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...
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...
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...
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...
Involuntary motor activities such as spasms arise from hyperreflexia in about 70% of individuals with spinal cord injuries (SCI). Despite this prevalence and the negative impact on health and safety, it is unclear what determines the severity of the spasms that develop. This study investigated the impact of injury severity...
One of the fundamental questions in developmental biology is how a single cell gives rise to a complex organism. More specifically, how a totipotent egg divides into cells that become increasingly restricted in their potential. Development is a process of increasingly restricted cellular potential, and here I home in on...
ABSTRACTFor several decades, dams have played an essential role in human development. In many low-and middle-income countries (LMICs), the construction of dams remains an integral part of industrialization and modernization. However, dam construction and associated infrastructure have significantly contributed to socioecological destruction and population displacement. For example, the construction of...
Pattern formation of biological structures involves the arrangement of different types of cells in an ordered spatial configuration. Patterning is thought to involve the spatial organization of molecular pre-patterns that precede and drive subsequent cell differentiation and coinciding morphogenesis. These molecular prepatterns are often, although not exclusively, organized through Turing...