Genetics, Cell Biology and Anatomy

• NAME/TRAINING:

James D. Shull, Ph.D.

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ACADEMIC DEGREES:

Ph.D., Biochemistry, University of Wisconsin-Madison, 1984
Postdoctoral Fellow, McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, 1984-1987

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PROFESSIONAL APPOINTMENT

Ardith and Anna Von Housen Professor;
Chairman, Department of Genetics, Cell Biology and Anatomy;
Director, Center for Molecular Genetics and Genomics;
Professor, Eppley Cancer Institute;
Professor, Department of Pathology and Microbiology;
Co-leader, Molecular and Biochemical Etiology Program, UNMC Eppley Cancer Center

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• CONTACT INFORMATION:

Contact Name: James D. Shull, Ph.D.
Phone Number: 559-4633
e-mail address: jshull@unmc.edu

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• GRANT SUPPORT (as Principal Investigator only):

Project Title: Genetic Susceptibility to Estrogen-Induced Mammary Cancer
Principal Investigator: James D. Shull
Granting Agency: National Institutes of Health (R01-CA77876-11 to 15)
Period of Support: 7-1-08 to 5-31-13
Total Support: $1,774,412

Project Title: Characterization of Emca4, a genetic determinant of mammary cancer susceptibility in rat that is orthologous to a determinant of breast cancer risk in humans
Principal Investigator: James D. Shull
Granting Agency: Susan G. Komen Foundation
Period of Support: 8-1-08 to 7-31-11
Total Support: $559,996

Project Title: Genetics of Estrogen Regulated Feeding Behavior
Principal Investigators: James D. Shull and Roger Reidelberger
Granting Agency: UNMC and Creighton University
Period of Support: 7-1-07 to 6-30-09
Total Support: $100,000

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• PUBLICATIONS (last 3-5 years):

Gould, K.A., Tochacek, M., Schaffer, B.S., Reindl, T.M., Murrin, C.R., Lachel, C.M., VanderWoude, E.A., Pennington, K.L., Flood, L.A., Bynote’, K.K., Meza, J.L., Newton, M.A. and Shull, J.D.  Genetic Determination of Susceptibility to Estrogen-Induced Mammary Cancer in the ACI Rat: Mapping of Emca1 and Emca2 to Chromosomes 5 and 18.  Genetics 168:2113-2125, 2004.

Strecker, T.E., Spady, T.J., Kaufman, A.E., Shen, F., McLaughlin, M.T., Pennington, K.L., Schaffer, B.S., Gould, K.A., Meza, J.L. and Shull, J.D.  Genetic Bases of Estrogen-Induced Pituitary Tumorigenesis: Identification of Genetic Loci Determining Estrogen-Induced Pituitary Growth in Reciprocal Crosses between the ACI and Copenhagen Rat Strains.  Genetics 169:2189-2197, 2005.

Gould, K.A., Pandey, J., Lachel, C.M., Murrin, C.R., Flood, L.A., Pennington, K.L., Schaffer, B.S., Tochacek, M., McComb, R.D., Meza, J.L., Wendell, D.L. and Shull, J.D.  Genetic Mapping of Eutr1, a Locus Controlling Estrogen-Induced Pyometritis in the Brown Norway Rat, to RNO5.  Mammalian Genome, 16:854-864, 2005.

Pandey, J., Gould, K.A., McComb, R.D., Shull, J.D. and Wendell, D.L.  Localization of Eutr2, a Locus Controlling Susceptibility to DES-Induced Uterine Inflammation and Pyometritis, to Proximal RNO5 Using a Congenic Rat Strain.  Mammalian Genome, 16:865-872, 2005.

Gould, K.A., Strecker, T.E., Hansen, K.K., Bynoté, Peterson, K.A. and Shull, J.D.  Genetic Mapping of Loci Controlling Sensitivity to Diethylstilbestrol-Induced Thymic Atrophy in the Brown Norway Rat.  Mammalian Genome 17:451-464, 2006.

Shull, J.D., Lachel, C.M., Strecker, T.E., Spady, T.J., Tochacek, M., Pennington, K.L., Murrin, C.R., Meza, J.L., Schaffer, B.S., Flood, L.A. and Gould, K.A.  Genetic Bases of Renal Agenesis in the ACI Rat: Mapping of Renag1 to Rat Chromosome 14.  Mammalian Genome 17:751-759, 2006.

Schaffer, B.S., Lachel, C.M., Pennington, K.L., Murrin, C.R., Strecker, T.E., Tochacek, M., Gould, K.A., Meza, J.L., McComb, R.D. and Shull, J.D.  Genetic Bases of Estrogen-Induced Tumorigenesis in the Rat: Mapping of Loci Controlling Susceptibility to Mammary Cancer in a Brown Norway x ACI Intercross.  Cancer Research 66:7793-7800, 2006.

Adamovic, T., Roshani, L., Chen, L., Schaffer, B.S., Helou, K., Levan, G., Olsson, B. and Shull, J.D.  Nonrandom Pattern of Chromosome Aberrations in 17β-Estradiol-Induced Rat Mammary Tumors: Indications of Distinct Pathways for Tumor Development.  Genes, Chromosomes and Cancer 46:459-469, 2007.

Shull, J.D., Lachel, C.M., Murrin, C.R., Pennington, K.L., Schaffer, B.S., Strecker, T.E. and Gould, K.A.  Genetic Control of Estrogen Action in the Rat: Mapping of QTL Impacting Pituitary Lactotroph Hyperplasia in a BN x ACI Intercross.  Mammalian Genome 18:657-669, 2007.

Shull, J.D.  The Rat Oncogenome: Comparative Genetics and Genomics of Rat Models of Mammary Carcinogenesis.  Breast Disease, 28:69-86, 2007.

Kurz, S.K., Hansen, K.K., McLaughlin, M.T., Shivaswamy, V., Schaffer, B.S., Gould, K.A., McComb, R.D., Meza, J.L. and Shull, J.D.  Tissue Specific Actions of the Ept1, Ept2, Ept6 and Ept9 Genetic Determinants of Responsiveness to Estrogens in the Female Rat.  Endocrinology 149:3850-3859, 2008.

Aitman, T., Critser, J.K., Cuppen, E., Dominiczak, A., Fernandez, X.M., Flint, J., Gauguier, D., Geurts, A.M., Gould, M., Harris, P.C., Holmdahl, R., Hubner, N., Izsvak, Z., Jacob, H., Kuramoto, T., Kwitek, A.E., Marrone, A., Mashimo, T., Moreno-Quinn, C., Mullins, J., Mullins, L., Olsson, T., Riley, L., Saar, K., Serikawa, T., Shull, J.D., Szpirer, C., Twigger, S.N., Voigt, B. and Worley, K.  Progress and Prospects in Rat Genetics: A Community View.  Nature Genetics 40:516-522, 2008.

Guryev, V., Saar, K., Adamovic, T., Cook, S., Pravenec, M., Aitman, T., Jacob, H., Shull, J.D., Hubner, N. and Cuppen, E.  Distribution and Functional Impact of DNA Copy Number Variation in the Rat. Nature Genetics 40:538-545, 2008.

Ruhlen, R.L., Willbrand, D.M., Besch-Williford, C.L., Ma, L., Shull, J.D. and Sauter, E.R.  Tamoxifen Induces Regression of Estradiol-Induced Mammary Cancer in ACI.COP-Ept2 Rat Model.  Breast Cancer Research and Treatment, in press, 2008.

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• PREVIOUS GRADUATE STUDENTS/POST-DOCTORAL FELLOWS (present location):

Currently training one doctoral student and four postdoctoral fellows.

Former doctoral students:
Tracy Strecker, Ph.D., 2004; postdoctoral fellow at Baylor University
Martin Tochacek, Ph.D., 2002; postdoctoral fellow at Duke University
Djuana Harvell, Ph.D., 2001; postdoctoral fellow at Univ. Colorado
Thomas Spady, Ph.D., 1999; research scientist San Diego Zoo.
Mary Snyder, M.D., 1998; surgery fellow, University of Wisconsin-Madison.
Carla Shaw-Bruha, Ph.D., 1997; research scientist, Transgenomics, Inc.
Cindy Gilchrist, Ph.D., 1994; senior scientist, Genetics Computing Group, Univ. Wisconsin-Madison.

Former postdoctoral fellows/trainees:
Karen A. Gould, Ph.D., 1999-2003; Assistant Professor, University of Nebraska Medical Center
Athena M. Lemus-Wilson, Ph.D., 1995-1997; currently Assistant Prof., Midwestern University, Chicago, IL.
Dominic Cosgrove, Ph.D., 1991; Associate Prof., Creighton, University, Omaha, NE.

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• CURRENT RESEARCH PROJECTS:

We utilize genetics-, genomics- and molecular biology-based approaches to study estrogen action in the regulation of cell proliferation and survival and determine the mechanisms through which estrogens contribute to development neoplasia, including breast cancer.  We have developed a novel rat model for estrogen-induced mammary cancer and have used this model in a variety of different genetic crosses to identify the genetic loci that modify susceptibility to mammary cancer.  Seven such genetic modifiers of mammary cancer risk have been identified, Emca1 through Emca7.  We are currently utilizing the recently released sequence for the rat genome to identify the genes that reside within each of the Emca loci and determine susceptibility to mammary cancer.  Data from our rat models form the bases for studies to assess the roles of the human homologs as determinants of breast cancer risk as well as studies to identify effective strategies to p revent and treat breast cancer.  In other studies, we have identified several genetic loci that modify estrogen action in the regulation of anterior pituitary function, uterine inflammation and thymic atrophy. 

In another project we are characterizing a rat model of unilateral renal agenesis, which is the absence of one kidney.  Approximately one in a thousand humans are born with a single kidney.  We have used our rat model of renal agenesis to map within the rat genome a major genetic determinant of renal agenesis and are s initiating studies to identify the gene responsible for this trait and to define its role in renal agenesis in humans.

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• SPECIALIZED LABORATORY/CLINICAL RESEARCH RESOURCES:

We have developed a series of congenic rat lines, each of which carries a single genetic determinant of breast cancer susceptibility identified in our laboratory.  These rat lines allow us to fine map within the rat genome the precise locations of the Emca modifiers of breast cancer susceptibility and to predict the locations of these genes within the human genome for comparative studies.

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