Forest M. White
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High-throughput screening for class I peptide MHC binding via yeast surface display Open
T cells rely on short peptides presented by highly polymorphic major histocompatibility complexes (MHCs) to selectively initiate adaptive immune responses. Despite its importance, few techniques can systematically evaluate stable peptide p…
Control of antigen presentation on MHC-I by a bacterial secretion system Open
Mycobacterium tuberculosis (Mtb) remains one of the world’s leading infectious killers. Although CD8□ T cells contribute to immune control of tuberculosis, the pathways through which bacterial antigens access major histocompatibility compl…
Immunopeptidomics can inform the design of mRNA vaccines for the delivery of <i>Mycobacterium tuberculosis</i> MHC class II antigens Open
No currently licensed vaccine reliably prevents pulmonary tuberculosis (TB), a leading cause of infectious disease mortality. Developing effective new vaccines requires identifying which Mycobacterium tuberculosis ( Mtb ) proteins are pres…
IMMU-67. On-Treatment Spatiotemporal Profiling of Glioblastoma During Oncolytic ImmunoTherapy Open
Glioblastoma (GBM) is the most common and deadliest primary brain tumor, with no effective therapies and a longstanding record of failed phase 3 clinical trials—often without mechanistic insight into why promising approaches fall short. To…
View article: TMIC-70. Integrative spatiotemporal proteomic and metabolomic characterization of immune infiltration following intracranial injection of oncolytic immunotherapy in glioblastoma patients
TMIC-70. Integrative spatiotemporal proteomic and metabolomic characterization of immune infiltration following intracranial injection of oncolytic immunotherapy in glioblastoma patients Open
Glioblastoma (GBM) is the most aggressive and lethal primary brain tumor in adults, characterized by rapid proliferation, an immunologically inert microenvironment, diffuse tumor cell infiltration and therapy resistance. Progress in develo…
View article: CTIM-40. IMMUNE PROFILING OF GBM TUMOR TISSUES COLLECTED LONGITUDINALLY FROM PATIENTS TREATED WITH AN ONCOLYTIC VIRUS
CTIM-40. IMMUNE PROFILING OF GBM TUMOR TISSUES COLLECTED LONGITUDINALLY FROM PATIENTS TREATED WITH AN ONCOLYTIC VIRUS Open
Glioblastoma (GBM) is a highly aggressive brain tumor associated with multiple cell subsets, including immune cells, which have been difficult to study longitudinally due to safety concerns about accessing the brain multiple times in a sin…
View article: CTIM-35. MULTI-OMIC AND SINGLE CELL ASSESSMENT OF SERIAL BIOPSIES REVEALS RESPONSES TO CAN-3110 ONCOLYTIC IMMUNOTHERAPY IN RECURRENT GLIOBLASTOMA THAT ARE NOT EVIDENT BY ROUTINE CLINICAL ANALYSES
CTIM-35. MULTI-OMIC AND SINGLE CELL ASSESSMENT OF SERIAL BIOPSIES REVEALS RESPONSES TO CAN-3110 ONCOLYTIC IMMUNOTHERAPY IN RECURRENT GLIOBLASTOMA THAT ARE NOT EVIDENT BY ROUTINE CLINICAL ANALYSES Open
Recurrent glioblastoma (rGBM) is incurable, and routine clinical monitoring is often insufficient to uncover mechanisms of treatment failure in clinical trials. To improve clinical monitoring and mechanistic insights from rGBM trials, we a…
View article: Persistent interferon signaling and clonal expansion mark early events in DNA methylation damage-induced liver cancer
Persistent interferon signaling and clonal expansion mark early events in DNA methylation damage-induced liver cancer Open
N-Nitrosodimethylamine (NDMA), a probable human carcinogen, induces toxic and mutagenic O 6 -methylguanine lesions that are repaired by the O 6 -methylguanine methyltransferase (MGMT). To elucidate mechanisms of NDMA-induced liver cancer p…
Tyrosine phosphoproteome profiling identifies cell-intrinsic signals limiting the efficacy of tyrosine kinase inhibitor therapies Open
Tyrosine kinases (TKs) are frequently mutated or overexpressed in cancer, and TK inhibitors (TKIs) are an important therapeutic modality against TK-driven cancers, but many patients show an underwhelming response to TKIs prescribed on the …
Complex I inhibition combined with TLR activation in the breast tumor microenvironment educates cytotoxic neutrophils Open
Although effective for immunologically hot tumors, immune checkpoint inhibitors minimally affect tumors that are not T cell inflamed, including breast cancer. An alternate strategy to combat immune cold breast tumors may be to reeducate in…
High-throughput screening for class I peptide MHC binding via yeast surface display Open
T cells rely on short peptides presented by highly polymorphic major histocompatibility complexes (MHCs) to selectively initiate adaptive immune responses. Despite its importance, few techniques can systemically evaluate stable peptide pre…
Targeted degradation of CDK9 potently disrupts the MYC-regulated network Open
CDK9 coordinates signaling events that regulate transcription and is implicated in oncogenic pathways, making it an actionable target for drug development. While numerous CDK9 inhibitors have been developed, success in the clinic has been …
The Hunt Lab Weighs in on Mass Spectrometry–Based Analysis of Protein Posttranslational Modifications Open
Protein posttranslational modifications have traditionally been challenging to identify due to their dynamic regulation and typically low stoichiometry. Methods for phosphopeptide enrichment from complex proteomes developed in the Hunt lab…
View article: Uncovering the signaling networks of disseminated glioblastoma cells <i>in vivo</i> with INSIGHT
Uncovering the signaling networks of disseminated glioblastoma cells <i>in vivo</i> with INSIGHT Open
Dysregulation of intracellular signaling networks underpins cancer. However, a systems-level elucidation of how signaling networks within distinct cell subpopulations drive cancer progression in vivo has been unattainable due to technical …
View article: Parallel phosphoproteomics and metabolomics map the global metabolic tyrosine phosphoproteome
Parallel phosphoproteomics and metabolomics map the global metabolic tyrosine phosphoproteome Open
Tyrosine phosphorylation of metabolic enzymes is an evolutionarily conserved posttranslational modification that facilitates rapid and reversible modulation of enzyme activity, localization, or function. Despite the high abundance of tyros…
Neoantigen architectures define immunogenicity and drive immune evasion of tumors with heterogenous neoantigen expression Open
Background Intratumoral heterogeneity (ITH) and subclonal antigen expression blunt antitumor immunity and are associated with poor responses to immune-checkpoint blockade immunotherapy (ICB) in patients with cancer. The underlying mechanis…
View article: Immunopeptidomics informs discovery and delivery of <i>Mycobacterium tuberculosis</i> MHC-II antigens for vaccine design
Immunopeptidomics informs discovery and delivery of <i>Mycobacterium tuberculosis</i> MHC-II antigens for vaccine design Open
No currently licensed vaccine reliably prevents pulmonary tuberculosis (TB), a leading cause of infectious disease mortality. Developing effective new vaccines will require identifying which of the roughly 4000 proteins in the Mycobacteriu…
PathMHC: a workflow to selectively target pathogen-derived MHC peptides in discovery immunopeptidomics experiments for vaccine target identification Open
Vaccine-elicited T cell responses can contribute to immune protection against emerging infectious disease risks such as antimicrobials-resistant (AMR) microbial pathogens and viruses with pandemic potential, but rapidly identifying appropr…
Structural and systems characterization of phosphorylation on metabolic enzymes identifies sex-specific metabolic reprogramming in obesity Open
Coordination of adaptive metabolism through cellular signaling networks and metabolic response is essential for balanced flow of energy and homeostasis. Post-translational modifications such as phosphorylation offer a rapid, efficient, and…
Targeted Degradation of CDK9 Potently Disrupts the MYC Transcriptional Network Open
Summary Cyclin-dependent kinase 9 (CDK9) coordinates signaling events that regulate RNA polymerase II (Pol II) pause-release states. It is an important co-factor for transcription factors, such as MYC, that drive aberrant cell proliferatio…