Grant MacGregor

Picture of Grant MacGregor
Associate Professor, Developmental & Cell Biology
School of Biological Sciences
Scientific Director, UCI Transgenic Mouse Facility
Associate Member, Chao Family Comprehensive Cancer Center
Member, Developmental Biology Center
D.Phil., University of Sussex, 1986, Radiation Mutagenesis & DNA Repair
B.Sc. (Hons), Edinburgh University, 1982, Molecular Biology
Phone: (949) 824-8253
University of California, Irvine
Developmental and Cell Biology
4213 McGaugh Hall
Mail Code: 2300
Irvine, CA 92697
Research Interests
Mammalian reproduction, development & homeostasis
Academic Distinctions
Honorary Membership, International Golden Key Society.

Honoree of Kappa Alpha Theta / Sigma Phi Epsilon "Apple Polishing" – selected by undergraduate students as 'Teacher that has made a great impact on our college career'.

Golden Apple Award for Excellence in Teaching, School of Biological Sciences, UC Irvine.

UCI Chancellor's Award for Excellence in Fostering Undergraduate Research.

1986 – 1989
Arthritis Foundation Post-Doctoral Fellowship.

1982 – 1985
UK MRC Graduate Research Studentship.
2002 - present
Associate Professor (Tenured), Department of Developmental & Cell Biology, School of Biological Sciences, UC Irvine, Irvine, CA

1999 - 2002
Associate Professor (Tenured) Center for Molecular Medicine; Adjunct Professor, Dept Human Genetics, Dept Cell Biology, Emory University School of Medicine, Atlanta, GA

1993 - 1999
Assistant Professor, Dept. of Genetics and Molecular Medicine, Emory University School of Medicine, Atlanta, GA.

Post-doctoral Fellow, Laboratory of Philippe Soriano Ph.D., Division of Molecular Medicine, Fred Hutchinson Cancer Research Center, Seattle, WA.

Post-doctoral Fellow, Laboratory of Paul Overbeek Ph.D., Dept of Cell Biology, Baylor College of Medicine, Houston, TX.

Post-doctoral Fellow, Laboratory of C. Thomas Caskey M.D., Institute for Molecular Genetics (now Human and Molecular Genetics), Baylor College of Medicine, Houston, TX
Research Abstract
Fibronectin type-III domain containing 3 (FNDC3) proteins are unique to higher eukaryotic organisms (i.e. some Diptera, urochordates and chordates). Humans have two FNDC3 genes, mice have three (one X-linked), fish have four and Drosophila and Ciona each has one. FNDC3 proteins are composed of a proline-rich N-terminus containing multiple consensus binding sites for WW-domain containing proteins. FNDC3 proteins also have eight or nine type-III fibronectin domain repeats and a hydrophobic carboxy terminus that functions as a tail-anchoring membrane domain. FNDC3 proteins are expressed in a wide range of cell types where they are localized to the cytosolic face of specific membrane compartments including the acrosome, lipid droplets, and plasma membrane. Current models predict that FNDC3 proteins function as scaffolding molecules to regulate sub-cellular localization of WW-domain proteins. Functional studies in mice, mammalian cells in vitro, and Drosophila have revealed essential functions for FNDC3 proteins in a wide range of processes.
(Reverse Chronological)
Journals, Peer-Reviewed
Strong MK, Southwell AL, Yonan JM, Hayden MR, MacGregor GR, Thompson LM, Steward O. (2013) Age-dependent resistance to excitotoxicity in Htt CAG140 mice and the effect of strain background. Journal of Huntington's Disease 2, 221-241.

Lin CS, Sharpley MS, Fan WW, Waymire KG, Sadun AA, Carelli V, Ross-Cisneros FN, Baciu P, McManus MJ, Pan BX, Gil DW, MacGregor GR, Wallace DC (2012) Mouse mtDNA mutant model of Leber hereditary optic neuropathy. Proc. Natl. Acad. Sci. (USA)109, 20065 - 20070.

Sharpley MS, Marciniak C, Eckel-Mahan K, McManus M, Waymire KG, Crimi M, Lin CS, Masubuchi S, Friend N, Koike M, Chalkia M, MacGregor GR, Sassone-Corsi P and Wallace DC (2012) Maternal inheritance of two different mouse mtDNAs is genetically stable and results in altered behavior and cognition. Cell 151, 333-343.

Fielder TJ, Yi CS, Masumi J, Waymire KG, Chen H-W, Wang S, Shi, K-X, Wallace, DC, MacGregor G.R. (2012) Comparison of male chimeric mice generated from microinjection of JM8.N4 embryonic stem cells into C57BL/6J and C57BL/6NTac blastocysts. Transgenic Research 18, DOI 10.1007/s11248-012-9605-3.

Navarro S.J., Trinh T., Lucas C.A., Ross A.J., Waymire K.G., MacGregor G.R. (2012) The C57BL/6J mouse stain background modifies the effect of a mutation in Bcl2l2. G3 : Genes, Genomes, Genetics 2, 99-102.

Nicholson A, Reifsnyder P, Malcolm R, Lucas C, MacGregor GR, Zhang W. and Leiter E. (2010) Diet-induced obesity in two C57BL/6 substrains with intact or mutant nicotinamide nucleotide transhydrogenase (Nnt) gene. Obesity 18, 1902 - 1905.

Ikegami. K, Horigome, D, Mukai, M, Livnat, I, MacGregor, GR, and Setou, M (2008) TTLL10 is a protein polylgycylase that can modify nucleosome assembly protein 1 FEBS Lett. 582, 1129-1134.

Fan, W.-W., Waymire, K.G., Narula, N., Li, P., Rocher, C., Coskun, P.E., Vannan, M.A., Narula, J., MacGregor, GR, Wallace, D.C. (2008) A mouse model of mitochondrial disease reveals germline selection against severe mtDNA mutations. Science 319, 958 - 962.

Yao, I., Takagi, T., Ageta, H., Kahyo, T., Sato, S., Hatanaka, K., Fukuda, Y., Chiba, T., Morone, N., Yuasa, M., Inokuchi, K., Ohtsuka, T., MacGregor, GR, Tanaka, K. and Setou, M. (2007) SCRAPPER-dependent ubiquitination of active zone protein RIM1 regulates synaptic vesicle release. Cell, 130, 943-957.

Ikegami K, , Heier RL, Taruishi M, Takagi H, Mukai M, Shimma S, Taira S, Hatanaka K, Morone N, Yao I, Campbell PK, Yuasa S, Janke C, MacGregor GR*, and Setou M* (2007) Loss of Alpha Tubulin Polyglutamylation in ROSA22 Mice is Associated with Abnormal Targeting of KIF1A and Modulated Synaptic Function (*co-corresponding authors) Proc. Natl. Acad. Sci. (USA) 104, p3213 - 3218.

Ikegami K., Mukai, M., Tsuchida J-I, Heier RL, MacGregor GR and Setou M. (2006) TTLL7 is a mammalian beta-tubulin polyglutamylase required for growth of MAP2-positive neurites. Journal of Biological Chemistry 281, 30707 – 30716.

Obholz KL, Akopyan AA, Waymire KG, MacGregor GR (2006) FNDC3A is required for adhesion between spermatids and Sertoli cell in mice. Developmental Biology 298, 498-513.

Kokoszka, JE, Waymire, KG, Levy, SE, Sligh, JE, Cai, J.-Y., Jones, D.P., MacGregor, GR, and Wallace, DC (2004) The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore. Nature, 427, 461-465.

MacGregor, GR (2002) An extreme bias in the germ line of XY C57BL/6 <-> XY FVB/N chimeric mice. Reproduction 124, 377-386.

Campbell, PK, Waymire, KG, Heier, RL, Scharer, C, Day, DE, Reimann, H, Jaje, JM, Friedrich, GA, Burmeister, M, Russell, LD, Bartness, TJ, Young, LJ, Zimmer, M, Jenne, DE and MacGregor, GR (2002) Mutation of a novel gene results in abnormal development of spermatid flagellum, loss of inter-male aggression and reduced body fat in mice. Genetics, 162, 307-320.

Russell, LD, Warren, J, Deblejuk, L, Mahar, PL, Waymire, KG, Richardson, LL, Amy, S P, Ross, AJ and MacGregor, GR (2001) Spermatogenesis in Bclw mutant mice. Biology of Reproduction 65, 318-332.

Ross, AJ, Amy, SP, Mahar, PL, Lindsten, T, Knudson, C.M., Thompson, C.B., Korsmeyer, S. J., MacGregor, GR (2001) BCLW mediates survival of post-mitotic Sertoli cells by regulating BAX activity. Developmental Biology 239, 295-308.

Wei, MC, Zong, W-X, Cheng, EH-Y, Lindsten, T, Panoutsakopoulou, T, Roth, KA, Ross, AJ, MacGregor, GR, Thompson, CB and Korsmeyer, SJ (2001) Pro-apoptotic BAX and BAK are essential for mitochondrial dysfunction and death following diverse apoptotic signals. Science 292, 727-730.

Zong, W-X, Lindsten, T, Ross, AJ, MacGregor, GR and Thompson, CB (2001) BH3-only proteins that bind pro-survival BCL2 family members fail to induce apoptosis in the absence of BAX and BAK. Genes & Development 15, 1481-1486.

Lindsten, T, Ross, AJ, Gottlieb-King, A, Zong, W-X, Rathmell, JC, Shiels, HA, Ulrich, E, Waymire, KG, Mahar, PL, Frauwirth, K, Chen, Y, Wei, M, Eng, VM, Adelman, DM, Simon, MC, Ma, A, Golden, JA, Evan, G Korsmeyer, SJ, MacGregor, GR and Thompson, CB (2000) The combined functions of the pro-apoptotic BCL2 family members BAK and BAX are essential for the normal development of multiple tissues. Molecular Cell 6, 1389-1399.

Sligh, JE, Levy, SE, Waymire, KG, Allard, P, Dillehay, DL, Nusinowitz, S, Heckenlively, JR, MacGregor, GR and Wallace, DC (2000) Maternal germ line transmission of mutant mitochondrial DNAs from embryonic stem cell derived chimeric mice. Proc. Natl. Acad. Sci (USA) 97, 14461-14466.

Esposito, LE, Kokoszka, JE, Waymire, KG, Cottrell, B, MacGregor, GR and Wallace, DC (2000) Mitochondrial oxidative stress in mice lacking glutathione peroxidase 1. Free Radical Biology & Medicine 28, 754-766.

Fedde, KN, Blair, L, Silverstein, J, Coburn, SP, Ryan, LM, Weinstein, RS, Waymire, KG, Narisawa, S, Millán, J-L, MacGregor, GR, and Whyte, MP (1999) Alkaline phosphatase knock-out mice recapitulate the metabolic and skeletal defects of infantile hypophosphatasia. J Bone Miner Res 14, 2015-2026.

Young, LJ, Nilsen, R, Waymire, KG, MacGregor, GR and Insel, TR (1999) Increased affiliative response to vasopressin in mice expressing the V1a receptor from a monogamous vole. Nature, 400, 766-768.

Levy, SE, Waymire, KG, Kim, YL, MacGregor, GR, Wallace, DC (1999) Transfer of chloramphenicol resistant mitochondrial DNA into the adult mouse. Transgenic Research 8, 137-145.

Metcalfe, AD, Gilmore, A, Klinowska, T, Oliver, J, Valentijn, AJ, Brown, R, Ross, AJ, MacGregor, GR, Hickman, JA and Streuli, CH (1999) Developmental regulation of BCL2 family protein expression in the involuting mammary gland. J. Cell Sci. 112, 1771-1783.

Abe, K, Ko, MSH and MacGregor, GR (1998) A systematic molecular genetic approach to study mammalian germ line development. International Journal of Developmental Biology, 42,1051-1066.

Ross, A, Waymire, KG, Moss, JE, Parlow, AF, Skinner, MK, Russell, LD and MacGregor, GR (1998) Testicular degeneration in Bclw deficient mice. Nature Genetics, 18, 251-256.

Graham, BH, Waymire, KG, Cottrell, B, Trounce, IA, MacGregor, GR and Wallace, DC (1997) A mouse model for mitochondrial myopathy and cardiomyopathy resulting from a deficiency in the heart / skeletal muscle isoform of the adenine nucleotide translocator. Nature Genetics 16, 226-234.

Young, LJ, Waymire, KG, Nilsen, R, MacGregor, GR, Wang, Z and Insel, TR (1997) The 5’ flanking region of the monogamous prairie vole oxytocin receptor gene directs tissue specific expression in transgenic mice. Ann. N.Y. Acad. Sci., 807, 514-517.

Abe, K, Hashiyama, M, MacGregor, GR, Yamamura, K-I. and Abe, K (1996) Purification of primordial germ cells from TNAP?-geo mouse embryos using FACS-gal. Developmental Biology 180, 468 - 472.

Waymire, KG, Jaje, JM, Mahuren, D, Guilarte, T, Coburn, SP and MacGregor, GR (1995) Mice lacking tissue non-specific alkaline phosphatase die from seizures due to defective metabolism of vitamin B-6. Nature Genetics, 11, 45-51.

MacGregor, GR, Zambrowicz, BP 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.

Meistrich, ML, Kasai, K, Olds-Clarke, P, MacGregor, GR, Berkowitz, AD and Tung, KSK (1994) Deficiency in fertilization by sperm from Azh mutant mice. Molecular Reproduction & Development, 37, 69-77.

Gelb, BD, Adams, V, Jones, SN, Griffin, LD, MacGregor, GR and McCabe, ERB (1992) Mitochondrial targeting of hexokinase in tumor cells. Proc. Natl. Acad. Sci (USA), 89, 202-206.

MacGregor, GR and Overbeek, PA (1991) Use of a simplified single site PCR to facilitate isolation of genomic DNA flanking a transgene integration site. PCR Methods and Applications 1, 129-135.

Russell, LD, Russell, JA, MacGregor, GR and Meistrich, ML (1991) Linkage of manchette microtubules to the nuclear envelope and observations of the role of the manchette in nuclear shaping during spermiogenesis. Am. J. Anat. 192, 97-120.

Russell, LD, Sinha Hikim, AP, Overbeek, PA and MacGregor, GR (1991) Testis structure in the sys (symplastic spermatids) mouse. Am. J. Anat. 192, 169-182.

MacGregor, GR, Russell, LD, VanBeek, MEAB, Hanten, GR, Kovak, MJ, Kozak, CA, Meistrich, ML and Overbeek, PA (1990) Symplastic spermatids (sys), a recessive insertional mutation in mice causing a defect in spermatogenesis. Proc. Natl. Acad. Sci. (USA) 87, 5016 -5020.

Moore, KA, Fletcher, FA, Alford, RL, Villalon, DK, Hawkins, DH, MacGregor, GR, Caskey, CT and Belmont, JW (1989) Expression vectors for human adenosine deaminase gene therapy. Genome 31, (2) 832 -839.

MacGregor, GR and Caskey, CT (1989) Construction of plasmids that express E.coli beta-galactosidase in mammalian cells. Nucl. Acid Res. 17, (6), 2365.

Griffin, LD, MacGregor, GR, Muzny, DM, Harter, J, Cook, RG and McCabe, ERB (1989) Hexokinase 1 (HK1) cDNA probe synthesis by mixed oligonucleotide primed amplification of cDNA (MOPAC) using high complexity primer mixtures. Biochemical Medicine and Metabolic Biology 41, 125 - 131.

Fletcher, FA, Moore, KA, MacGregor, GR, Belmont, JW and Caskey, CT (1988) Human gene expression in murine haematopoietic cells in vivo. Adv. Exp. Med. Biol. 241, 123-127.

Belmont, JW, MacGregor, GR, Wager-Smith, K, Fletcher, FA, Moore, KA, Hawkins, D, Villalon, D, Chang, SM-W and Caskey, CT (1988) Expression of human adenosine deaminase in murine haematopoietic cells. Mol. Cell Biol. 8, (12) 5116-5125.

MacGregor, GR, Mogg, AE, Burke, JF and Caskey, CT (1987) Histochemical staining of clonal mammalian cell lines expressing E. coli beta-galactosidase indicates heterogeneous expression of the bacterial gene. Somat. Cell Mol. Genet. 13, (3) 253 - 266.

MacGregor, GR, James, MR, Arlett, CF and Burke JF (1987) Analysis of mutations occurring during replication of an SV40 shuttle-vector in mammalian cells. Mut. Res. 183, 273 - 278.

MacGregor, GR and Burke JF (1987) Stability of a bacterial gene in a bovine papilloma virus based shuttle vector maintained extra-chromosomally in mammalian cells. J. Gen. Virol. 68, 247 - 252.

Book Chapters
MacGregor, GR, Fan, W-W, Waymire, KG and Wallace DC (2006) “Generating animal models of human mitochondrial genetic disease using mouse ES cells” In "ES Cells: A Practical Approach”, Eds E. Notarianni, M. Evans. Practical Approach Series, Oxford University Press, England 72-111.

Ross, AJ and MacGregor, GR (2001) “ Analysis of Bcl2 gene function in transgenic mice”, in “Transgenics in Endocrinology” Eds MM Matzuk, CW Brown and TR Kumar. Humana Press Inc, Totowa, NJ 115-145.

MacGregor, GR (1992) Optimization of Electroporation Using Reporter Genes. In "Handbook of Electroporation and Electrofusion". Eds Chang, DC, Chassey, BM, Saunders, JA and Sowers, A E Academic Press Inc., Orlando FL. 465-470.

MacGregor, GR, Nolan, GP, Fiering, S and Herzenberg, LA (1991) Use of the E.coli beta-Galactosidase gene as a reporter gene - In "Methods in Molecular Biology - Volume 7: Gene Expression in vivo " Ed. Murray, EJ Humana Press Inc. Clifton, N.J. 217-235.

MacGregor, GR, Nelson, DL, Chang, SMW and Caskey, CT (1989) Prospects for gene therapy for Lesch-Nyhan disease. In : Molecular Genetics of Disease of Brain, Nerve and Muscle. (Rowland, LP, Ed.) Oxford University Press. 417-425.

Fletcher, FA, Moore, KA, MacGregor, GR, Belmont, JW and Caskey, CT (1988) Human Gene Expression in Murine Haematopoietic Cells in vivo. In - "Molecular Biology of Haematopoiesis". Vol. 241 Eds., Tavassoli, M., Abraham, NG, Ascensao, JL, Zanjani, ED and Levine, A Plenum Publishing Corp. New York, NY 123-127.

Symposium Contributions
MacGregor, GR “The Function of BCLW in Mouse Spermatogenesis”. (2001) 7th International Congress of Andrology, Montreal, Canada, Eds. Robaire, B, Chemes, H and Morales, CR. Medimond Press, Englewood, NJ 153-177.

Cournoyer, D, Scarpa, M, Moore, KA, Fletcher, FA, MacGregor, GR, Belmont, JW and Caskey, CT (1991) Gene Replacement Therapy: Human and Animal Model Progress. In - "Nobel Symposium : Etiology of Human Disease at the DNA Level". Eds, Lindsten, J and Petterson, Lippincott-Raven Press, New York, NY 199-220.

MacGregor, GR, Fletcher,FA, Moore, KA, Chang, SM-W, Belmont, JW and Caskey, CT (1988) Long Term in vivo expression of Human Adenosine Deaminase in Murine Haematopoietic cells. In : Gene Transfer in Animals, UCLA Symposia on Molecular and Cellular Biology, Vol 87. Eds, Verma, IM, Mulligan, RC, and Beaudet, AL Alan R Liss, Inc., New York, NY. 375-396.

MacGregor, GR, Fletcher, FA, Moore, KA, Chang, SM-W, Belmont, JW and Caskey, CT (1988) Towards gene therapy for inherited ocular disease - studies of retro-virally mediated human adenosine deaminase expression in mice. In : Molecular Biology of the Eye : Genes, Vision and Ocular Disease. UCLA Symposia on Molecular and Cellular Biology, Vol 88. Eds, Paitigorsky, J., Zelenka, P. and Shinohara, T. Alan R Liss, Inc., New York, NY. 1-22.
<b>(as PI or Co-PI, all direct costs)</b>
NIH R21-HL102862 Function of FNDC3B in cardiovascular and pulmonary development. 04/01/2010 – 03/31/2012 $250,000
California Institute for Regenerative Medicine RS1-00416-1 Production of Oocytes from Human ES Cells. 05/01/2007 – 06/30/2010 $623,781
NIH U01-HD045913 A novel gene required for Sertoli-Spermatid adhesion. 12/01/2003 - 11/30/2009 $978,461
DOD OC990138 Role of Oocyte Loss in Ovarian Surface Mesothelial Cell Transformation. 4/1/2000 – 3/31/2003 (Co-PI with J. Tilly PhD @ MGH) $375,000
NIH R01-HD36437 The function of BCLW in mammalian development. 4/1/1998 – 3/31/2003 $567,688
American Cancer Society RPG CCG-88919 Functional analysis of the role of Bclw in mammalian development. 7/1/1998 – 6/30/2001 $268,000 (declined due to overlap with NIH award)
Emory University Research Fund Allocation Identification and analysis of overlapping functions of Bcl2 and Bclw during mouse embryonic development. 1/1/1998 – 12/31/1998 $15,000
Emory University Research Fund Allocation Analysis of the allocation and determination of primordial germ cells in the pre-gastrulation embryonic mouse 9/1/1994 – 8/31/1995 $15,000
Winship Cancer Center Institutional American Cancer Society Seed Grant The function of cathepsin L in murine development and tumor metastasis. 1/1/1995 – 12/31/1995 $13,500
Professional Societies
American Society for Cell Biology
Society for Study of Reproduction
Society for Developmental Biology
American Heart Association
Other Experience
Editorial Board, Spermatogenesis
Landes BioSciences 2010—-
Graduate Programs
Cellular and Molecular Biosciences
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