Tiemo Jürgen Klisch, Ph.D.
Assistant Professor, Department of Pediatrics , Baylor College of Medicine, and the Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital
Dr. Klisch studies the formation and progression of medulloblastoma (MB), an embryonic neuroepithelial tumor of the cerebellum in mice. MB is the most frequent malignant brain tumor in children representing up to 20% of tumors in the developing nervous system. The overall survival has increased dramatically in the last years due to sometimes harsh clinical protocols, combining surgery, irradiation and chemotherapy. Nevertheless, 20% of children affected do not respond to any treatment and die. Based on their molecular expression profiles, four major MB subtypes have emerged: Wnt, sonic hedgehog (Shh), group C, and group D. Although the Shh and Wnt signaling pathways are well understood and several mouse models have been established, recent attempts indicate that simple down regulation of the pathways at a receptor level is not the sole remedy. This highlights the need to better understand the basic molecular mechanisms that govern MB development in order to facilitate improved and more effective treatments.
The Klisch lab focuses on altering activities of key specific transcription factors, which in turn regulate complex genetic programs of multiple pathways, leading to a better understanding of the disease than targeting one particular molecular pathway. Additionally, a therapy that targets a single transcription factor exclusively expressed within the tumor, but not the normal tissue, is less likely to have undesired side effects.
Towards this goal, the Klisch lab aims to integrate transcriptional profiling of human primary medulloblastomas with genetic approaches in mice to understand and study central molecular networks critical for the genesis of medulloblastomas.
The Klisch lab's long-term goal is to develop novel treatment options as well as improve the survival of children with medulloblastoma.