Research efforts in our laboratory focus on those mechanisms which influence human genome stability. Specific areas of interest include chromatin structure/function, the role of genomic instability in human disease, the repair of DNA damage, and the evolutionary conservation of such genome stabilizing mechanisms. Numerical and/or structural changes in the genome have been associated with a broad spectrum of human maladies, including cancer and aging. There are a number of heritable human disorders that exhibit these clinical features and also exhibit cellular phenotypes consistent with defects in the maintenance of genomic integrity. Such disorders include xeroderma pigmentosum, ataxia telangiectasia, Bloom syndrome, Roberts syndrome and Progeria. Analysis of these disorders offers a unique avenue to a better understanding of those normal mechanisms which stabilize the human genome, as well as a means to identify how dysfunction contributes to these important disease processes. We have utilized the transfer of single, normal human chromosomes to cells from such disorders to map loci, which correct associated mutant phenotypes. This strategy has facilitated the cloning of specific genes involved in some disorders and is currently being used to map genes involved in others. One of our long-term interests has been Bloom syndrome, a disorder associated with spontaneous genomic instability and a predisposition to a very broad spectrum of cancers. The Bloom syndrome gene is in hand and a mouse model has been established. Another interest is the developmental disorder Roberts syndrome where we have recently mapped a gene which complements an associated defect in chromatin structure. New efforts are directed toward the disorder Progeria with strategies devised to map and identifying the defective gene(s). Finally, in collaboration with Dr. Skip Garner of the Center for Biomedical Inventions, we have developed a new Hyperspectral Imaging Microscope, an instrument useful in the analysis of chromosome instability in cancer cells. We are currently expanding the application of this instrument into projects focused on the early detection of cancer and automated analysis for histopathology.
RESEARCH INTERESTS
Human Chromosome Instability
DNA Repair
Human Genome Structure and Function
RECENT PUBLICATIONS
Makio Shozu M, Sebastian S, Takayama K, Hsu W-T, Schultz RA, Neely K, Bryant M, Bulun SE., "Estrogen Excess Associated with Novel Gain-of-Function Mutations Affecting the Aromatase Gene" New England Journal of Medicine, 348:1855-1865, Summer 2003
Huebschman ML. Schultz RA. Garner HR., "Characteristics and capabilities of the Hyperspectral Imaging Microscope." IEEE Engineering in Medicine & Biology Magazine., 21:104-117, 2002
International Human Genome Sequencing Consortium., "Initial Sequencing and Analysis of the Human Genome." Nature, 409:860-921, 2001
Wheeler RB, Sharp JD, Schultz RA, Joslin JM, Williams RE, Mole SE., "The Gene Mutated in Variant Late-Infantile Neuronal Ceroid Lipofuscinosis (CLN6) and in nclf Mutant Mice Encodes a Novel Predicted Transmembrane Protein." American Journal of Human Genetics, 70:537-542, 2002
Muneer S. Ramalingam V. Wyatt R. Schultz RA. Minna JD. Kamibayashi C., "Genomic organization and mapping of the gene encoding the PP2A B56 gamma regulatory subunit" Genomics, 79:344-348, 2002
SIGNIFICANT PUBLICATIONS
International Human Genome Sequencing Consortium., "Initial Sequencing and Analysis of the Human Genome." Nature, 409:860-921, Fall 2001
Schultz RA, Nielsen T, Zavaleta JR, Ruch R, Wyatt R, Garner HR., "Hyperspectral Imaging: A novel approach for microscopic analysis." Cytometry., 43:239-247, 2001
Luo G, Santoro I, McDaniel LD, Nishijima I, Mills M, Youssoufian H, Vogel H, Schultz RA, Bradley A., "Cancer predisposition caused by elevated mitotic recombination in Bloom mice." Nature Genetics, 26:424-429, 2000
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