A5084773457- Protein Degradation and Inhibitors
- Lung Cancer Treatments and Mutations
- Lung Cancer Research Studies
- Multiple Myeloma Research and Treatments
- Histone Deacetylase Inhibitors Research
- Head and Neck Cancer Studies
- Cancer-related gene regulation
- Helicobacter pylori-related gastroenterology studies
- Chromatin Remodeling and Cancer
- Cervical Cancer and HPV Research
- Cytokine Signaling Pathways and Interactions
- Cancer Immunotherapy and Biomarkers
- Oral Health Pathology and Treatment
- Peptidase Inhibition and Analysis
- Lymphoma Diagnosis and Treatment
- Cancer Mechanisms and Therapy
- Cancer-related molecular mechanisms research
- Tuberous Sclerosis Complex Research
- Epigenetics and DNA Methylation
- Genetics and Neurodevelopmental Disorders
- Cancer-related Molecular Pathways
- RNA modifications and cancer
- Click Chemistry and Applications
- Protein Tyrosine Phosphatases
- Histiocytic Disorders and Treatments
New York University
2023-2024
NYU Langone’s Laura and Isaac Perlmutter Cancer Center
2024
Weatherford College
2022
University of California, San Francisco
2016-2021
Pancreatic Cancer Action Network
2021
UCSF Helen Diller Family Comprehensive Cancer Center
2016-2021
Yale University
2013-2016
Abstract Cetuximab, the FDA-approved anti-EGFR antibody for head and neck squamous cell carcinoma (HNSCC), has displayed limited efficacy due to emergence of intrinsic acquired resistance. We others have demonstrated that cetuximab resistance in HNSCC is driven by alternative receptor tyrosine kinases (RTK), including HER3, MET, AXL. In an effort overcome circumvent toxicities associated with administration multiple RTK inhibitors, we sought identify a common molecular target regulates...
RAS mutations are among the most prevalent oncogenic drivers in cancers. proteins propagate signals only when associated with cellular membranes as a consequence of lipid modifications that impact their trafficking. Here, we discovered RAB27B, RAB family small GTPase, controlled NRAS palmitoylation and trafficking to plasma membrane, localization required for activation. Our proteomic studies revealed RAB27B upregulation CBL- or JAK2-mutated myeloid malignancies, its expression correlated...
We outline a framework for elucidating tumor genetic complexity through multidimensional protein-protein interaction maps and apply it to enhancing our understanding of head neck squamous cell carcinoma. This network uncovers 771 interactions from cancer noncancerous states, including WT mutant protein isoforms. Prioritization cancer-enriched reveals previously unidentified association the fibroblast growth factor receptor tyrosine kinase 3 with Daple, guanine-nucleotide exchange factor,...
Hyperactive mammalian target of rapamycin (mTOR) is associated with cognitive deficits in several neurological disorders including tuberous sclerosis complex (TSC). The phosphorylation the mRNA-binding protein FMRP reportedly depends on mTOR 1 (mTORC1) activity via p70 S6 kinase (S6K1). Because this thought to regulate translation messages important for synaptic plasticity, we explored whether S6K1-dependent residue (S499) altered TSC and states dysregulated TSC-mTORC1 signaling....
Abstract The fragile X mental retardation protein (FMRP) is an mRNA-binding regulator of translation that associates with 4-6% brain transcripts and central to neurodevelopment. Autism risk genes’ are overrepresented among FMRP-binding mRNAs, FMRP loss-of-function mutations responsible for syndrome, the most common cause monogenetic autism. It thought FMRP-dependent translational repression governed by phosphorylation serine residue 499 (S499). However, recent evidence suggests S499 not...
Human papillomavirus (HPV) type 16 is implicated in approximately 75% of head and neck squamous cell carcinomas (HNSCC) that arise the oropharynx, where viral expression E6 E7 oncoproteins promote cellular transformation, tumor growth, maintenance. An important oncogenic signaling pathway activated by PI3K pathway, a key driver carcinogenesis. The also mutation or amplification PIK3CA over half HPV(+) HNSCC. In this study, we investigated efficacy PI3K-targeted therapies HNSCC preclinical...
The epidermal growth factor receptor (EGFR) inhibitor cetuximab is the only FDA-approved oncogene-targeting therapy for head and neck squamous cell carcinoma (HNSCC). Despite variable treatment response, no biomarkers exist to stratify patients in HNSCC. Here, we applied unbiased hierarchical clustering reverse-phase protein array molecular profiles from patient-derived xenograft (PDX) tumors revealed 2 PDX clusters defined by networks associated with EGFR resistance. In vivo validation...
Cyclic STAT3 decoy (CS3D) is a second-generation, double-stranded oligodeoxynucleotide (ODN) that mimics genomic response element for signal transducer and activator of transcription 3 (STAT3), an oncogenic factor. CS3D competitively inhibits binding to target gene promoters, resulting in decreased expression proteins promote cellular proliferation survival. Previous studies have demonstrated antitumor activity preclinical models solid tumors. However, prior entering human clinical trials,...
The epidermal growth factor receptor inhibitor cetuximab is the only oncogene-targeted agent that has been FDA approved for treatment of head and neck squamous cell carcinoma (HNSCC). Currently, there are no biomarkers used in clinic to predict which HNSCC tumors will respond cetuximab, even regress with treatment, acquired resistance occurs majority cases. Though a number mechanisms have identified preclinical studies, therapies targeting these pathways yet effectively translated into...
Cyclic STAT3 decoy (CS3D) is a second-generation, double-stranded oligodeoxynucleotide (ODN) that mimics genomic response element for signal transducer and activator of transcription 3 (STAT3), an oncogenic factor. CS3D competitively inhibits binding to target gene promoters, resulting in decreased expression proteins promote cellular proliferation survival. Previous studies have demonstrated antitumor activity preclinical models solid tumors. However, prior entering human clinical trials,...
Abstract Head and neck squamous cell carcinoma (HNSCC), the sixth most common cancer worldwide, has a five-year survival rate of only 50%. The first targeted agent FDA approved for treatment HNSCC was cetuximab, monoclonal antibody targeting epidermal growth factor receptor (EGFR). Despite EGFR overexpression in up to 90% tumors ample evidence supporting as therapeutic target HNSCC, response single-agent cetuximab is below 20%, resistance cetuximab-containing therapy remains major obstacle...
Abstract Head and neck squamous cell carcinoma (HNSCC), the sixth most common cancer worldwide, has a five-year survival rate of 50%. The last few decades have seen only marginal improvements to due high rates resistance currently available treatments. oncogene-targeted agent that been FDA approved for treatment HNSCC is cetuximab, monoclonal antibody directed against epidermal growth factor receptor (EGFR). response single-agent cetuximab below 20%, both intrinsic acquired remain major...
<div>Abstract<p>Cetuximab, the FDA-approved anti-EGFR antibody for head and neck squamous cell carcinoma (HNSCC), has displayed limited efficacy due to emergence of intrinsic acquired resistance. We others have demonstrated that cetuximab resistance in HNSCC is driven by alternative receptor tyrosine kinases (RTK), including HER3, MET, AXL. In an effort overcome circumvent toxicities associated with administration multiple RTK inhibitors, we sought identify a common molecular...
<p>HER3 blockade enhances the sensitivity of HPV(+) cell lines to BKM120</p>
<p>Pan-phospho-RTK profiling identifies HER3 to be hyper-phosphorylated after BYL719 treatment in HPV(+) cell lines</p>
<p>Blockade of the PI3K pathway with BKM120 or BEZ235 increases HER3/AKT signaling</p>
<div>Abstract<p>Human papillomavirus (HPV) type 16 is implicated in approximately 75% of head and neck squamous cell carcinomas (HNSCC) that arise the oropharynx, where viral expression E6 E7 oncoproteins promote cellular transformation, tumor growth, maintenance. An important oncogenic signaling pathway activated by PI3K pathway, a key driver carcinogenesis. The also mutation or amplification PIK3CA over half HPV(+) HNSCC. In this study, we investigated efficacy PI3K-targeted...
<p>Clinical characteristics of patients prior to surgery and PDX establishment</p>
<p>Legend for supplemental figures</p>