Biography
Education
Institution | Degree | Dept or School | End Date |
---|---|---|---|
Memorial Sloan Kettering Cancer Center | Medical Oncology and cancer biology post-doctoral fellowship | 2011 | |
Brigham and Women's Hospital/Harvard | Internal Medicine | 2007 | |
New York University School of Medicine | M.D. | School of Medicine | 2005 |
New York University School of Medicine | Ph.D. | Cell and Molecular Biology | 2004 |
Board Certifications
American Board of Internal Medicine, Internal Medicine
American Board of Internal Medicine, Medical Oncology
Clinical Expertise
Bronchioloalveolar Carcinoma (BAC)
Chest Wall Tumors
Lung Carcinoid Tumors
Lung Metastases
Malignant Mesothelioma
Mediastinal Tumors
Non-Small Cell Lung Cancer
Small Cell Lung Cancer
Thymoma & Thymic Carcinoma
Target Therapies in Lung Cancer
Program Affiliations
Department of Medicine, Division of Hematology/Oncology
Thoracic Oncology Program
Member, UCSF Helen Diller Family Comprehensive Cancer Center
Member, UCSF Biomedical Sciences Graduate Program (BMS)
Member, California Institute for Quantitative Biosciences (QB3)
Grants and Funding
- UCSF Paul Calabresi K12 Career Development Program in Clinical Oncology | NIH | 2021-07-01 - 2026-06-30 | Role: Co-Principal Investigator
- (PQ7) Defining a new mode of RAS signaling in cancer from cytoplasmic protein granules | NIH | 2019-07-01 - 2024-06-30 | Role: Principal Investigator
- Rational Combined Inhibition of NF-kB and EGFR to Optimize Lung Cancer Treatment | NIH | 2013-02-01 - 2024-01-31 | Role: Principal Investigator
- Bay Area Team Against Resistance | NIH | 2017-09-30 - 2022-08-31 | Role: Principal Investigator
- The Cancer Target Discovery and Development Network at UCSF | NIH | 2017-08-10 - 2022-07-31 | Role: Co-Principal Investigator
- Characterization of YAP as a rational companion target in lung cancer | NIH | 2017-03-01 - 2022-02-28 | Role: Principal Investigator
- Optimizing biologically-based rational polytherapy in ALK+ lung cancer | NIH | 2017-01-11 - 2021-12-31 | Role: Principal Investigator
- Discovery of Rational Companion Therapeutic Targets to Optimize Cancer Treatment | NIH | 2012-09-15 - 2017-08-31 | Role: Principal Investigator
- Genetic Modifiers such as Fas Regulate Tumor-Cell Dependence on Mutant EGFR | NIH | 2011-09-21 - 2016-08-31 | Role: Principal Investigator
Research Narrative
I am a laboratory-based physician-scientist and an academic medical oncologist with a Ph.D. in cell and molecular biology. Clinical experiences inspire my laboratory investigations and provide opportunities to translate scientific discoveries aimed at improving the personalized treatment of cancer patients. The goal of my research program is to define the molecular pathogenesis of human cancers through both basic and translational studies with a particular focus on lung cancer, the leading cause of cancer mortality in the United States.
Our aim is to discover tumor-cell specific vulnerabilities that can be therapeutically exploited as novel treatment strategies to improve the survival of patients with lung, and potentially, other cancers. To accomplish our goals, we have a developed an integrated approach to define the molecular mechanisms by which oncogenes drive the growth of human lung cancers and by which tumors evade oncogene-targeted treatments.
Our approach leverages state-of-the-art functional genomics RNA interference screening methodologies, highly relevant preclinical models of lung cancer that accurately represent human lung cancer, and prospectively acquired human lung cancer specimens and clinical data. Using this approach we recently identified several novel mechanisms of resistance to EGFR (epidermal growth factor receptor) inhibitors in lung cancers with activating (oncogenic) mutations in EGFR. Our work has defined new rational companion therapeutic targets that when inhibited may enhance responses to EGFR inhibitors in lung cancer patients
The studies proposed in this project build upon our prior research because they will allow us to further define molecular determinants of oncogene dependence in human lung cancers. Moreover, we are uniquely positioned to translate our findings into lung cancer patients through validation of our findings in human lung cancer specimens and, subsequently, hypothesis-driven clinical trials in lung cancer patients.
Research Interests
Lung cancer
Molecular pathogenesis of human cancers
Molecularly-targeted cancer therapies
Next-generation functional genomics
Novel, rational therapeutic strategies
Activating mutations in EGFR
Mechanisms of Secondary Resistance
Publications
- Phase-Separated Biomolecular Condensation in Cancer: New Horizons and Next Frontiers.| | View in PubMed
- Unlocking the EGFR-mediated epitranscriptome: A pathway to novel therapies.| | View in PubMed
- The role of APOBEC3B in lung tumor evolution and targeted cancer therapy resistance.| | View in PubMed
- The essential chaperone DNAJC17 activates HSP70 to coordinate RNA splicing and G2-M progression.| | View in PubMed
- Long Non-Coding RNAs as Emerging Targets in Lung Cancer.| | View in PubMed
- Author Correction: 3-Phosphoinositide-dependent kinase 1 drives acquired resistance to osimertinib.| | View in PubMed
- FET fusion oncoproteins disrupt physiologic DNA repair networks and induce ATR synthetic lethality in cancer.| | View in PubMed
- FET fusion oncoproteins disrupt physiologic DNA repair networks in cancer.| | View in PubMed
- 3-Phosphoinositide-dependent kinase 1 drives acquired resistance to osimertinib.| | View in PubMed
- GATOR2-dependent mTORC1 activity is a therapeutic vulnerability in FOXO1 fusion-positive rhabdomyosarcoma.| | View in PubMed
- Phase 1 Study of Ceritinib Combined With Trametinib in Patients With Advanced ALK- or ROS1-Positive NSCLC.| | View in PubMed
- AXL and Error-Prone DNA Replication Confer Drug Resistance and Offer Strategies to Treat EGFR-Mutant Lung Cancer.| | View in PubMed
- Quantitative Framework for Bench-to-Bedside Cancer Research.| | View in PubMed
- Primary and metastatic tumors exhibit systems-level differences in dependence on mitochondrial respiratory function.| | View in PubMed
- Deficiency of the splicing factor RBM10 limits EGFR inhibitor response in EGFR-mutant lung cancer.| | View in PubMed
- Lineage tracing reveals the phylodynamics, plasticity, and paths of tumor evolution.| | View in PubMed
- Understanding Drug Sensitivity and Tackling Resistance in Cancer.| | View in PubMed
- Small-molecule targeted therapies induce dependence on DNA double-strand break repair in residual tumor cells.| | View in PubMed
- Remodeling of the tumor/tumor microenvironment ecosystem during KRAS G12C inhibitor clinical resistance in lung cancer.| | View in PubMed
- Digital multiplexed analysis of circular RNAs in FFPE and fresh non-small cell lung cancer specimens.| | View in PubMed
- Evolution of metastasis: new tools and insights.| | View in PubMed
- Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids.| | View in PubMed
- DDX56 modulates post-transcriptional Wnt signaling through miRNAs and is associated with early recurrence in squamous cell lung carcinoma.| | View in PubMed
- Targeting AXL in NSCLC.| | View in PubMed
- Exocyst protein subnetworks integrate Hippo and mTOR signaling to promote virus detection and cancer.| | View in PubMed
- Inhibition of SHP2 as an approach to block RAS-driven cancers.| | View in PubMed
- Liquid Biopsy for Advanced NSCLC: A Consensus Statement From the International Association for the Study of Lung Cancer.| | View in PubMed
- Stepwise evolution of therapy resistance in AML.| | View in PubMed
- Kinase-mediated RAS signaling via membraneless cytoplasmic protein granules.| | View in PubMed
- Single-cell lineages reveal the rates, routes, and drivers of metastasis in cancer xenografts.| | View in PubMed
- Allosteric SHP2 inhibitors in cancer: Targeting the intersection of RAS, resistance, and the immune microenvironment.| | View in PubMed
- Functional screening identifies aryl hydrocarbon receptor as suppressor of lung cancer metastasis.| | View in PubMed
- Long non-coding RNA ESCCAL-1 promotes esophageal squamous cell carcinoma by down regulating the negative regulator of APOBEC3G.| | View in PubMed
- Therapy-Induced Evolution of Human Lung Cancer Revealed by Single-Cell RNA Sequencing.| | View in PubMed
- Multi-faceted epigenetic dysregulation of gene expression promotes esophageal squamous cell carcinoma.| | View in PubMed
- Molecular Landscape of BRAF-Mutant NSCLC Reveals an Association Between Clonality and Driver Mutations and Identifies Targetable Non-V600 Driver Mutations.| | View in PubMed
- EGFR targeted therapy resistance: current status, challenges, and future outlook.| | View in PubMed
- Betacellulin drives therapy resistance in glioblastoma.| | View in PubMed
- AXL Targeting Abrogates Autophagic Flux and Induces Immunogenic Cell Death in Drug-Resistant Cancer Cells.| | View in PubMed
- Overcoming the challenges of cancer drug resistance through bacterial-mediated therapy.| | View in PubMed
- Co-occurring Alterations in the RAS-MAPK Pathway Limit Response to MET Inhibitor Treatment in MET Exon 14 Skipping Mutation-Positive Lung Cancer.| | View in PubMed
- BRAF Mutations Classes I, II, and III in NSCLC Patients Included in the SLLIP Trial: The Need for a New Pre-Clinical Treatment Rationale.| | View in PubMed
- Synthetic Essentiality of Metabolic Regulator PDHK1 in PTEN-Deficient Cells and Cancers.| | View in PubMed
- Targeting Oncogenic BRAF: Past, Present, and Future.| | View in PubMed
- CIC-DUX4 oncoprotein drives sarcoma metastasis and tumorigenesis via distinct regulatory programs.| | View in PubMed
- Engineering Multidimensional Evolutionary Forces to Combat Cancer.| | View in PubMed
- Dampening oncogenic RAS signaling.| | View in PubMed
- Emerging Targeted Therapies for the Treatment of Non-small Cell Lung Cancer.| | View in PubMed
- Polytherapy and Targeted Cancer Drug Resistance.| | View in PubMed
- Use of nonsteroidal anti-inflammatory drugs predicts improved patient survival for PIK3CA-altered head and neck cancer.| | View in PubMed
- Principles of Resistance to Targeted Cancer Therapy: Lessons from Basic and Translational Cancer Biology.| | View in PubMed
- Immunohistochemistry to Study YAP in Human Tissue Samples.| | View in PubMed
- Differential Subcellular Localization Regulates Oncogenic Signaling by ROS1 Kinase Fusion Proteins.| | View in PubMed
- Aurora kinase A drives the evolution of resistance to third-generation EGFR inhibitors in lung cancer.| | View in PubMed
- Pathologic Complete Response to Neoadjuvant Crizotinib in a Lung Adenocarcinoma Patient With a MET Exon 14 Skipping Mutation.| | View in PubMed
- Circulating tumor DNA analysis in patients with EGFR mutant lung cancer.| | View in PubMed
- Compensatory increases of select proteostasis networks after Hsp70 inhibition in cancer cells.| | View in PubMed
- Cancer mutations and targeted drugs can disrupt dynamic signal encoding by the Ras-Erk pathway.| | View in PubMed
- RAS nucleotide cycling underlies the SHP2 phosphatase dependence of mutant BRAF-, NF1- and RAS-driven cancers.| | View in PubMed
- Liquid Biopsy for Advanced Non-Small Cell Lung Cancer (NSCLC): A Statement Paper from the IASLC.| | View in PubMed
- TNF-driven adaptive response mediates resistance to EGFR inhibition in lung cancer.| | View in PubMed
- Emerging application of genomics-guided therapeutics in personalized lung cancer treatment.| | View in PubMed
- BRAF in Lung Cancers: Analysis of Patient Cases Reveals Recurrent BRAF Mutations, Fusions, Kinase Duplications, and Concurrent Alterations.| | View in PubMed
- Oncogenic Signaling Pathways in The Cancer Genome Atlas.| | View in PubMed
- The evolving understanding of immunoediting and the clinical impact of immune escape.| | View in PubMed
- Common Co-activation of AXL and CDCP1 in EGFR-mutation-positive Non-smallcell Lung Cancer Associated With Poor Prognosis.| | View in PubMed
- Non-Canonical Thinking for Targeting ALK-Fusion Onco-Proteins in Lung Cancer.| | View in PubMed
- Imaging PD-L1 Expression with ImmunoPET.| | View in PubMed
- Evolution and clinical impact of co-occurring genetic alterations in advanced-stage EGFR-mutant lung cancers.| | View in PubMed
- Understanding and targeting resistance mechanisms in NSCLC.| | View in PubMed
- Simultaneous evolutionary expansion and constraint of genomic heterogeneity in multifocal lung cancer.| | View in PubMed
- Current Landscape of Targeted Therapy in Lung Cancer.| | View in PubMed
- Convergent Akt activation drives acquired EGFR inhibitor resistance in lung cancer.| | View in PubMed
- Co-activation of STAT3 and YES-Associated Protein 1 (YAP1) Pathway in EGFR-Mutant NSCLC.| | View in PubMed
- Activation of signal transducer and activator of transcription 3 (STAT3) signaling in EGFR mutant non-small-cell lung cancer (NSCLC).| | View in PubMed
- A Case of Metastatic Atypical Neuroendocrine Tumor with ALK Translocation and Diffuse Brain Metastases.| | View in PubMed
- Resistance is futile: overcoming resistance to targeted therapies in lung adenocarcinoma.| | View in PubMed
- Novel computational method for predicting polytherapy switching strategies to overcome tumor heterogeneity and evolution.| | View in PubMed
- Dividing and conquering the variation among variants in EML4-ALK lung cancer.| | View in PubMed
- CD74-ROS1 Fusion in NSCLC Detected by Hybrid Capture-Based Tissue Genomic Profiling and ctDNA Assays.| | View in PubMed
- Superior Efficacy and Selectivity of Novel Small-Molecule Kinase Inhibitors of T790M-Mutant EGFR in Preclinical Models of Lung Cancer.| | View in PubMed
- Metastasis: From head to tail.| | View in PubMed
- Transcriptomic-metabolomic reprogramming in EGFR-mutant NSCLC early adaptive drug escape linking TGFβ2-bioenergetics-mitochondrial priming.| | View in PubMed
- Inactivation of Capicua drives cancer metastasis.| | View in PubMed
- Preclinical efficacy of a RAF inhibitor that evades paradoxical MAPK pathway activation in protein kinase BRAF-mutant lung cancer.| | View in PubMed
- HSP70 dependence in rhabdomyosarcoma: Seed or soil?| | View in PubMed
- Combined chemical-genetic approach identifies cytosolic HSP70 dependence in rhabdomyosarcoma.| | View in PubMed
- An improved CTC isolation scheme for pairing with downstream genomics: Demonstrating clinical utility in metastatic prostate, lung and pancreatic cancer.| | View in PubMed
- Neoadjuvant Oncogene-Targeted Therapy in Early Stage Non-Small-Cell Lung Cancer as a Strategy to Improve Clinical Outcome and Identify Early Mechanisms of Resistance.| | View in PubMed
- A framework for understanding and targeting residual disease in oncogene-driven solid cancers.| | View in PubMed
- RAS signaling in ALK fusion lung cancer.| | View in PubMed
- Tracking Down Response and Resistance to TRK Inhibitors.| | View in PubMed
- RAS-MAPK signaling influences the efficacy of ALK-targeting agents in lung cancer.| | View in PubMed
- RAS-MAPK dependence underlies a rational polytherapy strategy in EML4-ALK-positive lung cancer.| | View in PubMed
- Cell-Free DNA Next-Generation Sequencing in Pancreatobiliary Carcinomas.| | View in PubMed
- Oncogenic activation of the PI3-kinase p110β isoform via the tumor-derived PIK3Cβ(D1067V) kinase domain mutation.| | View in PubMed
- AXL receptor tyrosine kinase as a therapeutic target in NSCLC.| | View in PubMed
- The Hippo effector YAP regulates the response of cancer cells to MAPK pathway inhibitors.| | View in PubMed
- AXL mediates resistance to PI3Kα inhibition by activating the EGFR/PKC/mTOR axis in head and neck and esophageal squamous cell carcinomas.| | View in PubMed
- NF-κB-activating complex engaged in response to EGFR oncogene inhibition drives tumor cell survival and residual disease in lung cancer.| | View in PubMed
- AUY922 effectively overcomes MET- and AXL-mediated resistance to EGFR-TKI in lung cancer cells.| | View in PubMed
- Adaptive stress signaling in targeted cancer therapy resistance.| | View in PubMed
- The Hippo effector YAP promotes resistance to RAF- and MEK-targeted cancer therapies.| | View in PubMed
- RAS-MAPK in ALK targeted therapy resistance.| | View in PubMed
- YAP in MAPK pathway targeted therapy resistance.| | View in PubMed
- Plasma mRNA expression levels of BRCA1 and TS as potential predictive biomarkers for chemotherapy in gastric cancer.| | View in PubMed
- Novel therapeutic strategies for patients with NSCLC that do not respond to treatment with EGFR inhibitors.| | View in PubMed
- Mapping the molecular determinants of BRAF oncogene dependence in human lung cancer.| | View in PubMed
- The impact of EGFR T790M mutations and BIM mRNA expression on outcome in patients with EGFR-mutant NSCLC treated with erlotinib or chemotherapy in the randomized phase III EURTAC trial.| | View in PubMed
- Activating mutations cluster in the "molecular brake" regions of protein kinases and do not associate with conserved or catalytic residues.| | View in PubMed
- Recent advances in personalized lung cancer medicine.| | View in PubMed
- Genetics and biomarkers in personalisation of lung cancer treatment.| | View in PubMed
- FGFR fusions in the driver's seat.| | View in PubMed
- Mechanisms of resistance to EGFR targeted therapies.| | View in PubMed
- Secrets of drug resistance in NSCLC exposed by new molecular definition of EMT.| | View in PubMed
- Resiliency of lung cancers to EGFR inhibitor treatment unveiled, offering opportunities to divide and conquer EGFR inhibitor resistance.| | View in PubMed
- Mechanisms of Resistance to Epidermal Growth Factor Receptor Inhibitors and Novel Therapeutic Strategies to Overcome Resistance in NSCLC Patients.| | View in PubMed
- Activation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer.| | View in PubMed
- Genomic dissection of the epidermal growth factor receptor (EGFR)/PI3K pathway reveals frequent deletion of the EGFR phosphatase PTPRS in head and neck cancers.| | View in PubMed
- FAS and NF-κB signalling modulate dependence of lung cancers on mutant EGFR.| | View in PubMed
- Pretreatment EGFR T790M mutation and BRCA1 mRNA expression in erlotinib-treated advanced non-small-cell lung cancer patients with EGFR mutations.| | View in PubMed
- Analysis of K-Ras phosphorylation, translocation, and induction of apoptosis.| | View in PubMed
- PKC regulates a farnesyl-electrostatic switch on K-Ras that promotes its association with Bcl-XL on mitochondria and induces apoptosis.| | View in PubMed
- Analysis of Ras activation in living cells with GFP-RBD.| | View in PubMed
- Analysis of Ras and Rap activation in living cells using fluorescent Ras binding domains.| | View in PubMed
- Cannabinoid receptor-induced neurite outgrowth is mediated by Rap1 activation through G(alpha)o/i-triggered proteasomal degradation of Rap1GAPII.| | View in PubMed
- Identification of a Ras GTPase-activating protein regulated by receptor-mediated Ca2+ oscillations.| | View in PubMed
- Membranes as messengers in T cell adhesion signaling.| | View in PubMed
- Ras activation in Jurkat T cells following low-grade stimulation of the T-cell receptor is specific to N-Ras and occurs only on the Golgi apparatus.| | View in PubMed
- Shp2 regulates SRC family kinase activity and Ras/Erk activation by controlling Csk recruitment.| | View in PubMed
- Rap1 up-regulation and activation on plasma membrane regulates T cell adhesion.| | View in PubMed
- Intersectin activates Ras but stimulates transcription through an independent pathway involving JNK.| | View in PubMed
- Phospholipase Cgamma activates Ras on the Golgi apparatus by means of RasGRP1.| | View in PubMed
- Ras pathway signaling on endomembranes.| | View in PubMed
- Ras signalling on the endoplasmic reticulum and the Golgi.| | View in PubMed
- Toxoplasma gondii Rab5 enhances cholesterol acquisition from host cells.| | View in PubMed