A5024341499- Enzyme Structure and Function
- Protein Kinase Regulation and GTPase Signaling
- Cancer, Hypoxia, and Metabolism
- Lung Cancer Treatments and Mutations
- Vascular Malformations Diagnosis and Treatment
- Cancer-related Molecular Pathways
- Intracranial Aneurysms: Treatment and Complications
- Cellular transport and secretion
- Biochemical and Molecular Research
- Cell Adhesion Molecules Research
- Ubiquitin and proteasome pathways
- Intracerebral and Subarachnoid Hemorrhage Research
- Protein Tyrosine Phosphatases
- HER2/EGFR in Cancer Research
- Cellular Mechanics and Interactions
- Protein Structure and Dynamics
- Acute Myeloid Leukemia Research
- Microtubule and mitosis dynamics
- Melanoma and MAPK Pathways
- Cytokine Signaling Pathways and Interactions
- ATP Synthase and ATPases Research
- Lung Cancer Research Studies
- Mitochondrial Function and Pathology
- Cancer therapeutics and mechanisms
- Glycosylation and Glycoproteins Research
Yale University
2016-2025
Yale Cancer Center
2014-2025
University of New Haven
2013-2016
Emory University
2012
Winship Cancer Institute
2012
Case Western Reserve University
2007-2009
University of Colorado Denver
2009
University of Colorado Cancer Center
2009
University Hospitals Cleveland Medical Center
2009
University School
2007-2008
Receptor tyrosine kinase genes were sequenced in non–small cell lung cancer (NSCLC) and matched normal tissue. Somatic mutations of the epidermal growth factor receptor gene EGFR found 15of 58 unselected tumors from Japan 1 61 United States. Treatment with inhibitor gefitinib (Iressa) causes tumor regression some patients NSCLC, more frequently Japan. additional samples U.S. who responded to therapy a adenocarcinoma line that was hypersensitive inhibition by gefitinib, but not...
Mutations of the epidermal growth factor receptor (EGFR) gene have been identified in specimens from patients with non-small-cell lung cancer who a response to anilinoquinazoline EGFR inhibitors. Despite dramatic responses such inhibitors, most ultimately relapse. The mechanism drug resistance is unknown. Here we report case patient EGFR-mutant, gefitinib-responsive, advanced had relapse after two years complete remission during treatment gefitinib. DNA sequence his tumor biopsy specimen at...
Tyrosine phosphorylation of pyruvate kinase M2 gives tumor cells a metabolic advantage.
Cadherins are transmembrane proteins that mediate adhesion between cells in the solid tissues of animals. Here we present 3.1 angstrom resolution crystal structure whole, functional extracellular domain from C-cadherin, a representative "classical" cadherin. The suggests molecular mechanism for by classical cadherins, and it provides new framework understanding both cis (same cell) trans (juxtaposed cadherin interactions. adhesive interface is twofold symmetric interaction defined conserved...
Background Epidermal growth factor receptor (EGFR) mutations are present in the majority of patients with non-small cell lung cancer (NSCLC) responsive to EGFR tyrosine kinase inhibitors (TKIs) gefitinib or erlotinib. These EGFR-dependent tumors eventually become TKI resistant, and common secondary T790M mutation accounts for half acquired resistance gefitinib. However, key proapoptotic proteins involved TKI-induced death other remain unclear. The objective this study was identify mechanism...
Uterine serous carcinoma (USC) is a biologically aggressive subtype of endometrial cancer. We analyzed the mutational landscape USC by whole-exome sequencing 57 cancers, most which were matched to normal DNA from same patients. The distribution number protein-altering somatic mutations revealed that 52 tumors had fewer than 100 (median 36), whereas 5 more 3,000 mutations. in these latter showed hallmarks defects mismatch repair. Among remainder, we found significantly increased burden...
The Warburg effect describes an increase in aerobic glycolysis and enhanced lactate production cancer cells. Lactate dehydrogenase A (LDH-A) regulates the last step of that generates permits regeneration NAD+. LDH-A gene expression is believed to be upregulated by both HIF Myc cells achieve increased production. However, how oncogenic signals activate regulate cell metabolism remains unclear. We found receptor tyrosine kinase FGFR1 directly phosphorylates LDH-A. Phosphorylation at Y10 Y83...
Significance Some cancers, termed carcinosarcomas (CSs), have mixed cell types, with either epithelial or mesenchymal features. Sequencing the genomes of uterine and ovarian CSs demonstrated that these different types derive from a common precursor has many mutations typical cancers. In addition, we find tumors significant burden point amplification histone genes, suggesting potential role in sarcomatous transformation. Consistent this finding, expression specific gene carcinoma cells...
Dysfunction of the tubby protein results in maturity-onset obesity mice. Tubby has been implicated as a transcription regulator, but details molecular mechanism underlying its function remain unclear. Here we show that functions signal transduction from heterotrimeric GTP-binding (G protein)–coupled receptors. localizes to plasma membrane by binding phosphatidylinositol 4,5-bisphosphate through carboxyl terminal “tubby domain.” X-ray crystallography reveals atomic-level basis this...
Tubby-like proteins (TULPs) are found in a broad range of multicellular organisms. In mammals, genetic mutation tubby or other TULPs can result one more three disease phenotypes: obesity (from which the name “tubby” is derived), retinal degeneration, and hearing loss. These phenotypes indicate vital role for proteins; however, no biochemical function has yet been ascribed to any member this protein family. A structure-directed approach was employed investigate biological these proteins. The...