Understanding the complex genome-phenome associations behind human complex traits will be a primary focus for the practice of precision medicine in the future. Identifying the genetic variants that contribute to the inter- and intra- phenotypic variations of individuals, elucidating pleiotropic architecture of common complex traits, and demonstrating how personal biomedical...
Transfer of information across membranes is fundamental to the function of all organisms and is primarily initiated by transmembrane receptors. This is an allosteric process and involves conformational coupling between ligand-binding domain and signaling domain of a receptor. This allosteric mechanism of activation is unclear for many receptors. Moreover, for...
Breakthroughs in large-scale biological data collection have resulted in a wealth of -omics (genomics, metabolomics, etc.) datasets in the literature. However, the development of appropriate computational techniques for their analysis is lacking, yet crucial for fully extracting the rich information contained in these datasets. The work in this dissertation describes...
Platelets are circulating anucleate discs derived from megakaryocytes, and play major roles in hemostasis, inflammation, thrombosis, and vascular biology. Multi-phase culture systems for inducing in vitro platelet production from mature megakaryocytes have been explored to allow progenitor expansion, megakaryocyte maturation, and promotion of platelet formation and shedding. In this thesis,...
Caves are accessible windows into the shallow subsurface, serving as transitional ecosystems between the photosynthesis-dependent surface and the deeper subsurface. Without a source of solar energy to ultimately power carbon (C) fixation (photolithoautotrophy), cave ecosystems are either reliant on surface-derived nutrients, recovering reducing power from the microbial oxidation of redox-sensitive...
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...
In 2009, the Health Information Technology for Economic and Clinical Health Act (HITECH) promoted national use of electronic health records (EHR) in the US by giving incentives to providers who adopt ‘meaningful use’ of EHRs. As of 2017, nearly 86% of office-based physicians had adopted EHRs. EHRs have rich information...
Wastewater and bioreactors in wastewater treatment plants (WWTPs) are reservoirs for antibiotic resistance genes (ARGs), which can pass through treatment processes and migrate into the environment as they are released in effluent. WWTPs harbor a variety of ARGs that can be spread by horizontal gene transfer facilitated by mobile genetic...
The critical importance of alternative mRNA splicing and the RNA binding proteins that orchestrate this essential layer of post-transcriptional gene regulation is increasingly recognized in gene regulatory programs. We and others have shown that alternative splicing plays a causal role during the Epithelial-Mesenchymal transition, a cell-developmental program that is hijacked...
The embryonic neural crest is a unique vertebrate stem cell population that has the ability to retain its stem attributes while neighboring cells in the embryo undergo lineage restriction. These cells possess multi-germ layer developmental potential and can give rise to a diverse array of derivatives such as components of...