A5079956746- FOXO transcription factor regulation
- Nuclear Structure and Function
- Neuroendocrine Tumor Research Advances
- Phagocytosis and Immune Regulation
- Cancer, Lipids, and Metabolism
- Protein Degradation and Inhibitors
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Adipose Tissue and Metabolism
- DNA Repair Mechanisms
- Immune Cell Function and Interaction
- Effects of Radiation Exposure
- Neuroblastoma Research and Treatments
- Pancreatic and Hepatic Oncology Research
- Epigenetics and DNA Methylation
- Histone Deacetylase Inhibitors Research
- Ubiquitin and proteasome pathways
- Microtubule and mitosis dynamics
- Receptor Mechanisms and Signaling
- Advanced Proteomics Techniques and Applications
- Enzyme Structure and Function
- Neuroinflammation and Neurodegeneration Mechanisms
- Cancer-related molecular mechanisms research
- Immune cells in cancer
Columbia University Irving Medical Center
2019-2025
Columbia University
2020-2025
Herbert Irving Comprehensive Cancer Center
2021-2024
Government Ayurved College, Nanded
2024
Kettering University
2017-2023
Memorial Sloan Kettering Cancer Center
2011-2023
Vardhman Mahavir Medical College & Safdarjung Hospital
2016-2022
Safdarjang Hospital
2016-2020
New York Structural Biology Center
2018
Bundelkhand University
2013
Highlights•3F3-FMA is identified in a screen as selective ferroptosis-immunostaining reagent•The antigen of 3F3-FMA the transferrin receptor 1 protein (TfR1)•Anti-TfR1 antibodies can detect ferroptosis by immunofluorescence and flow cytometry•Anti-TfR1 anti-MDA xenograft cancer modelsSummaryFerroptosis type regulated cell death driven iron-dependent accumulation oxidized polyunsaturated fatty acid-containing phospholipids. There no reliable way to selectively stain ferroptotic cells tissue...
The distal appendages (DAPs) of centrioles have been proposed to anchor cilia the plasma membrane, but their molecular composition, assembly, and exact function in ciliogenesis remain poorly understood. Using quantitative centrosome proteomics superresolution microscopy, we identified five DAP components, including one previously described (CEP164), partially characterized (CEP89 [ccdc123]), three novel (CEP83 [ccdc41], SCLT1, FBF1) proteins. Analyses assembly revealed a hierarchy. CEP83...
Abstract Ferroptosis is mediated by lipid peroxidation of phospholipids containing polyunsaturated fatty acyl moieties. Glutathione, the key cellular antioxidant capable inhibiting via activity enzyme glutathione peroxidase 4 (GPX-4), generated directly from sulfur-containing amino acid cysteine, and indirectly methionine transsulfuration pathway. Herein we show that cysteine deprivation (CMD) can synergize with GPX4 inhibitor RSL3 to increase ferroptotic cell death in both murine human...
Increasing use of covalent and noncovalent inhibitors Bruton's tyrosine kinase (BTK) has elucidated a series acquired drug-resistant BTK mutations in patients with B cell malignancies. Here we identify inhibitor resistance distinct enzymatic activities, including some that impair activity while imparting novel protein-protein interactions sustain receptor (BCR) signaling. Furthermore, describe clinical-stage IKZF1/3 degrader, NX-2127, can bind proteasomally degrade each mutant proteoform,...
Loss of Bcl2-associated athanogene 3 (BAG3) is associated with dilated cardiomyopathy (DCM). BAG3 regulates sarcomere protein turnover in cardiomyocytes; however, the function other cardiac cell types understudied. In this study, we used an isogenic pair BAG3-knockout and wild-type human induced pluripotent stem cells (hiPSCs) to interrogate role hiPSC-derived fibroblasts (CFs). Analysis type-specific conditional knockout engineered heart tissues revealed essential contribution CF...
Centrioles are self-reproducing organelles that form the core structure of centrosomes or microtubule-organizing centers (MTOCs). However, whether duplication and MTOC organization reflect innate activities centrioles acquired conditionally is unclear. In this paper, we show newly formed full-length had no inherent capacity to duplicate organize pericentriolar material (PCM) but both after mitosis through a Plk1-dependent modification occurred in early mitosis. Modified initiated PCM...
Altered expression of XPO1, the main nuclear export receptor in eukaryotic cells, has been observed cancer, and XPO1 a focus anticancer drug development. However, mechanistic evidence for cancer-specific alterations function is lacking. Here, genomic analysis 42,793 cancers identified recurrent previously unrecognized mutational hotspots XPO1. mutations exhibited striking lineage specificity, with enrichment variety B-cell malignancies, introduction single amino acid substitutions initiated...
Dopaminergic neurons modulate neural circuits and behaviors via dopamine (DA) release from expansive, long range axonal projections. The elaborate cytoarchitecture of these is embedded within complex brain tissue, making it difficult to access the neuronal proteome using conventional methods. Here, we demonstrate APEX2 proximity labeling genetically targeted in mouse brain, enabling subcellular proteomics with cell-type specificity. By combining biotinylation mass spectrometry, mapped...
Abstract Cognitive dysfunction (CD) in heart failure (HF) adversely affects treatment compliance and quality of life. Although ryanodine receptor type 2 (RyR2) has been linked to cardiac muscle dysfunction, its role CD HF remains unclear. Here, we show hippocampal neurons from individuals mice with that the RyR2/intracellular Ca 2+ release channels were subjected post-translational modification (PTM) leaky. RyR2 PTM included protein kinase A phosphorylation, oxidation, nitrosylation...
Rotator cuff injuries result in more than 500,000 surgeries annually the United States, many of which fail. These typically involve repair injured tendon and removal subacromial bursa, a synovial-like tissue that sits between rotator acromion. The bursa has been implicated pathogenesis healing. Using proteomic profiling samples from nine patients with injury, we show responds to injury underlying tendon. In rat model supraspinatus tenotomy, evaluated bursa’s effect on tendon, uninjured...
Abstract Tryptophan catabolism is a major metabolic pathway utilized by several professional and non-professional antigen presenting cells to maintain immunological tolerance. Here we report that 3-hydroxy- l -kynurenamine (3-HKA) biogenic amine produced via an alternative of tryptophan metabolism. In vitro, 3-HKA has anti-inflammatory profile inhibiting the IFN-γ mediated STAT1/NF-κΒ in both mouse human dendritic (DCs) with consequent decrease release pro-inflammatory chemokines cytokines,...
Background: Hair greying is a hallmark of aging generally believed to be irreversible and linked psychological stress. Methods: Here, we develop an approach profile hair pigmentation patterns (HPPs) along individual human shafts, producing quantifiable physical timescales rapid transitions. Results: Using this method, show white/grey hairs that naturally regain across sex, ethnicities, ages, body regions, thereby quantitatively defining the reversibility in humans. Molecularly, grey...
A diet rich in saturated fat and carbohydrates causes low-grade chronic inflammation several organs, including the liver, ultimately driving nonalcoholic steatohepatitis. In this setting, environment-driven lipotoxicity glucotoxicity induce liver damage, which promotes dendritic cell activation generates a major histocompatibility complex class II (MHC-II) immunopeptidome enriched with peptides derived from proteins involved cellular metabolism, oxidative phosphorylation, stress responses....
Metastatic prostate cancer (PCa) inevitably acquires resistance to standard therapy preceding lethality. Here, we unveil a chromosomal instability (CIN) tolerance mechanism as therapeutic vulnerability of therapy-refractory lethal PCa. Through genomic and transcriptomic analysis patient datasets, find that castration chemotherapy-resistant tumors display the highest CIN mitotic kinase levels. Functional genomics screening coupled with quantitative phosphoproteomics identify MASTL survival...