About

Moses Williams is a Sculpture and Intermedia professor who has spent the last year as an artist-in-residence at the Utah Museum of Contemporary Art (UMOCA). His work culminated in the exhibition 'Parable Bodies,' which explores the relationship between living and non-living entities, questioning anthropocentric ideals by positioning human and non-human bodies in a reciprocal exchange that emphasizes interconnectedness. The exhibition features sculptural works that evoke a sense of ritualistic intent, with tactile, lustrous, visceral materials that suggest movement, metamorphosis, and the constancy of change. Williams's sculptures are designed to be experienced in relation to the viewer, with surfaces that are porous and mutable, merging physical, conceptual, energetic, and spiritual dimensions. His work references landscapes, plants, and creatures, presenting a relational web where all entities are interconnected through 'slippage, entanglement, and influence.' Additionally, his video 'Last Walker' depicts a traveler navigating vast landscapes guided by ceremony and contemplation, with his sculptures functioning as markers or stations on this journey, emphasizing the enigmatic complexity of all entities.

Research topics

• Biology
• Chemistry
• Biochemistry
• Virology
• Cancer research
• Cell biology
• Molecular biology
• Immunology
• Genetics

Selected publications

• Abstract A071: Inhibition of Shp-1 in combination with checkpoint inhibitors broadens the repertoire of tumor-infiltrating self-antigen-specific T cells and drives therapeutic rescue of T cell function

  Cancer Immunology Research · 2026-02-18

  articleSenior author

  Abstract While stimulation of CD8 T cells by immune checkpoint inhibitors (ICI) is effective in tumors with neoantigens and a high mutational burden, responsiveness is decreased in tumors with a low mutational burden and predominantly low-affinity tumor-self antigens. Targeting the intracellular phosphatase Src homology region 2 domain-containing phosphatase-1, Shp-1 (PTPN6), in combination with ICI lowers the T cell activation threshold and enhances the ability of low-affinity T cells to mount a productive anti-tumor response. However, the mechanisms behind this combinatorial effect are unclear. In this study, we aimed to determine whether temporal inhibition of Shp-1 (Shp-1i) during active tumor growth transcriptionally reprograms CD8 T cells and expands the tumor-self-antigen-specific repertoire. To address this question, we implanted Yale University Mouse Melanoma (YUMM1.1) tumor cells into WT mice, as the resulting tumors are ICI-resistant and lack abundant neo-antigens. MHC Class I-restricted tumor self-antigen TRP-2180-188 tetramer was used to isolate and measure the tumor self-antigen response. RNA single-cell sequencing and paired V(D)J sequencing were performed TRP-2-specific T cells isolated from the tumors of untreated and ICI+Shp-1i-treated mice. Following treatment TRP2-specific CD8 TIL largely converted from an exhausted (Lag3, Havcr2) to an effector (Gzmb, T-bet) transcriptional program while preserving a stem-like (Tcf7, Slamf6) population of expanded exhausted progenitor cells. V(D)J sequencing revealed that ICI+Shp-1i significantly expanded TRP2-specific CD8 clonal diversity in the tumor microenvironment, indicating the enhanced recruitment of sub-dominant or new TRP-2-specific T cell clones. We conclude that Shp-1i combines with ICI to broaden the repertoire of self-antigen-specific T cells and drive therapeutic rescue of T cell function through the recruitment of new clones that express a robust effector transcriptional program. Citation Format: Joseph G. Matous, Kaitlyn A. Flint, Christopher P. Hanson, Matthew A. Williams. Inhibition of Shp-1 in combination with checkpoint inhibitors broadens the repertoire of tumor-infiltrating self-antigen-specific T cells and drives therapeutic rescue of T cell function [abstract]. In: Proceedings of the AACR Immuno-Oncology Conference (AACR IO): Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2026 Feb 18-21; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2026;14(2 Suppl):Abstract nr A071.

  PublisherDOI

• Shp-1 regulates the activity of low-affinity T cells specific to endogenous self-antigen during melanoma tumor growth and drives resistance to immune checkpoint inhibition

  Journal for ImmunoTherapy of Cancer · 2025-04-01 · 4 citations

  articleOpen accessSenior author

  Background The presence of activated CD8 T cells in the tumor microenvironment is correlated with an effective immune response to immune checkpoint inhibitor (ICI) therapy. However, ICI predominantly targets high-affinity T cells, which may be less abundant in tumors with few neoantigens. Targeting the intracellular phosphatase Src homology region 2 domain-containing phosphatase-1 (Shp-1) in combination with ICI lowers the T cell activation threshold and enhances the ability of low-affinity T cells to mount a productive antitumor response. Methods In this study, we sought to determine whether temporal inhibition of Shp-1 during active tumor growth could rescue the activity of low-affinity T cells specific for endogenous self-antigens. To address this question, we implanted Yale University Mouse Melanoma (YUMM) tumor cell lines into WT mice and, on tumor establishment, administered an inhibitor of Shp-1 (TPI-1) with or without ICI treatment. We analyzed treatment-dependent changes in the immune infiltrate in the tumor via flow cytometry, major histocompatibility complex (MHC) tetramer-mediated detection of tyrosinase-related protein 2 (TRP-2) 180–188 -specific T cells and a micropipette-based two-dimensional affinity assay to measure the T cell receptor (TCR) affinity. Results Administration of ICI and a Shp-1 inhibitor to mice with established YUMM tumors, but neither agent alone, resulted in a significant delay in tumor growth and an increased frequency of CD8 tumor-infiltrating T cells with enhanced effector and reduced exhaustion characteristics. In particular, combined treatment increased the frequency of CD8 T cells specific for the MHC Class I-restricted tumor self-antigen TRP-2 180–188 . We found that the increase in effector T cells was almost entirely due to an increase in T cells with very low TCR affinity. Conclusions We conclude that approaches for altering TCR signaling threshold are effective in enhancing the antitumor response of low-affinity T cells specific for endogenous self-antigens in settings of ICI resistance and/or where neoantigens are not available to drive antitumor responses.

  PublisherDOI

• A microRNA-regulated transcriptional state defines intratumoral CD8+ T cells that respond to immunotherapy

  Cell Reports · 2025-02-01 · 10 citations

  articleOpen access

  T cell-dependent cancer immunity and ICI responses that may be leveraged for future therapeutics.

  PublisherDOI

• Abstract B021: Optimizing combination immunotherapy regimens in kidney cancer using ex-vivo multicellular 3D immune-microtumors and multiplex immunoassays

  Cancer Immunology Research · 2025-02-23

  articleOpen access

  Abstract Renal cell carcinoma (RCC) presents a challenging treatment landscape in oncology due to its varied therapeutic approaches and the lack of reliable, predictive clinical decision-making tools. Our study focuses on developing a functional precision medicine test to predict responses to combination immunotherapy/receptor tyrosine kinase (TKI) regimens in RCC by optimizing a 3D immune-microtumor platform. Using RCC resections and matched bloods, we isolated tumor cells and peripheral blood mononuclear cells (PBMCs) as single cells. Cells were labeled with fluorescent dyes to enable tracking of tumor, CD8+ and CD8- PBMC single-cell behaviors. Immunofluorescence (IF), RNAseq and flow cytometry (FCm) were used to deconvolute cell subpopulations within the tumor, while cytokine production was analyzed pre and post-encapsulation into 3D immune-microtumor cocultures using a Luminex assay. Our functional 3D assay assessed live cell behaviors such as cell viability, immune cell infiltration and killing (N=20). In a 20 patient cohort, IF analysis confirmed that cell-type diversity, including tumor, endothelial, immune cells, and cancer-associated fibroblasts, was preserved within 3D immune-microtumors from day 0 to day 4 of culture. Dose-determination of immune checkpoint inhibitors (ICIs) was conducted on primary PBMCs. A targeted 8-plex Luminex panel allowed the evaluation of ICI exposure time across five drugs (pembrolizumab, ipilimumab, nivolumab, avelumab, atezolizumab) and PBMC activation conditions (none; CD3; CD3/CD28) based on maximal differential cytokine release versus day 0 control, when measuring granzyme B, IFN-γ, TNF-α, IL-12, and IL-17. Dose-response assays were then conducted in the full 3D immune-microtumor setup (N=10). The functional assay revealed changes in tumor cell viability and immune cell infiltration upon ICI treatment in a dose-dependent fashion, alongside molecular readouts from PBMC FCm for checkpoint marker expression (incl. PD-1/PD-L1), tumor IF (incl. PD-L1), and ELISA for IFN-γ and granzyme B. Post optimization, the 3D immune-microtumor model was used to evaluate clinical responses to combination therapies for RCC (ICI + TKI) in our trial (PEAR-TREE N=20 ISRCTN10001405). Pembrolizumab alone led to a 26% rise in PBMC infiltration, a 14% increase in CD8+ cell infiltration, and a 15% rise in tumor cell death relative to untreated controls (N=5). When combined with either lenvatinib or axitinib, pembrolizumab further reduced tumor cell viability by 10% and 19%, respectively. Patient responses displayed intra-patient variability. In conclusion, this 3D immune-microtumor model provides an ex-vivo system for understanding individual patient responses to ICIs, supporting personalized treatment strategies in RCC. By testing FDA-approved treatments in this model and through our metastatic RCC clinical trial (NCT06264479) we are advancing a functional precision medicine approach that may shape future individualized cancer care. Citation Format: Roseanna Hare, Eleonora Peerani, Keqian Nan, Polina Maximchik, Jessica Hudson, Jonathan Ient, Nourdine Bah, Jay Kearney, Francesco Iori, Matthew Williams, Maxine Tran, Duleek Ranatunga. Optimizing combination immunotherapy regimens in kidney cancer using ex-vivo multicellular 3D immune-microtumors and multiplex immunoassays [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr B021.

  PublisherDOI

• Bond lifetime predicts CD4 T cell effector and memory potential 3626

  The Journal of Immunology · 2025-11-01

  articleOpen access

  Abstract Description Recognition of antigen and TCR signal strength is a critical step required for T cell survival, expansion, development of effector function and transition towards memory. To better understand T cell kinetic parameters impacting effector and memory bias, we utilized a panel of cloned TCRs specific for the immunodominant CD4 GP61-80 epitope of lymphocytic choriomeningitis virus (LCMV) that we previously show to favor either effector or memory fates. We analyzed the 2D affinity of 4 effector (effector-biased) and 4 memory (memory-biased) clones. All were tetramer positive and of high affinity; However, at the clonal level, affinity did not correlate with the effector or memory outcomes. Recent data on T cell responses to antigen have demonstrated the importance of bond lifetime between TCRs and antigen as they occur under applied cellular forces. After single molecule analysis between TCR and gp66:MHC antigen for 3 effector and 3 memory biased clones, effector fated cells demonstrated significantly longer bond lifetimes than memory fated clones. These data correlate with surrogate markers of TCR signal strength such as ZAP70 phosphorylation and CD25 expression. Our data identify bond lifetime between TCR and antigen as the dominant determining factor of CD4 cell effector versus memory fate during infection. Funding Sources Supported by NIH 5R01AI172253-02 Topic Categories Lymphocyte Differentiation and Peripheral Maintenance (LYM)

  PublisherOA PDFDOI

• Abstract LB126: Shp-1 regulates the activity of low affinity T cells specific to endogenous self-antigen during melanoma tumor growth and drives resistance to immune checkpoint inhibition

  Cancer Research · 2025-04-25

  articleSenior author

  Abstract The presence of activated CD8 T cells in the tumor microenvironment (TME) is correlated with an effective immune response to immune checkpoint inhibitor (ICI) therapy. However, ICI predominately targets high affinity T cells, which are exhaustion-prone and may be less abundant in tumors with few neoantigens. Low affinity T cells are abundant during many anti-tumor responses, and there is a need to better understand their contribution to the ICI-induced response and to determine the mechanisms controlling their activation. Targeting the intracellular phosphatase Src homology region 2 domain-containing phosphatase-1, Shp-1 (PTPN6), in combination with ICI lowers the T cell activation threshold and enhances the ability of low affinity T cells to mount a productive anti-tumor response. In this study, we sought to determine whether temporal inhibition of Shp-1 during active tumor growth could rescue the activity of low affinity T cells specific for endogenous self-antigens. To address this question, we implanted Yale University Mouse Melanoma (YUMM) tumor cell lines into WT mice, as the resulting tumors are ICI-resistant and lack abundant neo-antigens. Administration of ICI and a Shp-1 inhibitor to mice with established YUMM tumors, but neither agent alone, resulted in a significant delay in tumor growth and an increased frequency of CD8 tumor-infiltrating T cells with enhanced effector (PD-1+ Gzb+ Tbet+) and reduced exhaustion characteristics (2b4+ PD-1+). In particular, combined treatment increased the frequency of CD8 T cells specific for the MHC Class I-restricted tumor self-antigen TRP-2180-188. We utilized a micropipette-based 2D affinity assay to measure the T cell receptor (TCR) affinity of TRP-2-specific T cells in the tumor following treatment. We found that the increase in effector T cells was almost entirely due to an increase in T cells with very low TCR affinity. We conclude that approaches for altering TCR signaling threshold are effective in enhancing the anti-tumor response of low affinity T cells specific for endogenous self-antigens in settings of ICI resistance and/or where neo-antigens are not available to drive anti-tumor responses. Citation Format: Joseph G. Matous, Andrew G. Ramstead, Krystal R. Charley, Elizabeth M. Kolawale, Jacob N. Kisiolek, Brian D. Evavold, Matthew A. Williams. Shp-1 regulates the activity of low affinity T cells specific to endogenous self-antigen during melanoma tumor growth and drives resistance to immune checkpoint inhibition [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB126.

  PublisherDOI

• Abstract 3926: ARF6-dependent endocytic trafficking of the interferon-gamma receptor drives adaptive immune resistance and response to immune checkpoint blockade

  Cancer Research · 2024-03-22

  article

  Abstract Interferon-gamma (IFNγ)-driven adaptive immune resistance (AIR) in cancer begins at the plasma membrane where cytokine signaling is initiated. Cytotoxic CD8+ T cells secrete IFNγ, eliciting tumor-intrinsic IFNγ signaling and expression of immunosuppressive genes, which are critical for effective therapeutic response to anti-PD-1 and anti-CTLA-4 immune checkpoint blockade (ICB). Although the IFNγ receptor (IFNγR) is expressed in all cell types, its surface density can determine a cell’s responsiveness to ligand. Mechanistic control over this process remains a mystery. Herein we report that the endocytic trafficking protein ADP-Ribosylation Factor 6 (ARF6) is critical for IFNγ-driven AIR during primary tumor progression and in the setting of ICB therapy. The IFNγR1 subunit of the receptor is constitutively internalized in a ligand-independent manner. ARF6 is necessary for endocytic recycling of IFNγR1 and determines the steady-state surface density of the receptor. Loss of ARF6 results in lysosomal degradation of the receptor and controls IFNγR1 protein levels in melanoma, non-small cell lung cancer, colorectal cancer, and triple-negative breast cancer. IFNγ activates ARF6 in parallel with JAK1-STAT1 signaling, suggesting a positive feedback loop that allows tumor cells to dynamically respond to immune attack. Silencing ARF6 reduces tumor intrinsic IFNγ signaling and downstream expression of immunosuppressive genes. In murine melanoma, loss of ARF6 causes resistance to systemic ICB therapy. Likewise, low expression of ARF6 in patient tumors correlates with inferior outcomes with ICB. Our data provide new mechanistic insights into tumor immune escape, defined by ARF6-dependent adaptive immunity, and support that ARF6-dependent endomembrane trafficking of the IFNγ receptor shapes clinical outcomes of ICB therapy. Private Information Citation Format: Yinshen Wee, Junhua Wang, Emily C. Wilson, Coulson P. Rich, Aaron Rogers, Zhongzong Tong, Evelyn DeGroot, Y.N. Vashisht Gopal, Michael Davies, Huseyin Atakan Ekiz, Joshua K.H. Tay, Chris Stubben, Kenneth M. Boucher, Juan M. Oviedo, Keke C. Fairfax, Matthew A. Williams, Sheri L. Holmen, Roger K. Wolff, Allie H. Grossmann. ARF6-dependent endocytic trafficking of the interferon-gamma receptor drives adaptive immune resistance and response to immune checkpoint blockade [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3926.

  PublisherDOI

• 0–3 Piezoceramic-Thermoplastic Polymer Composites

  2024-10-15

  book-chapter1st authorCorresponding

  A number of thermoplastic polymers are evaluated with respect to their use in 0–3 piezoceramic polymer composites. Materials were conventionally poled in a heated silicone oil bath and characterised by measurements of electrical resistivity, dielectric properties, and piezoelectric coefficients. The composites were prepared using lead titanate and commercial modified lead titanate powders in a number of different thermoplastic polymers. The polymers were found to possess mainly high resistivities (>108 Ωm) even at the elevated temperatures used for poling. Poling problems were therefore encountered for the majority of the materials investigated due to the unfavourable resistivity mismatch. However, it was found that by using the commercial powder, which possessed a higher resistivity, a more balanced resistivity match was achieved and active composites could be produced with useful piezoelectric coefficients. For example, materials were prepared that exhibited a d 33 of 26 pCN–1 and g 33 of 88 mV mN–1. Further work on thermoplastic systems is expected to yield more active materials, which also have important processing advantages over conventional thermosetting systems.

  PublisherDOI

• Contributors 4th edition

  Elsevier eBooks · 2024-01-01

  book-chapterOpen access
  PublisherDOI

• Generation of antigen-specific memory CD4 T cells by heterologous immunization enhances the magnitude of the germinal center response upon influenza infection

  PLoS Pathogens · 2024-09-16 · 9 citations

  articleOpen access

  Current influenza vaccine strategies have yet to overcome significant obstacles, including rapid antigenic drift of seasonal influenza viruses, in generating efficacious long-term humoral immunity. Due to the necessity of germinal center formation in generating long-lived high affinity antibodies, the germinal center has increasingly become a target for the development of novel or improvement of less-efficacious vaccines. However, there remains a major gap in current influenza research to effectively target T follicular helper cells during vaccination to alter the germinal center reaction. In this study, we used a heterologous infection or immunization priming strategy to seed an antigen-specific memory CD4+ T cell pool prior to influenza infection in mice to evaluate the effect of recalled memory T follicular helper cells in increased help to influenza-specific primary B cells and enhanced generation of neutralizing antibodies. We found that heterologous priming with intranasal infection with acute lymphocytic choriomeningitis virus (LCMV) or intramuscular immunization with adjuvanted recombinant LCMV glycoprotein induced increased antigen-specific effector CD4+ T and B cellular responses following infection with a recombinant influenza strain that expresses LCMV glycoprotein. Heterologously primed mice had increased expansion of secondary Th1 and Tfh cell subsets, including increased CD4+ TRM cells in the lung. However, the early enhancement of the germinal center cellular response following influenza infection did not impact influenza-specific antibody generation or B cell repertoires compared to primary influenza infection. Overall, our study suggests that while heterologous infection or immunization priming of CD4+ T cells is able to enhance the early germinal center reaction, further studies to understand how to target the germinal center and CD4+ T cells specifically to increase long-lived antiviral humoral immunity are needed.

  PublisherDOI

Recent grants

• NIH Grant F32AI056809

  NIH · $139k · 2006

• Recruitment of melanoma-specific CD4+ T cells

  NIH · $362k · 2016–2019

• NIH Grant R01AI080830

  NIH · $1.8M · 2015

• NIH Grant T37TW000049

  NIH · $2.5M · 2005

• TCR-dependent activation, functional differentiation and memory formation of CD4+ T cells following infection

  NIH · $2.5M · 2018–2023

Frequent coauthors

• H. Atakan Ekiz

  Huntsman Cancer Institute

  29 shared

• Dirk B. Mendel

  Stanford University

  28 shared

• Choung U. Kim

  Gilead Sciences (United States)

  26 shared

• Willard Lew

  Gilead Sciences (United States)

  24 shared

• Michael J. Bevan

  University of Oxford

  21 shared

• Lijun Zhang

  Dalian Medical University

  20 shared

• Sheri L. Holmen

  Huntsman Cancer Institute

  20 shared

• W.G. Laver

  20 shared

Education

• Ph.D. Immunology and Molecular Pathogenesis

  Emory University

  2002

• B.S. Microbiology

  Brigham Young University

  1997