A5055354782- Ubiquitin and proteasome pathways
- Monoclonal and Polyclonal Antibodies Research
- PI3K/AKT/mTOR signaling in cancer
- Cancer-related molecular mechanisms research
- MicroRNA in disease regulation
- RNA modifications and cancer
- HER2/EGFR in Cancer Research
- RNA Interference and Gene Delivery
- Cancer Mechanisms and Therapy
- Cancer, Hypoxia, and Metabolism
- Peptidase Inhibition and Analysis
- RNA and protein synthesis mechanisms
- Glycosylation and Glycoproteins Research
- Cancer Research and Treatments
- Quinazolinone synthesis and applications
- Protein Degradation and Inhibitors
- Chronic Myeloid Leukemia Treatments
- Cancer Diagnosis and Treatment
- Cancer-related gene regulation
- Eosinophilic Disorders and Syndromes
- Protein Kinase Regulation and GTPase Signaling
- Cell Image Analysis Techniques
- Multiple Myeloma Research and Treatments
- Cystic Fibrosis Research Advances
- Acute Lymphoblastic Leukemia research
Cornell University
2010-2025
City University of New York
2021-2025
The Graduate Center, CUNY
2021-2025
Weill Cornell Medicine
2024-2025
Hunter College
2021-2025
Tisch Hospital
2025
Tisch Cancer Institute
2025
Memorial Sloan Kettering Cancer Center
2010-2021
UCSF Helen Diller Family Comprehensive Cancer Center
2020-2021
Icahn School of Medicine at Mount Sinai
2017-2021
KRAS is a small GTPase that among the most commonly mutated oncogenes in cancer. Here, we discuss biology, therapeutic avenues to target it, and mechanisms of resistance tumors employ response inhibition. Several strategies are under investigation for inhibiting oncogenic KRAS, including molecule compounds targeting specific mutations, pan-KRAS inhibitors, PROTACs, siRNAs, PNAs, mutant KRAS-specific immunostimulatory strategies. A central challenge effectiveness frequent development these...
New anticancer drugs that target oncogenic signaling molecules have greatly improved the treatment of certain cancers. However, resistance to targeted therapeutics is a major clinical problem and redundancy pathways provides back-up mechanisms allow cancer cells escape. For example, AKT PIM kinases produce parallel signals share many molecular targets, including activators cap-dependent translation. Here, we show kinase expression can affect outcome lymphoma chemotherapy. We observe same in...
Significance Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer and one deadly types, with a 5-y survival rate below 10%. One reason for this high mortality that PDAC cells have an enhanced ability to survive proliferate despite existing in nutrient-deprived environments. Understanding metabolic rewiring enables nutrient scavenging rapid processing can provide new strategies develop effective treatment options intractable disease. In study, convergent...
Abstract Downregulation of the PTEN tumor suppressor transcript is frequent in breast cancer and associates with poor prognosis triple-negative (TNBC) when comparing cancers to one another. Here we show that almost all cases, tumors adjacent normal ducts, expression decreased PRC2-associated methyltransferase EZH2 increased. We further find cases large cohorts, inversely correlates expression. Within highest expressing group, NOTCH alterations are frequent, also associate repression occurs...
KRAS is a proto-oncogene that contains activating mutations in up to 30% of tumors. Many conventional therapies inhibit both cancerous and normal cells, which may cause toxicity. Thus, programmable mutant-selective targeted inhibitors are needed. Peptide nucleic acids (PNAs) incorporate base sequences analogous DNA, with modified peptide backbones instead ribose-phosphate backbones, allowing PNAs hybridize DNA high avidity suppress transcription. Here, we developed G12D-selective PNA...
KRAS is a proto-oncogene that has activating mutations in ∼15-30% of all cancers. Conventional therapies non-selectively target tumor and normal cells which may cause high toxicities, programmable mutant-selective targeted inhibitors are lacking. Peptide nucleic acids (PNAs) have base sequences analogous to DNA, except they modified peptide backbones instead sugar-phosphate backbones, allowing them hybridize with DNA avidity suppress transcription. Here, we developed G12D-selective PNA...
The posttranscriptional control of gene expression by microRNAs (miRNAs) is highly redundant, and compensatory effects limit the consequences inactivation individual miRNAs. This implies that only a few miRNAs can function as effective tumor suppressors. It also basis our strategy to define functionally relevant miRNA target genes are not under redundant other We identified interconnected group exhibited reduced abundance in leukemia cells from patients with T cell acute lymphoblastic...
Abstract PTEN is well known as a tumor suppressor that inhibits the PI3K/AKT pathway, but role of its secreted isoform PTEN-Long (PTEN-L) not fully understood. We developed tools to study PTEN-L independent using cancer cell lines engineered express PTEN-L, mouse overexpress Pten-L, and Adeno-Associated Virus (AAV)-Pten-L treated xenograft models. AAV-Pten-L was be expressed in liver, where it efficiently into blood strong signal peptide for liver. Beyond ability inhibit signaling, we showed...
Inhibition of the eIF4A RNA helicase with silvestrol and related compounds is emerging as a powerful anti-cancer strategy. We find that synthetic analogue (CR-1-31 B) has nanomolar activity across many cancer cell lines. It especially active against aggressive MYC+/BCL2+ B lymphomas this likely reflects eIF4A-dependent translation both MYC BCL2. performed genome-wide CRISPR/Cas9 screen identified mechanisms resistance to new class therapeutics. identify three negative NRF2 regulators (KEAP1,...
Cadherin-17 (CDH17) is a calcium-dependent cell adhesion protein that overexpressed in several adenocarcinomas, including gastric, colorectal, and pancreatic adenocarcinoma. High levels of CDH17 have been linked to metastatic disease poor prognoses patients with these malignancies, fueling interest the as target for diagnostics therapeutics. Herein, we report synthesis, vitro validation, vivo evaluation CDH17-targeted
Epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase that frequently modified by glycosylation post-translationally. In cancer, EGFR amplifications and hotspot mutations such as L858R promote proliferation have been detected in significant fraction of non-small cell lung carcinomas breast adenocarcinomas. Molecular dynamic simulations suggested at asparagine residue 361 (N361) promotes dimerization ligand binding. We stably expressed glycosylation-deficient mutant...
Genetically and pathologically accurate mouse models of leukemia lymphoma have been developed in recent years. Adoptive transfer genetically modified hematopoietic progenitor cells enables rapid highly controlled gain- loss-of-function studies for these types cancer. In this Commentary, we discuss how versatile experimental approaches can be used as biological filters to pinpoint transformation-relevant activities from complex cancer genome data. We anticipate that the functional...
Understanding the mechanisms governing metabolic reprogramming that underlie potential vulnerabilities in cancer cells is key to developing novel therapeutic strategies. The catalytic enzyme UDP-glucose pyrophosphorylase 2 (UGP2) drives production of UDP-glucose. Our recent work demonstrated crucial role UGP2 growth and its regulation cellular processes.
Abstract KRAS is among the most frequently mutated oncogenic driver proteins in human cancers including lung, colorectal, and pancreatic cancers. Activating mutants cause increased cell proliferation through direct binding overactivation of effector proteins. Effector activation preference mutation specific, as G12D G12C purportedly bind both RAF PI3K, whereas G12R has been reported to but not PI3K. The mechanisms G12S action are under-investigated. Furthermore, mutations remain clinically...