Phenotypic variation is the functional unit that evolution acts upon and is the main contributor to the diversity of species. The phenotype of an individual is shaped by genetic and environmental factors. These genetic and environmental factors contribute to biomedically relevant traits such as an individual’s susceptibility to disease and...
Biological systems comprise diverse collections of cellular and non-cellular components with intricate relationships and dynamic interactions. To gain system-level understanding, we must be able to accurately model these systems, both experimentally and computationally. Agent-based models (ABMs) in particular are a uniquely intuitive, modular, and flexible framework capable of supporting multi-scale,...
With the ability to rapidly screen and manipulate genomes, the in depth study of the functional actors of biology—metabolites and proteins—is necessary to understand complex biochemistry in developmental and disease states. The analytical processes by which biological information is gained from metabolomics and proteomics experiments must also evolve with our...
The last decade has witnessed a rapid transformation in our understanding of the structure of chromatin, the nuclear complex of DNA and its structural proteins. While, barring mutations, the DNA sequence in each cell of the human body is the same, it is the structure of the chromatin complex that...
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...
Store-operated Ca2+ entry (SOCE) is a principal mechanism for generating cellular Ca2+ signals. Store-operated Ca2+ release-activated Ca2+ (CRAC) channels serve an essential role in generating Ca2+ elevations needed for transcriptional, enzymatic, and secretory effector cascades in many cell types. CRAC channels, comprised of the ER Ca2+ sensor STIM and the...
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,...
Transcription is tightly regulated to ensure genes are appropriately expressed both temporally and spatially. This tight regulation governs various processes within the cell, such as differentiation and cell identity, cellular maintenance, and dynamic responses to external signals. Transcription factors (TFs) coordinate these various gene programs and in particular, are key...
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...
The interaction of amyloid-β (Aβ) with endogenous metal ions is thought to play a role in the pathogenesis of Alzheimer’s disease (AD). However, limited tools exist to study and modulate Aβ-metal binding. The Meade lab has developed cobalt(III) Schiff base (Co(III)-sb) complexes as protein inhibitors that competitively displace metals from...