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...
Macrophages are innate immune cells that are traditionally thought to be specialists in phagocytosis. More recent evidence suggest that macrophages reside in nearly every organ and readily adapt to local microenvironmental signals, leading to highly plastic phenotypes across and within tissues. Therefore, rather than treating it as a homogenous cell...
To combat the rise of antibiotic-resistant pathogens in clinical settings, it is necessary to understand which environments and conditions select for antibiotic resistance. Analysis of environments hypothesized to select for antibiotic resistance has been revolutionized by metagenomic sequencing. The metagenomic pool of DNA sequences can be probed in silico using...
Uterine leiomyomas (fibroids) are a major source of gynaecologic morbidity in reproductive age women and are characterised by the excessive deposition of a disorganised extracellular matrix, resulting in rigid benign tumours. Clinically, leiomyoma patients usually present with pelvic pain, urinary incontinence, as well as heavy cyclic and non-cyclic bleeding. Curative...
Uterine leiomyomas (fibroids) are a major source of gynaecologic morbidity in reproductive age women and are characterised by the excessive deposition of a disorganised extracellular matrix, resulting in rigid benign tumours. Clinically, leiomyoma patients usually present with pelvic pain, urinary incontinence, as well as heavy cyclic and non-cyclic bleeding. Curative...
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,...
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...
Cells are complex, autonomous machines that integrate many environmental cues to execute a desired response. Though this property makes cells versatile, it presents significant design challenges when, to treat diseases, we must alter cellular responses. To understand changes to the complex regulatory pathways that cause diseases, studies often investigate the...