A5062256089- Protein Kinase Regulation and GTPase Signaling
- Metabolism, Diabetes, and Cancer
- Cytokine Signaling Pathways and Interactions
- Enzyme Structure and Function
- Protein Tyrosine Phosphatases
- Monoclonal and Polyclonal Antibodies Research
- HER2/EGFR in Cancer Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Fibroblast Growth Factor Research
- Ion channel regulation and function
- Ubiquitin and proteasome pathways
- PI3K/AKT/mTOR signaling in cancer
- Growth Hormone and Insulin-like Growth Factors
- Biochemical and Molecular Research
- Receptor Mechanisms and Signaling
- Kruppel-like factors research
- Glycosylation and Glycoproteins Research
- Cell Adhesion Molecules Research
- Endoplasmic Reticulum Stress and Disease
- Computational Drug Discovery Methods
- Axon Guidance and Neuronal Signaling
- Chronic Myeloid Leukemia Treatments
- Chemical Synthesis and Analysis
- Protein Structure and Dynamics
- DNA and Nucleic Acid Chemistry
New York University
2014-2024
NYU Langone’s Laura and Isaac Perlmutter Cancer Center
2019
Luther College
2015
Cancer Institute (WIA)
2012
University Medical Center
1996-1999
Columbia University Irving Medical Center
1996-1998
The University of Arizona Global Campus
1997
Columbia University
1988-1995
University of York
1994-1995
Stanford University
1989-1992
A new class of protein tyrosine kinase inhibitors was identified that is based on an oxindole core (indolinones). Two compounds from this inhibited the activity fibroblast growth factor receptor 1 (FGFR1) and showed differential specificity toward other kinases. Crystal structures domain FGFR1 in complex with two were determined. The occupies site which adenine adenosine triphosphate binds, whereas moieties extend contact residues hinge region between lobes. more specific inhibitor induces a...
The crystal structure of FGF2 bound to a naturally occurring variant FGF receptor 1 (FGFR1) consisting immunoglobulin-like domains 2 (D2) and 3 (D3) has been determined at 2.8 A resolution. Two FGF2:FGFR1 complexes form 2-fold symmetric dimer. Within each complex, interacts extensively with D2 D3 as well the linker between two domains. dimer is stabilized by interactions adjoining complex direct interaction receptor. positively charged canyon formed cluster exposed basic residues likely...
The crystal structure of the tyrosine kinase domain fibroblast growth factor receptor 1 (FGFR1K) has been determined in its unliganded form to 2.0 Å resolution and complex with an ATP analog 2.3 resolution. Several features distinguish FGFR1K from that insulin receptor. Residues activation loop appear interfere substrate peptide binding but not binding, revealing a second perhaps more general autoinhibitory mechanism for kinases. In addition, dimeric observed may provide insights into...
Nonalcoholic fatty liver disease (NAFLD) is a risk factor for type 2 diabetes (T2D), but whether NAFLD plays causal role in the pathogenesis of T2D uncertain. One proposed mechanism linking to hepatic insulin resistance involves diacylglycerol-mediated (DAG-mediated) activation protein kinase C-ε (PKCε) and consequent inhibition receptor (INSR) activity. However, molecular underlying PKCε INSR activity unknown. Here, we used mass spectrometry identify phosphorylation site Thr1160 as...
Homodimeric class I cytokine receptors are assumed to exist as preformed dimers that activated by ligand-induced conformational changes. We quantified the dimerization of three prototypic in plasma membrane living cells single-molecule fluorescence microscopy. Spatial and spatiotemporal correlation individual receptor subunits showed revealed associated Janus kinase 2 (JAK2) dimerizes through its pseudokinase domain. Oncogenic hyperactive JAK2 mutants promoted ligand-independent...
BackgroundSARS-CoV-2 vaccines currently authorized for emergency use have been highly successful in preventing infection and lessening disease severity. The maintain effectiveness against earlier SARS-CoV-2 Variants of Concern but the heavily mutated, transmissible Omicron variant presents an obstacle both to vaccine protection monoclonal antibody therapies.MethodsPseudotyped lentiviruses were incubated with serum from vaccinated boosted donors or therapeutic then applied target cells. After...
Metal ion coordination in the regulatory domain of protein kinase C (PKC) is suggested by conservation six cysteines and two histidines homologous regions found therein. By monitoring x-ray fluorescence from a purified sample rat PKC beta I overexpressed insect cells, direct evidence has been obtained that tightly binds four zinc ions (Zn2+) per molecule. Extended absorption fine structure (EXAFS) data are best fit an average Zn2+ one nitrogen three sulfur atoms. Of plausible models, only...