A5037110426- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Melanoma and MAPK Pathways
- RNA Research and Splicing
- PI3K/AKT/mTOR signaling in cancer
- Cancer, Hypoxia, and Metabolism
- interferon and immune responses
- Advanced biosensing and bioanalysis techniques
- Angiogenesis and VEGF in Cancer
- Protein Tyrosine Phosphatases
- Photoacoustic and Ultrasonic Imaging
- RNA regulation and disease
- Biotin and Related Studies
- Dermatology and Skin Diseases
- Hedgehog Signaling Pathway Studies
- Ubiquitin and proteasome pathways
- Axon Guidance and Neuronal Signaling
- Cell Adhesion Molecules Research
- Venous Thromboembolism Diagnosis and Management
- Genomics and Chromatin Dynamics
- Antimicrobial Resistance in Staphylococcus
- Immune cells in cancer
- Advanced Breast Cancer Therapies
- Bacterial biofilms and quorum sensing
UCSF Helen Diller Family Comprehensive Cancer Center
2021-2025
University of California, San Francisco
2021-2025
Stanford University
2012-2019
VA Palo Alto Health Care System
2012-2014
Stratford University
2013
Washington University in St. Louis
2010
Aberrations of protein-coding genes are a focus cancer genomics; however, the impact oncogenes on expression ~50% transcripts without potential, including long noncoding RNAs (lncRNAs), has been largely uncharacterized. Activating mutations in BRAF oncogene present >70% melanomas, 90% which produce active mutant BRAF(V600E) protein. To define impacts oncogenic melanocyte transcriptome, massively parallel cDNA sequencing (RNA-seq) was performed genetically matched normal human melanocytes...
Although our understanding of the molecular regulation adult neovascularization has advanced tremendously, vascular-targeted therapies for tissue ischemia remain suboptimal. The master regulatory transcription factors hypoxia-inducible factor (HIF) family are attractive therapeutic targets because they coordinately up-regulate multiple genes controlling neovascularization. Here, we used an inducible model epithelial HIF-1 activation, TetON-HIF-1 mouse, to test requirement VEGF in mediated...
Thousands of putative enhancers are characterized in the human genome, yet few have been shown to a functional role cancer progression. Inhibiting oncokinases, such as EGFR, ALK, ERBB2, and BRAF, is mainstay current therapy but hindered by innate drug resistance mediated up-regulation HGF receptor, MET. The mechanisms mediating genomic responses targeted unknown. Here, we identify lineage-specific at MET locus for multiple common tumor types, including melanoma enhancer 63 kb downstream from...
Drug combinations are key to circumvent resistance mechanisms compromising response single anti-cancer targeted therapies. The implementation of combinatorial approaches involving MEK1/2 or KRASG12C inhibitors in the context KRAS-mutated lung cancers focuses fundamentally on targeting KRAS proximal activators effectors. However, antitumor effect is highly determined by compensatory arising defined cell types tumor subgroups. A potential strategy find drug a larger fraction may capitalize...
Abstract KRAS receives and relays signals at the plasma membrane (PM) where it transmits extracellular growth factor to downstream effectors. SNORD50A/B were recently found bind inhibit its tumorigenic action by unknown mechanisms. proximity protein labeling was therefore undertaken in wild-type knockout cells, revealing that RNAs shape composition of proteins proximal KRAS, notably inhibiting SNARE vesicular transport SNAP23, SNAP29, VAMP3. To remain enriched on PM, undergoes cycles...
A major obstacle in studying angiogenesis is the inability to noninvasively image neovascular development an individual animal. We applied optical-resolution photoacoustic microscopy (OR-PAM) determine kinetics of hypoxia-inducible factor-1 (HIF-1)-mediated a transgenic mouse model. During continuous 30-day activation HIF-1α, we used OR-PAM monitor alterations microvasculature mice compared nontransgenic mice. has demonstrated potential precisely antiangiogenic therapy human cancers,...
Although oncogenic mutations in the three major Ras isoforms, KRAS, HRAS and NRAS, are present nearly a third of human cancers, therapeutic targeting remains challenge due to its structure complex regulation. However, an in-depth examination protein interactome may provide new insights into key regulators, effectors other mediators tumorigenic functions. Previous proteomic analyses have been limited by experimental tools that fail capture dynamic, transient nature cellular interactions....
Abstract Oncogenic protein dosage is tightly regulated to enable cancer cells adapt and survive. In healthy cells, translation initiation of onco-mRNA transcripts encoding oncogenes growth factors maintain accurate expression levels. However, this process broken in which rely on the maintenance high oncogenic proteins for their survival drive development. Whether at level translational control key cis trans remain unknown. The Myc oncogene a central paradigm an exquisitely major driver...
ABSTRACT Oncogenic protein dosage is tightly regulated to enable cancer cells adapt and survive. Whether this at the level of translational control key factors in cis trans remain unknown. The Myc oncogene a central paradigm an exquisitely major driver pancreatic ductal adenocarcinoma (PDAC). Using functional genome-wide CRISPRi screen PDAC cells, we identified activators selective MYC translation through its 5’ untranslated region (5’UTR) validated four RNA binding proteins (RBPs),...
Abstract Aberrations of protein-coding genes are a focus cancer genomics; however, the impact oncogenes on expression ~50% transcripts without potential, including long noncoding RNAs (lncRNAs), has been largely uncharacterized. Activating mutations in BRAF oncogene present >70% melanomas, 90% which produce active mutant BRAF(V600E) protein. To define impacts oncogenic melanocyte transcriptome, massively parallel cDNA sequencing (RNA-seq) was performed genetically matched normal human...
Abstract Resistance mechanisms compromise response to single targeted therapies, favoring the idea that combinatorial strategies are key circumvent this clinical problem. Combinatorial for cancers driven by oncogenic KRAS based on MEK1/2 or KRASG12C inhibitors have so far incorporated abrogation of proximal effectors involved in oncogenesis treatment resistance. However, antitumor effect is highly determined compensatory specifically arising certain cell types tumor subgroups. A potential...
Abstract Aberrations of protein-coding genes are a focus cancer genomics, however, the impact oncogenes on expression ~50% transcripts without potential, including long non-coding RNAs (lncRNAs), is largely uncharacterized. Activating mutations in BRAF oncogene present 60% melanomas, 90% which produce active mutant BRAFV600E. To define impacts oncogenic melanocyte transcriptome, massively parallel cDNA sequencing (RNA-Seq) was performed genetically matched normal human melanocytes with and...