Faculty
Shivanand R Patil Ph.D.
Chromosome abnormalities are a leading cause of genetic disease. Cytogenetic studies are utilized to detect chromosomal rearrangements in individuals with congenital malformations and/or mental retardation, malignancies and other genetic disorders. Research efforts in our laboratory are engaged in investigating the mechanisms leading to chromosome abnormalities and in utilizing molecular cytogenetics methods for gene mapping. We are also investigating the use of chromosome-specific probes for interphase nuclei in leukemias and solid tumors. In collaboration with others, molecular characterizations of certain syndromes are being carried out in families with uncommon chromosomal rearrangements.
Robert A Philibert M.D., Ph.D.
The Psychiatric Genetics Laboratory is located on the first-floor of the Medical Education Building. It is fully equipped for translational genetics. Major pieces of equipment include an epifluorescence microscope capable of 3-D imaging, a Biomek 3000 liquid handling robot and an Applied Biosystems 7900 HT real-time machine, two cell culture hoods, and a number of state-of-the-art thermal cyclers, incubators and centrifuges. The laboratory is headed by Rob Philibert M.D. Ph.D., an Associate Professor of Psychiatry and a member of both the Neuroscience and Genetics Program. The laboratory personnel are an eclectic mix of full-time research assistants, graduate students, database managers and work-study students. The laboratory group has three major foci. The first is the role of the MED12 gene in human health and behavior. MED12 is one of the essential members of the Mediator complex and was first genetically characterized in 1998 by Dr. Philibert. In the past five years, we have developed compelling evidence that sequence variation in MED12 increases vulnerability to unique endophenotype of schizophrenia. In order to exploit these findings, our laboratory is using clinical genetic, transgenic cell modeling and systems biology approaches to discern the exact genetic mechanisms through which variation at this locus increases propensity for psychosis and to design new therapies for certain types of positive symptoms. The second is the role of genetic variation and gene-environment interactions in the genesis of behavioral disorders. Dr. Philibert is a principal investigator with the Iowa Adoption Studies, the largest longitudinal adoption study of gene environment interactions in the United States. Using genotyping and gene expression techniques, our group which includes internationally known collaborators, is dissecting the roles of genetic variation and gene environment interactions in the initiation and maintenance of substance use disorders, depression and antisocial personality in this large cohort of subjects. The third is the development of transcriptional profiling as a method for dissecting the etiology of complex behavioral illnesses and as a diagnostic aid for psychiatric illness. Over the past several years, it has become apparent that the majority of the genetic complexity underlying differential vulnerability to behavioral illness is manifested by differential gene expression and not by differential protein sequence. In a series of groundbreaking papers, we have detailed the development of a new set of techniques to exploit these findings and using one of the largest private collections of cell lines in the United States, we are actively working with academic and commercial collaborators to bring transcriptional profiling to the bedside as a diagnostic and prognostic tool.
Robert C Piper Ph.D.
My lab is interested in understanding the mechanisms that govern the movement of proteins on their way to Lysosomes.
One process we wish to understand is how membrane fusion events within the late endocytic pathway are controlled. Using a variety of genetic and biochemical approaches we are currently finding and functionally characterizing proteins that execute this process. Our earlier work sought to define the various SNARE proteins that act at discrete steps in the endocytic pathway. We are now analyzing the role of tethering factors that interact with Rab GTPases, SNARE proteins and elements of the cytoskeleton. The overall hypothesis is that these tethering factors work at an early step in the fusion process by integrating several vesicle transport processes to ensure the proper fidelity of membrane fusion.
The other process we wish to understand is how are cell surface proteins targeted for degradation in the lysosome. This process depends on a complex trafficking step whereby proteins are sorted into vesicles that bud inward into the lumen of the endosome. This budding event stands as a pivotal regulatory step in the endocytic pathway. We now know that the attachment of ubiquitin confers sorting into this degradative pathway and that ubiquitin itself carries sorting information that is recognized by "ubiquitin-sorting receptors." Currently, we are discovering and characterizing these ubiquitin-sorting receptors and determining how they are regulated. We are also studying how the function of these sorting receptors is integrated into the formation of inward budding vesicles themselves.
