A5065665085- Epigenetics and DNA Methylation
- Renal cell carcinoma treatment
- Ferroptosis and cancer prognosis
- Cancer, Hypoxia, and Metabolism
- Microtubule and mitosis dynamics
- PI3K/AKT/mTOR signaling in cancer
- Antibiotic Resistance in Bacteria
- Genetics, Aging, and Longevity in Model Organisms
- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Amino Acid Enzymes and Metabolism
- Protein Degradation and Inhibitors
- Sulfur Compounds in Biology
- Plant nutrient uptake and metabolism
- RNA modifications and cancer
- Bacterial Genetics and Biotechnology
- Birth, Development, and Health
- Ubiquitin and proteasome pathways
- Genetic and Kidney Cyst Diseases
- Cancer-related gene regulation
- Histone Deacetylase Inhibitors Research
- Cancer Mechanisms and Therapy
- FOXO transcription factor regulation
- Cancer-related Molecular Pathways
- Spaceflight effects on biology
Icahn School of Medicine at Mount Sinai
2021-2023
Tisch Hospital
2022
Cancer Research Institute
2018-2019
University of Pennsylvania
2018-2019
Indian Institute of Technology Kharagpur
2015-2018
Cancer Genetics (United States)
2018
University of Massachusetts Chan Medical School
2010-2014
University of Delaware
1989
Significance Genetic and environmental manipulations have been identified that result in lifespan extension. The underlying assumption extension would also an increase healthspan is seemingly valid but infrequently examined. Here, we examined multiple pathways modulate to investigate the relationship between health. We analyzed wild-type four long-lived mutants unbiased cross-sectional study with assays until animals reached 80% maximum lifespan. show can be separated all of extend period...
The nematode Caenorhabditis elegans has been employed as a model organism to study human obesity due the conservation of pathways that regulate energy metabolism. To assay for fat storage in C. elegans, number fat-soluble dyes have including BODIPY, Nile Red, Oil Red O, and Sudan Black. However, dye-labeled assays produce results often do not correlate with stores elegans. An alternative label-free approach analyze recently described coherent anti-Stokes Raman scattering (CARS) microscopy....
Using a panel of cancer cell lines, we characterized novel degrader AKT, MS21. In mutant PI3K-PTEN pathway AKT degradation was superior to kinase inhibition for reducing growth and sustaining lower signaling over many days. degradation, but not inhibition, profoundly lowered Aurora B (AURKB) protein, which is known be essential division, induced G2-M arrest hyperploidy. PI3K activated phosphorylation AURKB on threonine 73, protected it from proteasome degradation. A (T73E) that mimics blocks...
Tumors exhibit enhancer reprogramming compared to normal tissue. The etiology is largely attributed cell-intrinsic genomic alterations. Here, using freshly resected primary CRC tumors and patient-matched adjacent colon, we find divergent epigenetic landscapes between cell lines. Intriguingly, this phenomenon extends highly recurrent aberrant super-enhancers gained in over normal. We one such super-enhancer activated epithelial cancer cells due surrounding inflammation the tumor...
The insulin/IGF-1 signaling (IIS) pathway is a conserved regulator of longevity, development, and metabolism. In Caenorhabditis elegans IIS involves activation DAF-2 (insulin/IGF-1 receptor tyrosine kinase), AGE-1 (PI 3-kinase), additional downstream serine/threonine kinases that ultimately phosphorylate negatively regulate the single FOXO transcription factor homolog DAF-16. Phosphatases help to maintain cellular homeostasis by counterbalancing kinase activity. However, few phosphatases...
Insulin/IGF-1 signaling plays a central role in longevity across phylogeny. In C. elegans, the forkhead box O (FOXO) transcription factor, DAF-16, is primary target of insulin/IGF-1 signaling, and multiple isoforms DAF-16 (a, b, d/f) modulate lifespan, metabolism, dauer formation, stress resistance. Thus far, phylogeny modulation mammalian FOXOs have focused on post-translational regulation with little focus transcriptional regulation. we previously shown that DAF-16d/f cooperates DAF-16a to...
Abstract Clear cell renal carcinoma (ccRCC) is the most common subtype of kidney cancer. While localized form this disease can be treated surgically, advanced and metastatic stages are resistant to chemotherapies. Although more innovative treatments, such as targeted or immune-based therapies, exist, need for new therapeutic options remains. ccRCC presents unique metabolic signatures multiple studies have reported a significant increase in levels reduced glutathione (GSH) its precursors...
dd-Carboxypeptidases (dd-CPases) are low-molecular-mass (LMM) penicillin-binding proteins (PBPs) that mainly involved in peptidoglycan remodelling, but little is known about the dd-CPases of mycobacteria. In this study, a putative dd-CPase Mycobacterium smegmatis, MSMEG_2433 characterized. The gene for membrane-bound form was cloned and expressed Escherichia coli its active form, as revealed by ability to bind Bocillin-FL (fluorescent penicillin). Interestingly, vivo expression could restore...
During the peptidoglycan (PG) maturation of mycobacteria, glycan strands are interlinked by both 3-3 (between two meso-diaminopimelic acids [meso-DAPs]) and 4-3 cross-links d-Ala meso-DAP), though there is a predominance (60 to 80%) cross-links. The dd-carboxypeptidases (dd-CPases) act on pentapeptides generate tetrapeptides that used ld-transpeptidases as substrates form Therefore, dd-CPases play crucial role in mycobacterial PG cross-link formation. However, physiology mycobacteria...
Clear cell renal carcinoma (ccRCC) is a subtype of kidney cancer defined by robust lipid accumulation, which prior studies have indicated plays an important role in tumor progression. We hypothesized that the peroxisome proliferator-activated receptor gamma (PPARγ), detected both ccRCC tumors and lines, promotes storage contributes to tumorigenesis this setting. PPARγ transcriptionally regulates number genes involved glucose metabolism adipocytes, yet its has not been described. The...
Abstract Subunits of SWI/SNF chromatin remodeling complexes are frequently mutated in human malignancies. The PBAF complex is composed multiple subunits, including the tumor-suppressor protein PBRM1 (BAF180), as well ARID2 (BAF200), that unique to this complex. various cancers, with a high mutation frequency clear cell renal carcinoma (ccRCC). Here, we integrate RNA-seq, histone modification ChIP-seq, and ATAC-seq data show loss results de novo gains H3K4me3 peaks throughout epigenome,...
Penicillin-binding protein 5 (PBP5), a dd-carboxypeptidase, maintains cell shape and intrinsic beta-lactam resistance in E. coli. A strain lacking PBP5 loses simultaneous lack of two other PBPs results aberrantly shaped cells. expression trans complements the restores lost resistance. has an 'Ω-loop'-like region similar to that class beta-lactamases. It was previously predicted Leu182 present 'Ω-like' loop corresponds Glu166 PER-1 beta-lactamase. Here, we studied physiological biochemical...
Cell wall impermeability and active efflux of drugs are among the primary reasons for drug resistance in mycobacteria. Efflux pumps tripartite membrane localized transport proteins that expel molecules outside cells. Several such annotated mycobacteria, but few have been characterized, like MSMEG_2991, a putative pump permease Mycobacterium smegmatis To substantiate this, we overexpressed MSMEG_2991 protein Escherichia coli 2443. Expression elevated towards structurally unrelated groups...
Abstract NADP+-specific glutamate dehydrogenase from Salmonella typhimurium, cloned and expressed in Escherichia coli, has been purified to homogeneity. The nucleotide sequence of S. typhimurium gdhA was determined the amino acid derived. analogue 2-[(4-bromo-2,3-dioxobutyl)thio]-1,N6-ethenoadenosine 2',5'-bisphosphate (2-BDB-T epsilon A-2',5'-DP) reacts irreversibly with enzyme yield a partially inactive enzyme. After about 60% loss activity, no further inactivation is observed. rate...
Supplementary Figure from Loss of PBRM1 Alters Promoter Histone Modifications and Activates ALDH1A1 to Drive Renal Cell Carcinoma
Supplementary Figure from Loss of PBRM1 Alters Promoter Histone Modifications and Activates ALDH1A1 to Drive Renal Cell Carcinoma
Supplementary Figure from Loss of PBRM1 Alters Promoter Histone Modifications and Activates ALDH1A1 to Drive Renal Cell Carcinoma
Supplementary Data from Loss of PBRM1 Alters Promoter Histone Modifications and Activates ALDH1A1 to Drive Renal Cell Carcinoma
Supplementary Figure from Loss of PBRM1 Alters Promoter Histone Modifications and Activates ALDH1A1 to Drive Renal Cell Carcinoma
Supplementary Figure from Loss of PBRM1 Alters Promoter Histone Modifications and Activates ALDH1A1 to Drive Renal Cell Carcinoma
Supplementary Figure from Loss of PBRM1 Alters Promoter Histone Modifications and Activates ALDH1A1 to Drive Renal Cell Carcinoma