Pediatric high-grade gliomas (pHGGs) are aggressive pediatric CNS tumors and an important subset are characterized by mutations in H3F3A, the gene that encodes Histone H3.3 (H3.3). Substitution of Glycine at position 34 of H3.3 with either Arginine or Valine (H3.3G34R/V), was recently described and characterized in a large cohort...
Tumor-initiating cells with reprogramming plasticity are thought to be essential for cancer development and metastatic regeneration in many cancers; however, the molecular mechanisms are not fully understood. We have previously identified that CD44, a breast tumor-initiating cell marker, drives mammosphere self-renewal and multicellular aggregation of circulating tumor cell (CTC) clusters,...
The treatment of AML remains to be a challenge due to the high rates of resistance and relapse experienced by patients after initial therapy. The MAPK-interacting kinases 1 and 2 (MNK1/2) have generated increasing interest as therapeutic targets for AML due to their critical role in malignant hematopoietic transformation via...
Uterine leiomyomas (fibroids) are a major source of gynaecologic morbidity in reproductive age women and are characterised by the excessive deposition of a disorganised extracellular matrix, resulting in rigid benign tumours. Clinically, leiomyoma patients usually present with pelvic pain, urinary incontinence, as well as heavy cyclic and non-cyclic bleeding. Curative...
Uterine leiomyomas (fibroids) are a major source of gynaecologic morbidity in reproductive age women and are characterised by the excessive deposition of a disorganised extracellular matrix, resulting in rigid benign tumours. Clinically, leiomyoma patients usually present with pelvic pain, urinary incontinence, as well as heavy cyclic and non-cyclic bleeding. Curative...
Prostate cancer (PCa) is the most common non-cutaneous cancer among U.S. men. Lack of effective treatments for advanced disease make it a significant public health concern. However, PCa’s long natural history makes it an excellent target for prevention approaches that reduce overtreatment of indolent disease, treatment related morbidity, and mortality....
Transcription is tightly regulated to ensure genes are appropriately expressed both temporally and spatially. This tight regulation governs various processes within the cell, such as differentiation and cell identity, cellular maintenance, and dynamic responses to external signals. Transcription factors (TFs) coordinate these various gene programs and in particular, are key...
Proper size control of organs and tissues is critical to their function, and it is necessary for the millions of precisely sized tubes that make up those organs— for example, excessive cell growth can lead to devastating diseases such as Polycystic Kidney Disease. The regulation of tube growth is therefore...
The literature has established glucokinase (GCK) to be the principal hexokinase (HK) in the liver, operating as a glucose sensor to regulate glucose metabolism and lipid homeostasis. We have recently proposed Hexokinase Domain Containing-1 (HKDC1) to be a novel 5th HK with expression in the liver. Here, we reveal HKDC1...
Many human diseases are chronic and ultimately fatal because they damage organs and tissues beyond the body’s normal repair mechanisms. Therefore, there is significant medical interest in developing pharmaceuticals that enhance the body’s natural injury repair mechanisms and engineering organs in the lab for transplantation. However, comparatively little is known...