A5088182912- Mitochondrial Function and Pathology
- Ubiquitin and proteasome pathways
- RNA and protein synthesis mechanisms
- ATP Synthase and ATPases Research
- Animal Genetics and Reproduction
- RNA modifications and cancer
- Protein Degradation and Inhibitors
- Enzyme Structure and Function
- DNA Repair Mechanisms
- Cancer-related Molecular Pathways
- Military History and Strategy
- Genetic factors in colorectal cancer
- Autophagy in Disease and Therapy
- Digital Transformation in Industry
- Genomic variations and chromosomal abnormalities
- Prostate Cancer Treatment and Research
- Cancer, Hypoxia, and Metabolism
- Iron Metabolism and Disorders
- Metabolomics and Mass Spectrometry Studies
- Advanced Proteomics Techniques and Applications
- Nuclear Issues and Defense
- Phagocytosis and Immune Regulation
- Inflammasome and immune disorders
- Folate and B Vitamins Research
- Defense, Military, and Policy Studies
Bristol-Myers Squibb (United States)
2020-2024
National Defense University
2020
Harvard University
2005-2011
Massachusetts General Hospital
2005-2011
Center for Systems Biology
2009
Broad Institute
2009
Center for Human Genetics
2006-2009
Cancer Research Institute
2007
University of California, San Francisco
2007
Stanford University
2006
The human oxidative phosphorylation (OxPhos) system consists of approximately 90 proteins encoded by nuclear and mitochondrial genomes serves as the primary cellular pathway for ATP biosynthesis. While core protein machinery OxPhos is well characterized, many its assembly, maturation, regulatory factors remain unknown. We exploited tight transcriptional control genes encoding to identify novel regulators. developed a computational procedure, which we call expression screening, integrates...
We introduce neutron-encoded (NeuCode) amino acid labeling of mice as a strategy for multiplexed proteomic analysis in vivo. Using NeuCode, we characterize an inducible knockout mouse model Bap1, tumor suppressor and deubiquitinase whose vivo roles outside cancer are not well established. NeuCode proteomics revealed altered metabolic pathways following Bap1 deletion, including profound elevation cholesterol biosynthetic machinery coincident with reduced expression gluconeogenic lipid...
There is a growing interest in using targeted protein degradation as therapeutic modality view of its potential to expand the druggable proteome. One avenue this via molecular glue based Cereblon E3 Ligase Modulating Drug compounds. Here, we report identification transcription factor ZBTB16 neosubstrate. We also two new modulators, CC-3060 and CC-647, that promote degradation. Unexpectedly, CC-647 target for by primarily engaging distinct structural degrons on different zinc finger domains....
Abstract CC-122 is a next-generation cereblon E3 ligase–modulating agent that has demonstrated promising clinical efficacy in patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL). Mechanistically, induces the degradation of IKZF1/3, leading to T-cell activation and robust cell-autonomous killing DLBCL. We report genome-wide CRISPR/Cas9 screening for DLBCL cell line SU-DHL-4 follow-up mechanistic characterization 6 lines identify genes regulating response CC-122....
Abstract The androgen receptor (AR) is a key driver of the cellular processes that contribute to pathology prostate cancers at most stages, and drugs inhibit activity this or interfere with biosynthesis have become cornerstone treatments for cancer. While both types therapy had significant positive impact on disease progression overall survival, de novo acquired resistance remains an impediment durable clinical response in patients metastatic castration-resistant cancer (mCRPC). mechanisms...
Abstract Tumors vary widely in chromosomal level genome instability. To gain a better understanding of the underlying defects which foster specific types aberrations, we investigated response cells related genetic backgrounds to challenge with methotrexate. We studied mismatch repair deficient HCT116 cells, two derivatives also XRCC5 (HCT116 Ku86+/−) or BLM BLM−/−), and competent HCT116+chr3 cells. show that colony formation occurred at significantly higher frequency Ku86+/− compared BLM−/−...