A5045105656- Cancer, Hypoxia, and Metabolism
- Microtubule and mitosis dynamics
- Renal and related cancers
- Cell death mechanisms and regulation
- Phagocytosis and Immune Regulation
- Prostate Cancer Treatment and Research
- Epigenetics and DNA Methylation
- Hormonal and reproductive studies
- RNA modifications and cancer
- Cancer-related Molecular Pathways
- Renal cell carcinoma treatment
- Advanced Malware Detection Techniques
- Congenital Heart Disease Studies
- Security and Verification in Computing
- Cancer-related gene regulation
- Retinoids in leukemia and cellular processes
- Cardiac Ischemia and Reperfusion
- Mitochondrial Function and Pathology
- Cancer Research and Treatments
- Histone Deacetylase Inhibitors Research
- Ubiquitin and proteasome pathways
- Cancer-related molecular mechanisms research
- Virus-based gene therapy research
- Cryptographic Implementations and Security
- Cancer Genomics and Diagnostics
Cleveland Clinic Lerner College of Medicine
2020-2025
Columbia University
2023-2025
Cleveland Clinic
2022-2024
Case Comprehensive Cancer Center
2023-2024
Johnson University
2024
Rutgers, The State University of New Jersey
2024
Case Western Reserve University
2020-2023
Cerner (United States)
2023
Christian Medical College
2022
Intel (United States)
2022
Oxygen sensing revisited The cellular response to hypoxia (oxygen deficiency) is a contributing factor in many human diseases. Previous studies examining the way which alters gene expression have focused on oxygen-sensing enzymes that regulate activity of transcription called hypoxia-inducible (see Perspective by Gallipoli and Huntly). Chakraborty et al. Batie now show can also affect through direct effects chromatin regulators. Certain histone demethylases, such as KDM6A KDM5A, were found...
Activation of the serine-threonine kinase Akt promotes survival and proliferation various cancers. Hypoxia resistance tumor cells to specific therapies. We therefore explored a possible link between hypoxia activity. found that was prolyl-hydroxylated by oxygen-dependent hydroxylase EglN1. The von Hippel-Lindau protein (pVHL) bound directly hydroxylated inhibited In lacking oxygen or functional pVHL, activated promote cell tumorigenesis. also identified cancer-associated mutations impair...
The transfer of intact mitochondria between heterogeneous cell types has been confirmed in various settings, including cancer. However, the functional implications on tumor biology are poorly understood. Here we show that is a prevalent phenomenon glioblastoma (GBM), most frequent and malignant primary brain tumor. We identified horizontal from astrocytes as mechanism enhances tumorigenesis GBM. This dependent network-forming intercellular connections GBM cells astrocytes, which facilitated...
Myeloid-derived suppressor cells (MDSCs) impair antitumor immune responses. Identifying regulatory circuits during MDSC development may bring new opportunities for therapeutic interventions. We report that the V-domain of T cell activation (VISTA) functions as a key enabler differentiation. VISTA deficiency reduced STAT3 and STAT3-dependent production polyamines, which causally impaired mitochondrial respiration expansion. In both mixed bone marrow (BM) chimera mice myeloid-specific...
Abstract Small cell lung cancer (SCLC) accounts for 15% of cancers and is almost always linked to inactivating RB1 TP53 mutations. SCLC frequently responds, albeit briefly, chemotherapy. The canonical function the gene product repress E2F transcription factor family. also plays both E2F-dependent E2F-independent mitotic roles. We performed a synthetic lethal CRISPR/Cas9 screen in an RB1−/− line that conditionally expresses identify dependencies are caused by loss discovered lines...
The three EglN prolyl hydroxylases (EglN1, EglN2, and EglN3) regulate the stability of HIF transcription factor. We recently showed that loss however, also leads to down-regulation Cyclin D1 decreased cell proliferation in a HIF-independent manner. Here we report EglN2 can hydroxylate FOXO3a on two specific residues vitro vivo. Hydroxylation these sites prevents binding USP9x deubiquitinase, thereby promoting proteasomal degradation FOXO3a. FOXO factors repress transcription. Failure...
More than 90% of small cell lung cancers (SCLCs) harbor loss-of-function mutations in the tumor suppressor gene RB1 . The canonical function product, pRB, is to repress E2F transcription factor family, but pRB also functions regulate cellular differentiation part through its binding histone demethylase KDM5A (also known as RBP2 or JARID1A). We show that promotes SCLC proliferation and SCLC's neuroendocrine phenotype by sustaining expression ASCL1. Mechanistically, we found sustains ASCL1...
Abstract Background Hypoxia is associated with poor prognosis in many cancers including glioblastoma (GBM). Glioma stem-like cells (GSCs) often reside hypoxic regions and serve as reservoirs for disease progression. Long non-coding RNAs (lncRNAs) have been implicated GBM. However, the lncRNAs that modulate GSC adaptations to hypoxia are poorly understood. Identification of these may provide new therapeutic strategies target GSCs under hypoxia. Methods induced by were identified RNA-seq. Lung...
Antiandrogen strategies remain the prostate cancer treatment backbone, but drug resistance develops. We show that androgen blockade in leads to derepression of retroelements (REs) followed by a double-stranded RNA (dsRNA)-stimulated interferon response blocks tumor growth. A forward genetic approach identified H3K9 trimethylation (H3K9me3) as an essential epigenetic adaptation antiandrogens, which enabled transcriptional silencing REs otherwise stimulate signaling and glucocorticoid receptor...
Dysregulated H3K27 demethylase activity in pVHL-deficient cells increases dependence on the EZH1 methyltransferase.
Progression of prostate cancer depends on androgen receptor, which is usually activated by androgens. Therefore, a mainstay treatment deprivation therapy. Unfortunately, despite initial response, resistance nearly always develops, and disease progresses to castration-resistant (CRPC), remains driven non-gonadal androgens synthesized in tissues. 3β-Hydroxysteroid dehydrogenase/Δ5-->4 isomerase 1 (3βHSD1) catalyzes the rate-limiting step synthesis. However, how 3βHSD1, especially...
Despite the propensity for gastric and esophageal adenocarcinomas to select recurrent missense mutations in TP53, precise functional consequence of these remains unclear. Here we report that endogenous mRNA protein levels mutant p53 were elevated cell lines patients with cancer. Functional studies showed was sufficient, but not necessary, enhancing primary tumor growth vivo. Unbiased genome-wide transcriptome analysis revealed hypoxia signaling induced by 2 cancer lines. Using real-time vivo...
Modern processors dynamically control their operating frequency to optimize resource utilization, maximize energy savings, and conform system-defined constraints. If, during the execution of a software workload, running average any electrical or thermal parameter exceeds its corresponding predefined threshold value, power management architecture will reactively adjust CPU ensure safe conditions. In this paper, we demonstrate how such management-based throttling activity forms source timing...
Nocturnal hypoxaemia, which is common in chronic obstructive pulmonary disease (COPD) patients, associated with skeletal muscle loss or sarcopenia, contributes to adverse clinical outcomes. In COPD, we have defined this as prolonged intermittent hypoxia (PIH) because the duration of occurs through sleep followed by normoxia during day, contrast recurrent brief hypoxic episodes apnoea (OSA). Adaptive cellular responses PIH are not known. Responses induced three cycles 8 h 16 were compared...
Abstract Background Reduced forced vital capacity (FVC) is associated with morbidity and mortality in individuals Duchenne muscular dystrophy (DMD). Non-invasive ventilation (NIV) often prescribed for the treatment of sleep-disordered breathing (SDB), chronic respiratory insufficiency. Despite common practice initiating NIV later progression DMD, factors influencing FVC subsequent to commencement remain unclear. Objective To evaluate demographic, clinical socioeconomic determinants FVC%...
Abstract Background: SLC1A1/EAAT3 functions as a trimeric, Na+-dependent dicarboxylic amino acids (glutamate and aspartate) transporter. Recent studies have identified an oncogenic dependency in several cancers, including clear cell renal carcinoma (ccRCC), blood-borne tumors, lung cancer. Unfortunately, despite this transporter’s potential therapeutic target, pharmacological inhibition of SLC1A1 has remained elusive due to the absence potent selective inhibitors. In earlier studies, we...
Adenovirus E1A drives oncogenesis by targeting key regulatory pathways that are critical for cellular growth control. The interaction of with p400 is essential many activities, but the downstream target this unknown. Here, we present evidence oncoprotein transcription factor Myc interaction. We show stabilizes protein via and promotes coassociation at genes, leading to their transcriptional induction. also requires its ability activate Myc-dependent gene expression induce apoptosis, forced...