Publications by authors named "J M Cleary"
Dysregulated epigenetic programs that restrict differentiation, reactivate fetal genes, and confer phenotypic plasticity are critical to colorectal cancer (CRC) development. By screening a small molecule library targeting epigenetic regulators using our dual reporter system, we found that inhibiting histone deacetylase (HDAC) 1/2 promotes CRC differentiation and anti-tumor activity. Comprehensive biochemical, chemical, and genetic experiments revealed that on-target blockade of the HDAC1/2 catalytic domain mediated the differentiated phenotype.
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- FGFR inhibitors have shown promise in treating FGFR-altered cholangiocarcinoma, but acquired resistance poses a challenge to their effectiveness.
- The study utilized diverse investigative methods, including DNA analysis and tissue biopsies, to explore resistance mechanisms in a cohort of patients.
- Results indicated that a significant number of patients with clinical benefits had specific FGFR2 mutations, but polyclonal resistance was influenced by low drug concentrations and specific mutation types affecting drug efficacy.
The spinocerebellar ataxias (SCAs) are a genetically heterogeneous group of rare dominantly inherited neurodegenerative diseases characterized by progressive ataxia. The most common mutation seen across the SCAs is a CAG repeat expansion, causative for SCA1, 2, 3, 6, 7, 12 and 17. We recently identified dysregulation of alternative splicing as a novel, presymptomatic transcriptomic hallmark in mouse models of SCAs 1, 3 and 7.
View Article and Find Full Text PDFPurpose: To develop a 3D distortion-free reduced-FOV diffusion-prepared gradient-echo sequence and demonstrate its application in vivo for diffusion imaging of the spinal cord in healthy volunteers.
Methods: A 3D multi-shot reduced-FOV diffusion-prepared gradient-echo acquisition is achieved using a slice-selective tip-down pulse in the phase-encoding direction in the diffusion preparation, combined with magnitude stabilizers, centric k-space encoding, and 2D phase navigators to correct for intershot phase errors. The accuracy of the ADC values obtained using the proposed approach was evaluated in a diffusion phantom and compared to the tabulated reference ADC values and to the ADC values obtained using a standard spin echo diffusion-weighted single-shot EPI sequence (DW-SS-EPI).