Life Sciences Commons^™

Comprehensive Sequencing With Surface Tagmentation Based Technology, Kuan Feng

Biomedical Sciences ETDs

Next-generation sequencing technologies (NGS) have undergone extensive improvements since the invention of the 454 sequencing system in 2005. With tremendous progress in throughput, speed and a dramatic reduction in per-base cost, DNA sequencing is widely used in basic science as well as translational research. However, it is still a challenge to acquire a complete human genome. The long-range information is often missing due to the short length of NGS reads, which leaves many gaps in between scaffolds rather than an entire piece for each chromosome. Moreover, without the long-range information, haplotype-resolved genome sequencing and structural variant detection can be difficult, …

Developing Droplet Based 3d Cell Culture Methods To Enable Investigations Of The Chemical Tumor Microenvironment, Jacqueline A. De Lora

Biomedical Sciences ETDs

Adaptation of cancer cells to changes in the biochemical microenvironment in an expanding tumor mass is a crucial aspect of malignant progression, tumor metabolism, and drug efficacy. In vitro, it is challenging to mimic the evolution of biochemical gradients and the cellular heterogeneity that characterizes cancer tissues found in vivo. It is well accepted that more realistic and controllable in vitro 3D model systems are required to improve the overall cancer research paradigm and thus improve on the translation of results, but multidisciplinary approaches are needed for these advances. This work develops such approaches and demonstrates that new droplet-based cell-encapsulation …

Regulations Of Pathogenic Cd4+ T Helper Lymphocytes In Inflammatory Diseases, Handong Zheng

Biomedical Sciences ETDs

In this comprehensive project, three interrelated studies with distinct foci were employed to understand the regulations of specific CD4⁺ T helper cell population in inflammatory diseases.

Pathogenic TH17 cells play an essential role in the initiation and development of both human multiple sclerosis (MS) and animal experimental autoimmune encephalomyelitis (EAE). Nevertheless, the underlying mechanism by which the pathogenicity of TH17 cells is controlled in the autoimmune neuro-inflammation remains unclear. In aim 1, we revealed that lumican (Lum), an extracellular matrix (ECM) protein, negatively regulates encephalitic TH17 cell responses. Our findings highlighted a TH17 cell-intrinsic effect of Lum in suppressing …

Studying Egfr Signaling Through Single Molecule Imaging And Computational Modeling, Emanuel Salazar Cavazos

Biomedical Sciences ETDs

Signaling through the Epidermal Growth Factor Receptor (EGFR) plays an important role in both physiological and cancer-related processes. In this work, single-molecule microscopy measurements and computational modeling were closely integrated to better understand the mechanisms that regulate EGFR signaling. Technical improvements were made over the previously described Single-Molecule Pull-down (SiMPull) assay to facilitate direct detection of the phosphorylation state of thousands of individual receptors, and thereby estimate both the fraction of receptors phosphorylated at specific tyrosine residues and the frequency of multisite phosphorylation. These improvements enabled the first direct detection of multisite phosphorylation on full-length Epidermal Growth Factor Receptor (EGFR), …