Dr. Gerard Schellenberg is the Associate Director for Research of the Geriatrics Reseach Education and Clinical Center at the Veterans Affairs Puget Sound Health Care System in Seattle. He is also a Research Professor in the Division of Gerontology and Geriatric Medicine in the Department of Medicine at the University of Washington in Seattle. He also has a joint appointment in the Division of Neurogenetics, Department of Neurology and an adjunct appointment in the Department of Pharmacology at the University of Washington.
Dr. Schellenberg is a molecular geneticist with extensive experience in human disease research. He has worked on the genetics of numerous different genetics diseases. In collaborative work with Ellen Wijsman he mapped an cloned the gene for Werner's syndrome, is a rare autosomal recessive disorder related to premature aging. In other work with Dr. Wijsman, he and collaborators mapped and cloned the Presenilin 2 gene for Alzheimer's disease. Other work includes identifying the gene (tau) and mutations responsible for frontotemporal dementia with parkinsonism - chromosome 17 type. He also works on complex disorders such as late-onset Alzheimer's disease, schizophrenia, and autism. His laboratory is capable of several high-throughput genotyping platforms and DNA sequencing. An extension of his genetic work involves animal models related to the diseases that he studies the genetics of. In particular, he has generated mouse and C. elegans models of tau-related diseases.
Alzheimer's Disease. Dr. Schellenberg has been working on the genetics and molecular biology of Alzheimer's disease since 1985. In 1987, he and his co-workers identified ApoCII as a potential candidate region for late-onset Alzheimer's disease. This gene is approximately 30 kb from ApoE which was subsequently identified as a genetic susceptibility gene for late-onset AD. Working on early-onset Alzheimer's disease, in 1992, Dr. Schellenberg and co-workers identified a region on chromosome 14 that contained a gene for early-onset familial AD. This work was published in Science. This gene, presenilin 1, was later cloned by another group and is known to be the gamma-secretase enzyme that produces the Abeta peptide found in Alzheimer's disease amyloid plaques. In 1995, Dr. Schellenberg's group genetically mapped another early-onset familial AD gene to chromosome 1 and cloned the responsible gene. This gene, presenilin 2, is closely homologous to presenilin 1. The mapping and cloning were published back-to-back in Science. Both presenilin 1 and 2 are now extensively studied by numerous laboratories world-wide to understand the pathogenesis of AD.
Frontotemporal Dementia and Tau. Dr. Schellenberg, has also worked on frontotemporal dementia, an autosomal dominant neurodegenerative disorder. In 1998, Dr. Schellenberg's group and 2 other groups simultaneously reported that mutations in the gene for tau caused this disease. Tau is the protein that makes up neurofibrillry tangles. The identification of tau mutations clearly established that alterations in tau could induce neurodegeneration. Also, the mutations demonstrate that neurofibrillary tangles are an important part of neurodegeneration observed in AD, and numerous other diseases where neurofibrillary tangles are observed. The implications of this work extend far past familial frontotemporal dementia where the original tau mutations were identified. Tau mutations are now being used extensively by many of the laboratories in the world to understand the role of tau and neurofibriillary tangles in neurodegenerative disease.
Amyotrophic lateral sclerosis/parkinsonism dementia - Guam type. Recently work has begun in Dr. Schellenberg's laboratory on a unique form of amyotrophic lateral sclerosis/parkinsonism dementia complex (ALS/PDC) found exclusively in the Chamorro people of Guam. Clinically the ALS for of the disease is indistinguishable from ALS seen in other parts of the world. However, autopsies of Chamorro ALS subjects show extensive neurofibrillary tangles in the hippocampus, neocortex and other select regions of the brain. The PDC form of the disease is mild parkinsonism typically accompanied by dementia. Work is now underway to identify the gene(s) responsible for this disease.
Schizophrenia Genetics. Another project recently initiated is work on the genetics of schizophrenia. Dr. Schellenberg is collaborating with Dr. Ming Tsuang on genetic analysis of 160 families with 2 or more affected sibs and/or close relatives.
Autism Genetics. Dr. Schellenberg's laboratory is the study of the genetics of autism. This disorder is genetically and phenotypically complex and is probably the result of multiple inherited factors. Work is in progress to attempt to identify the genes responsible for this disease. Dr. Schellenberg is working with Dr. Geri Dawson to assemble multiplex families with 2 or more affected subjects with autism. The immediate goal is to identify, sample and characterize 250 such families. Presently, 110 families have been fully processed. Both parents, all affected sibs, and 1 normal sib is being fully phenotyped for this study. Sibling linkage analyses utilizing phenotypic and genotype data from all family members of multiple-incidence families will be used in order to increase statistical power of detecting genes responsible for autism via sibling linkage analysis. Quantitative trait linkage analysis utilizing quantitative assessments of autistic traits from all family members of multiple-incidence families will be used to enhance ability to identify autism loci.
Awards. In 1994, he was awarded the Potamkin Prize for Alzheimer's Disease Research by the Potamkin Foundation and the American Academy of Neurology. In 1995, he, Thomas Bird, and Ellen Wijsman, were awarded the Metropolitan Life Foundation Award for Medical Research.
