Marc Lalande Ph.D. holds the Physicians Health Services Chair in Genetics and Developmental Biology. He is Professor and Chairman of the Department of Genetics and Developmental Biology, and Associate Dean for Research Planning and Coordination at the University Of Connecticut School Of Medicine. He is also Head of the University of Connecticut Stem Cell Working Group. Dr. Lalande’s research is on the role of epigenetics in disease and development. Epigenetics refers the study of heritable changes in gene function that occur without an alteration in DNA sequence.

One goal of our research is to develop new knowledge in the field of diagnosis, prevention, treatment, and amelioration of mental retardation. We study Angelman syndrome (AS), one of the better known causes of mental retardation. AS is a neurogenetic disorder characterized by severe mental retardation, 'puppet-like' ataxic gait with jerky arm movements, seizures, EEG abnormalities, hyperactivity and bouts of inappropriate laughter. The genetic abnormality in AS is passed exclusively through the maternal germline because of the epigenetic process called genetic imprinting. Individuals with AS fail to inherit a normal active maternal copy of the gene encoding ubiquitin protein ligase E3A (UBE3A). Only the maternal copy of UBE3A is active in brain with the paternal copy being silenced due to imprinting. The loss of UBE3A in the brain of AS patients causes the accumulation of proteins in brain that result in the clinical problems in AS. The accumulating proteins have not yet been discovered, and the Lalande lab is attempting to identify the targets of UBE3A. For these studies, we have developed techniques to knockout UBE3A in stem cells and then produce neurons from the UBE3A-negative stem cells. We are also investigating the molecular process that silences the paternal UBE3A allele in brain using a mouse model of the disease. This work is supported by the Physicians Health Services endowment.

The Lalande lab is also actively involved in a project to better understand how smoking contributes to the increased risk of low birth weight and premature deliveries and to identify biomarkers of prenatal tobacco exposure. The goals of this research are to first examine whether abnormal epigenetic regulation of insulin-like growth factor 2 (IGF2) is associated with reduced fetal/placental growth in women who smoke. This project may help us better understand at a molecular level how smoking causes low birth weight babies. The rationale for this study is based on the observation that tobacco smoking can alter normal patterns of DNA methylation and the knowledge that DNA methylation regulates IGF2 genetic imprinting. We propose to study whether fetal tissue (umbilical cord), placenta and maternal blood of smokers and non-smokers show differences in methylation at the IGF2/H19 locus. These novel investigations will permit us to determine whether the increased risk of adverse obstetrical outcomes as result of tobacco usage have an epigenetic basis and may help explain the variation of fetal growth among smokers and the link between polycyclic aromatic hydrocarbons and birth weight. This research project is supported by the Connecticut Department of Public Health.