- Cancer therapeutics and mechanisms
- Glioma Diagnosis and Treatment
- PI3K/AKT/mTOR signaling in cancer
- Nanoparticle-Based Drug Delivery
- Cancer, Hypoxia, and Metabolism
- Advanced NMR Techniques and Applications
- Cancer Genomics and Diagnostics
- Pancreatic and Hepatic Oncology Research
- Enzyme Structure and Function
- Neuroendocrine Tumor Research Advances
- Amino Acid Enzymes and Metabolism
- Chronic Myeloid Leukemia Treatments
- Immune Cell Function and Interaction
- Gene expression and cancer classification
- Ubiquitin and proteasome pathways
- Medical Imaging Techniques and Applications
- Innovative Microfluidic and Catalytic Techniques Innovation
- Protein Kinase Regulation and GTPase Signaling
- Lanthanide and Transition Metal Complexes
- Drug Transport and Resistance Mechanisms
- Microwave-Assisted Synthesis and Applications
- CAR-T cell therapy research
- Cancer Research and Treatments
- Neuroblastoma Research and Treatments
- Tuberous Sclerosis Complex Research
Memorial Sloan Kettering Cancer Center
2018-2024
Cornell University
2016-2023
Weill Cornell Medicine
2017
Sichuan Agricultural University
2014
Chinese Academy of Medical Sciences & Peking Union Medical College
2012
Abstract Somatic mutations in cytosolic or mitochondrial isoforms of isocitrate dehydrogenase (IDH1 IDH2, respectively) contribute to oncogenesis via production the metabolite 2-hydroxyglutarate (2HG). Isoform-selective IDH inhibitors suppress 2HG and induce clinical responses patients with IDH1- IDH2-mutant malignancies. Despite promising activity inhibitors, mechanisms that mediate resistance inhibition are poorly understood. Here, we describe four cases identify mutant isoform switching,...
MicroRNA (miRNA) actively participates in a broad range of cellular processes such as proliferation, differentiation, cell survival and apoptosis. Deregulated expression miRNA may affect growth eventually lead to cancer. In this study, we found that hsa-miR491-5p (miR491-5p) displays significantly high level normal human pancreas tissue versus pancreatic cancer cells. Targeted site prediction indicated both Bcl-XL TP53 contain miR-491-5p recognizing sites their 3' UTRs. Overexpression the...
Abstract Metabolic flexibility has emerged as a critical determinant of CD8+ T-cell antitumor activity, yet the mechanisms driving metabolic T cells have not been determined. In this study, we investigated influence nuclear cap-binding complex (CBC) adaptor protein ARS2 on mature cells. doing so, discovered novel signaling axis that endows activated with glucose catabolism. upregulation driven by CD28 reinforced splicing factor recruitment to pre-mRNAs and affected approximately one-third...
PTEN functions as a guardian of the genome through multiple mechanisms. We have previously established that maintains structural integrity chromosomes. In this report, we demonstrate fundamental role in controlling chromosome inheritance to prevent gross genomic alterations. Disruption or depletion protein phosphatase activity causes abnormal content, manifested by enlarged polyploid nuclei. further identify polo-like kinase 1 (PLK1) substrate phosphatase. can physically associate with PLK1...
Abstract Accumulating evidence suggests that ubiquitin‐like with plant homeodomain and ring finger domains 1 (UHRF1) is overexpressed in non‐small cell lung cancer (NSCLC); however, the expression function of UHRF1 subtype NSCLC are still unclear. Here, we investigate prognosis traits large cohorts explore molecular characters during up‐regulation. We find predominantly squamous carcinoma (SCC). Surprisingly, up‐regulated only associated overall survival adenocarcinoma (ADC) knockdown...
The blood brain barrier can limit the efficacy of systemically delivered drugs in treating neurological malignancies; therefore, alternate routes drug administration must be considered. Abl-kinase inhibitor, dasatinib, is modified to give compound 1 ([18F]-1) so that 18F-positron emission tomography (PET) and fluorescent imaging both used observe delivery murine orthotopic glioma. In vitro Western blotting, binding studies (IC50 = 22 ± 5 nmol/L), cell viability assays 46 30 nmol/L) confirm...
Abstract Viral infection of cells leads to metabolic changes, but how viral changes whole-body and tissue metabolism in vivo has not been comprehensively studied. In particular, it is unknown might be differentially affected by an acute that the immune system can successfully clear, compared a chronic persistent infection. Here we used metabolomics isotope tracing identify mice infected with or forms lymphocytic choriomeningitis virus (LCMV) for three eight days. Both types alter metabolite...
Elucidations of the factors that promote growth disseminated tumor cells (DTCs) into life-threatening lesions stand to provide much needed prognostic and therapeutic targets translational utility for patients with metastatic cancer. To identify such regulators, we conducted gain-of-function cDNA library screening discover genes foster prostate cancer cell colonization mouse lungs as an experimental model. Our efforts identified metabolic enzyme aldolase A (ALDOA) a driver motility,...
Abstract Somatic mutations in cytosolic or mitochondrial isoforms of isocitrate dehydrogenase (IDH1 IDH2, respectively) contribute to oncogenesis via production the metabolite 2-hydroxyglutarate (2HG). Isoform-selective IDH inhibitors suppress 2HG and induce clinical responses patients with IDH1- IDH2-mutant malignancies. Despite promising activity inhibitors, mechanisms that mediate resistance inhibition are poorly understood. Here, we describe four cases identify mutant isoform switching,...
Abstract CD8 T cell activation prompts extensive transcriptome remodeling underlying effector differentiation and function. Regulation of composition by the mitogen-inducible nuclear cap-binding complex (CBC) adaptor protein ARS2 has critical type-specific consequences, including thymic survival. Here we show that was upregulated CD28 during peripheral cells, essential for anti-tumor immunity, facilitated activation-induced alternative splicing. The novel splicing function mediated at least...
<div>Abstract<p>Somatic mutations in cytosolic or mitochondrial isoforms of isocitrate dehydrogenase (<i>IDH1</i> <i>IDH2</i>, respectively) contribute to oncogenesis via production the metabolite 2-hydroxyglutarate (2HG). Isoform-selective IDH inhibitors suppress 2HG and induce clinical responses patients with <i>IDH1</i>- <i>IDH2</i>-mutant malignancies. Despite promising activity inhibitors, mechanisms that mediate resistance...
<p>Next-generation sequencing and droplet digital PCR</p>
<p>Figures S1 through S4</p>
<p>Supplemental Methods. DNA constructs, Gel electrophoresis and western blotting, Metabolite extraction analysis</p>
<p>Figures S1 through S4</p>
<p>Next-generation sequencing and droplet digital PCR</p>
<p>Supplemental Methods. DNA constructs, Gel electrophoresis and western blotting, Metabolite extraction analysis</p>
<div>Abstract<p>Somatic mutations in cytosolic or mitochondrial isoforms of isocitrate dehydrogenase (<i>IDH1</i> <i>IDH2</i>, respectively) contribute to oncogenesis via production the metabolite 2-hydroxyglutarate (2HG). Isoform-selective IDH inhibitors suppress 2HG and induce clinical responses patients with <i>IDH1</i>- <i>IDH2</i>-mutant malignancies. Despite promising activity inhibitors, mechanisms that mediate resistance...
<p>Data was not quantitated due to mouse movement at 2 hours. (mouse began wake from isoflurane anesthesia)</p>
<p>Supporting Video S2. Sagittal PET(red)/ MR(grey) projection showing dynamic, CED delivery of [18F]-1 (Video Fig.3Bi)</p>