A5022247782- Melanoma and MAPK Pathways
- Cancer, Hypoxia, and Metabolism
- Cancer Immunotherapy and Biomarkers
- Cancer, Lipids, and Metabolism
- CAR-T cell therapy research
- Cancer Genomics and Diagnostics
- Cancer Research and Treatments
- Cancer Mechanisms and Therapy
- Immunotherapy and Immune Responses
- 3D Printing in Biomedical Research
- Metabolomics and Mass Spectrometry Studies
- Immune Cell Function and Interaction
- RNA modifications and cancer
- Protein Degradation and Inhibitors
- Synthesis and biological activity
- PARP inhibition in cancer therapy
- Glioma Diagnosis and Treatment
- Innovative Microfluidic and Catalytic Techniques Innovation
- Cancer and Skin Lesions
- Acute Lymphoblastic Leukemia research
- Nonmelanoma Skin Cancer Studies
- Prostate Cancer Treatment and Research
- Chronic Lymphocytic Leukemia Research
- Cancer-related Molecular Pathways
- Immune cells in cancer
University of California, Los Angeles
2016-2025
California NanoSystems Institute
2016-2025
APLA Health
2011-2025
UCLA Jonsson Comprehensive Cancer Center
2013-2024
Broad Center
2018-2024
Institute for Molecular Medicine
2015-2024
UCLA Medical Center
2013-2024
UCLA Health
2014-2024
Harvard University Press
2022-2023
International Paper (United States)
2022-2023
Approximately 75% of objective responses to anti–programmed death 1 (PD-1) therapy in patients with melanoma are durable, lasting for years, but delayed relapses have been noted long after initial tumor regression despite continuous therapy. Mechanisms immune escape this context unknown.
PD-L1 and PD-L2 are ligands for the PD-1 immune inhibiting checkpoint that can be induced in tumors by interferon exposure, leading to evasion. This process is important immunotherapy based on blockade. We examined specific molecules involved interferon-induced signaling regulates expression melanoma cells. These studies revealed interferon-gamma-JAK1/JAK2-STAT1/STAT2/STAT3-IRF1 axis primarily expression, with IRF1 binding its promoter. responded equally beta gamma regulated through both...
Loss-of-function mutations in JAK1/2 can lead to acquired resistance anti-programmed death protein 1 (PD-1) therapy. We reasoned that they may also be involved primary anti-PD-1 JAK1/2-inactivating were noted tumor biopsies of 23 patients with melanoma and 16 mismatch repair-deficient colon cancer treated PD-1 blockade. Both cases had a high mutational load but did not respond Two out 48 human cell lines mutations, which led lack PD-L1 expression upon interferon gamma exposure mediated by an...
The recent discovery of mutations in metabolic enzymes has rekindled interest harnessing the altered metabolism cancer cells for therapy. One potential drug target is isocitrate dehydrogenase 1 (IDH1), which mutated multiple human cancers. Here, we examine role mutant IDH1 fully transformed with endogenous mutations. A selective R132H-IDH1 inhibitor (AGI-5198) identified through a high-throughput screen blocked, dose-dependent manner, ability enzyme (mIDH1) to produce R-2-hydroxyglutarate...
It has been convincingly demonstrated that genotoxic stresses cause the accumulation of tumor suppressor gene p53. One important consequence increased p53 protein levels in response to DNA damage is activation a G1-phase cell cycle checkpoint. also shown checkpoints are activated other stresses, such as lack oxygen. Here we show hypoxia and heat, agents induce cellular stress primarily by inhibiting oxygen-dependent metabolism denaturing proteins, respectively, an increase levels. The...
MEK inhibition enhanced the antitumor activity of combined BRAF and immunotherapy.
Comparing independent high-throughput gene-expression experiments can generate hypotheses about which programs are shared between particular biological processes. Current techniques to compare expression profiles typically involve choosing a fixed differential threshold summarize results, potentially reducing sensitivity small but concordant changes. We present threshold-free algorithm called Rank-rank Hypergeometric Overlap (RRHO). This steps through two gene lists ranked by the degree of...
Abstract Cellular amino acid uptake is critical for mTOR complex 1 (mTORC1) activation and cell proliferation. However, the regulation of not well-understood. Here we describe a role asparagine as an exchange factor: intracellular exchanges with extracellular acids. Through synthetase knockdown altering media concentrations, show that levels regulate acids, especially serine, arginine histidine. its factor role, regulates mTORC1 activity protein synthesis. In addition, serine influences...
Interfering with Interferons Infections Mycobacteria, including Mycobacterium leprae or M. tuberculosis , vary substantially in their clinical presentation. For instance, some cases of the infection is self-healing very few lesions. In contrast, people experience disseminated form, where skin lesions abound and bacteria are abundant. patients infected Teles et al. (p. 1448 published online 28 February) found that disease associates a type I interferon gene signature, whereas form II...
Bruton tyrosine kinase (BTK) links the B-cell antigen receptor (BCR) and Toll-like receptors with NF-κB. The role of BTK in primary central nervous system (CNS) lymphoma (PCNSL) is unknown. We performed a phase I clinical trial ibrutinib, first-in-class inhibitor, for patients relapsed or refractory CNS lymphoma. Clinical responses to ibrutinib occurred 10 13 (77%) PCNSL, including five complete responses. only PCNSL resistance harbored mutation within coiled-coil domain CARD11, known...
Abstract Purpose: To evaluate the immunomodulatory effects of cytotoxic T–lymphocyte-associated protein 4 (CTLA4) blockade with tremelimumab in peripheral blood mononuclear cells (PBMC). Experimental Design: We used next-generation sequencing to study complementarity-determining region 3 (CDR3) from rearranged T-cell receptor (TCR) variable beta (V-beta) PBMCs 21 patients, at baseline and 30 60 days after receiving tremelimumab. Results: After tremelimumab, there was a median 30% increase...
Abstract Purpose: PD-L1 is the main ligand for immune inhibitory receptor PD-1. This frequently expressed by melanoma cells. In this study, we investigated whether expression controlled driver mutations and modified oncogenic signaling inhibition. Experimental Design: Expression of was in a panel 51 cell lines containing different mutations, including with innate acquired resistance to BRAF inhibitors (BRAFi). The effects targeted therapy drugs on cells were investigated. Results: No...
Consistent compositional shifts in the gut microbiota are observed IBD and other chronic intestinal disorders may contribute to pathogenesis. The identities of microbial biomolecular mechanisms metabolic products responsible for disease phenotypes remain be determined, as do means by which such functions therapeutically modified.The composition metabolites microbiome samples 47 subjects were determined. Samples obtained endoscopic mucosal lavage from cecum sigmoid colon regions, each sample...
Colony stimulating factor 1 (CSF-1) recruits tumor-infiltrating myeloid cells (TIM) that suppress tumor immunity, including M2 macrophages and myeloid-derived suppressor (MDSC). The CSF-1 receptor (CSF-1R) is a tyrosine kinase targetable by small molecule inhibitors such as PLX3397. In this study, we used syngeneic mouse model of BRAF(V600E)-driven melanoma to evaluate the ability PLX3397 improve efficacy adoptive cell therapy (ACT). model, found combined treatment produced superior...
Some (re)programming notes on cancer Epithelial cancers develop resistance to targeted therapies in a number of different ways. Several types do so by undergoing phenotypic conversion highly aggressive called small cell neuroendocrine carcinoma (SCNC). Whether distinct accomplish this “reprogramming” through the same mechanism has been unclear. Park et al. show that set oncogenic factors transforms both normal lung and prostate epithelial cells into SCNCs resemble clinical samples (see...
Although human cancers have complex genotypes and are genomically unstable, they often remain dependent on the continued presence of single-driver mutations—a phenomenon dubbed “oncogene addiction.” Such dependencies been demonstrated in mouse models, where conditional expression systems revealed that oncogenes able to initiate cancer required for tumor maintenance progression, thus validating pathways control as therapeutic targets. Here, we implement an integrative approach combines...