BIH Lecture: Microglia as genetic and genomic integrators of disease risk

Einstein BIH Visiting Fellow: Prof. David H. Gutmann; Washington University School of Medicine, Stl. Louis, USA

Host: Prof. Helmut Kettenmann, MDC

Neurofibromatosis type 1 (NF1) is a neurogenetic disorder in which children and adults are prone to the development of numerous nervous system abnormalities, including brain and nerve tumors, learning disabilities, seizures, sleep disturbances, and autism. While caused by a germline mutation in the NF1 gene, each individual with NF1 is unique with respect to the spectrum of disease features and severity. Over the past decade, research in the Gutmann laboratory has demonstrated that the specific germline mutation (genetic) and sex (genomic) are two critical factors that underlie clinical variability. In his talk, Professor Gutmann will discuss an emerging concept that brain macrophage-like cells (microglia) function as central integrators of genetic and genomic factors relevant to disease heterogeneity.

About Professor David H. Gutmann

David H. Gutmann received his undergraduate, graduate (PhD) and medical (MD) degrees from the University of Michigan, where he trained in immunogenetics in the laboratory of Dr. John Niederhuber. During his residency in Neurology at the University of Pennsylvania, he had the good fortune of working with Dr. Kenneth Fischbeck who sparked his interest in neurogenetics. He then returned to the University of Michigan for research fellowship training in Human Genetics with Dr. Francis Collins. During this time, he identified the neurofibromatosis type 1 (NF1) protein and began to elucidate its function as a RAS regulator. In late 1993, he was recruited to Washington University, becoming a full professor in 2001 and the Donald O. Schnuck Family Professor in 2002. He established the St. Louis Children’s Hospital Neurofibromatosis Clinical Program in 1994 and the Washington University Neurofibromatosis Center in 2004. His laboratory is currently focused on understanding the genomic, molecular and cellular basis for nervous system problems affecting children and adults with NF1 using both human biospecimens and novel genetically-engineered mouse strains. Over the past 25 years, his team has developed numerous mouse models of NF1-associated optic glioma, somatic growth defects, attention deficit, autism, plexiform neurofibroma, and spatial learning impairments as well as NF2-associated meningioma. They have used these preclinical models to define the cellular origins of tumors, the contribution of the tumor microenvironment, and the major growth control pathways that dictate brain development in NF. He has published over 430 peer-reviewed manuscripts, and has been recognized for his achievements with numerous awards, including the 2012 Children’s Tumor Foundation Frederich von Recklinghausen Lifetime Achievement Award, the 2013 Washington University Distinguished Faculty Research Award, the 2014 Riley Church Lectureship and the 2017 Alexander von Humboldt Award.  He also serves as a member of the National Institute of Neurological Disorders and Stroke Advisory Council.