A5043296636- Telomeres, Telomerase, and Senescence
- Cancer-related Molecular Pathways
- Epigenetics and DNA Methylation
- Diabetes and associated disorders
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Cancer Cells and Metastasis
- Heat shock proteins research
- Drug Transport and Resistance Mechanisms
- Microtubule and mitosis dynamics
- Genetics, Aging, and Longevity in Model Organisms
- DNA Repair Mechanisms
- Ferroptosis and cancer prognosis
- Cancer Genomics and Diagnostics
- Neonatal Respiratory Health Research
- Endoplasmic Reticulum Stress and Disease
- PI3K/AKT/mTOR signaling in cancer
- Computational Drug Discovery Methods
- Hedgehog Signaling Pathway Studies
- RNA modifications and cancer
- Genomic variations and chromosomal abnormalities
- Protein Structure and Dynamics
- Proteoglycans and glycosaminoglycans research
- Cancer therapeutics and mechanisms
- Cancer, Lipids, and Metabolism
BioElectronics (United States)
2018-2019
Exelixis (United States)
2011-2012
Genentech
2007
UCSF Helen Diller Family Comprehensive Cancer Center
2001-2006
University of California, San Francisco
2001-2006
Lawrence University
1997
Ferroptosis is a form of programmed cell death associated with inflammation, neurodegeneration, and ischemia. Vitamin E (alpha-tocopherol) has been reported to prevent ferroptosis, but the mechanism by which this occurs controversial. To elucidate biochemical vitamin activity, we systematically investigated effects its major vitamers metabolites on lipid oxidation ferroptosis in striatal model. We found that specific endogenous metabolite E, alpha-tocopherol hydroquinone, was dramatically...
Background Mitochondrial disease is a family of genetic disorders characterized by defects in the generation and regulation energy. Epilepsy common symptom mitochondrial disease, vast majority cases, refractory to commonly used antiepileptic drugs. Ferroptosis recently-described form iron- lipid-dependent regulated cell death associated with glutathione depletion production lipid peroxides lipoxygenase enzymes. Activation ferroptosis pathway has been implicated growing number disorders,...
BackgroundHeparan sulfate proteoglycans (HSPGs) use highly sulfated polysaccharide side-chains to interact with several key growth factors and morphogens, thereby regulating their accessibility biological activity. Various sulfotransferases sulfatases differing specificities control the pattern of HSPG sulfation, which is functionally critical. Among these enzymes in mouse are two secreted 6-O-endosulfatases, Sulf1 Sulf2, modify HSPGs extracellular matrix on cell surface. The roles Sulf2...
Aneuploidy, frequently observed in premalignant lesions, disrupts gene dosage and contributes to neoplastic progression. Theodor Boveri hypothesized nearly 100 years ago that aneuploidy was due an increase centrosome number (multipolar mitoses) the resultant abnormal segregation of chromosomes. We performed immunocytochemistry, quantitative immunofluorescence, karyotypic analysis, time-lapse microscopy on primary human diploid epithelial cells fibroblasts better understand mechanism involved...
AbstractCultured human mammary epithelial cells (HMEC) encounter two distinct barriers to indefinite growth. The first barrier, originally termed selection, can be overcome through loss of expression the cyclin-dependent kinase inhibitor p16INK4A. resultant p16(-), p53(+) post-selection HMEC a second agonescence, associated with critically shortened telomeres and widespread chromosomal aberrations. Although some cell death is present at majority population retains long-term viability. We now...
p16(INK4a) (p16) and p53 are tumor suppressor genes that inactivated during carcinogenesis in many tumors. Here we show p16 gene activity inversely modulates status function primary human mammary epithelial cells. Reduced levels of protein stabilize through inhibition proteolytic degradation, this increase enhances the cellular response to radiation, represses proliferation, transcriptionally activates downstream targets. Stabilization is mediated retinoblastoma/E2F/p14(ARF)/murine double...
The phosphoinositide 3-kinases (PI3Ks) have been linked to an extraordinarily diversified group of cellular functions making these enzymes compelling targets for the treatment disease. A large body evidence has PI3Kγ modulation autoimmune and inflammatory processes it intriguing target drug discovery. Our high-throughput screening (HTS) campaign revealed two hits that were nominated further optimization studies. in vitro activity first HTS hit, designated as sulfonylpiperazine scaffold, was...
Background Many proteins that are dysregulated or mutated in cancer cells rely on the molecular chaperone HSP90 for their proper folding and activity, which has led to considerable interest as a drug target. The diverse array of client encompasses oncogenic drivers, cell cycle components, variety regulatory factors, so inhibition perturbs multiple cellular processes, including mitogenic signaling control. Although many reports have investigated context cycle, no large-scale studies examined...
Phenotypic reversion of the rubber-band, muscle-defective phenotype conferred by unc-93(e1500) was used to determine utility N-ethyl-N-nitrosourea (ENU) as a mutagen for genetic research in Caenorhabditis elegans. In this system, ENU produces revertants at frequency 3 x 10(-4), equivalent that commonly mutagen, EMS. The gene identity 154 ENU-induced shows distribution alleles between three possible suppressor genes differs from induced A higher percentage are unc-93 and many fewer sup-9...
Abstract Interleukin-2 (IL-2) has been shown to suppress immune pathologies by preferentially expanding regulatory T cells (Treg). However, this therapy limited off-target complications due pathogenic cell expansion. Recent efforts have focused on developing a more selective IL-2. It is well documented that certain anti-mouse IL-2 antibodies induce conformational changes result in targeting of Treg cells. We report the generation first fully human anti-IL-2 antibody, F5111.2 stabilizes...