A5004528793- Chronic Lymphocytic Leukemia Research
- Enzyme function and inhibition
- Lymphoma Diagnosis and Treatment
- Chromatin Remodeling and Cancer
- Computational Drug Discovery Methods
- Viral-associated cancers and disorders
- Cancer-related gene regulation
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Nuclear Receptors and Signaling
- Biochemical and Molecular Research
- Chronic Myeloid Leukemia Treatments
- Synthesis and Characterization of Heterocyclic Compounds
- Eosinophilic Disorders and Syndromes
- Reproductive System and Pregnancy
- Synthesis and Catalytic Reactions
- Renal cell carcinoma treatment
- Ovarian cancer diagnosis and treatment
- Phenothiazines and Benzothiazines Synthesis and Activities
- Preterm Birth and Chorioamnionitis
- Acute Lymphoblastic Leukemia research
- Epigenetics and DNA Methylation
- Neonatal Respiratory Health Research
- Reproductive Biology and Fertility
- Advanced Biosensing Techniques and Applications
- Enzyme Structure and Function
National Institutes of Health
2015-2024
National Cancer Institute
2017-2024
Columbia University Irving Medical Center
2023-2024
Center for Cancer Research
2021-2023
Columbia University
2023
National Center for Advancing Translational Sciences
2015-2019
MGH Institute of Health Professions
2019
University of Cambridge
2016
Diffuse large B-cell lymphomas (DLBCLs) are phenotypically and genetically heterogeneous. Gene-expression profiling has identified subgroups of DLBCL (activated B-cell–like [ABC], germinal-center [GCB], unclassified) according to cell origin that associated with a differential response chemotherapy targeted agents. We sought extend these findings by identifying genetic subtypes based on shared genomic abnormalities uncover therapeutic vulnerabilities tumor genetics.
Abstract Drug resistance in Plasmodium parasites is a constant threat. Novel therapeutics, especially new drug combinations, must be identified at faster rate. In response to the urgent need for antimalarial combinations we screened large collection of approved and investigational drugs, tested 13,910 pairs many promising combinations. The activity known regimens was confirmed myriad classes positively interacting pairings were discovered. Network clustering analyses reinforced established...
Abstract The use of Bruton tyrosine kinase (BTK) inhibitors to block B-cell receptor (BCR)–dependent NF-κB activation in lymphoid malignancies has been a major clinical advance, yet acquired therapeutic resistance is recurring problem. We modeled the development BTK inhibitor ibrutinib activated (ABC) subtype diffuse large lymphoma, which relies on chronic active BCR signaling for survival. primary mode was epigenetic, driven part by transcription factor TCF4. resultant phenotypic shift...
Key Points A novel PCM1-FGFR1 gene rearrangement was identified in a patient with myeloid neoplasm eosinophilia. Futibatinib, an oral selective small molecule inhibitor of FGFR1-4, resulted durable complete hematologic and cytogenetic remission.
Significance The tricarboxylic acid (TCA) cycle plays a central role in the metabolism of many pathogens, but few inhibitors this pathway currently exist. Our study describes first small molecule inhibitor, to our knowledge, fumarate hydratase enzyme TCA Mycobacterium tuberculosis . We also report discovery an allosteric regulatory site that confers selectivity inhibitor’s activity over homologous human enzyme. findings illustrate potential target vulnerable metabolic enzymes effectively and...
With the growing worldwide prevalence of antibiotic-resistant strains tuberculosis (TB), new targets are urgently required for development treatments with novel modes action. Fumarate hydratase (fumarase), a vulnerable component citric acid cycle in Mycobacterium (Mtb), is metabolic target that could satisfy this unmet demand. A key challenge targeting Mtb fumarase its similarity to human homolog, which shares an identical active site. potential solution selectivity problem was previously...
Abstract Sphere forming cells persist in the ascitic fluid of patients with high-grade serous ovarian cancer after first-line therapy and likely contribute to relapse metastasis. These residual tumor spheres, which are enriched for by up 95% based on detectable TP53 mutations, slow growing, resistant platinum-based chemotherapy, remain a large obstacle towards durable remission. Screening established, rapidly dividing monolayer cell lines proliferation assays has failed produce...
<div>Abstract<p>The use of Bruton tyrosine kinase (BTK) inhibitors to block B-cell receptor (BCR)–dependent NF-κB activation in lymphoid malignancies has been a major clinical advance, yet acquired therapeutic resistance is recurring problem. We modeled the development BTK inhibitor ibrutinib activated (ABC) subtype diffuse large lymphoma, which relies on chronic active BCR signaling for survival. The primary mode was epigenetic, driven part by transcription factor TCF4....
<div>Abstract<p>The use of Bruton tyrosine kinase (BTK) inhibitors to block B-cell receptor (BCR)–dependent NF-κB activation in lymphoid malignancies has been a major clinical advance, yet acquired therapeutic resistance is recurring problem. We modeled the development BTK inhibitor ibrutinib activated (ABC) subtype diffuse large lymphoma, which relies on chronic active BCR signaling for survival. The primary mode was epigenetic, driven part by transcription factor TCF4....
<p>Supplementary Methods</p>
<p>Oligo and Primer Tables</p>