A5027845922- Hippo pathway signaling and YAP/TAZ
- Protein Degradation and Inhibitors
- Multiple Myeloma Research and Treatments
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Ubiquitin and proteasome pathways
- Chromosomal and Genetic Variations
- CRISPR and Genetic Engineering
- Gastrointestinal Tumor Research and Treatment
- Chemical Reactions and Isotopes
- PI3K/AKT/mTOR signaling in cancer
- Sarcoma Diagnosis and Treatment
- Cancer-related gene regulation
- Cell death mechanisms and regulation
- Chronic Lymphocytic Leukemia Research
- Peptidase Inhibition and Analysis
- Chronic Myeloid Leukemia Treatments
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- RNA and protein synthesis mechanisms
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- NF-κB Signaling Pathways
- Genomics and Phylogenetic Studies
- CAR-T cell therapy research
- Plant Disease Resistance and Genetics
Rutgers, The State University of New Jersey
2020-2025
Columbia University Irving Medical Center
2023-2024
Massachusetts General Hospital
2018-2023
Georgetown University
2022
Stanford University
2022
Center for Cancer Research
2018-2021
Rutgers Sexual and Reproductive Health and Rights
2021
Harvard University
2016-2019
Dana-Farber Cancer Institute
2015-2019
Montgomery General Hospital
2019
The release of paused RNA polymerase II into productive elongation is highly regulated, especially at genes that affect human development and disease. To exert control over this rate-limiting step, we designed sequence-specific synthetic transcription factors (Syn-TEFs). These molecules are composed programmable DNA-binding ligands flexibly tethered to a small molecule engages the machinery. By limiting activity targeted loci, Syn-TEFs convert constituent modules from broad-spectrum...
Abstract As a master regulator of chromatin function, the lysine methyltransferase EZH2 orchestrates transcriptional silencing developmental gene networks. Overexpression is commonly observed in human epithelial cancers, such as non–small cell lung carcinoma (NSCLC), yet definitive demonstration malignant transformation by deregulated remains elusive. Here, we demonstrate causal role overexpression NSCLC with new genetically engineered mouse models adenocarcinoma. Deregulated silences normal...
Abstract To date, no consistent oncogenic driver mutations have been identified in most adult soft tissue sarcomas; these tumors are thus generally insensitive to existing targeted therapies. Here we investigated alternate mechanisms underlying sarcomagenesis identify potential therapeutic interventions. Undifferentiated pleomorphic sarcoma (UPS) is an aggressive tumor frequently found skeletal muscle where deregulation of the Hippo pathway and aberrant stabilization its transcriptional...
Abstract Transposable elements (TEs) must replicate in germline cells to pass novel insertions offspring. In Drosophila melanogaster ovaries, TEs can exploit specific developmental windows of opportunity evade host silencing and increase their copy numbers. However, TE activity the distinct cell types testis are not well understood. Here, we reanalyze publicly available single-cell RNA-seq datasets quantify expression testis. We develop a method for identification gene modules find that...
Aberrant activation of transposable elements (TEs) has been a well-documented source genomic instability and disease, stemming from their insertion into genes imposition epigenetic effects on nearby loci. However, the extent to which disruptive involve concomitant or subsequent formation DNA:RNA hybrids (R-loops) remains unknown. Here we used immunoprecipitation followed by high-throughput sequencing (DRIP-seq) map R-loop profiles TEs satellites in D. melanogaster ovaries control rhino...
Activating mutations in the KIT or PDGFRA receptor tyrosine kinases are hallmarks of gastrointestinal stromal tumor (GIST). The biological underpinnings recurrence following resection disease progression beyond kinase mutation poorly understood. Utilizing chromatin immunoprecipitation with sequencing samples and cell lines, we describe enhancer landscape GIST, highlighting genes that reinforce extend our understanding these neoplasms. A group core transcription factors can be distinguished...
The relationship between promoter proximal transcription factor-associated gene expression and super-enhancer-driven transcriptional programs are not well defined. However, their distinct genomic occupancy suggests a mechanism for specific separable control. We explored the functional interrelationship E2F factors BET co-activators in multiple myeloma. found that factor E2F1 its heterodimerization partner DP1 represent dependency myeloma cells. Global chromatin analysis reveals regulatory...
Gastrointestinal stromal tumor (GIST) is a mesenchymal neoplasm characterized by activating mutations in the related receptor tyrosine kinases KIT and PDGFRA. GIST relies on expression of these unamplified kinase (RTK) genes through large enhancer domain, resulting high levels oncogene required for growth. Although inhibition an effective therapy many patients with GIST, disease progression from kinase-resistant common no other classes systemic exist. In this study, we identify regulatory regions
Abstract Acquired drug resistance to even the most effective anti-cancer targeted therapies remains an unsolved clinical problem. Although many drivers of acquired have been identified 1‒6 , underlying molecular mechanisms shaping tumor evolution during treatment are incompletely understood. The extent which therapy actively drives by promoting mutagenic processes 7 or simply provides selective pressure necessary for outgrowth drug-resistant clones 8 open question. Here, we report that lung...
Long-range oncogenic enhancers play an important role in cancer. Yet, whether similar regulation of tumor suppressor genes is relevant remains unclear. Loss expression PTEN associated with the pathogenesis various cancers, including T-cell leukemia (T-ALL). Here, we identify a highly conserved distal enhancer (PE) that interacts promoter multiple hematopoietic populations, T-cells, and acts as hub transcription factors T-ALL. Consistently, loss PE leads to reduced levels T-ALL cells....
Histone acetyltransferases KAT2A and KAT2B are paralogs highly expressed in the intestinal epithelium, but their functions not well understood. In this study, double knockout of murine Kat2 genes epithelium was lethal, resulting robust activation interferon signaling interferon-associated phenotypes including loss stem cells. Use pharmacological agents sterile organoid cultures indicated a cell-intrinsic double-stranded RNA trigger for signaling. Acetyl-proteomics sequencing...
When users search online for a business, the engine may present them with list of related business recommendations. We address problem constructing useful and diverse such recommendations that would include an optimal combination substitutes complements. Substitutes are similar potential alternatives to searched whereas complements local businesses can offer more comprehensive better rounded experience user visiting locality. In our setting, each belongs category in ontology categories. Two...