A5055296283- Immune cells in cancer
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Signaling Pathways in Disease
- Immune Cell Function and Interaction
- Ubiquitin and proteasome pathways
- Cutaneous lymphoproliferative disorders research
- Cancer Genomics and Diagnostics
- Parkinson's Disease Mechanisms and Treatments
- Cellular transport and secretion
- Autophagy in Disease and Therapy
- Cancer-related molecular mechanisms research
- Cutaneous Melanoma Detection and Management
- Cytokine Signaling Pathways and Interactions
- Nonmelanoma Skin Cancer Studies
- CAR-T cell therapy research
University of California, San Francisco
2020-2025
Yale University
2023
Intratumoral heterogeneity (ITH)-defined as genetic and cellular diversity within a tumor-is linked to failure of immunotherapy an inferior anti-tumor immune response. We modeled heterogeneous tumors comprised "hot" "cold" tumor populations (giving rise T cell-rich cell-poor tumors, respectively) introduced fluorescent labels enable precise spatial tracking. found the cold cell population exerted "dominant cold" effect in mixed tumors. Strikingly, analysis revealed that cells themselves...
Immunotherapy is now widely used to treat cancer, but its efficacy in many cancer types remains modest. To overcome current barriers, preclinical mouse models that faithfully recapitulate the diversity of types, tumor genetics, mutation burdens, and neoantigen patterns human tumors are essential. Currently, there relatively few transplantable murine squamous cell carcinomas (SCC). Here we describe a novel series 11 skin SCC lines, Carcinogen-Induced Tumor (CIT) syngeneic FVB strain. The CIT...
Missense mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial Parkinson’s disease (PD); however, pathways regulating LRRK2 subcellular localization, function, and turnover not fully defined. We performed quantitative mass spectrometry–based interactome studies to identify 48 novel interactors, including microtubule-associated E3 ubiquitin ligase TRIM1 (tripartite motif family 1). recruits microtubule cytoskeleton for ubiquitination proteasomal degradation...
Abstract Intratumoral heterogeneity (ITH)—defined as genetic and cellular diversity within a tumor—is linked to failure of immunotherapy an inferior anti-tumor immune response. The underlying mechanism this association is unknown. To address question, we modeled heterogeneous tumors comprised pro-inflammatory (“hot”) immunosuppressive (“cold”) tumor population, labeled with YFP RFP tags respectively enable precise spatial tracking. resulting mixed-population exhibited distinct regions +...
Abstract Missense mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial Parkinson’s Disease (PD); however, pathways regulating LRRK2 subcellular localization, function, and turnover not fully defined. We performed quantitative mass spectrometry-based interactome studies to identify 48 novel interactors, including microtubule-associated E3 ubiquitin ligase TRIM1 ( Tri partite M otif Family 1). recruits microtubule cytoskeleton for ubiquitination proteasomal...
Abstract Intratumoral heterogeneity (ITH) – cellular and molecular diversity within a tumor is linked to failure of immunotherapy in multiple cancer types. A high degree ITH associated with poor infiltration T cells into the resistance immune checkpoint blockade (ICB) therapy. To determine how distinct populations heterogeneous tumors shape microenvironment this impacts therapy response, we modeled composed an RFP-tagged immunosuppressive population YFP-tagged pro-inflammatory population....
<h3>Background</h3> Intratumoral heterogeneity—defined as genetic and cellular diversity within a tumor—is linked to the failure of immunotherapy in multiple cancer types.<sup>1 2</sup> The reasons for this are not well understood. Recent multi-region studies have found that many two-thirds patient tumors contain both distinct 'hot' 'cold' tumor regions, defined by high low T cell infiltrates, respectively.<sup>3</sup> We developed novel system reproducibly model heterogeneity mice, employed...
<h3>Background</h3> Although immune checkpoint inhibition has moved into the frontline setting for advanced and metastatic head neck cancer (HNC), only a minority of patients experience durable treatment responses.<sup>1</sup> Therapeutic resistance is associated with elevated hypoxia STAT3 signaling infiltration by myeloid derived suppressor cells (MDSC).<sup>2 3</sup> In this study, we tested hypothesis that resistant phenotypes are driven tumor cell autonomous innate signaling....
Background Intratumoral heterogeneity (ITH) is cellular and molecular diversity within a tumor. ITH linked to failure of immunotherapy in multiple cancer types. One the suggested mechanisms this absence productive immune response, which can be driven by dominance tumor population that creates immunosuppressive microenvironment. However, mediate such dominant effects how affects efficacy checkpoint blockade (ICB) therapy are poorly understood. Methods We generated library squamous skin cell...