Laura B K Herzing, PhD
Assistant Professor of Pediatrics
Feinberg School of Medicine
Ann Marie and Francis Klocke, MD Research Scholar in Human Molecular Genetics
Children's Memorial Research Center
Research Interests:
Dr. Herzing's work focuses on identifying epigenetic changes in gene expression that underlie neurodevelopmental disorders such as autism, Angelman and Rett syndromes, and epilepsy. Using both patient samples and mouse models of these disorders, her goal is to identify when the critical expression changes occur, and whether their effects can be reversed or improved. Rett Syndrome (RS) is a progressive neurologic disorder that has many clinical features in common with autism and Angelman syndrome (AS). Like children with autism, girls with RS often initially appear to develop normally, then lose or fail to gain milestones. A few children born with AS carry a mutation in MeCP2, the gene associated with RS, although most carry a deletion of the UBE3A gene. Dr. Herzing has demonstrated that there is also a developmental and tissue-specific alteration in expression of Ube3a and adjacent genes in RS and RS mouse models, which could explain the phenotypic overlap between AS, RS and autism. These genes, several of which are imprinted, are also duplicated in as many as 2% of patients with autism, and Dr. Herzing has shown that these patients exhibit enhanced expression of these genes. Working on the hypothesis that misregulation, rather than mutation, of the candidate UBE3A, ATP10C and GABRB3 genes leads to autism, Dr. Herzing is using transgenic and RNAi technologies to lower or elevate the expression of these genes in mouse models. Careful assessment of resultant behavioral alterations will permit determination of the role such candidate genes have in the development of autism. These animals will also serve as vehicles to validate treatments and therapies for autism in a model system based on human etiology. Many children with these disorders also develop seizures, and epilepsies in general remain a major childhood medical concern. The development of most pediatric epilepsies is likely influenced by a change in expression of ion-channel genes. Dr. Herzing is working to expand a collaboration with The University of Chicago and Milwaukee Childrens Hospital, to facilitate ion-channel gene expression studies in tissue recovered from patients undergoing epilepsy surgery. Results from these studies will inform the development and interrogation of animal models for seizure development, and will help define the mechanisms underlying idiopathic epilepsy and seizures associated with syndromes and disorders such as autism, RS and AS.
Faculty Publications:
Viemari, J. C., Roux, J. C., Tryba, A. K., Saywell, V., Burnet, H., Pena, F., Zanella, S., Bevengut, M., Barthelemy-Requin, M., Herzing, L. B. et al. (2005). Mecp2 deficiency disrupts norepinephrine and respiratory systems in mice. J Neurosci 25, 11521-30.
Herzing, L. B., Cook, E. H., Jr. and Ledbetter, D. H. (2002). Allele-specific expression analysis by RNA-FISH demonstrates preferential maternal expression of UBE3A and imprint maintenance within 15q11- q13 duplications. Hum Mol Genet 11, 1707-18.
Kim, S. J., Herzing, L. B., Veenstra-VanderWeele, J., Lord, C., Courchesne, R., Leventhal, B. L., Ledbetter, D. H., Courchesne, E. and Cook, E. H., Jr. (2002). Mutation screening and transmission disequilibrium study of ATP10C in autism. Am J Med Genet 114, 137-43.
Herzing, L. B., Kim, S. J., Cook, E. H., Jr. and Ledbetter, D. H. (2001). The human aminophospholipid-transporting ATPase gene ATP10C maps adjacent to UBE3A and exhibits similar imprinted expression. Am J Hum Genet 68, 1501-5.
Herzing, L. B., Romer, J. T., Horn, J. M. and Ashworth, A. (1997). Xist has properties of the X-chromosome inactivation centre. Nature 386, 272-5.
