A5055213943- Acute Myeloid Leukemia Research
- RNA modifications and cancer
- Chronic Myeloid Leukemia Treatments
- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Cancer-related gene regulation
- Acute Lymphoblastic Leukemia research
- Cytokine Signaling Pathways and Interactions
- Epigenetics and DNA Methylation
- Histone Deacetylase Inhibitors Research
- RNA Interference and Gene Delivery
- Coronary Interventions and Diagnostics
- Chronic Lymphocytic Leukemia Research
- Peptidase Inhibition and Analysis
- Childhood Cancer Survivors' Quality of Life
- Cancer-related Molecular Pathways
- Retinoids in leukemia and cellular processes
- Autophagy in Disease and Therapy
- Virus-based gene therapy research
- Blood disorders and treatments
- Neuroblastoma Research and Treatments
- Immune Cell Function and Interaction
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- NF-κB Signaling Pathways
Stanford University
2016-2025
Stanford Medicine
2012-2025
Mattel Children's Hospital
2003-2023
UCLA Jonsson Comprehensive Cancer Center
2003-2023
Lucile Packard Children's Hospital
2012-2023
California NanoSystems Institute
2009-2023
Nanosys (United States)
2023
Wakamoto Pharmaceutical (Japan)
2015
Cardiovascular Institute of the South
2015
University of California, Los Angeles
2003-2012
The intracellular levels of many proteins are regulated by ubiquitin-dependent proteolysis. One the best-characterized enzymes that catalyzes attachment ubiquitin to is a ligase complex, Skp1-Cullin-F box complex containing Hrt1 (SCF). We sought artificially target protein SCF for ubiquitination and degradation. To this end, we tested methionine aminopeptidase-2 (MetAP-2), which covalently binds angiogenesis inhibitor ovalicin. A chimeric compound, protein-targeting molecule 1 (Protac-1),...
Genetic loss of function analysis is a powerful method for the study protein function. However, some cell biological questions are difficult to address using traditional genetic strategies often due lack appropriate model systems. Here, we present general strategy design and syntheses molecules capable inducing degradation selected proteins in vivo via ubiquitin−proteasome pathway. Western blot fluorometric analyses indicated two different targets: green fluorescent (GFP) fused with FK506...
Transcription factors are key regulators of the pattern gene expression in a cell and directly control central processes such as proliferation, survival, self-renewal, invasion. Given this critical role, function transcription is normally regulated closely, often through transient phosphorylation. Although not modified by mutations cancer cells, they frequently become activated constitutively affecting "upstream" pathways. By continually driving target genes, these oncogenic play role tumor...
Pediatric cancers often mimic fetal tissues and express proteins normally silenced postnatally that could serve as immune targets. We developed T cells expressing chimeric antigen receptors (CARs) targeting glypican-2 (GPC2), a expressed on neuroblastoma (NB) several other solid tumors. CARs engineered using standard designs control NBs with transgenic GPC2 overexpression, but not those clinically relevant site density (∼5,000 molecules/cell, range 1-6 × 10
The proteome contains hundreds of proteins that in theory could be excellent therapeutic targets for the treatment human diseases. However, many these are from functional classes have never been validated as viable candidates development small molecule inhibitors. Thus, to exploit fully potential Human Genome Project advance medicine, there is a need develop generic methods inhibiting protein activity do not rely on target protein's function. We previously demonstrated normally stable...
To identify previously unknown small molecules that inhibit cell cycle machinery, we performed a chemical genetic screen in Xenopus extracts. One class of inhibitors, termed ubistatins, blocked progression by inhibiting cyclin B proteolysis and inhibited degradation ubiquitinated Sic1 purified proteasomes. Ubistatins the binding substrates to proteasome targeting ubiquitin-ubiquitin interface Lys 48 -linked chains. The same is recognized ubiquitin-chain receptors proteasome, indicating...
The cyclic-AMP response element-binding protein (CREB) is a nuclear transcription factor activated by phosphorylation at Ser133 multiple serine/threonine (Ser/Thr) kinases. Upon phosphorylation, CREB binds the transcriptional co-activator, CBP (CREB-binding protein), to initiate CREB-dependent gene transcription. critical regulator of cell differentiation, proliferation and survival in nervous system. Recent studies have shown that involved tumor initiation, progression metastasis,...
Conserved embryonic signaling pathways such as Hedgehog (Hh), Wingless and Notch have been implicated in the pathogenesis of several malignancies. Recent data suggests that Hh plays a role normal B-cell development, we hypothesized may be important precursor acute lymphocytic leukemia (B-ALL). We found expression pathway components was common human B-ALL cell lines clinical samples. Moreover, activity could modulated by ligand or inhibitors including cyclopamine novel SMOOTHENED (SMO)...
Summary Mutations in ribosomal proteins are associated with a congenital syndrome, Diamond–Blackfan anaemia (DBA), manifested by red blood cell aplasia, developmental abnormalities and increased risk of malignancy. Recent studies suggest the involvement p53 activation DBA. However, which pathways involved how they contribute to DBA phenotype remains unknown. Here we show that zebrafish mutant for rpl11 gene had defects both development haematopoietic stem cells (HSCs) maintenance erythroid...
The p38/stress-activated protein kinase2 (p38/SAPK2) is activated by cellular stress and proinflammatory cytokines. Several transcription factors have been reported to be regulated p38/SAPK2, this kinase involved in the control of expression various genes. In human Jurkat T-cells, induction early growth response gene-1 (egr-1) anisomycin completely inhibited SB203580, a specific inhibitor p38/SAPK2a -b. Northern blot reporter gene experiments indicate that block at level mRNA biosynthesis....