Genetic Drivers of Pediatric and Young Adult Glioblastoma: Dr. Koschmann is engaged in a project studying the molecular mechanisms by which mutations in the histone chaperone protein ATRX promote pediatric glioblastoma (GBM) and affect its response to therapy. He developed the first animal model of ATRX-deficient GBM. Data from the project demonstrated the role of ATRX in GBM tumor progression, treatment response and loss of tumor genetic stability, and provided a platform for future development of targeted therapy for patients with ATRX-deficient GBM. This work was selected as the top pediatric basic science abstract at the 2015 Society of Neuro-Oncology (SNO) meeting and was published in Science Translational Medicine in 2016. Additionally, Dr. Koschmann has collaborated in multiple research projects which have pursued mechanisms of tumor progression, DNA damage repair, and epigenetic regulation in animal models of GBM. Through these models, we have developed a program of translational research to improve therapies for pediatric and young adult GBM.
Precision Medicine in Pediatric Neuro-Oncology: Dr. Koschmann is currently pursuing translational and clinical research projects in precision medicine in Pediatric Oncology and Neuro-Oncology. Along with other members of the UM Translational Neuro-Oncology Laboratory, he has created a program in which pediatric and adult glioma samples from surgeries performed at the University of Michigan are used to generate novel primary cell cultures. Dr. Koschmann uses these cell cultures to study mechanisms of glioma growth and targeted treatment response. As a co-investigator in the MiOncoseq Research Program (PIs Chinnayain/Mody), Dr. Koschmann pairs DNA/RNA sequencing of the patient’s tumor, germline and, primary tumor cell cultures with the development of targeted therapies. These results are presented in the multi-disciplinary and multi-institutional UM Brain Tumor (CNS) Precision Medicine conference, which he facilitates. This conference has led to multiple academic collaborations, including an article describing the co-sequencing and in vitro targeting of a novel pediatric high-grade glioma cell culture. Dr. Koschmann has co-authored multiple manuscripts regarding clinical pediatric oncology and neuro-oncology patient populations.