A5005913399- Lung Cancer Treatments and Mutations
- HER2/EGFR in Cancer Research
- Monoclonal and Polyclonal Antibodies Research
- Ion channel regulation and function
- Genomics and Rare Diseases
- Advanced Breast Cancer Therapies
- Chronic Lymphocytic Leukemia Research
- RNA and protein synthesis mechanisms
- PI3K/AKT/mTOR signaling in cancer
- Cardiac electrophysiology and arrhythmias
- Microbial Metabolic Engineering and Bioproduction
- HIV/AIDS drug development and treatment
- Photosynthetic Processes and Mechanisms
- Neuroendocrine Tumor Research Advances
- Protein Structure and Dynamics
- Biochemical and Molecular Research
- HIV Research and Treatment
- Genomics and Phylogenetic Studies
- Ion Transport and Channel Regulation
- Bioinformatics and Genomic Networks
- Cancer Genomics and Diagnostics
- Glycogen Storage Diseases and Myoclonus
- Glycosylation and Glycoproteins Research
- Receptor Mechanisms and Signaling
- DNA and Nucleic Acid Chemistry
Washington University in St. Louis
2018-2024
Vanderbilt University
2014-2024
Laboratoire de Biochimie
2023
Vanderbilt University Medical Center
2012-2021
Indiana University School of Medicine
2021
Baylor Genetics
2021
Baylor College of Medicine
2021
Indiana University – Purdue University Indianapolis
2021
Sheehan Medical (United States)
2019
University of California, Berkeley
2011-2018
Here, we report that novel epidermal growth factor receptor (EGFR) gene fusions comprising the N-terminal of EGFR linked to various fusion partners, most commonly RAD51, are recurrent in lung cancer. We describe five patients with metastatic cancer whose tumors harbored fusions, four whom were treated tyrosine kinase inhibitors (TKI) documented antitumor responses. In vitro, EGFR-RAD51 oncogenic and can be therapeutically targeted available TKIs therapeutic antibodies. These results support...
Oncogenic EGFR mutations are found in 10% to 35% of lung adenocarcinomas. Such mutations, which present most commonly as small in-frame deletions exon 19 or point 21 (L858R), confer sensitivity tyrosine kinase inhibitors (TKI). In analyzing the tumor from a 33-year-old male never-smoker, we identified novel alteration cancer: 18-25 domain duplication (EGFR-KDD). Through analysis larger cohort samples, detected additional cases EGFR-KDD lung, brain, and other cancers. vitro, is constitutively...
Abstract We report a HER2T798I gatekeeper mutation in patient with HER2L869R-mutant breast cancer acquired resistance to neratinib. Laboratory studies suggested that HER2L869R is neratinib-sensitive, gain-of-function upon dimerization mutant HER3E928G, also present the cancer, amplifies HER2 signaling. The was treated neratinib and exhibited sustained partial response. Upon clinical progression, detected plasma tumor cell-free DNA. Structural modeling of this increased bulk isoleucine...
Androgen receptor (AR) action throughout prostate development and in maintenance of the prostatic epithelium is partly controlled by interactions between AR forkhead box (FOX) transcription factors, particularly FOXA1. We sought to identity additional FOXA1 binding partners that may mediate prostate-specific gene expression. Here we identify nuclear factor I (NFI) family factors as novel proteins. All four members (NFIA, NFIB, NFIC, NFIX) can interact with FOXA1, knockdown studies...
Abstract Mediating the terminal reaction of gluconeogenesis and glycogenolysis, integral membrane protein glucose-6-phosphate catalytic subunit 1 (G6PC1) regulates hepatic glucose production by catalyzing hydrolysis (G6P) within lumen endoplasmic reticulum. Consistent with its vital contribution to homeostasis, inactivating mutations in G6PC1 causes glycogen storage disease (GSD) type 1a characterized hepatomegaly severe hypoglycemia. Despite physiological importance, structural basis G6P...
Everyday life is not a place for the sacred. Instead, sacred stands apart from ordinary, profane affairs: it finds its home in churches, mosques and synagogues, spaces sanctified by their connection to world of transcendent dedicated honour. If this seems rather pedestrian distinction, not. At very least, has been distinction vital anthropological description world. ‘In every primitive community . .’, social anthropologist Bronislaw Malinowski argued 1925, ‘there have found two clearly...
Abstract Background Disassembly of the viral capsid following penetration into cytoplasm, or uncoating, is a poorly understood stage retrovirus infection. Based on previous studies HIV-1 CA mutants exhibiting altered stability, we concluded that formation optimal intrinsic stability crucial for Results To further examine connection between and infectivity, isolated second-site suppressors unstable (P38A) hyperstable (E45A) capsids. We identified respective suppressor mutations, T216I R132T,...
Abstract Purpose: We describe herein a novel P447_L455 deletion in the C2 domain of PIK3CA patient with an ER+ breast cancer excellent response to PI3Kα inhibitor alpelisib. Although deletions are relatively rare, significant portion cluster within amino acids 446–460 domain, suggesting these residues critical for p110α function. Experimental Design: A computational structural model PIK3CAdelP447-L455 complex p85 regulatory subunit and MCF10A cells expressing PIK3CAH450_P458del were used...
Centrin is an EF-hand calcium-binding protein closely related to the prototypical calcium sensor calmodulin. It found in microtubule-organizing centers of organisms ranging from algae and yeast man. In vitro, C-terminal domain centrin binds centrosomal Kar1p a calcium-dependent manner, whereas N-terminal does not show any appreciable affinity for Kar1p. To obtain deeper insights into structural basis centrin's function, we have characterized affinities Chlamydomonas reinhardtii peptide...
γ-aminobutyric acid type A (GABA(A)) receptors are heteropentameric glycoproteins. Based on consensus sequences, the GABA(A) receptor β2 subunit contains three potential N-linked glycosylation sites, Asn-32, Asn-104, and Asn-173. Homology modeling indicates that Asn-32 Asn-104 located before α1 helix in loop L3, respectively, near top of subunit-subunit interface minus side, Asn-173 is Cys-loop bottom N-terminal domain. Using site-directed mutagenesis, we demonstrated all predicted sites...
The Synechococcus elongatus KaiA, KaiB, and KaiC proteins in the presence of ATP generate a post-translational oscillator that runs temperature-compensated manner with period 24 h. KaiA dimer stimulates phosphorylation hexamer at two sites per subunit, T432 S431, KaiB dimers antagonize action induce subunit exchange. Neither mechanism KaiA-stimulated nor KaiB-mediated dephosphorylation is understood detail present. We demonstrate here A422V mutant sheds light on former mechanism. It was...
The inward rectifier potassium (Kir) channel Kir7.1 (KCNJ13) has recently emerged as a key regulator of melanocortin signaling in the brain, electrolyte homeostasis eye, and uterine muscle contractility during pregnancy. pharmacological tools available for exploring physiology therapeutic potential have been limited to relatively weak nonselective small-molecule inhibitors. Here, we report discovery fluorescence-based high-throughput screen novel inhibitor, VU714. Site-directed mutagenesis...
The renal inward rectifying potassium channel Kir1.1 plays key roles in regulating electrolyte homeostasis and blood pressure. Loss-of-function mutations the cause a life-threatening salt water balance disorder infants called antenatal Bartter syndrome (ABS). Of more than 30 ABS identified, approximately half are located intracellular domain of channel. mechanisms underlying dysfunction for most these unknown. By mapping onto an atomic model Kir1.1, we found that several localized to...
Centrin is an essential component of microtubule-organizing centers in organisms ranging from algae and yeast to humans. It EF-hand calcium-binding protein with homology calmodulin but distinct calcium binding properties. In a previously proposed model, the C-terminal domain centrin serves as constitutive anchor target proteins, N-terminal sensor signals. The three-dimensional structure Chlamydomonas rheinhardtii has been determined presence by solution NMR spectroscopy. found occupy open...