Transcription plays a pivotal role in the transfer of genetic information within living organisms. It serves as the initial step in gene expression, allowing cells to convert the instructions encoded in their DNA into functional molecules. Eukaryotic transcription initiation is a complex and dynamic process that requires joint efforts from...
This dissertation focuses on quantifying protein folding stability determinants and presenting initial experiments that can guide the development of a novel assay that identifies cell-penetrating miniproteins. First, despite over a century of scholarship on protein folding stability, applying this knowledge to design proteins computationally remains limited. Usually, protein designers generate...
This dissertation focuses on quantifying protein folding stability determinants and presenting initial experiments that can guide the development of a novel assay that identifies cell-penetrating miniproteins. First, despite over a century of scholarship on protein folding stability, applying this knowledge to design proteins computationally remains limited. Usually, protein designers generate...
Kaposi’ sarcoma-associated herpesvirus (KSHV) causes primary effusion lymphoma (PEL). PEL cell lines require expression of the cellular FLICE inhibitory protein (cFLIP) for survival, although KSHV encodes a viral homolog of this protein (vFLIP). Cellular and viral FLIP proteins have several functions, including, most importantly, the inhibition of pro-apoptotic caspase 8...
The negative early and late health consequences from exposure to artificial sources of radiation are particularly apparent in victims of radiological emergencies who were diagnosed with cancer, radiation pneumonitis, among other conditions. The renaissance of nuclear energy, increased use of ionizing radiation in the medical field, and nuclear threats from...
Glioblastoma (GBM) is the most common aggressive primary malignant brain tumorin adults with a median age of onset of 65 years of age. Although advanced age is often associated with worse GBM patient survival, the predominant source(s) of maladaptive aging
effects remains to be established. Here we studied intra-tumoral and...
Cancer is a complex and heterogeneous disease characterized by aberrant gene regulation. Gene regulation is fundamentally orchestrated by the 3D genome organization which involves chromatin looping, compartmentalization, and the formation of topologically associating domains (TADs). Structural variations (SVs), such as genomic rearrangements, deletions, inversions, and duplications, are commonly observed in...
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...
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...
The reprogramming of somatic cells to a spontaneously contracting cardiomyocyte-like state using defined transcription factors has proven successful in mouse fibroblasts. However, this process has been less successful in human cells, thus limiting the potential clinical applicability of this technology in regenerative medicine. We hypothesized that this issue is due...