A5003135912- Cancer Mechanisms and Therapy
- Microtubule and mitosis dynamics
- Ubiquitin and proteasome pathways
- Cancer, Lipids, and Metabolism
- Lipid metabolism and biosynthesis
- Endoplasmic Reticulum Stress and Disease
- Genetic Neurodegenerative Diseases
- PI3K/AKT/mTOR signaling in cancer
- Genetics and Neurodevelopmental Disorders
- Heat shock proteins research
- Protein Kinase Regulation and GTPase Signaling
- Mitochondrial Function and Pathology
- Prion Diseases and Protein Misfolding
- Neurological diseases and metabolism
- Genomics, phytochemicals, and oxidative stress
- DNA Repair Mechanisms
Duke University
2022-2024
Emory University
2019-2020
Although platinum compounds are the first-line treatment for ovarian cancer, majority of patients relapse and develop resistance to treatment. However, mechanism underlying is unclear. The goal our study decipher by which a metabolic kinase, diacylglycerol kinase alpha (DGKA), confers in cancer.Metabolic RNAi synthetic lethal screening was used identify cisplatin driver cancer. DGKA variants were demonstrate need activity resistance. Phospho-proteomic genomic screens performed downstream...
Microtubule-associated serine/threonine kinase 1 (MAST1) is a central driver of cisplatin resistance in human cancers. However, the molecular mechanism regulating MAST1 levels cisplatin-resistant tumors unknown. Through proteomics screen, we identified heat shock protein 90 B (hsp90B) chaperone as direct binding partner essential for its stabilization. Targeting hsp90B sensitized cancer cells to predominantly through destabilization. Mechanistically, interaction with blocked ubiquitination...
The spinocerebellar ataxias (SCAs) are a class of incurable diseases characterized by degeneration the cerebellum that results in movement disorder. Recently, new heritable form SCA, ataxia type 48 (SCA48), was attributed to dominant mutations STIP1 homology and U box-containing 1 (STUB1); however, little is known about how these cause SCA48. STUB1 encodes for protein C terminus Hsc70 interacting (CHIP), an E3 ubiquitin ligase. CHIP regulate proteostasis recruiting chaperones via N-terminal...
ABSTRACT Among sequenced organisms, the genome of Dictyostelium discoideum is unique in that it encodes for a massive amount repeat-rich sequences coding region genes. This results proteome encoding thousands proteins, with nearly 24% Q/N-rich regions are predicted to be prion like nature. To begin investigating role prion-like proteins , we decided investigate ERF3, ortholog well-characterized yeast protein Sup35. ERF3 lacks required formation yeast, raising question whether this aggregates...
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<div>AbstractPurpose:<p>Although platinum compounds are the first-line treatment for ovarian cancer, majority of patients relapse and develop resistance to treatment. However, mechanism underlying is unclear. The goal our study decipher by which a metabolic kinase, diacylglycerol kinase alpha (DGKA), confers in cancer.</p>Experimental Design:<p>Metabolic RNAi synthetic lethal screening was used identify cisplatin driver cancer. DGKA variants were demonstrate need...
<div>AbstractPurpose:<p>Although platinum compounds are the first-line treatment for ovarian cancer, majority of patients relapse and develop resistance to treatment. However, mechanism underlying is unclear. The goal our study decipher by which a metabolic kinase, diacylglycerol kinase alpha (DGKA), confers in cancer.</p>Experimental Design:<p>Metabolic RNAi synthetic lethal screening was used identify cisplatin driver cancer. DGKA variants were demonstrate need...
<p>Supplementary Fig S1</p>
<p>Supplementary Fig S6</p>
<p>Supplementary Fig S7</p>
<p>Supplementary Fig S2</p>
<p>Supplementary Fig S4</p>
<p>Supplementary Fig S3</p>
<p>Supplementary Fig S5</p>
<p>Supplementary Fig S1</p>
<p>Supplementary Table S1</p>
Abstract Although platinum compounds are the first-line treatment for ovarian cancer, majority of patients relapse and develop resistance to treatment. However, mechanism underlying is unclear. Here, we report a unique that mediated by lipid messenger, phosphatidic acid (PA), in cancer. A phospho-proteomics screen revealed PA, which predominantly produced diacylglycerol kinase alpha (DGKA) activates transcription factor c-JUN. DGKA PA facilitate JNK recruitment c-JUN nuclear localization...
The E3 ubiquitin ligase, C-terminus of Hsc70 Interacting Protein (CHIP), is a critical regulator cellular proteostasis that when mutated causes spinocerebellar ataxia type 48 (SCA48). CHIP binds chaperones and thought to target misfolded proteins for degradation during stress. Here we show heat stress induces reversible conformational change in results dissociation from chaperones. During necessary the proper ubiquitination RNA binding loss leads failure full activation transcriptional...