A5028453851- Cancer Genomics and Diagnostics
- Protein Degradation and Inhibitors
- CRISPR and Genetic Engineering
- Health Systems, Economic Evaluations, Quality of Life
- Bioinformatics and Genomic Networks
- Acute Myeloid Leukemia Research
- Computational Drug Discovery Methods
- Biochemical and Molecular Research
- Lung Cancer Treatments and Mutations
- Cancer-related gene regulation
- Chronic Myeloid Leukemia Treatments
- Acute Lymphoblastic Leukemia research
- Cancer, Hypoxia, and Metabolism
- Neuroblastoma Research and Treatments
- CAR-T cell therapy research
- Chronic Lymphocytic Leukemia Research
- Ubiquitin and proteasome pathways
- Renal and related cancers
- Cancer Immunotherapy and Biomarkers
- Radiomics and Machine Learning in Medical Imaging
- RNA modifications and cancer
- Signaling Pathways in Disease
- Pancreatic and Hepatic Oncology Research
- Drug Transport and Resistance Mechanisms
- Chromatin Remodeling and Cancer
Pfizer (United States)
2025
Seagen (United States)
2020-2024
Kettering University
2017-2023
Memorial Sloan Kettering Cancer Center
2016-2023
New York University
2019-2021
NYU Langone Health
2019-2020
NYU Langone’s Laura and Isaac Perlmutter Cancer Center
2019
Columbia University Irving Medical Center
2012-2017
Fred Hutch Cancer Center
2010-2016
Seattle University
2015
Molecular characterization has the potential to advance management of pediatric cancer and high-risk hematologic disease. The clinical integration genome sequencing into standard practice been limited utility identify clinically impactful information beyond targetable alterations underestimated. Precision in Pediatric Sequencing (PIPseq) Program at Columbia University Medical Center instituted prospective next generation (NGS) for disorders risk treatment failure. We performed whole exome...
Abstract Predicting in vivo response to antineoplastics remains an elusive challenge. We performed a first-of-kind evaluation of two transcriptome-based precision cancer medicine methodologies predict tumor sensitivity comprehensive repertoire clinically relevant oncology drugs, whose mechanism action we experimentally assessed cognate cell lines. enrolled patients with histologically distinct, poor-prognosis malignancies who had progressed on multiple therapies, and developed low-passage,...
N-Myc is a transcription factor that forms heterodimers with the protein Max and binds gene promoters by recognizing DNA sequence, CACGTG, called E-box. The identification of N-myc target genes an important step for understanding biological functions in both physiological pathological contexts. In this study, we describe N-Myc-responsive through chromatin immunoprecipitation methylation-sensitive restriction analysis. Results show direct regulator several identified genes, methylation CpG...
The histone variant H2A.Z has been implicated in the regulation of gene expression, and plants antagonizes DNA methylation. Here, we ask whether a similar relationship exists mammals, using mouse B-cell lymphoma model, where chromatin states can be monitored during tumorigenesis. Using native immunoprecipitation with microarray hybridization (ChIP-chip), found progressive depletion around transcriptional start sites (TSSs) MYC-induced transformation pre-B cells and, subsequently,...
Histone deacetylase (HDAC) inhibitors reactivate tumor suppressor gene transcription; induce cancer cell differentiation, growth arrest, and programmed death; are among the most promising new classes of anticancer drugs. Myc oncoproteins can block differentiation promote proliferation malignant transformation, in some cases by modulating target transcription. Here, we show that tissue transglutaminase (TG2) was commonly reactivated HDAC neuroblastoma breast cells but not normal contributed...
Increased expression of specific ATP-binding cassette (ABC) transporters is known to mediate the efflux chemotherapeutic agents from cancer cells. Therefore, establishing how ABC transporter genes are controlled at their transcription level may help provide insight into role these multifaceted in malignant phenotype. We have investigated gene a large neuroblastoma data set 251 tumor samples. Clustering analysis demonstrated strong association between differential patterns samples and...
Neuroblastoma is the most common extracranial solid tumor of childhood. One important factor that predicts a favorable prognosis robust expression TRKA and p75NTR neurotrophin receptor genes. Interestingly, often attenuated in aggressive MYCN-amplified tumors, suggesting causal link between elevated MYCN activity transcriptional repression p75NTR, but precise mechanisms involved are unclear. Here, we show acts directly to repress gene transcription. Specifically, found levels were critical...
The origin of metazoans required the evolution mechanisms for maintaining differentiated cell types within a multicellular individual, in part through spatially patterns gene transcription. unicellular ancestor was presumably capable regulating expression temporally response to changing environmental conditions, and spatial differentiation may represent co-option preexisting regulatory mechanisms. Myc is critical regulator growth, proliferation, death that found all but absent other...
NUTM1-rearranged tumors are defined by the presence of a gene fusion between NUTM1 and various partners typically follow clinically aggressive disease course with poor outcomes despite conventional multimodality therapy. display histologic features poorly differentiated carcinoma areas focal squamous differentiation express BRD4-NUTM1 defining distinct clinicopathologic entity-NUT (NC). NCs mesenchymal have rarely been described in literature. In this report, we describe characterization two...
Pancreatic ductal adenocarcinoma is a lethal disease characterized by late diagnosis, propensity for early metastasis and resistance to chemotherapy. Little known about the mechanisms that drive innate therapeutic in pancreatic cancer. The ataxia-telangiectasia group D-associated gene (ATDC) overexpressed cancer promotes tumor growth metastasis. Our study reveals increased ATDC levels protect cells from reactive oxygen species (ROS) via stabilization of nuclear factor erythroid 2-related 2...
Abstract Resistance to chemotherapeutic agents remains one of the major impediments a successful treatment chronic myeloid leukemia (CML). Misregulation activity specific group ATP-binding cassette transporters (ABC) is responsible for reducing intracellular concentration drugs in leukemic cells. Moreover, consistent body evidence also suggests that ABC play role cancer progression beyond efflux cytotoxic drugs. Despite large number studies investigated function transporters, little known...
Abstract Regulatory T cells (Tregs) are known to suppress antitumor immune responses and their presence in the tumor microenvironment (TME) is associated with cancer progression; therefore, Treg depletion a promising strategy enhance immunotherapy. PF-08046032 novel antibody-drug conjugate (ADC) designed target Tregs TME via CD25, alpha chain of IL-2 receptor frequently upregulated by intratumoral Tregs. composed an affinity-detuned anti-CD25 antibody linked monomethyl auristatin E (MMAE),...
Pleomorphic xanthoastrocytoma (PXA) is a World Health Organization (WHO) Grade II glioma occurring primarily in children and young adults. Most PXAs harbor the known activating mutation BRAF V600E. We report case of locally recurrent PXA with anaplastic features 10-yr-old female. The was negative by immunohistochemical (IHC) staining for V600E mutation. Whole-exome transcriptome sequencing tumor confirmed absence V600E, but identified copy-number alterations (including loss suppressor CDKN2A...
Pancreatic adenocarcinoma (PDA) is an aggressive disease driven by oncogenic KRAS and characterized late diagnosis therapeutic resistance. Here we show that deletion of the ataxia-telangiectasia group D-complementing ( Atdc ) gene, whose human homolog up-regulated in majority pancreatic adenocarcinoma, completely prevents PDA development context KRAS. ATDC required for KRAS-driven acinar–ductal metaplasia (ADM) its progression to intraepithelial neoplasia (PanIN). As a result, mice lacking...
Precision medicine approaches are ideally suited for rare tumors where comprehensive characterization may have diagnostic, prognostic, and therapeutic value. We describe the clinical case molecular of an adolescent with metastatic poorly differentiated carcinoma (PDC). Given rarity poor prognosis associated PDC in children, we utilized genomic analysis preclinical models to validate oncogenic drivers identify vulnerabilities. whole exome sequencing (WES) transcriptome germline somatic...
Despite the important role of PI3K/AKT/mTOR axis in pathogenesis cancer, to date there have been few functional oncogenic fusions identified involving AKT genes. A 12-year-old female with a histopathologically indeterminate epithelioid neoplasm was found harbor novel fusion between LAMTOR1 and AKT1 Through expanded use access, she became first pediatric patient be treated oral ATP-competitive pan-AKT inhibitor ipatasertib. Treatment resulted dramatic tumor regression, demonstrating through...
In this study, we report that the human p14 ARF associates in vivo with N‐Myc and inhibits mediated transcriptional activation. We have determined region (aa 140–300) encompassing BoxIII is required for efficient interaction vivo. Furthermore, demonstrate SK‐N‐BE neuroblastoma cell line over‐expression delocalized from nucleoplasm into nucleoli regions are also important co‐localization. Finally, determine N‐terminal of protein involved binding to c‐Myc proteins.
Abstract Glioblastoma heterogeneity and plasticity remain controversial, with proposed subtypes representing the average of highly heterogeneous admixtures independent transcriptional states. Single-cell, protein-activity-based analysis allowed full quantification >6,000 regulatory signaling proteins, thus providing a previously unattainable single-cell characterization level. This helped identify four novel, molecularly distinct that successfully harmonize across multiple GBM datasets,...
Cancer cells exhibit altered metabolic requirements compared to their normal counterparts. This reprogramming is mediated by activation of oncogenes such as MYC. Here, we summarize our recent findings demonstrating a dependency deregulated MYC on MLXIP-MLX, critical components the nutrient-sensing arm extended transcriptional network.