Roman J. Giger, Ph.D.

George L. Streeter Collegiate Professor of Cell and Developmental Biology
Professor of Neurology, University of Michigan Medical School

Biography

Dr. Giger received his Ph.D. in Biochemistry from the University of Zurich, Switzerland. As a graduate student he studied gene structure and regulation of the neural cell adhesion molecule contactin-2 (axonin-1), an Ig-CAM important for brain development and formation of axon connections. As a postdoctoral fellow he discovered mechanisms that repel developing axons from entering tissues that express growth inhibitory molecules, including members of the Semaphorin family of axon guidance molecules. His team recently showed that mice deficient for Semaphorin 5A (Sema5A) or its receptor, PlexinA2 (Plxna2), exhibit defects in brain wiring and synaptic density. Behavioral studies with Plxna2 mutant mice revealed defects in episodic memory and sensorimotor gating. Both Sema5a and Plxna2 mutant mice show defects in sociability.

Mutations in human SEMA5A and PLXNA2 are associated with neuropsychiatric illness, including autism spectrum disorder and schizophrenia. While genetic discoveries are key for the identification of allelic variants associated with mental illness, the major challenge remains obtaining a deeper understanding of the biochemical pathways altered by disease alleles and developing a more nuanced understanding of how these altered pathways disrupt brain function relevant to disease symptomatology. Supported by the National Institute of Mental Health (NIMH), the Giger lab pursues a molecular approach to understand how Sema/PlexinA signaling regulates development and experience-dependent refinement of neuronal circuits in the mammalian brain. They combine gene editing in the mouse, using CRISPR/Cas9 technology, with electrophysiological recordings and biochemical strategies to identify signaling pathways initiated by Sema/PlexinA, to define developmental epochs of vulnerability and the neural substrate associated with impaired behaviors. The long-term goal is to use newly generated knowledge from these studies to develop new therapeutic strategies.