A5036053901- Histone Deacetylase Inhibitors Research
- Protein Degradation and Inhibitors
- Peptidase Inhibition and Analysis
- Genomics and Chromatin Dynamics
- Multiple Myeloma Research and Treatments
- RNA Research and Splicing
- Acute Myeloid Leukemia Research
- RNA modifications and cancer
- Click Chemistry and Applications
- Hematopoietic Stem Cell Transplantation
- CAR-T cell therapy research
- Protein Kinase Regulation and GTPase Signaling
- Cholinesterase and Neurodegenerative Diseases
- Single-cell and spatial transcriptomics
- Reproductive tract infections research
- interferon and immune responses
- HIV/AIDS oral health manifestations
- NF-κB Signaling Pathways
- Syphilis Diagnosis and Treatment
- Signaling Pathways in Disease
- Cardiovascular Effects of Exercise
- Cardiac Ischemia and Reperfusion
- Chronic Myeloid Leukemia Treatments
- Neurogenetic and Muscular Disorders Research
- Chromatin Remodeling and Cancer
Fred Hutch Cancer Center
2023-2025
Baylor College of Medicine
2019-2020
Harvard University
2010-2019
Dana-Farber Cancer Institute
2011-2016
Imaging Center
2012
Pediatric Oncology Group
2012
Massachusetts General Hospital
2010
Enzymatic inhibitors of Janus kinase 2 (JAK2) are in clinical development for the treatment myeloproliferative neoplasms (MPNs), B cell acute lymphoblastic leukemia (B-ALL) with rearrangements cytokine receptor subunit receptor–like factor (CRLF2), and other tumors constitutive JAK2 signaling. In this study, we identify G935R, Y931C, E864K mutations within domain that confer resistance across a panel JAK inhibitors, whether present cis V617F (observed MPNs) or R683G B-ALL). do not reduce...
Multiple myeloma (MM) has proven clinically susceptible to modulation of pathways protein homeostasis. Blockade proteasomal degradation polyubiquitinated misfolded proteins by the proteasome inhibitor bortezomib (BTZ) achieves responses and prolongs survival in MM, but long-term treatment with BTZ leads drug-resistant relapse most patients. In a proof-of-concept study, we previously demonstrated that blocking aggresomal breakdown histone deacetylase 6 (HDAC6) tubacin enhances BTZ-induced...
N1-Hydroxy-N8-ferrocenyloctanediamide, JAHA (7), an organometallic analogue of SAHA containing a ferrocenyl group as phenyl bioisostere, displays nanomolar inhibition class I HDACs, excellent selectivity over IIa and anticancer action in intact cells (IC50 = 2.4 μM, MCF7 cell line). Molecular docking studies 7 HDAC8 (a,b) suggested that the moiety can overlap with aryl cap should display similar HDAC inhibition, which was borne out vitro assay values against (μM, SD parentheses): SAHA, 1.41...
A novel, isoform-selective inhibitor of histone deacetylase 8 (HDAC8) has been discovered by the repurposing a diverse compound collection. Medicinal chemistry optimization led to identification highly potent (0.8 nM) and selective HDAC8.
Genome-wide hypertranscription is common in human cancer and predicts poor prognosis. To understand how might drive cancer, we applied our formalin-fixed paraffin-embedded (FFPE)–cleavage under targeted accessible chromatin method for mapping RNA polymerase II (RNAPII) genome-wide FFPE sections. We demonstrate global RNAPII elevations mouse gliomas assorted tumors small clinical samples discover regional corresponding to de novo HER2 amplifications punctuated by likely selective sweeps....
The ferrocene analogue <bold>4b</bold> had an IC<sub>50</sub> = 4 nM (HDAC1), 180 (HDAC8) and was effective in a <italic>Xenopus</italic> model of tubulin deacetylation. Analogue <bold>4a</bold> displayed mainly μM values against HDACs apart from HDAC6 (IC<sub>50</sub> 69 nM).
Abstract For more than a century, formalin-fixed paraffin-embedded (FFPE) sample preparation has been the preferred method for long-term preservation of biological material. However, use FFPE samples epigenomic studies difficult because chromatin damage from long exposure to high concentrations formaldehyde. Previously, we introduced Cleavage Under Targeted Accessible Chromatin (CUTAC), an antibody-targeted accessibility mapping protocol based on CUT&Tag. Here show that simple...
Syphilis is a sexually transmitted bacterial infection of the spirochete, Treponema pallidum. While primary syphilis often involves genitalia, oral manifestations are observed in subset patients. These lesions associated with submandibular and cervical lymphadenopathy. This case report syphilitic lesion located on hard palate cavity, only very few cases described previously. We describe rare 59-year-old African American man presenting subjective fevers, chills, marked submental...
Hypertranscription is common in human cancers and predicts poor prognosis. However detection of hypertranscription indirect, relying on accurately quantifying mRNA levels estimating cell numbers. Previously, we introduced FFPE-CUTAC, a genome-wide method for mapping RNA Polymerase II (RNAPII) formalin-fixed paraffin-embedded (FFPE) sections. Here use FFPE-CUTAC to demonstrate both transgene-driven mouse gliomas assorted tumors at active regulatory elements replication-coupled histone genes...
A HDAC, kinase inhibitor hybrid, (<italic>Z</italic>)-N1-(3-((1<italic>H</italic>-pyrrol-2-yl)methylene)-2-oxoindolin-5-yl)-N8-hydroxyoctanediamide, <bold>6</bold>, showed impressive anticancer action in a number of biochemical and cell-based assays.
Treatment of acute leukemia with intensive chemotherapy leads to an increased risk myelosuppression. Luteinizing hormone (LH) blockade improves hematopoietic recovery in mice after radiation or chemotherapy, through protection the stem cells which express LH receptor. We hypothesized that following patients leukemia. conducted a retrospective analysis on pre-menopausal women myeloid (AML) lymphoblastic (ALL) who received and leuprolide given for abnormal uterine bleeding prevention...
Abstract For more than a century, Formalin Fixed Paraffin Embedded (FFPE) sample preparation has been the preferred method for long-term preservation of biological material. However, use FFPE samples epigenomic studies difficult because chromatin damage from long exposure to high concentrations formaldehyde. Previously, we introduced Cleavage Under Targeted Accessible Chromatin (CUTAC), an antibody-targeted accessibility mapping protocol based on CUT&Tag. Here show that simple...
Abstract Small molecule inhibitors of membrane-bound MCL-1 and BCL-2 Mcl-1 Bcl-2 are anti-apoptotic members the family proteins. These proteins sequester activators Bax-Bak oligomerization inhibit subsequent mitochondrial depolarization. Knockdown has induced apoptosis in a variety cancers, signifying that these malignancies dependent on for survival. Thus, their inhibition by small molecules is an emerging strategy cancer therapy. While specific pan-inhibitors have emerged, there remains...