A5017218287- Protein Degradation and Inhibitors
- Multiple Myeloma Research and Treatments
- Ubiquitin and proteasome pathways
- Chronic Lymphocytic Leukemia Research
- CAR-T cell therapy research
- Lymphoma Diagnosis and Treatment
- CRISPR and Genetic Engineering
- Cancer Mechanisms and Therapy
- Galectins and Cancer Biology
- Acute Myeloid Leukemia Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cancer-related Molecular Pathways
- Immune Cell Function and Interaction
- Marine animal studies overview
- Histone Deacetylase Inhibitors Research
- Wnt/β-catenin signaling in development and cancer
- Retinoids in leukemia and cellular processes
- Advanced biosensing and bioanalysis techniques
- Ichthyology and Marine Biology
- RNA Interference and Gene Delivery
- interferon and immune responses
- Healthcare Systems and Practices
- Neurofibromatosis and Schwannoma Cases
- Marine Biology and Environmental Chemistry
- Chromatin Remodeling and Cancer
Memorial Sloan Kettering Cancer Center
2024
Kettering University
2024
Broad Institute
2016-2023
Dana-Farber Cancer Institute
2010-2023
Harvard University
2011-2023
Brigham and Women's Hospital
2017-2019
Community Cancer Center
2014
Department of Embryology
2010
The somatic genetic basis of chronic lymphocytic leukemia, a common and clinically heterogeneous leukemia occurring in adults, remains poorly understood.
Thalidomide-targeted degradation Thalidomide and its analogs improve the survival of patients with multiple myeloma other blood cancers. Previous work showed that drugs bind to E3 ubiquitin ligase Cereblon, which then targets for two specific zinc finger (ZF) transcription factors a role in cancer development. Sievers et al. found more ZF proteins than anticipated are destabilized by thalidomide analogs. A proof-of-concept experiment revealed chemical modifications can lead selective...
Cell-based therapies are emerging as effective agents against cancer and other diseases. As autonomous "living drugs," these lack precise control. Chimeric antigen receptor (CAR) T cells effectively target hematologic malignancies but can proliferate rapidly cause toxicity. We developed ON OFF switches for CAR using the clinically approved drug lenalidomide, which mediates proteasomal degradation of several proteins by inducing interactions between CRL4
Increasing use of covalent and noncovalent inhibitors Bruton's tyrosine kinase (BTK) has elucidated a series acquired drug-resistant BTK mutations in patients with B cell malignancies. Here we identify inhibitor resistance distinct enzymatic activities, including some that impair activity while imparting novel protein-protein interactions sustain receptor (BCR) signaling. Furthermore, describe clinical-stage IKZF1/3 degrader, NX-2127, can bind proteasomally degrade each mutant proteoform,...
Heterobifunctional proteolysis-targeting chimeric compounds leverage the activity of E3 ligases to induce degradation target oncoproteins and exhibit potent preclinical antitumor activity. To dissect mechanisms regulating tumor cell sensitivity different classes pharmacological "degraders" oncoproteins, we performed genome-scale CRISPR-Cas9-based gene editing studies. We observed that myeloma resistance degraders targets (BET bromodomain proteins, CDK9) operating through CRBN (degronimids)...
Nuclear hormone receptors (NRs) are ligand-binding transcription factors that widely targeted therapeutically. Agonist binding triggers NR activation and subsequent degradation by unknown ligand-dependent ubiquitin ligase machinery. is critical for therapeutic efficacy in malignancies driven retinoic acid estrogen receptors. Here, we demonstrate the UBR5 drives of multiple agonist-bound NRs, including receptor alpha (RARA), retinoid x (RXRA), glucocorticoid, estrogen, liver-X, progesterone,...
Background. Patients with advanced hematologic malignancies remain at risk for relapse following reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (allo-HSCT). We conducted a prospective clinical trial to test whether vaccination whole leukemia cells early after facilitates the expansion of leukemia-reactive T and thereby enhances antitumor immunity.