Principal Investigator/Program Director: Meyskens, Frank L. 5P30CA062203-17 BIOGRAPHICAL SKETCH Provide the following information for the key personnel and other significant contributors. Follow this format for each person. DO NOT EXCEED FOUR PAGES. NAME POSITION TITLE MacGregor, Grant Ralph Associate Professor of Developmental and Cell Biology eRA COMMONS USER NAME GRANTMACGREGOR EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.) INSTITUTION AND LOCATION DEGREE (if applicable) MM/YY Edinburgh University, Scotland B.Sc. (Hons) 06/82 Sussex University, Falmer, England D.Phil. 06/86 Baylor College of Medicine, Houston, TX Post-Doc 06/86 – 06/93 FIELD OF STUDY Molecular Biology DNA Repair & Mutagenesis Developmental Genetics A. Personal Statement I am an Associate Professor in the Department of Developmental & Cell Biology. My lab investigates the mechanism of action of the novel Fndc3 gene family, required for a wide range of developmental and homeostasis processes in mammals using the mouse as a model genetic system. I have over twenty-five years experience in generation and analysis of genetically modified mice. At a previous institution, I ran a Transgenic Mouse Core Facility for ten years. In 2009 I succeeded Dr. Arthur Lander as Scientific Director of the UCI Transgenic Mouse Core Facility (TMF). Since then we have worked to reinvigorate the TMF's service function with a view to serving the cancer research community by (a) increasing its efficiency, (b) introducing new services and (c) revising the TMF website to make it easier for Cancer Center Faculty to gain access to information and materials required for their research. B. Positions and Honors Positions and Employment 1986-1989 Postdoc research with C. Thomas Caskey, MD in gene therapy. 1990-1992 Postdoc research with Paul Overbeek PhD in mammalian development and reproduction. 1992-1993 Postdoc research with Philippe Soriano PhD in mammalian development and reproduction. 1993-1996 Assistant Professor, Dept. of Genetics and Molecular Medicine, Emory University School of Medicine, Atlanta, GA. 1997-2002 Associate Professor (tenured), Center for Molecular Medicine; Adjunct Associate Professor, Dept Human Genetics & Dept Cell Biology; Emory University School of Medicine. 2002Associate Professor (tenured), Dept Developmental and Cell Biology; Center for Molecular and Mitochondrial Medicine and Genetics, Developmental Biology Center; University of California, Irvine, CA. Other Experience and Professional Memberships 1993Member, Society for Study of Reproduction, Society for Developmental Biology, Genetics Society of America. 2003Member, American Society for Cell Biology. 1999-2002 Member, NSF Center for Behavioral Neuroscience, Emory University, Atlanta, GA. 1993-2002 Director, Transgenic Mouse Core Facility, Center for Molecular Medicine, Emory University, Atlanta, GA. 2004-2008 Associate Director, Optical Biology Core, Developmental Biology Center, University of California, Irvine, CA. 2009Scientific Director, Transgenic Mouse Core Facility, University of California, Irvine, CA. 1995, 1999 ad hoc reviewer American Cancer Society; Develop, Diff and Cancer Study Section. PHS 398/2590 (Rev. 06/09) Page 34 Biographical Sketch Format Page Meyskens, Frank L. 5P30CA062203-17 2002, '07, '10 ad hoc reviewer, Research Grants Council, Hong Kong, 2003 ad hoc reviewer, Canadian Institute for Health Research. 2003, '04 ad hoc reviewer, National Institute of Health, REB SRG. 2008-2010 ad hoc reviewer, National Institute of Health, CMIR IRG. 2008, '09 ad hoc reviewer, for Genome BC, Canadian Genome Funding Agency. 2011 ad hoc reviewer for Netherlands Government Research Agency Principal Investigator/Program Director: Honors 1982-1985 1986-1989 2004 2006 Competitive MRC Graduate Research Studentship. Competitive Arthritis Foundation Post-Doctoral Fellowship. UCI Chancellor's Award for Excellence in Fostering Undergraduate Research. UCI Biological Sciences Golden Apple Award for Teaching B. Selected peer-reviewed publications (in chronological order: from total of 44). Most relevant to the current application 1. MacGregor, G.R., Zambrowicz, B.P. and Soriano, P. (1995). Tissue non-specific alkaline phosphatase is expressed in both embryonic and extra-embryonic lineages during mouse embryogenesis but is not required for migration of primordial germ cells. Development, 121, 1487-1496. PMID: 7789278 2. Waymire, K.G., Jaje, J.M., Mahuren, D., Guilarte, T., Coburn, S.P. and MacGregor, G.R. (1995). Mice lacking tissue non-specific alkaline phosphatase die from seizures due to defective metabolism of vitamin B-6. Nat. Genet., 11, 45-51. PMID: 755031 3. Graham, B.H., Waymire, K.G., Cottrell, B., Trounce, I.A., MacGregor, G.R. and Wallace, D.C. (1997). A mouse model for mitochondrial myopathy and cardiomyopathy resulting from a deficiency in the heart skeletal muscle isoform of the adenine nucleotide translocator. Nat. Genet., 16, 226-234. PMID: 9207786 4. Sligh, J.E., Levy, S.E., Waymire, K.G., Allard, P., Dillehay, D.L., Nusinowitz, S., Heckenlively, J.R., MacGregor, G.R. and Wallace, D.C. (2000). Maternal germ line transmission of mutant mitochondrial DNAs from embryonic stem cell derived chimeric mice. Proc. Natl. Acad. Sci (USA), 97, 14461-14466. PMID: 11106380 5. MacGregor, G.R. (2002). An extreme bias in the germ line of XY C57BL/6 <-> XY FVB/N chimeric mice. Reproduction 124, 377-386. PMID: 12201811 Additional recent publications of importance to the field (in chronological order) 1. Ross, A., Waymire, K.G., Moss, J.E., Parlow, A.F., Skinner, M.K., Russell, L.D. and MacGregor, G.R. (1998). Testicular degeneration in Bclw deficient mice. Nat. Genet., 18, 251-256. PMID: 9500547 2. Metcalfe, A.D., Gilmore, A., Klinowska, T., Oliver, J., Valentijn, A.J., Brown, R., Ross, A.J., MacGregor, G.R., Hickman, J.A. and Streuli, C.H. (1999). Developmental regulation of BCL2 family protein expression in the involuting mammary gland. J. Cell Sci., 112, 1771-1783. PMID: 10318769 3. Lindsten, T., Ross, A.J., Gottlieb-King, A., Zong, W-X., Rathmell, J.C., Shiels, H.A., Ulrich, E., Waymire, K.G., Mahar, P.L., Frauwirth, K., Chen, Y., Wei, M., Eng, V.M., Adelman, D.M., Simon, M.C., Ma, A., Golden, J.A., Evan, G. Korsmeyer, S.J., MacGregor, G.R. and Thompson, C.B. (2000). The combined functions of the pro-apoptotic BCL2 family members BAK and BAX are essential for the normal development of multiple tissues. Mol. Cell, 6, 1389-1399. PMID: 11163212 4. Wei, M.C., Zong, W-X., Cheng, E.H-Y., Lindsten, T., Panoutsakopoulou, T., Roth, K.A., Ross, A.J., MacGregor, G.R., Thompson, C.B. and Korsmeyer, S.J. (2001). Pro-apoptotic BAX and BAK are essential for mitochondrial dysfunction and death following diverse apoptotic signals. Science, 292, 727-730. PMID: 11326099 5. Zong, W-X., Lindsten, T., Ross, A.J., MacGregor, G.R. and Thompson, C.B. (2001). BH3-only proteins that bind pro-survival BCL2 family members fail to induce apoptosis in the absence of BAX and BAK. Genes Dev., 15, 1481-1486. PMID: 11410528 6. Ross, A.J., Amy, S.P., Mahar, P.L., Lindsten, T., Knudson, C.M., Thompson, C.B., Korsmeyer, S. J., MacGregor, G.R. (2001). BCLW mediates survival of post-mitotic Sertoli cells by regulating BAX activity. Dev. Biol., 239, 295-308. PMID: 11784036 PHS 398/2590 (Rev. 06/09) Page 35 Biographical Sketch Format Page Meyskens, Frank L. 5P30CA062203-17 7. Kokoszka, J.E., Waymire, K.G., Levy, S.E., Sligh, J.E., Cai, J.-Y., Jones, D.P., MacGregor, G.R., and Wallace, D.C. (2004). The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore. Nature, 427, 461-465. PMID: 14749836 8. Obholz. K.L., Akopyan. A.A., Waymire, K.G., MacGregor, G.R. (2006). FNDC3A is required for adhesion between spermatids and Sertoli cell in mice. Dev. Biol., 298, 498-513. PMID: 16904100 9. Fan, W.-W., Waymire, K.G., Narula, N., Li, P., Rocher, C., Coskun, P.E., Vannan, M.A., Narula, J., MacGregor, G.R., Wallace, D.C. (2008). A mouse model of mitochondrial disease reveals germline selection against severe mtDNA mutations. Science, 319, 958 - 962. PMID: 18276892 10. Nicholson, A., Reifsnyder, P., Malcolm, R., Lucas, C., MacGregor, G.R., Zhang, W. and Leiter E. (2010). Comparison of diet induced obesity responsiveness of two C57BL/6 substrains expressing a wildtype or mutant Nicotinamide Nucleotide Transhydrogenase (Nnt) gene. Obesity, 18, 1902 - 1905. PMID: 20057372 Principal Investigator/Program Director: C. Research Support Ongoing Research Support 5P30CA062203-16 (Meyskens) 02/01/09-01/31/14 NIH/NCI University of California Irvine Cancer Center Support Grant Infrastructure and Research award to support cancer research at UC Irvine and beyond. Role: Director Transgenic Mouse Facility 1R21HL 102862-01 (MacGregor) 04/01/10 – 03/31/12 NIH / NHLBI, NICHD (dual) Function of FNDC3B in cardiovascular and pulmonary development The goal of this project is to investigate how loss of FNDC3B in mice results in neonatal death due to cardiovascular and pulmonary dysfunction. Role: PI Completed Research Support (past three years only) 1UO1-HD045913-01 (MacGregor) 12/01/03 - 11/30/09 NIH / NICHD A novel gene required for Sertoli-Spermatid adhesion The major goal of this project was a functional analysis of a novel gene product that is required for adhesion between elongating spermatids and Sertoli cells in the testis and to evaluate its candidacy as a target for development of novel approaches to male contraception. Role: PI RS1-00416-1 (MacGregor) 05/01/07 – 06/30/10 California Institute for Regenerative Medicine (CIRM) Seed Research Grant Program Production of Oocytes from Human ES Cells The goal of this project was to develop methods to convert human ES cells into primordial oocyte follicles in vitro. Role: PI RC1-00110-1 (Donovan) 05/01/07 – 07/31/11 California Institute for Regenerative Medicine (CIRM) Comprehensive Research Grant Program Improved hES Cell Growth and Differentiation P.I Donovan The goal of this project is development of reliable methods for genetically modifying hES cells as a tool to study their growth and differentiation as well as to develop methods for producing differentiated cell types for further studies. Role: Collaborator PHS 398/2590 (Rev. 06/09) Page 36 Biographical Sketch Format Page