A5051689094- Cancer, Hypoxia, and Metabolism
- Neonatal Respiratory Health Research
- Congenital Diaphragmatic Hernia Studies
- PI3K/AKT/mTOR signaling in cancer
- Lung Cancer Treatments and Mutations
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Lung Cancer Research Studies
- Protein Kinase Regulation and GTPase Signaling
- Biochemical and Molecular Research
- Cancer Genomics and Diagnostics
- Lung Cancer Diagnosis and Treatment
- Endoplasmic Reticulum Stress and Disease
- Metabolism, Diabetes, and Cancer
- Cancer-related Molecular Pathways
- Microbial Metabolic Engineering and Bioproduction
- Genomics and Chromatin Dynamics
- 14-3-3 protein interactions
- Cellular transport and secretion
- Fungal and yeast genetics research
- Tracheal and airway disorders
- DNA Repair Mechanisms
- Bioinformatics and Genomic Networks
- Renal and related cancers
- Glutathione Transferases and Polymorphisms
University of Michigan
2021-2025
Massachusetts Institute of Technology
2006-2024
Dana-Farber Cancer Institute
2016-2024
Massachusetts General Hospital
2013-2024
Allen Institute
2020
Whitehead Institute for Biomedical Research
2006-2011
Howard Hughes Medical Institute
2011
Broad Institute
2006-2008
University of California, San Francisco
2005
Max Planck Institute of Molecular Cell Biology and Genetics
2005
A search for substrates of a growth-promoting kinase revealed regulatory feedback loop involved in tumor suppression.
Small cell lung cancer (SCLC) is an aggressive subtype with extremely poor prognosis. No targetable genetic driver events have been identified, and the treatment landscape for this disease has remained nearly unchanged over 30 years. Here, we taken a CRISPR-based screening approach to identify vulnerabilities in SCLC that may serve as potential therapeutic targets. We used single-guide RNA (sgRNA) library targeting ~5000 genes deemed encode "druggable" proteins perform loss-of-function...
Recently synthesized proteins are sorted at the trans-Golgi network into specialized routes for exocytosis. Surprisingly little is known about underlying molecular machinery. Here, we present a visual screen to search involved in cargo sorting and vesicle formation. We expressed GFP-tagged plasma membrane protein yeast deletion library identified mutants with altered marker localization. This revealed requirement of several enzymes regulating synthesis sphingolipids ergosterol correct...
Using scRNA-seq and microscopy, we describe a cell that is enriched in the lower airways of developing human lung identified by unique coexpression SCGB3A2/SFTPB/CFTR . To functionally interrogate these cells, apply single-cell barcode-based lineage tracing method, called CellTagging, to track fate cells during airway organoid differentiation vitro. Lineage reveals have distinct potential from basal giving rise predominantly pulmonary neuroendocrine subset multiciliated distinguished high C6...
The yeast phosphatidylinositol 4-kinase Pik1p is essential for proliferation, and it controls Golgi homeostasis transport of newly synthesized proteins from this compartment. At the Golgi, 4-phosphate recruits multiple cytosolic effectors involved in formation post-Golgi vesicles. A second pool catalytically active localizes to nucleus. physiological significance regulation dual localization lipid kinase remains unknown. Here, we show that binds redundant 14-3-3 Bmh1p Bmh2p. We provide...
Abstract Lung cancer (LC) remains the top cause of cancer-associated mortality worldwide, with a 10-year overall survival rate only 5%. While most LCs are smoking related, 25% non-small cell LC (NSCLC) diagnosed in patients little or no history. Fusions involving anaplastic lymphoma kinase (ALK) oncogenic driver ∼3–7% NSCLC. inhibitors targeting domain ALK have proven effective, inevitably, resistance develops limited subsequent efficacious options. We aimed to integrate multiomic...
Abstract ALK fusions are the third most-prevalent mutation in lung adenocarcinoma (LUAD). Afflicting never-smokers, ALK-positive cancer presents unique diagnostic challenges and treatment resistance compared to other LUAD subtypes. To better understand time course of tumorigenesis Alk-mutant LUAD, make inferences regarding cell origin, earliest cellular changes that occur ALK-dependent transformation, we studied a previously published mouse tumor model whereby Eml4-Alk translocation is...
The evolutionarily conserved target of rapamycin complex 1 (TORC1) controls cell growth in response to nutrient availability and factors. TORC1 signaling is hyperactive cancer, regulators may represent therapeutic targets for human diseases. To identify novel signaling, we performed a genome-scale RNA interference screen on microarrays Drosophila melanogaster cells expressing RPS6, effector whose phosphorylated form detected by immunofluorescence. Our revealed that the TORC1-S6K-RPS6 axis...
Alveolar type 2 (AT2) cells function as stem in the adult lung and aid repair after injury. The current study aimed to understand signaling events that control differentiation of this therapeutically relevant cell during human development. Using explant organoid models, we identified opposing effects TGFβ- BMP-signaling, where inhibition activation BMP-signaling context high WNT- FGF-signaling efficiently differentiated early progenitors into AT2-like vitro. manner exhibit surfactant...
A challenge for screening new candidate drugs to treat cancer is that efficacy in cell culture models not always predictive of patients. One limitation standard a reliance on non-physiological nutrient levels propagate cells. Which nutrients are available can influence how cells use metabolism proliferate and impact sensitivity some drugs, but general assessment physiological affect response small molecule therapies lacking. To enable compounds determine the environment impacts drug...
ABSTRACT Control of cellular identity requires coordination developmental programs with environmental factors such as nutrient availability, suggesting that modulating aspects metabolism could alter cell state along differentiation trajectories. Here we find nucleotide depletion and DNA replication stress are common drivers progression across a variety normal transformed hematopoietic systems. stress-induced transitions begin during S phase independent ATR/ATM checkpoint signaling,...
Substance P (SP) is a peptide neurotransmitter that involved in multiple responses both the central and peripheral nervous systems through G-protein-coupled receptor. The primary structure of rat SP receptor contains number conserved cysteine residues. To localize identify residues participate binding, intact Chinese hamster ovary cells expressing were treated with various sulfhydryl reagents effect these on radioiodinated binding affinity dissociation rate was determined. We used series...
Abstract Background: Lung cancer (LC) remains the top cause of cancer-associated mortality worldwide, with a 10-year overall survival rate only 5%. While most LCs are smoking related, in US, 25% non-small cell LC (NSCLC) diagnosed patients little or no history. Fusions involving anaplastic lymphoma kinase (ALK) oncogenic driver ~3-7% NSCLC. inhibitors targeting domain ALK (TKIs) have proven extremely effective, inevitably, resistance develops limited effective treatment options....