- Mitochondrial Function and Pathology
- Cancer, Hypoxia, and Metabolism
- RNA modifications and cancer
- ATP Synthase and ATPases Research
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- Signaling Pathways in Disease
- Cancer Cells and Metastasis
- Autophagy in Disease and Therapy
- Telomeres, Telomerase, and Senescence
- Bone Metabolism and Diseases
- Nitric Oxide and Endothelin Effects
- Alcohol Consumption and Health Effects
- Viral Infectious Diseases and Gene Expression in Insects
- Metabolism, Diabetes, and Cancer
- NF-κB Signaling Pathways
- Animal testing and alternatives
- Histone Deacetylase Inhibitors Research
- Protein Tyrosine Phosphatases
- Heat shock proteins research
- Eosinophilic Esophagitis
- Nanoplatforms for cancer theranostics
- Biochemical Analysis and Sensing Techniques
- FOXO transcription factor regulation
- Myeloproliferative Neoplasms: Diagnosis and Treatment
Incyte (United States)
2023-2025
IQ Samhällsbyggnad
2023
Applied Technologies (United States)
2023
Columbia University Irving Medical Center
2019-2020
National Center on Addiction and Substance Abuse at Columbia University
2020
University of Pennsylvania
2007-2019
Cancer Research Institute
2015
Sinha Institute of Medical Science & Technology
2002-2003
Jadavpur University
2002
Targeting multiple components of the MAPK pathway can prolong survival patients with BRAFV600E melanoma. This approach is not curative, as some BRAF-mutated melanoma cells are intrinsically resistant to inhibitors (MAPKi). At systemic level, our knowledge how signaling pathways underlie drug resistance needs be further expanded. Here, we have shown that a low basal level mitochondrial biogenesis depend on this process survive MAPKi. Intrinsically exploited an integrated stress response,...
Expression of type I interferons (IFNs) can be induced by DNA-damaging agents, but the mechanisms and significance this regulation are not completely understood. We found that transcription factor IRF3, activated in an ATM-IKKα/β-dependent manner, stimulates cell-autonomous IFN-β expression response to double-stranded DNA breaks. Cells tissues with accumulating damage produce endogenous stimulate IFN signaling vitro vivo. In turn, acts amplify DNA-damage responses, activate p53 pathway,...
Aberrant Notch signaling is implicated in several cancers, including breast cancer. However, the mechanistic details of specific receptors and function ligand-mediated that promote cancer remains elusive. In our studies we show DLL1, a ligand, significantly overexpressed ERα+ luminal Intriguingly, DLL1 overexpression correlates with poor prognosis cancer, but not other subtypes addition, this effect to as ligands (DLL3, JAGGED1, JAGGED2) do influence clinical outcome patients. Genetic...
Mitochondrial respiratory stress (also called mitochondrial retrograde signaling) activates a Ca(2+)/calcineurin-mediated signal that culminates in transcription activation/repression of large number nuclear genes. This is propagated through activation the regulatory proteins NFκB c-Rel/p50, C/EBPδ, CREB, and NFAT. Additionally, heterogeneous ribonucleoprotein A2 (hnRNPA2) functions as coactivator up-regulating Cathepsin L, RyR1, Glut-4, target genes signaling. Activation IGF1R, which causes...
The NFκBs regulate an array of physiological and pathological processes, including propagation mitochondrial respiratory stress signaling in mammalian cells. We showed previously that activates NFκB using a novel calcineurin-requiring pathway is different from canonical or non-canonical pathways. This study shows IκBβ essential for the signaling. Knock down IκBβ, but not IκBα, mRNA reduced stress-mediated activation nuclear translocation cRel:p50, inhibiting expression target genes RyR1...
We have previously shown that disruption of mitochondrial membrane potential by depletion DNA (mtDNA) or treatment with a ionophore, carbonyl cyanide m-chlorophenylhydrazone, initiates stress signaling, which causes resistance to apoptosis, and induces invasive behavior in C2C12 myocytes A549 cells. In the present study we show calcineurin (Cn), activated as part this plays an important role increased glucose uptake glycolysis. Here report that, although both insulin insulin-like growth...
Mitochondrial dysfunction and altered transmembrane potential initiate a mitochondrial respiratory stress response, also known as retrograde in wide spectrum of cells. The response activates calcineurin, which regulates transcription factors, including new nuclear factor-kappaB (NF-kappaB) pathway, different from the canonical noncanonical pathways. In this study using combination small interfering RNA-mediated mRNA knock down, transcriptional analysis, chromatin immunoprecipitation, we...
Abstract Reduced mitochondrial DNA copy number, mutations or disruption of electron transfer chain complexes induce mitochondria-to-nucleus retrograde signaling, which induces global change in nuclear gene expression ultimately contributing to various human pathologies including cancer. Recent studies suggest that these changes cause transcriptional reprogramming genes although the mechanism this cross talk remains unclear. Here, we provide evidence signaling regulates chromatin acetylation...
We previously discovered that small extracellular vesicles (sEV) isolated from melanoma cells produce immunosuppressive adenosine (ADO) via the ATP→ADP→AMP→ADO pathway and CD73 is 'gateway' ecto-nucleotidase used by sEV to generate ADO. Here we extend these findings CD39(+)CD73(+) CD39(+)CD73(-) breast cancer cells. were supernatants of a triple-negative cell line ± genetic knockout CD73. A newly developed high pressure liquid chromatography assay with fluorescence detection was for...
The mitochondria-to-nucleus retrograde signaling (MtRS) pathway aids in cellular adaptation to stress. We earlier reported that the Ca
During alcohol consumption, the esophageal mucosa is directly exposed to high concentrations of ethanol (EtOH). We therefore investigated response normal human epithelial cell lines EPC1, EPC2 and EPC3 acute EtOH exposure. While these cells were able tolerate 2% for 8 h in both three-dimensional organoids monolayer culture conditions, RNA sequencing suggested that induced mitochondrial dysfunction. With treatment, EPC1 also demonstrated decreased ATPB protein expression by immunofluorescence...
In the past decade mitochondria have emerged as an important cellular signaling hub controlling metabolism, epigenetics, and cell fate. Dysfunctional initiate a retrograde nuclear response that influences reprograming observed in various human pathologies, including cancer. New data suggest loss of cytochrome c oxidase function promotes Warburg effect upregulates several genes with roles tumor development.