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...
Stimulation of the cGAS-STING (cycle GMP-AMP synthase-Stimulator of Interferon Genes) pathway increases T cell activation and tracking into the tumor and reverses the immunosuppressive phenotype of myeloid cells. Direct targeting of the STING receptor using synthetic cyclic dinucleotide (CDN) ligands represents an attractive immunotherapeutic strategy for the treatment of lymphocyte-depleted...
Nuclear receptors (NRs) are an important family of transcription factors that often regulate genes in response to ligands and by way of direct interactions with coactivator proteins. Many NR-coactivator pairs have been identified that cooperate to regulate transcription but fully understanding how NRs recruit specific coactivators involves learning which of...
The worldwide community of patients affected by Basal Cell Carcinoma of the skin (BCC) is larger than that of any other cancer. While BCC is rarely lethal, currently available treatment strategies often leave patients with disfiguring scars on their faces, heads, and necks. Moreover, the high recurrence rates of BCC...
Eukaryotic genomes are organized into chromatin, which acts to regulate access to the organism’s genetic material. A large and diverse class of proteins, known as chromatin modifiers and remodelers, are responsible for regulating the composition and structure of chromatin by monitoring nucleosomes. Chromatin remodelers are involved in multiple cellular processes,...
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...
This thesis proposes a robust multi-pronged approach to study the effect of nanoparticles on cells. In the first place, this work is focused on investigation of the protein corona that accumulates on the surface of nanoparticles internalized by the cells and their poly-pathway effects on protein availability and messenger RNA...
Meiosis is a highly regulated process necessary for proper chromosome division. Zincfluxes regulate mammalian meiosis; between prophase I and metaphase II, total intracellular zinc
increases by 50%, while 20% of zinc is released in “zinc sparks” following fertilization. Although
zinc fluxes had been shown to be conserved in mammals, it...
Proteins represent a critical class of biomolecules, universally employed by all living organisms to fulfill essential structural, functional, and enzymatic roles necessary to support life. In nature, these polymers are composed generally of twenty natural amino acid (AA) building blocks, which can be modified with covalent adducts known as post-translational...
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...