A5047017969- PI3K/AKT/mTOR signaling in cancer
- Cancer Immunotherapy and Biomarkers
- Mast cells and histamine
- Lung Cancer Treatments and Mutations
- Cancer Genomics and Diagnostics
- Defense, Military, and Policy Studies
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Immunotherapy and Immune Responses
- Technology Assessment and Management
- Cancer, Hypoxia, and Metabolism
- Military and Defense Studies
- Lung Cancer Research Studies
- Ferroptosis and cancer prognosis
- Synthesis and Biological Evaluation
- RNA modifications and cancer
- Pancreatic and Hepatic Oncology Research
- Coastal and Marine Management
- Coral and Marine Ecosystems Studies
- Education and Military Integration
- T-cell and B-cell Immunology
- Glutathione Transferases and Polymorphisms
- Human Resource Development and Performance Evaluation
- CAR-T cell therapy research
- Cholangiocarcinoma and Gallbladder Cancer Studies
- vaccines and immunoinformatics approaches
Yale Cancer Center
2017-2024
Yale University
1979-2023
MUSC Hollings Cancer Center
2022
Medical University of South Carolina
2022
University of New Haven
2018-2021
World Health Organization - Afghanistan
2019
Bahrain Center for Strategic International and Energy Studies
2019
United States Department of Veterans Affairs
1979
Mechanisms of acquired resistance to immune checkpoint inhibitors (ICI) are poorly understood. We leveraged a collection 14 ICI-resistant lung cancer samples investigate whether alterations in genes encoding HLA Class I antigen processing and presentation machinery (APM) components or interferon signaling play role PD-1 PD-L1 antagonistic antibodies. Recurrent mutations copy-number changes were not detected our cohort. In one case, we found homozygous loss B2M that caused lack cell-surface...
BackgroundAlthough EGFR mutant tumors exhibit low response rates to immune checkpoint blockade overall, some do respond these therapies; however, there is a lack of understanding the characteristics lung responsive blockade.Patients and methodsWe retrospectively analyzed de-identified clinical molecular data on 171 cases treated with inhibitors from Yale Cancer Center, Memorial Sloan Kettering University California Los Angeles, Dana Farber Institute. A separate cohort 383 cancer sequencing...
In lung adenocarcinoma, oncogenic EGFR mutations co-occur with many tumor suppressor gene alterations; however, the extent to which these contribute growth and response therapy in vivo remains largely unknown. By quantifying effects of inactivating 10 putative genes a mouse model EGFR-driven Trp53-deficient we found that Apc, Rb1, or Rbm10 inactivation strongly promoted growth. Unexpectedly, Lkb1 Setd2-the strongest drivers KRAS-driven model-reduced These results are consistent mutational...
Immunotherapy resistance in non-small cell lung cancer (NSCLC) may be mediated by an immunosuppressive microenvironment, which can shaped the mutational landscape of tumor. Here, we observed genetic alterations PTEN/PI3K/AKT/mTOR pathway and/or loss PTEN expression >25% patients with NSCLC, higher frequency squamous carcinomas (LUSC). Patients PTEN-low tumors had levels PD-L1 and PD-L2 showed worse progression-free survival when treated immunotherapy. Development a Pten-null LUSC mouse model...
The TAM receptor, Axl, has been implicated as a candidate entry receptor for Zika virus (ZIKV) infection but shown inessential in mice. To probe the role of Axl murine ZIKV infection, we developed mouse model lacking and interferon alpha/beta (Ifnar−/−Axl−/−), conferring susceptibility to ZIKV. This validated that is not required mice are resistant pathogenesis. resistance correlates lower pro-interleukin-1β production less apoptosis microglia ZIKV-infected occurs through both intrinsic...
Journal Article Cytomegalovirus Infection in Guinea Pigs. III. Persistent Viruria, Blood Transmission, and Viral Interference Get access Frank J. Bia, Bia Virology Laboratory, Veterans Administration Medical Center, West Haven, ConnecticutInfectious Diseases Section of the Department Medicine, New ConnecticutDepartment Laboratory Yale University School Connecticut Please address requests for reprints to Dr. Laboratory/151 B, 06516. Search other works by this author on: Oxford Academic PubMed...
Despite the established use of immune checkpoint inhibitors (ICIs) to treat non-small cell lung cancer (NSCLC), only a subset patients benefit from treatment and ∼50% whose tumors respond eventually develop acquired resistance (AR). To identify novel drivers AR, we generated murine Msh2 knock-out (KO) that initially responded but developed AR anti-PD-1, alone or in combination with anti-CTLA-4. Resistant harbored decreased infiltrating T cells reduced cell-intrinsic MHC-I MHC-II levels, yet...
Melanoma is an aggressive skin cancer that has become increasingly prevalent in western populations. Current treatments such as surgery, chemotherapy, and high-dose radiation have had limited success, often failing to treat late stage, metastatic melanoma. Alternative strategies immunotherapies been successful treating a small percentage of patients with disease, although these date not proven enhance overall survival. Several melanoma antigens (Ags) proposed targets for immunotherapeutics...
Abstract Immune checkpoint inhibitors (ICIs) targeting PD-L1/PD-1 have dramatically improved the management of NSCLC patients. Nevertheless, more than 50% patients will present primary resistance or develop secondary within 12-25 months after treatment initiation. The mechanisms to ICIs may depend on tumor-intrinsic molecular/genetic alterations that generate an immunosuppressive tumor microenvironment (isTME). Using In silico analyses (TCGA and AACR-GENIE cohorts), protein expression...
Abstract Cancer genome sequencing has uncovered substantial complexity in the mutational landscape of tumors. Given this complexity, experimental approaches are necessary to establish impact combinations genetic alterations on tumor biology and uncover genotype-dependent effects drug sensitivity. In lung adenocarcinoma, EGFR mutations co-occur with many putative suppressor gene alterations, however extent which these contribute growth their response therapy vivo not been explored...
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<div>Abstract<p>Immunotherapy resistance in non-small cell lung cancer (NSCLC) may be mediated by an immunosuppressive microenvironment, which can shaped the mutational landscape of tumor. Here, we observed genetic alterations PTEN/PI3K/AKT/mTOR pathway and/or loss PTEN expression >25% NSCLC patients, with higher frequency squamous carcinomas (LUSCs). Patients PTEN-low tumors had levels PD-L1 and PD-L2 showed worse progression-free survival when treated immunotherapy....
<p>Supplementary Materials and Methods</p>
<p>Supplementary Figure Legends</p>