A5012712111- Multiple Myeloma Research and Treatments
- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Peptidase Inhibition and Analysis
- Acute Myeloid Leukemia Research
- Synthesis and biological activity
- Histone Deacetylase Inhibitors Research
- Chronic Lymphocytic Leukemia Research
- Cancer therapeutics and mechanisms
- Cancer Mechanisms and Therapy
- Cancer Treatment and Pharmacology
- RNA Interference and Gene Delivery
- Immunotherapy and Immune Responses
- Synthesis and Characterization of Heterocyclic Compounds
- Marine Sponges and Natural Products
- Chronic Myeloid Leukemia Treatments
- PI3K/AKT/mTOR signaling in cancer
- Immune Cell Function and Interaction
- Cell death mechanisms and regulation
- Cancer, Hypoxia, and Metabolism
- Advanced biosensing and bioanalysis techniques
- Bone health and treatments
- CAR-T cell therapy research
- Telomeres, Telomerase, and Senescence
- Cancer-related Molecular Pathways
Dana-Farber Cancer Institute
2015-2024
Harvard University
2015-2024
Weatherford College
2024
Broad Institute
2017-2024
Massachusetts Institute of Technology
2021-2024
Multiple Myeloma Research Foundation
2008-2023
Massachusetts General Hospital
2003-2015
Queen's University Belfast
2015
Brigham and Women's Hospital
2006-2014
Harvard University Press
2007-2013
Thalidomide-like drugs such as lenalidomide are clinically important treatments for multiple myeloma and show promise other B cell malignancies. The biochemical mechanisms underlying their antitumor activity unknown. Thalidomide was recently shown to bind to, inhibit, the cereblon ubiquitin ligase. Cereblon loss in zebrafish causes fin defects reminiscent of limb seen children exposed thalidomide utero. Here we that lenalidomide-bound acquires ability target proteasomal degradation two...
We have shown that thalidomide (Thal) and its immunomodulatory derivatives (IMiDs), proteasome inhibitor PS-341, As2O3 act directly on multiple myeloma (MM) cells in the bone marrow (BM) milieu to overcome drug resistance. Although Thal/IMiDs, inhibit nuclear factor (NF)-κB activation, they also varied other actions. In this study, we therefore specifically address role of NF-κB blockade mediating anti-MM activity. To characterize effect specific MM cell growth survival vitro, used an IκB...
Cytotoxic chemotherapy targets elements common to all nucleated human cells, such as DNA and microtubules, yet it selectively kills tumor cells. Here we show that clinical response these drugs correlates with, may be partially governed by, the pretreatment proximity of cell mitochondria apoptotic threshold, a property called mitochondrial priming. We used BH3 profiling measure priming in cells from patients with multiple myeloma, acute myelogenous lymphoblastic leukemia, ovarian cancer. This...
Histone deacetylases (HDACs) affect cell growth at the transcriptional level by regulating acetylation status of nucleosomal histones. HDAC inhibition induces differentiation and/or apoptosis in transformed cells. We recently showed that inhibitors, such as suberoylanilide hydroxamic acid (SAHA), potently induce human multiple myeloma (MM) In this study, we focused on MM a model to study profile inhibitor treatment tumor cells and address their pathophysiological implications with...
The prognosis for adults with precursor B-cell acute lymphoblastic leukemia (B-ALL) remains poor, in part from a lack of therapeutic targets. We identified the type I cytokine receptor subunit CRLF2 functional screen B-ALL-derived mRNA transcripts that can substitute IL3 signaling. demonstrate is overexpressed approximately 15% adult and high-risk pediatric B-ALL MLL, TCF3, TEL, BCR/ABL rearrangements, but not these rearrangements or other lymphoid malignancies. overexpression result...