Medical Cell Biology Commons^™

Atrx Inactivation And Idh1-R132h Drive Preferential Sensitivity To Proton Vs. X-Ray Radiotherapy In Glioma Stem Cells, Ángel Adrián Garcés

Dissertations & Theses (Open Access)

Background: Glioma Stem Cells (GSCs) are self-renewable, treatment resistant cells in the glioma tumor mass known to promote tumor development. In contrast to traditional photon-based radiation therapy (XRT), proton radiation therapy (PRT) may induce more complex DNA damage and therefore might have the potential to eliminate GSCs. Although previous studies have individually linked IDH mutations, specifically IDH1^R132H, and ATRX inactivating mutations to improved patient outcomes and suppressed DNA damage repair compared to their respective wild-types, the mechanisms by which these two genetic alterations interact in GSCs treated with PRT compared to XRT are currently unknown. We hypothesize that …

Lgr5 Regulation Of Stat3 Signaling And Drug Resistance In Colorectal Cancer, Tressie Posey, Tressie Alexandra Posey

Dissertations & Theses (Open Access)

LGR5 Regulation of STAT3 Signaling and Drug Resistance in Colorectal Cancer

Tressie Alexandra Capri Posey B.S.

Advisory Professor: Kendra Carmon, Ph.D.

The greatest difficulty in treating colorectal cancer (CRC) is the development of drug resistance which leads to relapse after treatment and progression to metastasis. Cancer stem cells (CSCs) are believed to drive relapse because of their capacity to self-renew, acquire resistance mechanisms, and differentiate promoting tumor growth and heterogeneity. Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), is a bona-fide marker of CSCs and has been considered a viable target for CSC specific therapeutic development. While we showed targeting LGR5 …

Modulating Immunometabolism To Improve The Activity Of Car-Nk Cells Targeting Cd70 In Renal Cell Carcinoma, Hind Rafei

Dissertations & Theses (Open Access)

Despite the approval of several therapies for metastatic clear cell renal cell carcinoma (ccRCC), disease resistance and relapse are common, and therapies with novel mechanisms of action are urgently needed. Chimeric antigen receptor (CAR) T-cell therapy has shown remarkable responses in hematologic malignancies, but many obstacles hinder success in solid tumors including the paucity of highly specific targets and the hostility of the tumor microenvironment (TME). Moreover, the limitations of generating an autologous cell product, such as cost of manufacture, and the challenges of toxicity with CAR-T cells highlight the need to develop new cell therapy products that are at …

Vascular Disease Pathogenesis In Smooth Muscle Dysfunction Syndrome And Majewski Osteodysplastic Primordial Dwarfism Type Ii, Jamie Wright

Dissertations & Theses (Open Access)

Vascular diseases are a leading cause of morbidity and mortality world-wide. Understanding their pathogenesis is crucial to better diagnosis and management of these life-threatening conditions. Through the study of rare mutations that lead to early onset and severe vascular diseases, we can elucidate underlying mechanisms for vascular disease pathogenesis and develop better treatments to prevent and manage more common causes of vascular diseases. In this study we look at two rare diseases that lead to severe vascular phenotypes, Smooth Muscle Dysfunction Syndrome (SMDS) and Majewski Osteodysplastic Primordial Dwarfism Type II (MOPDII). SMDS is a rare condition due to pathogenic variants …