Read full article)
  12. Kim C, Jay DC, Williams MA (2014). Dynamic functional modulation of CD4+ T cell recall responses is dependent on the inflammatory environment of the secondary stimulus. PLoS Pathog, 10(5), e1004137. (Read full article)
  13. Kim C, Wilson T, Fischer KF, Williams MA (2013). Sustained interactions between T cell receptors and antigens promote the differentiation of CD4⁺ memory T cells. Immunity, 39(3), 508-20. (Read full article)
  14. Eyob H, Ekiz HA, Derose YS, Waltz SE, Williams MA, Welm AL (2013). Inhibition of ron kinase blocks conversion of micrometastases to overt metastases by boosting antitumor immunity. Cancer Discov, 3(7), 751-60. (Read full article)
  15. Jay DC, Mitchell DM, Williams MA (2013). Bim mediates the elimination of functionally unfit Th1 responders from the memory pool. PLoS One, 8(6), e67363. (Read full article)
  16. Mitchell DM, Williams MA (2013). Disparate roles for STAT5 in primary and secondary CTL responses. J Immunol, 190(7), 3390-8. (Read full article)
  17. Khanolkar A, Williams MA, Harty JT (2013). Antigen experience shapes phenotype and function of memory Th1 cells. PLoS One, 8(6), e65234. (Read full article)
  18. Williams MA, Schmidt RL, Lenz LL (2012). Early events regulating immunity and pathogenesis during Listeria monocytogenes infection. Trends Immunol, 33(10), 488-95. (Read full article)
  19. Kim C, Jay DC, Williams MA (2012). Stability and function of secondary Th1 memory cells are dependent on the nature of the secondary stimulus. J Immunol, 189(5), 2348-55. (Read full article)
  20. Shakya A, Kang J, Chumley J, Williams MA, Tantin D (2011). Oct1 is a switchable, bipotential stabilizer of repressed and inducible transcriptional states. J Biol Chem, 286(1), 450-9. (Read full article)
  21. Mitchell DM, Ravkov EV, Williams MA (2010). Distinct roles for IL-2 and IL-15 in the differentiation and survival of CD8+ effector and memory T cells. J Immunol, 184(12), 6719-30. (Read full article)
  22. Ravkov EV, Williams MA (2009). The magnitude of CD4+ T cell recall responses is controlled by the duration of the secondary stimulus. J Immunol, 183(4), 2382-9. (Read full article)
  23. Williams MA, Ravkov EV, Bevan MJ (2008). Rapid culling of the CD4+ T cell repertoire in the transition from effector to memory. Immunity, 28(4), 533-45. (Read full article)
  24. Williams MA, Tyznik AJ, Bevan MJ (2006). Interleukin-2 signals during priming are required for secondary expansion of CD8+ memory T cells. Nature, 441(7095), 890-3. (Read full article)