A5031895263- Advanced Breast Cancer Therapies
- Neuroblastoma Research and Treatments
- Monoclonal and Polyclonal Antibodies Research
- Radiopharmaceutical Chemistry and Applications
- Cancer Genomics and Diagnostics
- Retinoids in leukemia and cellular processes
- Protein Degradation and Inhibitors
- Pancreatic and Hepatic Oncology Research
- RNA modifications and cancer
- RNA Research and Splicing
- HER2/EGFR in Cancer Research
- Hippo pathway signaling and YAP/TAZ
- PARP inhibition in cancer therapy
- Cancer-related Molecular Pathways
- Cancer Treatment and Pharmacology
- CAR-T cell therapy research
- Cancer Cells and Metastasis
- Lymphoma Diagnosis and Treatment
- Bioinformatics and Genomic Networks
- Pluripotent Stem Cells Research
- Skin and Cellular Biology Research
- Sarcoma Diagnosis and Treatment
- Cellular Mechanics and Interactions
- Synthesis and Biological Evaluation
- Cancer Research and Treatments
Georgetown University
2014-2024
Georgetown University Medical Center
2014-2023
HUN-REN Research Centre for Natural Sciences
2018
Semmelweis University
2018
Vince Lombardi Cancer Clinic
2014
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor survival rates and frequently carries oncogenic KRAS mutation. However, has thus far not been a viable therapeutic target. We found that the abundance of YAP mRNA, which encodes Yes-associated protein (YAP), regulated by Hippo pathway during tissue development homeostasis, was increased in human PDAC compared normal pancreatic epithelia. In genetically engineered Kras(G12D) Kras(G12D):Trp53(R172H) mouse models,...
Looping together genes in cancer A subset of human cancers are characterized by aberrant fusion two specific genes. In some cases, the activity resultant protein drives tumor growth. Most appear to arise from simple reciprocal chromosomal translocations. Anderson et al. found that characteristic gene a bone and soft tissue called Ewing sarcoma is produced far more complicated mechanism (see Perspective Imielinski Ladanyi). nearly half tumors examined, was created formation dramatic genomic...
Significance Alternative splicing of RNA allows a limited number coding regions in the human genome to produce proteins with diverse functionality. has also been implicated as an oncogenic process. Identifying aspects cancer cells that differentiate them from noncancer remains ongoing challenge, and our research suggests alternatively spliced mRNA subsequent protein isoforms will provide new anticancer targets. We determined key oncoprotein Ewing sarcoma (ES), EWS-FLI1, regulates alternative...
Therapy resistance represents a clinical challenge for advanced non-small cell lung cancer (NSCLC), which still remains an incurable disease. There is growing evidence that cancer-initiating or stem cells (CSCs) provide reservoir of slow-growing dormant populations with tumor-initiating and unlimited self-renewal ability are left behind by conventional therapies reigniting post-therapy relapse metastatic dissemination. The metabolic pathways required the expansion CSCs incompletely defined,...
Abstract Nonalcoholic fatty liver disease (NAFLD) and its evolution to inflammatory steatohepatitis (NASH) are the most common causes of chronic damage transplantation that reaching epidemic proportions due upraising incidence metabolic syndrome, obesity, diabetes. Currently, there is no approved treatment for NASH. The mitochondrial citrate carrier, Slc25a1, has been proposed play an important role in lipid metabolism, suggesting a potential this protein pathogenesis disease. Here, we show...
A drug sensitizes Ewing’s sarcoma cells to chemotherapy by inducing mitotic arrest and priming the for apoptosis.
Transcription factors are commonly deregulated in cancer, and they have been widely considered as difficult to target due their nonenzymatic mechanism of action. Altered expression levels members the ETS-transcription often observed many different tumors, including lymphomas. Here, we characterized two small molecules, YK-4-279 its clinical derivative, TK-216, targeting ETS via blocking protein-protein interaction with RNA helicases, for antilymphoma activity.The study included preclinical...
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with limited and, very often, ineffective medical and surgical therapeutic options. The treatment of patients advanced unresectable PDAC restricted to systemic chemotherapy, intervention which most eventually develop resistance. Recently, nab-paclitaxel (n-PTX) has been added the arsenal first-line therapies, combination gemcitabine n-PTX modestly prolonged median overall survival. However, almost invariably succumb...
Connections between epigenetic reprogramming and transcription or splicing create novel mechanistic networks that can be targeted with tailored therapies. Multiple subunits of the chromatin remodeling BAF complex, including ARID1A, play a role in oncogenesis, either as tumor suppressors oncogenes. Recent work demonstrated EWS-FLI1, oncogenic driver Ewing sarcoma (ES), plays regulation through interactions complex. However, specific interact EWS-FLI1 precise complex ES oncogenesis remain...
Targeted monoclonal antibody therapy is a promising therapeutic strategy for cancer, and antibody-dependent cell-mediated cytotoxicity (ADCC) represents crucial mechanism underlying these approaches. The majority of patients have limited responses to due the development resistance. Models ADCC provide system uncovering immune-resistance mechanisms. We continuously exposed epidermal growth factor receptor (EGFR+) A431 cells KIR-deficient NK92-CD16V effector anti-EGFR cetuximab. Persistent...
Abstract Glioblastoma (GBM) is an aggressive and incurable tumor of the brain with limited treatment options. Current first-line standard care DNA alkylating agent temozolomide (TMZ), but this strategy adds only ~4 months to median survival due rapid development resistance. While some mechanisms TMZ resistance have been identified, they are not fully understood. There few effective strategies manage therapy resistant GBM, we lack diverse preclinical models acquired in which test therapeutic...
Abstract Liquid biopsy approaches provide an opportunity for both cancer detection and clinical assessment in a non-invasive manner. Here we apply blood-based lung screening test to 578 individuals diagnosed with through real-world diagnostic prospective trial (LEMA, NCT02894853). Pre-treatment plasma samples were processed the DELFI assay, validated cell-free DNA (cfDNA) based on locked machine learning analysis of genome-wide fragmentation patterns. Clinical data, including tumor stage...
RNA helicases impact structure and metabolism from transcription through translation, in part protein interactions with factors. However, there is limited knowledge on the role of factor influence upon helicase activity. A (RHA) a DExH-box that plays multiple roles cellular biology, some functions requiring its activity as while others scaffold. The oncogenic EWS-FLI1 requires RHA to enable Ewing sarcoma (ES) oncogenesis growth; small molecule, YK-4-279 disrupts this complex cells. Our...
CD133, a cancer stem cell (CSC) marker in tumors, including melanoma, is associated with tumor recurrence, chemoresistance, and metastasis. Patient-derived melanoma lines were transduced Tet-on vector expressing generating doxycycline (Dox)-inducible lines. Cells exposed to Dox for 24 h induce CD133 expression, followed by RNA-seq bioinformatic analyses, revealing genes pathways that are significantly up- or downregulated CD133. The most upregulated gene after was amphiregulin (AREG),...
Neuroblastoma is an embryonic childhood cancer with high mortality. 13-cis retinoic acid (13-cisRA) improves survival for some patients, but many recur, suggesting clinical resistance. The mechanism of resistance and the normal differentiation pathway are poorly understood. Three-amino-acid loop extension (TALE) family genes master regulators differentiation. Because retinoids promote in neuroblastoma, we evaluated TALE gene expression neuroblastoma.We RA-sensitive -resistant neuroblastoma...
Hematopoietic cells are continuously replenished from progenitor that reside in the bone marrow. To evaluate molecular changes during this process, we analyzed transcriptomes of freshly harvested human marrow (lineage-negative) and differentiated (lineage-positive) by single-molecule real-time (SMRT) full-length RNA-sequencing. This analysis revealed a ~5-fold higher number transcript isoforms than previously detected showed distinct composition individual characteristic for subpopulations....
Abstract To explore how airborne microbial patterns change with height above the Earth’s surface, we flew NASA’s C-20A aircraft on two consecutive days in June 2018 along identical flight paths over US Sierra Nevada mountain range at four different altitudes ranging from 10,000 ft to 40,000 ft. Bioaerosols were analyzed by metagenomic DNA sequencing and traditional culturing methods characterize composition diversity of atmospheric samples compared experimental controls. The relative...
Co-culture of human primary epithelial cells with irradiated 3T3 fibroblast feeder (J2 cells) and the Rho kinase inhibitor Y-27632 (Y) allows for unrestricted growth origin by process termed conditional reprogramming. To better understand nature signaling processes associated conditionally reprogrammed cells, effect two critical components co-culture conditions, J2 Y, on foreskin keratinocytes (HFKs) was evaluated gene expression profiling, reverse-phase protein arrays siRNA screening. Y...
Abstract AIB1Δ4 is an N-terminally truncated isoform of the oncogene amplified in breast cancer 1 (AIB1) with increased expression high-grade human ductal carcinoma situ (DCIS). However, role DCIS malignant progression has not been defined. Here we CRISPR-engineered RNA splice junctions to produce normal and early-stage epithelial cells that expressed only AIB1Δ4. These showed enhanced motility invasion 3D cell culture. In zebrafish, AIB1Δ4-expressing enabled parental when present a mixed...