Medical Molecular Biology Commons^™

Molecular Pathogenesis Of A Novel Subgroup Of Peripheral T-Cell Lymphomas, Jiayu Yu

Theses & Dissertations

Peripheral T-cell Lymphoma (PTCL) consists of numerous distinct disease entities. With the current diagnostic criteria over a third of the cases cannot be further classified and are called "not otherwise specified" (PTCL-NOS). Using gene expression profiling (GEP) of tumors, we identified two novels PTCL-NOS molecular subgroups either characterized by high expression of GATA3 (33%), which is associated with Th2 cell differentiation, or high expression of TBX21 (49%) which regulates Th1 cell maturation. Therefore, stratifying patients for diagnosis and identifying the underlying genetic basis to improve clinical therapy becomes critical to prognosis.

First, we performed DNA copy number analysis by using …

Candida Cell-Surface-Specific Monoclonal Antibodies Protect Mice Against Candida Auris Invasive Infection, Jonothan Rosario-Colon, Karen Eberle, Abby Adams, Evan Courville, Hong Xin

School of Graduate Studies Faculty Publications

Candida auris is a multidrug-resistant fungal pathogen that can cause disseminated bloodstream infections with up to 60% mortality in susceptible populations. Of the three major classes of antifungal drugs, most C. auris isolates show high resistance to azoles and polyenes, with some clinical isolates showing resistance to all three drug classes. We reported in this study a novel approach to treating C. auris disseminated infections through passive transfer of monoclonal antibodies (mAbs) targeting cell surface antigens with high homology in medically important Candida species. Using an established A/J mouse model of disseminated infection that mimics human candidiasis, we showed that …

Hiv-1 Drug Resistance To Integrase Strand Transfer Inhibitors In Hiv-1 Non-B Subtypes, Emmanuel Ndashimye

Electronic Thesis and Dissertation Repository

Human immunodeficiency syndrome (HIV-1) has infected over 75 million people and over 35 million have succumbed to virus related illnesses. Despite access to a variety of antiretroviral therapy (ART) options, ART programs have been disproportionally spread in the world with low-and middle-income countries (LMICs) facing challenges to access the most potent ART options. With less potent ART remaining in use in LMICs, HIV-1 drug resistance (HIVDR) presents a growing challenge in LMICs. Since approval of the first-generation integrase strand transfer inhibitor (INSTIs), Raltegravir (RAL) in 2007, INSTIs remain the best choice as a backbone of ART. Access to second generation …

A High-Throughput Approach To Characterizing Arv1 On The Regulation Of Lipid Homeostasis Uncovers A Novel Interaction With Epidermal Growth Factor Receptor, Nicholas Anthony Wachowski

Graduate School of Biomedical Sciences Theses and Dissertations

Acyl-CoA cholesterol acyl transferase related enzyme-2 required for viability 1 (ARV1) was first recognized in Saccharomyces cerevisiae in a study done in 2000 by Tinkelenberg et al. In yeast, the deletion of ARV1 results in numerous defects including abnormal sterol trafficking [1], the reduction of sphingolipid metabolism [2], synthesis of glycosylphosphatidylinositol (GPI) anchor [3], ER stress [4], and hypersensitivity of fatty acids leading to lipoapoptosis [5]. Arv1 germline deletion in mice displayed a lean phenotype with increased energy [6]. In humans, ARV1 mutations lead to epileptic encephalopathy [7].

Non-alcoholic fatty liver disease (NAFLD) consists of simple steatosis to non-alcoholic steatohepatitis …

Therapeutic Potential Of Trp Channels In The Targeting Of Rheumatoid Arthritis Synovial Fibroblasts, Brittany Isabella Schwam

Theses and Dissertations (ETD)

Rheumatoid arthritis is a chronic inflammatory disease primarily affecting the synovium, articular cartilage, and bone within a joint, but it is a unique form of arthritis wherein effects are systemic. The cause of this autoimmune disease remains unknown, but there are many environmental and genetic factors that play into susceptibility. Research is still far from drug-free remission despite great advancements over the past few decades. The majority of therapies developed rely on immunosuppressant or immunomodulator molecules and come with risk of infection, high costs, and toxic, uncontrolled side effects. Those diagnosed maintain a significant unmet need for targeted therapies.

There …