- Advanced Proteomics Techniques and Applications
- Fungal and yeast genetics research
- Ubiquitin and proteasome pathways
- Cancer, Hypoxia, and Metabolism
- Mitochondrial Function and Pathology
- Microtubule and mitosis dynamics
- Endoplasmic Reticulum Stress and Disease
- Genomics and Phylogenetic Studies
- Immunotherapy and Immune Responses
- PI3K/AKT/mTOR signaling in cancer
- Mass Spectrometry Techniques and Applications
- vaccines and immunoinformatics approaches
- Genomics and Chromatin Dynamics
- Glycosylation and Glycoproteins Research
- Cellular transport and secretion
- Prostate Cancer Treatment and Research
- Cancer Immunotherapy and Biomarkers
- Epigenetics and DNA Methylation
- RNA and protein synthesis mechanisms
- Metabolomics and Mass Spectrometry Studies
- Cancer, Lipids, and Metabolism
- Bioinformatics and Genomic Networks
- ATP Synthase and ATPases Research
- Monoclonal and Polyclonal Antibodies Research
- RNA modifications and cancer
Cornell University
2017-2025
Weill Cornell Medicine
2017-2025
Harvard University
2011-2024
Presbyterian Hospital
2021
Boston University
2012
Harvard University Press
2010
Howard Hughes Medical Institute
2003-2005
University of California, San Francisco
2003-2005
The eukaryotic cell division cycle is characterized by a sequence of orderly and highly regulated events resulting in the duplication separation all cellular material into two newly formed daughter cells. Protein phosphorylation cyclin-dependent kinases (CDKs) drives this cycle. To gain further insight how regulates cycle, we sought to identify proteins whose regulated. Using stable isotope labeling along with two-step strategy for phosphopeptide enrichment high mass accuracy spectrometry,...
Pyruvate constitutes a critical branch point in cellular carbon metabolism. We have identified two proteins, Mpc1 and Mpc2, as essential for mitochondrial pyruvate transport yeast, Drosophila, humans. Mpc2 associate to form an ~150-kilodalton complex the inner membrane. Yeast Drosophila mutants lacking MPC1 display impaired metabolism, with accumulation of upstream metabolites depletion tricarboxylic acid cycle intermediates. Loss yeast results defective uptake, silencing or MPC2 mammalian...
Mammalian mitochondria contain about 1100 proteins, nearly 300 of which are uncharacterized. Given the well-established role mitochondrial defects in human disease, functional characterization these proteins may shed new light on disease mechanisms. Starting with yeast as a model system, we investigated an uncharacterized but highly conserved protein (named here Sdh5). Both and Sdh5 interact catalytic subunit succinate dehydrogenase (SDH) complex, component both electron transport chain...
Many proteins that respond to DNA damage are recruited lesions. We used a proteomics approach coupled isotopic labeling with chromatin fractionation and mass spectrometry uncover associate damaged DNA, many of which involved in repair or nucleolar function. show polycomb group members by poly(ADP ribose) polymerase (PARP) lesions following UV laser microirradiation. Loss components results IR sensitivity mammalian cells Caenorhabditis elegans . PARP also recruits two the repressive...
Aneuploidy causes severe developmental defects and is a near universal feature of tumor cells. Despite its profound effects, the cellular processes affected by aneuploidy are not well characterized. Here, we examined consequences on proteome aneuploid budding yeast strains. We show that although protein levels largely scale with gene copy number, subunits multi-protein complexes notable exceptions. Posttranslational mechanisms attenuate their expression when encoding genes in excess. Our...
Abstract Copper serves as a co-factor for host of metalloenzymes that contribute to malignant progression. The orally bioavailable copper chelating agent tetrathiomolybdate (TM) has been associated with significant survival benefit in high-risk triple negative breast cancer (TNBC) patients. Despite these promising data, the mechanisms by which depletion impacts metastasis are poorly understood and this remains major barrier advancing TM randomized phase II trial. Here, using two independent...
Neoantigens generated by somatic nonsynonymous mutations are key targets of tumor-specific T cells, but only a small number predicted to be immunogenic presented MHC molecules on cancer cells. Vaccination studies in mice and patients have shown that the majority neoepitopes elicit cell responses fail induce significant antitumor activity, for incompletely understood reasons. We report radiotherapy upregulates expression genes containing poorly mouse model triple-negative breast cancer. with...
Despite recent therapeutic advances, prostate cancer remains a leading cause of cancer-related death. A subset castration-resistant cancers become androgen receptor (AR) signaling independent and develop neuroendocrine (NEPC) features through lineage plasticity. These NEPC tumors, associated with aggressive disease poor prognosis, are driven, in part, by aberrant expression N-Myc, mechanisms that remain unclear. Integrative analysis the N-Myc transcriptome, cistrome, interactome using vivo,...
The interpretation of quantitative phosphoproteomics studies is complicated because each differential phosphorylation event integrates both changes in protein expression and phosphorylation. Here we investigated this phenomenon by performing parallel comparisons S. cerevisiae. In two experiments comparing yeast mutants bearing deletions FUS3 or STE7 with their wild-type counterparts, quantified over 4100 proteins, including all members the mating pathway. We also identified 12,499 unique...
The Hippo pathway controls metazoan organ growth by regulating cell proliferation and apoptosis. Many components have been identified, but our knowledge of the composition structure this is still incomplete. Using existing as baits, we generated mass spectrometry a high-confidence Drosophila protein-protein interaction network (Hippo-PPIN) consisting 153 proteins 204 interactions. Depletion 67% RNA interference regulated transcriptional coactivator Yorkie (Yki) either positively or...