Center for Human Molecular Genetics

Center Director: Stephan Zuchner, MD

Dr. Zuchner is a neurologist and molecular biologist with extensive experience in the mapping of Mendelian diseases and cloning of causal genes. His work on Charcot-Marie-Tooth disease has led to the recent identification of causal mutations for two types of CMT. Dr. Zuchner's work focuses on molecular neurogenetics and psychiatric genetics.

Increasingly, human genetics relies on the convergence of multiple layers of genomic information. In the study of disease genes, evidence to support the identification of a disease gene and information about a gene's biological mechanisms and therefore its potential role in disease etiology is crucial. Beyond the identification of disease related genetic variation, understanding the molecular consequences of such variation for genomic organization, RNA and protein function, and molecular pathway organization gains importance for subsequent disease modeling and the development of therapeutic approaches.

The CHMG is developing a world-class research program for the discovery and characterization of human disease genes utilizing innovative molecular genetic methods. Faculty members working in the CHGM consist of scientists with expertise in molecular genetics, genomics, functional genomics, and epigenetics as they relate to human disease. The CHMG will provide state-of-the-art molecular genetic know-how and technology for the discovery and molecular characterization of human disease genes. The CHMG is comprised of three Divisions: 

Division for Functional Genomics
Division Director, Gaofeng Wang, Ph.D.

The Division for Functional Genomics focuses on genomic sciences as they relate to human disease. Utilizing the vast amount of data produced by the various -omics projects, the CHGM will describe gene functions and interactions. The areas of specific interest include:

• Genomic variation analysis (mutations, SNPs, copy number variations)
• Comparative genomic analysis of conserved coding and non-coding elements
• Expression analysis
• Metabolomics

Division for Regulatory Genetics
Division Director, Derek Dykxhoorn Ph.D. 

The Division for Regulatory Genetics investigates dynamic aspects of gene and genome regulation in human disease. Areas of interest include:

• Transcription factors and their binding sites
• Micro RNA mechanisms
• Molecular pathways

Division for Epigenetics
Division Director, Juan Young, Ph.D.

The importance of the establishment, maintenance and proper interpretation of DNA methylation patterns is most dramatically highlighted by alterations causing or contributing to the development of human diseases.  Mutations in components of the DNA methylation machinery underlie several inherited syndromes, including the autism spectrum disorder and Rett syndrome. Patients with Rett syndrome have neurodevelopmental defects associated with mutations in MeCP2, which encodes the methyl CpG binding protein2 that binds to methylated DNA. Aberrant DNA methylation has also been associated with common acquired autoimmune, cardiovascular and neurological diseases, indicating important functions of DNA methylation in these systems. The overall goal of our research program is to elucidate genetic and biochemical pathways of cellular function that are affected by abnormalities in DNA methylation-regulated processes. Our preferred model system is the mouse, but we also study cultured cells and apply a variety of ex vivo and in vitro techniques.