A5009011087- Lung Cancer Treatments and Mutations
- RNA modifications and cancer
- Ferroptosis and cancer prognosis
- Cancer Immunotherapy and Biomarkers
- Protein Degradation and Inhibitors
- Monoclonal and Polyclonal Antibodies Research
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Cancer-related gene regulation
- Lung Cancer Research Studies
- Protein Kinase Regulation and GTPase Signaling
- Cardiac Imaging and Diagnostics
- Ubiquitin and proteasome pathways
- Multiple Myeloma Research and Treatments
- Peptidase Inhibition and Analysis
- Cytokine Signaling Pathways and Interactions
- Immune Cell Function and Interaction
- Coronary Interventions and Diagnostics
- Cardiovascular Function and Risk Factors
- Heart Rate Variability and Autonomic Control
- Click Chemistry and Applications
- Cancer, Stress, Anesthesia, and Immune Response
- Lung Cancer Diagnosis and Treatment
- interferon and immune responses
- Cardiac electrophysiology and arrhythmias
- Melanoma and MAPK Pathways
University of California, Irvine
2022-2023
California State University, Long Beach
2023
Scripps Clinic
2020-2022
Long Beach Medical Center
2022
Scripps (United States)
2020-2021
Scripps Institution of Oceanography
2020-2021
Dana-Farber Cancer Institute
2012-2014
Harvard University
2013-2014
Massachusetts General Hospital
2013-2014
Broad Institute
2013-2014
The success in lung cancer therapy with programmed death (PD)-1 blockade suggests that immune escape mechanisms contribute to tumor pathogenesis. We identified a correlation between EGF receptor (EGFR) pathway activation and signature of immunosuppression manifested by upregulation PD-1, PD-L1, CTL antigen-4 (CTLA-4), multiple tumor-promoting inflammatory cytokines. observed decreased CTLs increased markers T-cell exhaustion mouse models EGFR-driven cancer. PD-1 antibody improved the...
Amplification of MYC is one the most common genetic alterations in lung cancer, contributing to a myriad phenotypes associated with growth, invasion, and drug resistance. Murine genetics has established both centrality somatic Kras as well dependency mutant tumors on function. Unfortunately, drug-like small-molecule inhibitors KRAS have yet be realized. The recent discovery, hematologic malignancies, that bromodomain extra-terminal (BET) inhibition impairs expression transcriptional function...
Although the roles of mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) signaling in KRAS-driven tumorigenesis are well established, KRAS activates additional pathways required for tumor maintenance, inhibition which likely to be necessary effective KRAS-directed therapy. Here, we show that IκB (IKK)-related kinases Tank-binding kinase-1 (TBK1) IKKε promote by regulating autocrine CCL5 interleukin (IL)-6 identify CYT387 as a potent JAK/TBK1/IKKε inhibitor....
The LKB1/STK11 tumor suppressor encodes a serine/threonine kinase, which coordinates cell growth, polarity, motility, and metabolism. In non-small lung carcinoma, LKB1 is somatically inactivated in 25% to 30% of cases, often concurrently with activating KRAS mutations. Here, we used an integrative approach define novel therapeutic targets KRAS-driven LKB1-mutant cancers. High-throughput RNA interference screens cancer lines from genetically engineered mouse models driven by activated or...
Triple-negative breast cancers (TNBCs) are a heterogeneous set of that defined by the absence hormone receptor expression and HER2 amplification. Here, we found inducible IκB kinase-related (IKK-related) kinase IKBKE JAK/STAT pathway activation compose cytokine signaling network in immune-activated subset TNBC. We treatment cultured IKBKE-driven cancer cells with CYT387, potent inhibitor TBK1/IKBKE JAK signaling, impairs proliferation, while inhibition alone does not. CYT387 inhibited both...
Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) have been discovered several cancer types cause the neurometabolic syndrome D2-hydroxyglutaric aciduria (D2HGA). The mutant enzymes exhibit neomorphic activity resulting production of acid (D-2HG). To study pathophysiological consequences accumulation D-2HG, we generated transgenic mice with conditionally activated IDH2 R140Q R172K alleles. Global induction expression adults resulted dilated cardiomyopathy, white matter abnormalities...
The rapid development of digital health devices has enabled patients to engage in their care an unprecedented degree and holds the possibility significantly improving diagnosis, treatment monitoring many medical conditions. Combined with emergence artificial intelligence algorithms, biometric datasets produced from these present new opportunities create precision-based, personalized approaches for healthcare delivery. For effective implementation such innovations patient care, clinicians...
Background Phase space is a mechanical systems approach and large-scale data representation of an object in 3-dimensional space. Whether such techniques can be applied to predict left ventricular pressures non-invasively at the point-of-care unknown. Objective This study prospectively validated phase machine-learned based on novel electro-mechanical pulse wave method collection through orthogonal voltage gradient (OVG) photoplethysmography (PPG) for prediction elevated end diastolic pressure...
Introduction Elevated left ventricular end diastolic pressure (LVEDP) is a consequence of compromised compliance and an important measure myocardial dysfunction. An algorithm was developed to predict elevated LVEDP utilizing electro-mechanical (EM) waveform features. We examined the hierarchical clustering selected features from these EM waveforms in order identify patient subgroups assess their possible prognostic significance. Materials methods Patients presenting with cardiovascular...
Abstract Although KRAS is the most commonly mutated oncogene in human cancer, has proven difficult to target pharmacologically, and no effective therapies exist for KRAS-mutant cancers. Recently, there been evidence that targeted therapy combinations inhibiting multiple downstream effectors of may be a promising approach We developed pooled shRNA-drug screen strategy identify genes that, when inhibited, cooperate with MEK inhibitors kill cancer cells. The anti-apoptotic BH3 family gene...
<p>Supplementary Methods - PDF file 201K, Supplementary Methods</p>
<p>Supplementary Figures - PDF file 770K, Supplementary Figure 1. JQ1 treatment induces apoptosis proliferation arrest in a subset of NSCLC cells 2. promotes depletion 57kDa MYC time dependent manner 3. FOSL1 is induced by regardless the status LKB1 4. mutant kras mouse induce apoptosis</p>
<p>Supplementary Methods - PDF file 201K, Supplementary Methods</p>
<p>Supplementary Figures - PDF file 770K, Supplementary Figure 1. JQ1 treatment induces apoptosis proliferation arrest in a subset of NSCLC cells 2. promotes depletion 57kDa MYC time dependent manner 3. FOSL1 is induced by regardless the status LKB1 4. mutant kras mouse induce apoptosis</p>
<div>Abstract<p><b>Purpose:</b> Amplification of <i>MYC</i> is one the most common genetic alterations in lung cancer, contributing to a myriad phenotypes associated with growth, invasion, and drug resistance. Murine genetics has established both centrality somatic <i>Kras</i> as well dependency mutant tumors on MYC function. Unfortunately, drug-like small-molecule inhibitors KRAS have yet be realized. The recent discovery, hematologic...
<div>Abstract<p><b>Purpose:</b> Amplification of <i>MYC</i> is one the most common genetic alterations in lung cancer, contributing to a myriad phenotypes associated with growth, invasion, and drug resistance. Murine genetics has established both centrality somatic <i>Kras</i> as well dependency mutant tumors on MYC function. Unfortunately, drug-like small-molecule inhibitors KRAS have yet be realized. The recent discovery, hematologic...
<p>- PDF file 2020K, Supplementary figures 1-11. For the mouse experiments tumor bearing lungs were classified as mildly sick and severely based on burden determined by right lung lobe weights. Oncogene induced immunosuppressive environment manifested compromised T cell function, elevation in levels of promoting cytokines, changes hematopoietic population was observed mildy mice addition to EGFR mutant mice. Anti PD-1 antibody treatment did not show efficacy Kras driven tumors despite...
<p>- PDF file 2020K, Supplementary figures 1-11. For the mouse experiments tumor bearing lungs were classified as mildly sick and severely based on burden determined by right lung lobe weights. Oncogene induced immunosuppressive environment manifested compromised T cell function, elevation in levels of promoting cytokines, changes hematopoietic population was observed mildy mice addition to EGFR mutant mice. Anti PD-1 antibody treatment did not show efficacy Kras driven tumors despite...
<div>Abstract<p>The success in lung cancer therapy with programmed death (PD)-1 blockade suggests that immune escape mechanisms contribute to tumor pathogenesis. We identified a correlation between EGF receptor (EGFR) pathway activation and signature of immunosuppression manifested by upregulation PD-1, PD-L1, CTL antigen-4 (CTLA-4), multiple tumor-promoting inflammatory cytokines. observed decreased CTLs increased markers T-cell exhaustion mouse models EGFR-driven cancer. PD-1...