Histone deacetylases (HDACs) are enzymes that catalyze the removal of acetylation from lysine residues of their substrates, the effect of which is to regulate a range of cellular processes, including gene transcription, cell cycle regulation, migration, and DNA damage repair, among others....
Diffuse intrinsic pontine gliomas (DIPGs) are deadly tumors comprising 10-15% of all childhood central nervous system (CNS) cancers. Standard treatment consists of focal radiation which results in only transient response. Given the increasing promise of immunotherapy, there have been ongoing...
Preterm birth is a global problem that affects 10% of pregnancies and always results in the premature loss of the placenta. As the interface between maternal and fetal circulation, the placenta is a crucial organ for healthy pregnancy and fetal development. Thus, preterm birth may have...
Acute myeloid leukemias (AML) are a group of cancers of the myeloid line of blood cells that arise out of the bone marrow, progress rapidly, and interfere with the production of normal immune cells. Most AML patients who achieve a remission with standard cytotoxic chemotherapy will go on to...
Mutations in TP53 occur in ~10-15% of patients with AML and are associated with an erythroid phenotype, mutual exclusivity with recurrent drivers, and a poor prognosis. Molecular heterogeneity and the lack of a physiological relevant mouse model have resulted in a failure to understand the...
Expanded polyglutamine tracts cause nine neurodegenerative disorders, including spinal and bulbar muscular atrophy (SBMA). In SBMA, the polyglutamine expansion occurs in the androgen receptor (AR), a ligand-dependent transcription factor. Transcriptional dysregulation and mitochondrial impairment...
Poly(A)-specific ribonuclease (PARN) is an RNA processing enzyme that regulates biological processes, such as telomere maintenance, through its enzymatic activity. PARN is a 3’ exoribonuclease that cleaves RNA bases at the 3’ end, one nucleotide at a time. PARN has the highest substrate affinity...
Anxiety disorders, such as Posttraumatic stress disorder (PTSD), are associated with an increased risk of developing cardiovascular disease. While the exact mechanisms underlying this relationship are not entirely clear, recent evidence suggests that a hormonal system involved in the maintenance...
The last decades have seen major advances in our understanding of how DNA breaks are detected, signaled to cell-cycle checkpoints, and repaired. However, a more complete understanding of how the genomic landscape influences DNA double strand break (DSB) generation and repair is needed. To address...
Chronic pancreatitis represents a well-known risk factor for the development of pancreatic cancer. Although the causative environmental and genetic factors are poorly understood, the accompanying inflammation results in tissue injury and accumulation of DNA damage which facilitates cellular...