Faculty
John R Kirby Ph.D.
Toshihiro Kitamoto Ph.D.
How does the nervous system control complex behavior? How do experience and genetic variation modify it? The goal of our research is to answer these fundamental questions in neuroscience. We use the fruitfly, Drosophila melanogaster as an experimental animal, and integrate knowledge of the nervous system at the molecular, cellular, systemic and whole animal levels. The current focus is on male courtship behavior. This behavior consists of a highly stereotypical sequence of activities that are genetically determined, but also shows considerable experience-dependent plasticity called \"courtship conditioning\". By examining the behavior of various genetic variants, we study the function of particular genes in different aspects of courtship. In addition, using a recently developed strategy that allows one to perturb synaptic transmission rapidly and reversibly in a spatially restricted manner in intact animals, we investigate the significance of particular neuronal subsets in sexual orientation, courtship initiation, and courtship memory. Our multidisciplinary research is expected to provide new insights into the basic mechanisms underlying higher-order brain functions that control complex behavior.
Al L Klingelhutz Ph.D.
In the broadest sense, my goal is to understand the biology and genetics of human cancer and aging. One of my primary interest is in how epithelial cells become immortal and subsequently malignant after infection with human papillomavirus (HPV). We are specifically focusing on the roles of genetic instability and telomerase activation in this process. I also am studying how telomere loss and other factors are involved in induction of cellular senescence. Specific areas of research are the following: 1) Defining the roles of telomere loss and telomerase dysfunction in keratinocyte aging and transformation; 2) Examining the regulation of cellular genes by HPV E6 and E7 during the process of infection and transformation; 3) Establishment and utilization of relevant model systems to study HPV-associated immortalization and malignant progression of human epithelial cells; 3) Defining mechanisms of genetic instability and determining the role of specific genomic alterations in the development of head and neck cancers; 5) Determining how the cell cycle inhibitor, p16INK4a, is regulated during telomere-independent senescence of human epithelial cells. It is hoped that these studies will increase our understanding of the processes that cause cancer and aging and will lead to better methods to prevent, diagnose, and treat human disease.
Markus H Kuehn Ph.D.
My laboratory studies genetic factors that underlie or contribute to optic neuropathies - in particular glaucoma and the neurodegeneration associated with idiopathic intracranial hypertension (IIH). Data from our studies have shown that components of the complement system are synthesized in the retina in glaucoma and that activation of complement accelerates retinal ganglion cell death. In addition, variations in certain complement component genes appear to be associated with glaucoma. A second area of interest is IIH. The genetics of this condition and the cellular events that result in the degeneration of the retina are poorly understood. We are currently involved in a study designed to determine which genes are involved in the regulation of intracranial pressure and if certain genotypes are correlated with the development of the disease in human patients.
Anne E Kwitek Ph.D.
Common human diseases such as hypertension, diabetes and obesity can lead to serious complications such as heart attacks, congestive heart failure, kidney failure and early death. Both environmental and genetic factors contribute to these complex (multifactorial) diseases. Identifying their genetic component(s) will lead to better understanding of their dysfunctional mechanisms and improve our ability to prevent or more effectively treat their complications.
My laboratory uses physiological and comparative genomic approaches to identify genes and mechanisms leading to complex disease - hypertension, diabetes and obesity in particular - using both rat models and human populations. We use genetic linkage strategies to genetically map genes, and genetically unique rat strains to positionally clone and/or test candidate genes within a specific region of the genome. We then compare the genomes between the species, via comparative genomics, to translate the data from the rat to human and back again. Because the rat and human genes are 90% identical, it is likely the same genes or pathways will also play a role in many diseases.
