James David Fackenthal, PhD


I received a B.S in Biology/Geology in 1983 from the University of Rochester. Afterward I worked for a couple of years as lab tech/non-matriculated graduate student, studying pattern formation in Drosophila. I continued Drosophila work as a graduate student with Elizabeth Raff at Indiana University (Ph.D., 1993), this time focusing on tubulin structure and microtubule function during spermatogenesis. In 1993 I began a postdoctoral fellowship at the University of Chicago, applying my interest in germ cell formation to the study of meiotic regulation in yeast. As I learned more about cell cycle regulation I became interested in cancer genetics, so now I work with Funmi Olopade at the University of Chicago Department of Medicine, where we study protein structure and splicing regulations of the breast cancer susceptibility genes BRCA1 and BRCA2, as well as the role of the PTEN gene in tumor progression.

Inherited susceptibility to breast and ovarian cancer is primarily caused by germline mutations in BRCA1 or BRCA2. These tumor suppressor genes encode large proteins with numerous functions, including DNA repair, transcription, cell cycle control, and mitotic fidelity. However, the protein structural requirements for these functions are poorly characterized, and the transcription and splicing regulation of these genes is not well understood. We are therefore assembling the complete spectrum and frequency of BRCA1/2 sequence variants in 1, 000 breast cancer patients and 1, 000 control subjects from Nigeria. We have found that this population has the greatest diversity of gene variations identified thus far, and includes alleles already identified in descendant populations. This collection of alleles, genotypes, and resulting haplotypes will be a valuable resource for probing variations in BRCA1/2 gene expression levels, altered regulation of splice variants, and protein activities. Initial studies using this collection have established haplotype structures that are similar to those seen in other populations, but are extended to include additional markers. We are also using these markers in conjunction with nonsense-mediated message decay assays to characterize changes in splice variant frequencies associated with deleterions mutations. Finally, we are collaborating with a group at Argonne National Laboratories to identify and characterize the structural domains of the BRCA1 and BRCA2 proteins, using our collection of variants to test the physiological consequences of amino acid substitutions in specific functional domains.

CV for James David Fackenthal, PhD

Education
B.S. in Biology/Geology, University of Rochester, Department of Geology, May 1983.
Ph.D. in Molecular, Cellular, and Developmental Biology, Indiana University, Department of Biology, November 1993. Dissertation Title: Structural and Functional Analysis of the Testis-Specific Beta-2-Tubulin in Drosophila melanogaster.
Awards
Predoctoral N.I.H. Training Grant in Genetics, Department of Biology, Indiana University, January 1988-December 1990.
N.I.H Postdoctoral Fellowship, October 1994-September 1997.

Research and Related Experience
Laboratory Technician and non-matriculated graduate student, University of Rochester, Department of Biology, March 1984-August 1986.

Graduate Student Associate Instructor, Indiana University, Department of Biology, September 1986-August 1987.

Graduate Student Research Associate, Indiana University, Department of Biology, September 1987- November 1993.

Postdoctoral Fellow, University of Chicago, Department of Molecular Genetics and Cell Biology, November 1993-September 1997.

Postdoctoral Research Associate, University of Chicago, Department of Molecular Genetics and Cell Biology, September 1997-April 1999.

Senior Research Technologist, University of Chicago, Department of Medicine, April 1999-Sept. 2001.

Research Associate (Instructor), University of Chicago, Department of Medicine, Sept. 2001-August 2002.

Research Associate (Assistant Professor), University of Chicago, Department of Medicine, Sept. 2002-present.

Membership in Professional Societies
American Association for the Advancement of Science
American Association for Cancer Research
American Society for Cell Biology
Genetics Society of America

Awards to trainees
Basic Science Award to Kevin Long (U of Chicago Medical Student), Division of Biological Sciences and the Pritzker School of Medicine Eighth Annual Summer Research Forum, 2002.

Publications
1. Stephenson, E.C., Chao, Y., and Fackenthal, J.D. (1988) Molecular Analysis of the swallow Gene of Drosophila melanogaster. Genes and Development 2:1655-1665.
2. Fackenthal, J.D., Turner, F.R., and Raff, E.C. (1993) Tissue-specific Microtubule Functions in Drosophila Spermatogenesis Require the Beta-2-tubulin Isotype-Specific Carboxy Terminus. Developmental Biology 158: 213-227.
3. Fackenthal, J.D., Hutchens, J.A., Turner, F.R., and Raff, E.C. (1995) Structural Analysis of Mutations in the Drosophila Beta-2-Tubulin Isoform Reveals Regions in the Beta-tubulin Molecule Required for General and Tissue-Specific Microtubule Functions. Genetics 139:267-286.
4. Raff, E.C., Fackenthal, J.D., Hutchens, J.A., Hoyle, H.D., and Turner, F.R. (1997) Microtubule Architecture Specified by a ß-Tubulin Isoform. Science 275: 70-73.
5. Gao, Q., Tomlinson, G., Das, S., Cummings, S., Sveen, L., Fackenthal, J., Schumm, P., and Olopade, O. (2000) Prevalence of BRCA1 and BRCA2 mutations Among Clinic-based Populations of African American Women with Breast Cancer. Human Genetics 107(2):186-191.
6. Gao, Q*.,Adebamowo, C.,* Fackenthal, J.*, Das, S., Sveen, L., Falusi, A., Olopade, O. (2000) Protein Truncating BRCA1 and BRCA2 mutations in African women with pre-menopausal breast cancer. Human Genetics 107(2):192-194.
7. Fackenthal, J, Marsh, D.J., Richardson, A-L., Cummings, S.A., Eng, C., Robinson, B., and Olopade, O.I. (2001) Male Breast Cancer in Cowden Syndrome Patients with Germline PTEN Mutations. J Med Genet 38: 159-164.
8. Fackenthal, J., Cartegni, L., Krainer, A., and Olopade, O.I. (2002) BRCA2 T2722R is a deleterious allele that causes exon skipping. Am J Hum Genet 71:625 *equal contribution

Manuscripts in Preparation
1. Nanda, R., Fackenthal, JD, Grushko, T., Schumm, P, Pomykala, H., and Olopade, OI. (in preparation) Clinicopathological features of BRCA1 and BRCA2-associated tumors.
2. Fackenthal, JD, Sveen, L.,Gao, Q., Adebamowo, C., Das, S., and Olopade, OI. (in preparation) Complete allelic analysis of BRCA1 and BRCA2 variants in young African breast cancer patients.
3. Fackenthal, JD, Hagos, F., Kretzschmar, E., Lee G, Neuhausen, S., Das, S., and Olopade, OI. (in preparation) Contribution of PTEN mutations to male breast cancer.

Invited Reviews
1. Olopade, O. and Fackenthal, J.D. (2000) Breast Cancer Genetics: Implications for Clinical Practice. Hematology/Oncology Clinics of North America, vol. 14 (3). Metcalfe D.D. and Soter, N.A., (eds.) W.B. Saunders, Philadelphia. 705-725.
2. Fackenthal, J.D. and Olopade, O. (2000) Inherited Susceptibility to Breast and Ovarian Cancer. Advances in Oncology 16(3):10-18
3. Olopade, O.I. Fackenthal, J.D., Dunston, G., Tainsky, M., Collins, F., Broome, C. (submitted to Cancer). African American Breast Cancer Summit Position Paper.
4. Fackenthal,, JD and Olopade, OI (in preparation for Endocrine-Related Cancer). Cancer genetics of BRCA1 and BRCA2.

Published Abstracts and Presentations
1. Fackenthal, J.D., Hutchens, J.A., and Raff, E.C. (1990) Analysis of Various B2t Alleles Reveals Regions of Beta-2-tubulin Required for Specific Functions. 31st Annual Drosophila Research Conference (poster).
2. Fackenthal, J.D. and Raff, E.C. (1990) Mutations in the Testis-specific Beta-2-tubulin Gene. Midwest Drosophila Conference (slide talk).
3. Fackenthal, J.D. and Raff, E.C. (1990) Expression of a Beta-tubulin Lacking the Diverged Carboxy Terminus in Drosophila melanogaster. J. Cell Biol. 111:174a. The American Society for Cell Biology 30th Annual Meeting (poster and published abstract).
4. Fackenthal, J.D. and Raff, E.C. (1991) The Carboxy Terminus of the Drosophila Beta-2- tubulin is Required for Stability and a Tissue-specific Function. J. Cell Biol. 115:372a. The American Society for Cell Biology 31st Annual Meeting (slide talk and published abstract).
5. Fackenthal, J.D. and Raff, E.C. (1991) The Role of the Beta-tubulin Carboxy Terminus in Spermatogenesis. 32nd Annual Drosophila Research Conference (poster).
6. Fackenthal, J.D., Turner, F.R., and Raff, E.C. (1993) Tissue-specific microtubule functions in Drosophila spermatogenesis require the Beta-2-tubulin isotype-specific carboxy terminus. 34th Annual Drosophila Research Conference (poster).
7. Raff, E.C., Hoyle, H.D., Dettman, R.W., Fackenthal, J.D., Hutchens, J.A., and Turner, F.R. (1996) Genetic Analysis of Microtubule Function in Drosophila. Dev. Biol. 175:376. Society for Developmental Biology 1996 Annual Symposium (presentation with published abstract).
8. Henninger, L., Fackenthal, J.D., and Esposito, R.E. (1996) SPO13 and Control of Meiotic Chromosome Segregation in Saccharomyces cerevisiae. 1996 Yeast Genetics and Molecular Biology Meeting (poster).
9. Fackenthal, J.D. and Esposito, R.E. (1998) CDC28 Regulates the Levels of Spo13p, a Nuclear Phosphoprotein Required for Two-Division Meiosis in Saccharomyces cerevisiae. 1998 Yeast Genetics and Molecular Biology Meeting (slide talk, GSA Travel Award).
10. Olopade, O.I. and Fackenthal, J.D. (2000) Inherited Susceptibility to Breast Cancer. American Association for Cancer Research, Ninety-First Annual Meeting (slide talk with published abstract)
11. Fackenthal, J.D., Gao, Q., Sveen, L., Jensen, J., Adebamowo, C., Das, S., and Olopade, O.I. (2000). Frequency of BRCA1 and BRCA2 mutations in young African breast cancer patients. American Association for Cancer Research, Ninety-First Annual Meeting (poster with published abstract)
12. Fackenthal, J.D., Gao, Q., Sveen, L., Jensen, J., Adebamowo, C., Das, S., and Olopade, O.I. (2000) BRCA1/2 missense mutations in African and US breast cancer populations. Keystone Symposium: Advances in Human Breast and Prostate Cancer (poster)
13. Lee G, Fackenthal, JD, S Neuhausen and Olopade, OI. (2001) Contribution of PTEN mutations to male breast cancer. Midwest Central Society meeting, 2001 (poster)
14. Fackenthal, J.D., Sveen, L., Kretzschmar, E., Das, S., Adebamowo, C., and Olopade, OI. (2001) BRCA1/2 Mutations in African Breast Cancer Patients. Third Annual Workshop on the Function of BRCA1 and BRCA2, Breakthrough Breast Cancer, Cambridge. (poster)
15. Fackenthal, JD, Adebamowo, C., Ogundiran, T., and Olopade, OI. (2002) Analysis of BRCA2 exon splice enhancer mutations. American Association for Cancer Research, Ninety-Third Annual Meeting (poster with published abstract)
16. Fackenthal, J., Lee, G., Hagos, F., Kretzschmar, E., Das, S., Neuhausen, S., and Olopade, OI. (2002) PTEN mutations are associated with male breast cancer. American Association for Cancer Research, Ninety-Third Annual Meeting (platform talk with published abstract)
17. Byrd, J., Fackenthal, J., Hagos, F., and Olopade, OI. (2002) Loss of heterozygosity on chromosome 16q21-24 in familial and sporadic acute myeloid leukemia. American Association for Cancer Research, Ninety-Third Annual Meeting (poster with published abstract)