A5030193536- Chronic Myeloid Leukemia Treatments
- Acute Myeloid Leukemia Research
- Acute Lymphoblastic Leukemia research
- Chronic Lymphocytic Leukemia Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- RNA Research and Splicing
- RNA regulation and disease
- CAR-T cell therapy research
- Hedgehog Signaling Pathway Studies
- RNA Interference and Gene Delivery
- Immune Cell Function and Interaction
- Eosinophilic Disorders and Syndromes
- Cytokine Signaling Pathways and Interactions
- Multiple Myeloma Research and Treatments
- Virus-based gene therapy research
- RNA modifications and cancer
- Protein Degradation and Inhibitors
- Cancer Genomics and Diagnostics
- interferon and immune responses
- Kruppel-like factors research
- Epigenetics and DNA Methylation
- Prostate Cancer Treatment and Research
- MicroRNA in disease regulation
- Viral Infections and Immunology Research
- Cancer Cells and Metastasis
University of California, San Diego
2016-2025
UC San Diego Health System
2017-2025
Sanford Consortium for Regenerative Medicine
2015-2024
Moores Cancer Center
2013-2024
California Institute for Regenerative Medicine
2024
Korea University
2022
La Jolla Alcohol Research
2015-2020
Institute of Biomedical Science
2019
Regenerative Medicine Institute
2019
University of California System
2010-2018
A workshop was convened by the AACR to discuss rapidly emerging cancer stem cell model for tumor development and progression. The meeting participants were charged with evaluating data suggesting that cancers develop from a small subset of cells self-renewal properties analogous organ
The progression of chronic myelogenous leukemia (CML) to blast crisis is supported by self-renewing leukemic stem cells. In normal mouse hematopoietic cells, the process self-renewal involves beta-catenin-signaling pathway. We investigated whether cells in CML also use beta-catenin pathway for self-renewal.We used fluorescence-activated cell sorting isolate common myeloid progenitors, granulocyte-macrophage and megakaryocyte-erythroid progenitors from marrow during several phases marrow....
Object No definitive treatment exists to restore lost brain function following a stroke. Transplantation of cultured neuronal cells has been shown be safe and effective in animal models stroke Phase 1 human trial. In the present study authors tested usefulness neuron transplantation followed by participation 2-month rehabilitation program compared with alone patients substantial fixed motor deficits associated basal ganglia Methods Human (LBS-Neurons; Layton BioScience, Inc.) were delivered...
Myelofibrosis is a myeloid malignancy associated with anemia, splenomegaly, and constitutional symptoms. Patients frequently harbor JAK-STAT activating mutations that are sensitive to TG101348, selective small-molecule Janus kinase 2 (JAK2) inhibitor.In multicenter phase I trial, oral TG101348 was administered once day patients high- or intermediate-risk primary post-polycythemia vera/essential thrombocythemia myelofibrosis.Fifty-nine were treated, including 28 in the dose-escalation phase....
Myelofibrosis is a hematologic malignancy characterized by splenomegaly and debilitating symptoms. Thrombocytopenia poor prognostic feature limits use of Janus kinase 1 (JAK1)/Janus 2 (JAK2) inhibitor ruxolitinib.To compare the efficacy safety JAK2 pacritinib with that best available therapy (BAT), including ruxolitinib, in patients myelofibrosis thrombocytopenia.For this phase 3 randomized international multicenter study-the PERSIST-2 study-of vs BAT, 311 platelet count 100 × 109/L or less...
Mutations in the splicing factor SF3B1 are found several cancer types and have been associated with various defects. Using transcriptome sequencing data from chronic lymphocytic leukemia, breast uveal melanoma tumor samples, we show that hundreds of cryptic 3' splice sites (3'SSs) used cancers mutations. We define necessary sequence context for observed SSs propose 3'SS selection is a result mutations causing shift sterically protected region downstream branch point. While most 3'SSs present...
Targeting the BCL-X
The classic Philadelphia chromosome–negative myeloproliferative neoplasms (MPN) consist of myelofibrosis, polycythemia vera, and essential thrombocythemia are a heterogeneous group clonal blood disorders characterized by an overproduction cells. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for MPN were developed as result meetings convened multidisciplinary panel with expertise MPN, the goal providing recommendations management adults. include diagnostic workup, risk...
Although a large proportion of patients with polycythemia vera (PV) harbor valine-to-phenylalanine mutation at amino acid 617 (V617F) in the JAK2 signaling molecule, stage hematopoiesis which arises is unknown. Here we isolated and characterized hematopoietic stem cells (HSC) myeloid progenitors from 16 PV patient samples 14 normal individuals, testing whether could be found level or progenitor V617F-positive had altered differentiation potential. In all analyzed, there were increased...
Recent evidence suggests that a rare population of self-renewing cancer stem cells (CSC) is responsible for progression and therapeutic resistance. Chronic myeloid leukemia (CML) represents an important paradigm understanding the genetic epigenetic events involved in CSC production. CML progresses from chronic phase (CP) hematopoietic (HSC) harbor BCR-ABL translocation, to blast crisis (BC), characterized by aberrant activation beta-catenin within granulocyte-macrophage progenitors (GMP). A...
SummaryLeukemia stem cells (LSCs) play a pivotal role in the resistance of chronic myeloid leukemia (CML) to tyrosine kinase inhibitors (TKIs) and its progression blast crisis (BC), part, through alternative splicing self-renewal survival genes. To elucidate splice-isoform regulators human BC LSC maintenance, we performed whole-transcriptome RNA sequencing, splice-isoform-specific quantitative RT-PCR (qRT-PCR), nanoproteomics, stromal coculture, xenotransplantation analyses. Cumulatively,...
The molecular etiology of human progenitor reprogramming into self-renewing leukemia stem cells (LSC) has remained elusive. Although DNA sequencing uncovered spliceosome gene mutations that promote alternative splicing and portend leukemic transformation, isoform diversity also may be generated by RNA editing mediated adenosine deaminase acting on (ADAR) enzymes regulate cell maintenance. In this study, whole-transcriptome normal, chronic phase, serially transplantable blast crisis myeloid...
Myeloproliferative neoplasms (MPNs) are a group of heterogeneous disorders the hematopoietic system that include myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET). PV ET characterized by significant thrombohemorrhagic complications high risk transformation to MF acute myeloid leukemia. The diagnosis management has evolved since identification mutations implicated in their pathogenesis. These NCCN Guideline Insights discuss recommendations outlined Guidelines for...
Targeted molecular therapy has yielded remarkable outcomes in certain cancers, but specific therapeutic targets remain elusive for many others. As a result of two independent RNA interference (RNAi) screens, we identified pathway dependence on member the Janus-activated kinase (JAK) tyrosine family, TYK2, and its downstream effector STAT1, T-cell acute lymphoblastic leukemia (T-ALL). Gene knockdown experiments consistently showed TYK2 both T-ALL primary specimens cell lines, small-molecule...
The oncogenic transcription factor TAL1/SCL is aberrantly expressed in 60% of cases human T cell acute lymphoblastic leukemia (T-ALL) and initiates T-ALL mouse models. By performing global microRNA (miRNA) expression profiling after depletion TAL1, together with genome-wide analysis TAL1 occupancy by chromatin immunoprecipitation coupled to massively parallel DNA sequencing, we identified the miRNA genes directly controlled its regulatory partners HEB, E2A, LMO1/2, GATA3, RUNX1. most...