Research

Susan A. Berry

The underlying theme of Dr. Berry's research is the developmental regulation of growth-related genes. Her major work is defining the molecular action of growth hormone. These efforts use the model of the rat serpin multigene family, as several rat serpins are growth hormone responsive and developmentally expressed. As such, they are also useful for investigation of the role(s) that hormones have in influencing the program of orderly gene expression in development. In addition, the serpins respond to acute phase stimuli (inflammation). Several lines of evidence suggest there may be an interaction between this normal physiologic response to stress and growth regulation. Investigation of this interaction may provide new insights into the modulation of growth and the roles of serpins in this modulation. Her current project is to isolate and characterize a growth hormone reducible nuclear factor.

An additional goal of this work is to define molecular mechanisms by which gene expression can be altered during maturation, and to evaluate the participation of hormonal signals in development. Prenatal growth is not mediated by the same hormonal stimuli as growth after birth, prompting the proposal that prenatal growth regulation may be under the control of a placentally-mediated autonomous growth axis. Placenta is a rich source of growth homone-releasing hormone (GHRH), and also expresses several growth hormone-like genes as well as peptide growth factors. Ongoing investigation of the role of placental GHRH in placental and/or fetal growth is an additional research priority.

Lisa A. Schimmenti

The Schimmenti lab has a commitment to pediatric research in the areas of birth defects and developmental disability.  Our laboratory has three main projects. Our major area of interest is in the development of ocular birth defects, primarily coloboma, microphthalmia and anophthalmia.  We have an NIH funded project to study the impact of genetic testing on the Early Hearing Detection and Intervention Process (EHDI).  We recently began to study the genetics of autism through a locally indentified family with a chromosome deletion and autisitic members.

Ocular birth defects affect 1 in 10.000 children and account for 10% of childhood blindness.  In collaboration with Michael R. Eccles at the University of Otago, New Zealand, we identified the first family with optic nerve colobomas and renal hypoplasia that had a mutation in the developmental regulator PAX2.  Since that time, our laboratory has worked on further characterization of the phenotype associated with PAX2 mutations.  We have also begun to search for other genes that cause ocular coloboma and the related malformations microphthalmia and anophthalmia.  We are using zebrafish models to identify other genes that are important for ocular development and how they relate to the developmental defects that we observe in human patients.

Hearing loss is a common birth defect that affects 1 in 1000 newborns.  Recently many states in the US have adopted EHDI protocols to screen for hearing loss in the newborn period.  Concurrent with the adoption of EHDI protocols came discoveries that much of non-syndromic hearing loss is caused by common mutations in two genes, GJB2 and GJB6.  In collaboration with a faculty team at UCLA, we obtained funding through NIH-NIDCD to study the impact of genetic testing for hearing loss in the newborn period.  This study will measure the impact of genetic testing on parents based on knowledge, perceived personal control and anxiety parameters.  We have completed the first of four years of this study.

Autism and related disorders have reached epidemic proportions in Minnesota as well as the rest of the world.  We identified a large family through the Autism Spectrum Disorders Clinic at the University of Minnesota that carries a 7 megabase genomic deletion on chromosome 10.  We are in the process of mapping this deletion and searching for candidate genes in the region that can contribute to impaired social interaction and language disability that we observe in children with autism.

Chester B. Whitley

Toward gene therapy. Dr. Whitley uses molecular genetic techniques to study mucopolysaccharidosis (MPS) storage diseases, a group of lethal genetic disorders. Recent work has automated DNA sequencing for mutation analysis for molecular genetic diagnosis. The results are providing predictive testing and aid in the interpretation of outcomes for children treated by bone marrow transplantation. Such clinical trials of marrow transplantation have defined the extent of metabolic correction and have provided rationale to investigate gene therapy. Current studies in Dr. Whitley's laboratory are evaluating retroviral-mediated gene transfer in hematopoietic cells and reversal of the disease process in vitro thus providing the impetus to initiate clinical trials of gene therapy.