Muhibullah S Tora

BME PhD Thesis Defense

Date: March 26th, 2021

Time: 10:00 AM

Zoom: https://zoom.us/j/96046342081?pwd=TlB4RWNTREIyekt4TmlabjRyVDZzdz09

Committee Members:

Nicholas Boulis, MD (Georgia Tech/Emory, Department of Biomedical Engineering) (Advisor)

John Oshinski, PhD (Georgia Tech/Emory, Department of Biomedical Engineering)

Robert Gross, MD, PhD (Georgia Tech/Emory, Department of Biomedical Engineering)

Steven Sloan, MD, PhD (Emory University, Department of Genetics)

Peter Canoll, MD PhD (Columbia University, Department of Pathology)

Title: Development and Characterization of Porcine Models of Glioma

Summary: Glioblastoma (GBM) is a debilitating disease process with untenable morbidity and mortality and is the most common brain tumor in adults, with 5-year survival at approximately 4%. Its counterpart in the spinal cord is a rare disease process with similarly poor outcomes. Unfortunately, there have been limited changes to the outcomes despite countless clinical trials. In part, this represents the aggressive nature of this disease process. On the other hand, this highlights the need for advanced preclinical models of the disease, especially for the evaluation of surgical therapies in more anatomically relevant platforms. Prior work has demonstrated the development of de-novo glioma modeling through viral vector-driven gene transfer with striking histopathologic, immunohistochemical, and transcriptomic similarity to the human disease. However, these are limited to rodent models wherein various translational strategies are stifled due to anatomic constraints. By scaling strategies employed and validated in rodents to pigs, this research outlines the development and characterization of the first porcine models of high-grade glioma in both the brain and spinal cord using lentiviral gene transfer. This work establishes an initial platform for surgical translational studies and is the first step toward advancing glioma modeling in large mammalian models.