NSD2, a histone methyltransferase specific for methylation of histone 3 lysine 36 (H3K36), exhibits a glutamic acid to lysine mutation at residue 1099 (E1099K) in childhood acute lymphocytic leukemia (ALL). Cells harboring this mutation can become the predominant clone in relapsing disease. We studied the effects of this mutant enzyme...
Interleukin 33 (IL-33) is a complex inflammatory cytokine with diverse functions. In the context of cancer development, depending on the model, the implementation and dosage, and the immune cells involved, IL-33 can elicit dramatically different outcomes. Recent studies, including our own, have explored definitive contributions of the adaptive immunity in...
The histone methyltransferase DOT1L methylates lysine 79 (K79) on histone H3 and is implicated in active transcription. Here we show that DOT1L is overexpressed in Prostate cancer (PCa) and is associated with poor clinical outcome. Genetic and chemical inhibition of DOT1L selectively impaired viability of androgen receptor (AR)-signaling competent PCa...
Background: Glioblastoma (GBM) tumors are the most malignant brain cancers and are characterized as Grade IV astrocytomas by the World Health Organization. GBM tumors can be classified into three molecular subtypes known as proneural, classical, and mesenchymal. In addition, GBM tumors also have a small population of cells known as...
Down syndrome occurs in approximately 1 in 700 births annually in the United States. It is caused by trisomy of chromosome 21, and is characterized by dysmorphic features and congenital abnormalities. Although children with DS have a decreased risk of developing solid tumors, they have an increased risk of acquiring...
Background: Cancer-related cognitive impairment (CRCI) is among the most frequently reported adverse events during and following cancer treatment. Between 17% to 75% of chemotherapy-treated cancer patients evidence long-term cognitive deficits as many as 20 years after treatment. The variability in prevalence and the mechanisms of persistent CRCI are not well...
Mammalian transcriptional regulation is well-known to be complex and highly context dependent. Different genetic and epigenetic features, including single nucleotide polymorphisms (SNPs) that function as cis- or trans-expression quantitative trait loci (eQTLs), transcription factor (TF) interaction profile with cis-regulatory elements (CREs), methylation of CpG dinucleotide sequences, and histone modification that...
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disease, affecting children and adults. Chemotherapy regimens show high response rates but have debilitating effects and carry risk of relapse. Until now, no targeted therapy has been approved. In addition, 40% of patients will relapse and their treatment options are limited because...
Tissue-infiltrating neutrophils (polymorphonuclear neutrophils [PMNs]) are a prominent feature of inflammatory bowel disease (IBD) and colorectal cancer (CRC), where these immune cells can promote cytotoxicity or exacerbate disease outcomes. We recently showed that in acute colon injury, PMNs can increase DNA double-strand break (DSB) burden and promote genomic instability via...
RAS is one of the most frequently mutated oncogenes in cancer with ~30% of all human tumors harboring a mutation in either HRAS, NRAS, or KRAS isoforms. Despite countless efforts for the development of small molecule inhibitors for RAS, it remains an elusive target in the clinic. Here I demonstrate...
