A5079033969- Cancer therapeutics and mechanisms
- Amyotrophic Lateral Sclerosis Research
- Genetic and Kidney Cyst Diseases
- Cytokine Signaling Pathways and Interactions
- Epigenetics and DNA Methylation
- Hedgehog Signaling Pathway Studies
- Microtubule and mitosis dynamics
- Drug Transport and Resistance Mechanisms
- Computational Drug Discovery Methods
- DNA and Nucleic Acid Chemistry
- Cancer-related Molecular Pathways
- RNA Interference and Gene Delivery
- Neurogenetic and Muscular Disorders Research
- Synthesis and Characterization of Heterocyclic Compounds
- Receptor Mechanisms and Signaling
- Advanced biosensing and bioanalysis techniques
- biodegradable polymer synthesis and properties
- Metal complexes synthesis and properties
- Synthesis and biological activity
- Cancer, Hypoxia, and Metabolism
- Molecular Biology Techniques and Applications
- Cancer Genomics and Diagnostics
- Advanced Breast Cancer Therapies
- Erythrocyte Function and Pathophysiology
- Neuroinflammation and Neurodegeneration Mechanisms
NewYork–Presbyterian Hospital
2024
Columbia University
2017-2024
Columbia University Irving Medical Center
2024
Project ALS
2022-2024
New York Hospital Queens
2024
Fox Chase Cancer Center
2015-2019
Novosibirsk State University
2015-2016
Novosibirsk State Medical University
2016
Abstract Fused in sarcoma (FUS) is an RNA-binding protein that genetically and pathologically associated with rare aggressive forms of amyotrophic lateral sclerosis (ALS) frontotemporal dementia (FTD). To explore the mechanisms by which mutant FUS causes neurodegeneration ALS-FTD, we generated a series knock-in mouse lines express equivalent ALS-associated FUSP525L FUSΔEX14 protein. In mice, show progressive, age-dependent motor neuron loss as consequence dose-dependent gain toxic function,...
Anti-Müllerian hormone (AMH) and its type II receptor AMHR2, both previously thought to primarily function in gonadal tissue, were unexpectedly identified as potent regulators of transforming growth factor (TGF-β)/bone morphogenetic protein (BMP) signaling epithelial-mesenchymal transition (EMT) lung cancer. AMH is a TGF-β/BMP superfamily member, AMHR2 heterodimerizes with I receptors (ALK2, ALK3) also used by the for BMP (BMPR2). regulates expression BMPR2, ALK2, ALK3, supports kinase...
The serine-threonine kinases Aurora A (AURKA) and p21-activated kinase 1 (PAK1) are frequently overexpressed in breast tumors, with overexpression promoting aggressive cancer phenotypes poor clinical outcomes. Besides the well-defined roles of these proteins control cell division, proliferation, invasion, both support MAPK pathway activation can contribute to endocrine resistance by phosphorylating estrogen receptor alpha (ERα). PAK1 directly phosphorylates AURKA its functional partners,...
Autosomal-dominant polycystic kidney disease (ADPKD) is associated with progressive formation of renal cysts, enlargement, hypertension, and typically end-stage disease. In ADPKD, inherited mutations disrupt function the polycystins (encoded by PKD1 PKD2), thus causing loss a cyst-repressive signal emanating from cilium. Genetic studies have suggested ciliary maintenance essential for ADPKD pathogenesis. Heat shock protein 90 (HSP90) clients include multiple proteins linked to maintenance....
Amyotrophic lateral sclerosis (ALS) is a rapidly progressing, highly heterogeneous neurodegenerative disease, underscoring the importance of obtaining information to personalize clinical decisions quickly after diagnosis. Here, we investigated whether ALS-relevant signatures can be detected directly from biopsied patient fibroblasts. We profiled familial ALS (fALS) fibroblasts, representing range mutations in fused sarcoma (FUS) gene and ages onset. To differentiate FUS fALS healthy control...
For many tumors, signaling exchanges between cancer cells and other in their microenvironment influence overall tumor signaling. Some of these depend on expression the primary cilium nontransformed cell populations, as extracellular ligands including Sonic Hedgehog (SHH), PDGFRα, others function through receptors spatially localized to cilia. Cell ciliation is regulated by proteins that are themselves therapeutic targets. We investigated whether kinase inhibitors clinical interest with...
Purpose Primary central nervous system, diffuse large B-cell lymphoma, post-transplant lymphoproliferative disorder in the cerebellopontine angle after an allogeneic stem cell transplantation has never been reported literature. Typically, lymphoma is non-polyploid. We report first case of a patient with polyploid who presented back pain. Case presentation A 45-year-old man history nodular sclerosing classic Hodgkin stage IIB treated systemic chemotherapy, external radiation and autologous...
The primary monocilium, or cilium, is a single antenna-like organelle that protrudes from the surface of most mammalian cell types, and serves as signaling hub. Mutations cilia-associated genes result in severe genetic disorders termed ciliopathies. Among these, common autosomal dominant polycystic kidney disease (ADPKD); less diseases include Bardet-Biedl syndrome, Joubert nephronophthisis, others. Important cascades with receptor systems localized exclusively part at cilia Sonic Hedgehog...
Here, we report the synthesis of a series dehydroabietylamine (DAA) salts. We studied cytotoxic activity DAA salts and their antiviral properties against influenza virus A(H1N1)pdm09 further compared these parameters to those itself organic acids used as counterions. observed that DAA, its hydrochloride (DAA∙HCl) had similar cytotoxicity profiles in three cancer cell lines: MDA-MB-231, MCF-7, U-87 MG. Meanwhile same with respect melanoma line SK-Mel-8 was higher than DAA∙HCl: CTD50 values 5...
ABSTRACT A major challenge for understanding and treating Amyotrophic Lateral Sclerosis (ALS) is that most patients have no known genetic cause. Even within defined subtypes, display considerable clinical heterogeneity. It unclear how to identify subsets of ALS share common molecular dysregulation or could respond similarly treatment. Here, we developed a scalable microscopy machine learning platform phenotypically subtype readily available, primary patient-derived fibroblasts. Application...
Abstract Amyotrophic Lateral Sclerosis (ALS) is a heterogeneous neurodegenerative disorder that affects motor neurons in the brain and spinal cord, causing progressive loss of voluntary muscle control1,2. ALS heterogeneity includes age manifestation, rate progression, anatomical sites symptom onset. In addition, disease-causing mutations specific genes have been identified are used to catalog different subtypes ALS3. Interestingly, several ALS-associated shown affect immune functions,...
Abstract The purpose of this study is to characterize resistance mechanisms non-small cell lung cancer (NSCLC) heat shock protein 90 (HSP90) inhibition. Unexpectedly, we identified anti-Mullerian hormone (AMH) and its type II receptor (AMHR2) as two associated genes. AMH AMHR2 are TGF-ß/BMP superfamily members that share common I receptors with BMP, resulting in overlapping signaling outputs. have thus far predominantly been studied the context gonadal development, regulation female...
Abstract Estrogen receptor alpha (ERα) signaling plays a critical role in the development and progression of hormone receptor-positive (HR+) breast cancer. One mechanism tumor HR+ cancer is phosphorylation ERα by non-receptor protein kinases, leading to ligand-independent activation ERα. Mitotic kinases Aurora A (AURKA) p21-activated kinase 1 (PAK1) are frequently overexpressed can phosphorylate on serine 305, increasing ability induce transcription target genes implicated tumorigenesis. In...
<p>Supplementary Video S4. Time-lapse images of hTERT-RPE1-Arl13b-GFP cells starved in serum-free Opti-MEM for 48 hours, then incubated 3 hours 1 µM ganetespib.</p>
<p>Supplementary Video S5. Time-lapse images of hTERT-RPE1-Arl13b-GFP cells starved in serum-free Opti-MEM for 48 hours, then incubated 3 hours 2.5 µM sunitinib.</p>
<p>Supplementary Video S7. Time-lapse images of hTERT-RPE1-Arl13b-GFP cells starved in serum-free Opti-MEM for 48 hours, then incubated 3 hours 2.5 µM erlotinib + 20% FBS.</p>
<p>Supplementary Video S6. Time-lapse images of hTERT-RPE1-Arl13b-GFP cells starved in serum-free Opti-MEM for 48 hours, then incubated 3 hours 2.5 µM IRAK1/4 inhibitor + 20% FBS.</p>
<p>Supplementary Figure S1. Additional analysis of siRNA effects on ciliation and target depleton. Supplementary S2. Sorafenib is similar to sunitinib in inducing ciliary resorption. S3. Effect compounds AURKA catalytic activity. S4. Representative images demonstrating the effect (A) ganetespib (B) cilia resorption hTERT-RPE1-Arl13b-GFP cells. S5. Cilia length upon treatment with indicated cilia-stabilizing hTERT-RPE1 NIH3T3 cell lines. S6. Drug correspond changes cycle over time. S7....