Medicine and Health 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, …

The Tetraspanin Cd82 Regulates Hematopoietic Stem Cell Fitness And Bone Marrow Retention, Chelsea Saito-Reis

Biomedical Sciences ETDs

The maintenance of the hematopoietic stem and progenitor cell (HSPC) population is critical to sustaining the adult blood and immune system throughout an organism’s lifespan. The bone marrow microenvironment plays a key role in the regulation of HSPC maintenance and functions. Previous work from our lab has identified the tetraspanin CD82 as an important modulator of HSPC interactions with the bone marrow niche. However, the mechanisms as to how CD82 contributes to the maintenance, trafficking and retention of HSPCs with the niche remained unclear. First, we investigated how CD82 promotes HSPC quiescence, homing and engraftment using a global CD82 knock …

Niemann-Pick C1, Its Connection To Obesity, And Its Impact On Human Evolution, Joseph Joshua Castillo

Biomedical Sciences ETDs

Niemann-Pick type-C disease is a rare autosomal recessive neurodegenerative disease that classically presents in the first decade, leading to ataxia, vertical-gaze palsy, loss of communication skills, epileptic seizures, and eventually death. The stark reality about NPC disease underlines the important role the NPC1 protein plays in whole-body lipid homeostasis. It is no surprise, then, that the NPC1 gene has been associated with other diseases as well, such as obesity, diabetes, and Ebola virus infection. In this manuscript, a connection will be made that intertwines genetics, biochemical and molecular mechanisms, physiology, and evolutionary pressures, and will explain how a gene, discovered …

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 …

Inpatient Initiated Methadone For Chronic Non-Cancer Pain At The University Of New Mexico, Steven Fishburn

Biomedical Sciences ETDs

ABSTRACT

Introduction

Inpatient initiation of methadone is ideal due to associated risks of cardiac arrhythmias and a high incidence of overdose. Evidence based guidelines have been developed for initiation of methadone for chronic noncancer pain (CNCP). The purpose of this study is to describe the frequency of pretreatment testing and high-risk prescribing in patients initiated on methadone at the University of New Mexico Hospital (UNMH).

Methods

A retrospective observational study was conducted using electronic health record data from UNMH, a southwest tertiary care center. We collected data on frequency of (1) pretreatment testing and (2) discharges with concomitant high-risk prescriptions. …

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), …

Shape And Surface Chemistry Dictate Cellular Internalization Pathways Of Mesoporous Silica Nanoparticles., Annikka Jensen

Biomedical Sciences ETDs

Advances in the field of nanoparticle biomedical applications have made large strides towards achieving targeted deliver­y of therapeutics and imaging agents. However, less is understood on how the shape of a targeted nanoparticle will alter the level of cellular internalization. The research conducted herein demonstrated that by encasing the bare MSNP with a zwitterionic supported lipid bilayer, referred to as a protocell, the aspect ratio of the MSNP was maintained. However, the non-targeted protocell’s conformal coating drastically diminished the ability of the cell’s active sensory system to recognize the protocell. This finding indicates the cell envokes non-specific macropinocytosis in response …

Effect Of Exercise Interventions On Fatigue For Breast Cancer: A Systematic Review And Meta-Analysis, Julien Succar

Biomedical Sciences ETDs

We conducted a systematic review and meta-analysis on the effect of different exercise interventions on fatigue in patients with breast cancer undergoing active therapy. We found that exercise generally improves fatigue outcomes at 12 weeks after initiation of the exercise intervention. Aerobic exercise intervention improved fatigue, but anaerobic and combination regimens did not show improvement compared to controls. Moreover, no exercise intensity was found to be superior compared to controls. Our findings revealed that there is a need for standardization of exercise regimens in studies in order to identify the most effective exercise regimen.

Designing Synthetic Environments To Control Valvular Interstital Cells In Vitro, Kent E. Coombs

Biomedical Sciences ETDs

Aortic valve disease (AVD) is a large contributor to health costs in the United States affecting 2.8% of the population greater than 75 years old. With a growing elderly population due to medical advances, AVD will continue to rise in prevalence over time. Current treatments for AVD are insufficient due to a lack of preventative therapies and the bioprosthetic valves used for surgical replacement have major limitations. Tissue engineered heart valves (TEHVs) present an ideal solution to current AVD needs because of their biocompatibility, capability to integrate with the host’s tissue, and ability to utilize the natural repair mechanisms of …

Intestinal Permeability And Microbial Dysbiosis In Acute Coronary Syndrome (Miacs Study), Tarik Alhmoud

Biomedical Sciences ETDs

Background: Acute Coronary Syndrome (ACS) is a leading cause of morbidity and mortality. Metabolic syndrome and obesity are major risk factors for atherosclerosis and ACS. Dysbiosis plays an important role in metabolic syndrome and obesity. Studies show a markedly increased risk of heart attacks in patients with high levels of the pro-atherogenic metabolite trimethylamine-N-Oxide (TMAO). TMAO is produced by the intestinal microbial flora through metabolism of dietary phospholipids; Gram-negative bacteria (Phylum Proteobacteria) is the major source of TMAO metabolism. Patients with obesity and metabolic syndrome have a defective intestinal tight-junctional (TJ) barrier, which allows paracellular permeation of luminal antigens such …

V-Atpase Roles In Prostate Cancer, Yamhilette Licon Munoz

Biomedical Sciences ETDs

Vacuolar ATPase (V-ATPase) is responsible for maintaining the acidic pH of the endomembrane system in eukaryotic cells. V-ATPase active transport of protons generates the differential luminal pH in lysosomes, endosomes, and the Golgi. In addition to intracellular V-ATPase, cancer cells have V-ATPase at the plasma membrane. Plasmalemmal V-ATPase acidifies the extracellular milieu and enhances cell motility and invasion, evidence that V-ATPase contributes to tumorigenic phenotypes. We studied V-ATPase cellular functions in prostate cancer (PCa), the most commonly diagnosed cancer for men in the United States. V-ATPase inhibitors decreased invasion and migration of PCa cells. In aggressive PCa cell lines, C4-2B …

Mathematical Modeling Of Nanoparticle Biodistribution, Prashant Dogra

Biomedical Sciences ETDs

The prospects of nanoparticle-based drug delivery and imaging have been hindered by insufficient understanding of the effects of nanoparticle physicochemical properties on their in vivo disposition. Here, we present an integrative mathematical modeling and in vivo imaging approach to quantify the relationship between nanoparticle physicochemical properties, namely, size, surface charge, and surface chemistry, on their in vivo disposition kinetics in healthy rats. We developed simple master equations in closed-form to accurately represent the time-dependent concentration of nanoparticles in different regions of the body and obtain functional relationships for predictive purpose to support rational design of nanomedicine. We further used …