Regulatory T (Treg) cells are required to control immune responses and maintain homeostasis, but are a significant barrier to antitumor immunity. Conversely, Treg instability, characterized by loss of the master transcription factor Foxp3 and acquisition of proinflammatory properties, can promote autoimmunity and/or facilitate more effective tumor immunity. A comprehensive understanding...
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...
Meiosis is a specialized form of cell division that gives rise to haploid reproductive cells by replicating the genetic material once and undergoing two rounds of partitioning. While most forms of cell division require centrosomes to assemble a bipolar microtubule-based spindle that segregates chromosomes, female gametes (oocytes) are unique in...
Neuroblastoma is one of the most common childhood cancers with one of the lowest survival rates, accounting for 15% of childhood cancer mortality. Approximately 15% of patients do not respond to initial treatment, and about half of children treated for high-risk neuroblastoma will relapse following remission. Ionizing radiation has long...
Biologically active small molecules remain the foundation for the medical management of human disease. Their impacts on human health, longevity, culture, and society are difficultly overstated. In large part, medicines derived from organic compounds are the result of the tireless efforts of chemical practitioners––both past and present––who have dedicated much...
Multiple facets of the natural trajectory of glioma remain poorly understood, which results in a universally poor prognosis for patients with glioma. Many patients with glioma experience tumor-associated epilepsy (TAE) throughout their disease course, but the mechanism by which TAE occurs, who is at continued risk for TAE, and whether...
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...
Desmosomal cadherins are a recent evolutionary innovation that make up the adhesive core of highly specialized intercellular junctions called desmosomes. Desmosomal cadherins, desmogleins and desmocollins, are related to the classical cadherins but their cytoplasmic domains are tailored for anchoring intermediate filaments instead of actin to sites of cell-cell adhesion. The...
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,...
