A5075471637- Lung Cancer Research Studies
- Neuroendocrine Tumor Research Advances
- Peptidase Inhibition and Analysis
- RNA modifications and cancer
- Glycosylation and Glycoproteins Research
- Signaling Pathways in Disease
- Fibroblast Growth Factor Research
- Cancer Research and Treatments
- Cancer-related gene regulation
- Cancer therapeutics and mechanisms
- Cancer Mechanisms and Therapy
- Neuroblastoma Research and Treatments
- Bacteriophages and microbial interactions
- Monoclonal and Polyclonal Antibodies Research
- Neonatal Respiratory Health Research
- Chromatin Remodeling and Cancer
- Epigenetics and DNA Methylation
- Cancer Cells and Metastasis
- Histone Deacetylase Inhibitors Research
- Lung Cancer Treatments and Mutations
- Advanced biosensing and bioanalysis techniques
- Galectins and Cancer Biology
- Pancreatic and Hepatic Oncology Research
- Cancer, Stress, Anesthesia, and Immune Response
- Cancer Genomics and Diagnostics
University of Virginia
2016-2024
University of Virginia Cancer Center
2018-2023
Pediatrics and Genetics
2015-2023
Stanford Medicine
2023
University of Virginia Health System
2005-2022
Stanford University
2010-2018
University of California, Davis
2013
UCSF Helen Diller Family Comprehensive Cancer Center
2010
University of California, San Francisco
2010
Cincinnati Children's Hospital Medical Center
2004-2008
Small cell lung cancer (SCLC) is an aggressive neuroendocrine subtype of with high mortality. We used a systematic drug repositioning bioinformatics approach querying large compendium gene expression profiles to identify candidate U.S. Food and Drug Administration (FDA)-approved drugs treat SCLC. found that tricyclic antidepressants related molecules potently induce apoptosis in both chemonaïve chemoresistant SCLC cells culture, mouse human tumors transplanted into immunocompromised mice,...
Goblet cell hyperplasia and mucous hypersecretion contribute to the pathogenesis of chronic pulmonary diseases including cystic fibrosis, asthma, obstructive disease. In present work, mouse SAM pointed domain-containing ETS transcription factor (SPDEF) mRNA protein were detected in subsets epithelial cells lining trachea, bronchi, tracheal glands. SPDEF interacted with C-terminal domain thyroid 1, activating genes expressed selectively airway cells, Sftpa, Scgb1a1, Foxj1, Sox17. Expression...
Small-cell lung carcinoma (SCLC) is a neuroendocrine subtype of cancer. Although SCLC patients often initially respond to therapy, tumors nearly always recur, resulting in 5-year survival rate less than 10%. A mouse model has been developed based on the fact that RB and p53 tumor suppressor genes are mutated more 90% human SCLCs. Emerging evidence models suggests p130, gene related RB, may act as cells. To test this idea, we used conditional mutant mice delete p130 combination with Rb adult...
Thyroid transcription factor-1 (TTF-1/Nkx-2.1) is required for formation of the lung and differentiation peripheral respiratory epithelial cells. TTF-1 activates target genes, including surfactant proteins critical function. A recently identified protein TAZ (transcriptional co-activator with PDZ-binding motif) contains a WW domain COOH-terminal motif that are proposed to mediate its interactions various transcriptional proteins. To determine role in regulation gene expression lung, sites...
Since the lung is repeatedly subjected to injury by pathogens and toxicants, maintenance of pulmonary homeostasis requires rapid repair its epithelial surfaces. Ciliated bronchiolar cells, previously considered as terminally differentiated, underwent squamous cell metaplasia within hours after with naphthalene. Expression transcription factors active in morphogenesis differentiation embryonic lung, including beta-catenin, Foxa2, Foxj1, Sox family members (Sox17 Sox2), was dynamically...
Small cell lung carcinoma (SCLC) is a neuroendocrine subtype of cancer that affects more than 200,000 people worldwide every year with very high mortality rate. Here, we used mouse genetics approach to characterize the origin for SCLC; in this model, tumors are initiated by deletion Rb and p53 tumor suppressor genes epithelium adult mice. We found SCLCs often arise epithelium, where cells located, majority early lesions were composed proliferating cells. In addition, mice which deleted...
, encoding an acetyltransferase, is among the most frequently mutated genes in small cell lung cancer (SCLC), a deadly neuroendocrine tumor type. We report acceleration of SCLC upon
The extent to which early events shape tumor evolution is largely uncharacterized, even though a better understanding of these may help identify key vulnerabilities in advanced tumors. Here, using genetically defined mouse models small cell lung cancer (SCLC), we uncovered distinct metastatic programs attributable the type origin. In one model, tumors gain ability through amplification transcription factor NFIB and widespread increase chromatin accessibility, whereas other become absence...
Small cell lung cancer (SCLC) is a devastating neuroendocrine carcinoma. MYCL (L-Myc) frequently amplified in human SCLC, but its roles SCLC progression are poorly understood. We isolated preneoplastic cells from mouse model of and found that ectopic expression L-Myc, c-Myc, or N-Myc conferred tumor-forming capacity. focused on which promoted pre-rRNA synthesis transcriptional programs associated with ribosomal biogenesis. Deletion Mycl two genetically engineered models resulted strong...
Head-out water immersion at thermoneutral temperature (34-35°C) increases cardiac output for a given O2 consumption, leading to relative hyperperfusion of peripheral tissues. To determine if subjects immersed in colder show similar responses and explore the significance hyperperfusion, cardiovascular functions were investigated (impedance cardiography) on 10 men rest while performing exercise leg cycle ergometer (ΔM = ~95 W·m-2) air 34.5°C 30°C, respectively. In resting water, increased by...
Hedgehog (Hh) signaling regulates cell fate and self-renewal in development cancer. Canonical Hh is mediated by ligand binding to the receptor Patched (Ptch), which turn activates Gli-mediated transcription through Smoothened (Smo), molecular target of pathway inhibitors used as cancer therapeutics. Small lung (SCLC) a common, aggressive malignancy with universally poor prognosis. Although preclinical studies have shown that block capacity SCLC cells, lack activating mutations cast doubt...
Oncogenic KRas activates mitochondrial fission through Erk-mediated phosphorylation of the GTPase Drp1. Drp1 deletion inhibits tumorigenesis KRas-driven pancreatic cancer, but role dynamics in other Ras-driven malignancies is poorly defined. Here we show that vitro and vivo growth lung adenocarcinoma unaffected by inhibited Opa1, regulates inner membrane fusion proper cristae morphology. Mechanistically, Opa1 knockout disrupts morphology electron transport chain (ETC) assembly activity,...
EP300, a transcription coactivator important in proliferation and differentiation, is frequently mutated diverse cancer types, including small cell lung (SCLC). While these mutations are thought to result loss of EP300 function, the impact on tumorigenesis remains largely unknown. Here, we demonstrate that mutants lacking acetyltransferase domain accelerate tumor development mouse models SCLC. However, unexpectedly, complete
Purpose: The ganglioside fucosyl-GM1 (FucGM1) is a tumor-associated antigen expressed in large percentage of human small cell lung cancer (SCLC) tumors, but absent most normal adult tissues, making it promising target immuno-oncology. This study was undertaken to evaluate the preclinical efficacy BMS-986012, novel, nonfucosylated, fully IgG1 antibody that binds specifically FucGM1.Experimental Design: antitumor activity BMS-986012 evaluated vitro assays using SCLC cells and mouse xenograft...