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Keith Latham, PhD
Adjunct Professor, Biochemistry
Additional Web Sites: www.lathamlab.org, www.preger.org,
Department of Biochemistry
University of Virginia
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My research focuses on understanding the remarkable properties of the mammalian oocyte, which exists as a highly differentiated cell type endowed with the unique capacity for creating an embryonic genome from the two terminally differentiated gamete genomes, activating that embryonic genome, and regulating its function during much of the preimplantation period. My research seeks to understand these fundamental, life-generating processes at the molecular level, by employing a combination of microsurgery, quantitative gene expression analyses, and structural studies. My research program is comprised of several NIH-funded research programs, focused on the following areas:
- Understanding the mechanisms of nuclear reprogramming in cloned embryos made by nuclear transfer and in normal fertilized embryos. Systems genetics has revealed novel candidates of key oocyte factors with essential roles in the cloning process.
- Understanding the mechanisms regulating cell death in the newly fertilized embryo.
- Understanding the potential effect of assisted reproduction technologies on progeny.
- Understanding determinants of oocyte quality.
- Understanding the roles of follicular cells in developing high quality oocytes. Recent studies revealed a surprising reversion of cumulus cells to a granulosa cell phenotype.
- Understanding the composition and molecular controls of meiotic spindles.
- Understanding effects of environmental toxin exposures on long-term phenotype.
- The continued development of a National Resource for the study of gene expression and regulation in non-human primate embryos.
- Additional studies related to the control of gene transcription in the newly fertilized embryo are also ongoing.
Recently, the Latham lab, in collaboration with the Merali lab, performed a proteomics analysis, comparing normal mouse oocyte MII stage meiotic spindles and spindles that form after somatic cell nuclear transfer for cloning, to identify protein defects. Clathrin heavy chain (CLTC) was identified as a major deficiency in cloned embryo spindles. Knockdown of CLTC in GV stage oocytes resulted in chromosome congression defects upon maturation, and conversely enhancing CLTC expression in clones reduced congression defects.
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Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)
24280258. Hao L, Midic U, Garriga J, Latham KE, Contribution of CBX4 to cumulus oophorus cell phenotype in mice, and attendant effects in cumulus cell cloned embryos. Physiol Genomics :()2013 Nov 26
23852387. Romasko EJ, Amarnath D, Midic U, Latham KE, Association of maternal mRNA and phosphorylated EIF4EBP1 variants with the spindle in mouse oocytes: localized translational control supporting female meiosis in mammals. Genetics 195:2(349-58)2013 Oct
22920179. Latham KE, Sapienza C, Engel N, The epigenetic lorax: gene-environment interactions in human health. Epigenomics 4:4(383-402)2012 Aug
22907487. Cheng Y, Amarnath D, Latham KE, Uniparental embryos in the study of genomic imprinting. Methods Mol Biol 925:(3-19)2012
22584025. Cheng Y, Zhong Z, Latham KE, Strain-specific spontaneous activation during mouse oocyte maturation. Fertil Steril 98:1(200-6)2012 Jul
21751213. Mtango NR, Sutovsky M, Vandevoort CA, Latham KE, Sutovsky P, Essential role of ubiquitin C-terminal hydrolases UCHL1 and UCHL3 in mammalian oocyte maturation. J Cell Physiol 227:5(2022-9)2012 May
21678411. Mtango NR, Sutovsky M, Susor A, Zhong Z, Latham KE, Sutovsky P, Essential role of maternal UCHL1 and UCHL3 in fertilization and preimplantation embryo development. J Cell Physiol 227:4(1592-603)2012 Apr
21487073. Lee YS, VandeVoort CA, Gaughan JP, Midic U, Obradovic Z, Latham KE, Extensive effects of in vitro oocyte maturation on rhesus monkey cumulus cell transcriptome. Am J Physiol Endocrinol Metab 301:1(E196-209)2011 Jul
20883044. Han Z, Liang CG, Cheng Y, Duan X, Zhong Z, Potireddy S, Moncada C, Merali S, Latham KE, Oocyte spindle proteomics analysis leading to rescue of chromosome congression defects in cloned embryos. J Proteome Res 9:11(6025-32)2010 Nov 5
20691866. Han Z, Cheng Y, Liang CG, Latham KE, Nuclear transfer in mouse oocytes and embryos. Methods Enzymol 476:(171-84)2010
20573994. Potireddy S, Midic U, Liang CG, Obradovic Z, Latham KE, Positive and negative cis-regulatory elements directing postfertilization maternal mRNA translational control in mouse embryos. Am J Physiol Cell Physiol 299:4(C818-27)2010 Oct
19661122. Liang CG, Han Z, Cheng Y, Zhong Z, Latham KE, Effects of ooplasm transfer on paternal genome function in mice. Hum Reprod 24:11(2718-28)2009 Nov
19229137. Engel N, Tront JS, Erinle T, Nguyen N, Latham KE, Sapienza C, Hoffman B, Liebermann DA, Conserved DNA methylation in Gadd45a(-/-) mice. Epigenetics 4:2(98-9)2009 Feb 16
19129515. Hao L, Vassena R, Wu G, Han Z, Cheng Y, Latham KE, Sapienza C, The unfolded protein response contributes to preimplantation mouse embryo death in the DDK syndrome. Biol Reprod 80:5(944-53)2009 May
19073997. Cheng Y, Wang K, Kellam LD, Lee YS, Liang CG, Han Z, Mtango NR, Latham KE, Effects of ooplasm manipulation on DNA methylation and growth of progeny in mice. Biol Reprod 80:3(464-72)2009 Mar
18842187. Mtango NR, Harvey AJ, Latham KE, Brenner CA, Molecular control of mitochondrial function in developing rhesus monkey oocytes and preimplantation-stage embryos. Reprod Fertil Dev 20:7(846-59)2008
18703408. Mtango NR, Potireddy S, Latham KE, Oocyte quality and maternal control of development. Int Rev Cell Mol Biol 268:(223-90)2008
18697858. Lee YS, Latham KE, Vandevoort CA, Effects of in vitro maturation on gene expression in rhesus monkey oocytes. Physiol Genomics 35:2(145-58)2008 Oct 8
18646051. Mtango NR, Potireddy S, Latham KE, Expression of microRNA processing machinery genes in rhesus monkey oocytes and embryos of different developmental potentials. Mol Reprod Dev 76:3(255-69)2009 Mar
18577693. Han Z, Vassena R, Chi MM, Potireddy S, Sutovsky M, Moley KH, Sutovsky P, Latham KE, Role of glucose in cloned mouse embryo development. Am J Physiol Endocrinol Metab 295:4(E798-809)2008 Oct
18562704. Han Z, Mtango NR, Patel BG, Sapienza C, Latham KE, Hybrid vigor and transgenerational epigenetic effects on early mouse embryo phenotype. Biol Reprod 79:4(638-48)2008 Oct
17914069. Mtango NR, Latham KE, Differential expression of cell cycle genes in rhesus monkey oocytes and embryos of different developmental potentials. Biol Reprod 78:2(254-66)2008 Feb
17694452. Han Z, Vandevoort CA, Latham KE, Therapeutic cloning: status and prospects. Curr Opin Mol Ther 9:4(392-7)2007 Aug
17551977. Vassena R, Han Z, Gao S, Latham KE, Deficiency in recapitulation of stage-specific embryonic gene transcription in two-cell stage cloned mouse embryos. Mol Reprod Dev 74:12(1548-56)2007 Dec
17550997. Mtango NR, Latham KE, Ubiquitin proteasome pathway gene expression varies in rhesus monkey oocytes and embryos of different developmental potential. Physiol Genomics 31:1(1-14)2007 Sep 19
17416905. Zheng P, Vassena R, Latham KE, Effects of in vitro oocyte maturation and embryo culture on the expression of glucose transporters, glucose metabolism and insulin signaling genes in rhesus monkey oocytes and preimplantation embryos. Mol Hum Reprod 13:6(361-71)2007 Jun
17234177. Vassena R, Han Z, Gao S, Baldwin DA, Schultz RM, Latham KE, Tough beginnings: alterations in the transcriptome of cloned embryos during the first two cell cycles. Dev Biol 304:1(75-89)2007 Apr 1
17147927. Latham KE, The Primate Embryo Gene Expression Resource in embryology and stem cell biology. Reprod Fertil Dev 18:8(807-10)2006
16860309. Potireddy S, Vassena R, Patel BG, Latham KE, Analysis of polysomal mRNA populations of mouse oocytes and zygotes: dynamic changes in maternal mRNA utilization and function. Dev Biol 298:1(155-66)2006 Oct 1
16310175. Miyara F, Han Z, Gao S, Vassena R, Latham KE, Non-equivalence of embryonic and somatic cell nuclei affecting spindle composition in clones. Dev Biol 289:1(206-17)2006 Jan 1
16155959. Vassena R, Dee Schramm R, Latham KE, Species-dependent expression patterns of DNA methyltransferase genes in mammalian oocytes and preimplantation embryos. Mol Reprod Dev 72:4(430-6)2005 Dec
15868680. Latham KE, Sapienza C, Developmental potential as a criterion for understanding and defining embryos. Conn Law Rev 36:4(1171-6)2004 Summer
15744049. Wu G, Hao L, Han Z, Gao S, Latham KE, de Villena FP, Sapienza C, Maternal transmission ratio distortion at the mouse Om locus results from meiotic drive at the second meiotic division. Genetics 170:1(327-34)2005 May
15703371. Zheng P, Schramm RD, Latham KE, Developmental regulation and in vitro culture effects on expression of DNA repair and cell cycle checkpoint control genes in rhesus monkey oocytes and embryos. Biol Reprod 72:6(1359-69)2005 Jun
15661358. Latham KE, X chromosome imprinting and inactivation in preimplantation mammalian embryos. Trends Genet 21:2(120-7)2005 Feb
15656778. Latham KE, Early and delayed aspects of nuclear reprogramming during cloning. Biol Cell 97:2(119-32)2005 Feb
15537860. Han Z, Chung YG, Gao S, Latham KE, Maternal factors controlling blastomere fragmentation in early mouse embryos. Biol Reprod 72:3(612-8)2005 Mar
15483220. Gao S, Wu G, Han Z, de la Casa-Esperón E, Sapienza C, Latham KE, Recapitulation of the ovum mutant (Om) phenotype and loss of Om locus polarity in cloned mouse embryos. Biol Reprod 72:2(487-91)2005 Feb
15237216. Gao S, Latham KE, Maternal and environmental factors in early cloned embryo development. Cytogenet Genome Res 105:2-4(279-84)2004
15008822. Latham KE, Cloning: questions answered and unsolved. Differentiation 72:1(11-22)2004 Feb
14733747. Gao S, McGarry M, Latham KE, Wilmut I, Cloning of mice by nuclear transfer. Cloning Stem Cells 5:4(287-94)2003
14729478. Gao S, Chung YG, Parseghian MH, King GJ, Adashi EY, Latham KE, Rapid H1 linker histone transitions following fertilization or somatic cell nuclear transfer: evidence for a uniform developmental program in mice. Dev Biol 266:1(62-75)2004 Feb 1
14724134. Zheng P, Patel B, McMenamin M, Paprocki AM, Schramm RD, Nagl NG Jr, Wilsker D, Wang X, Moran E, Latham KE, Expression of genes encoding chromatin regulatory factors in developing rhesus monkey oocytes and preimplantation stage embryos: possible roles in genome activation. Biol Reprod 70:5(1419-27)2004 May
14724133. Zheng P, Patel B, McMenamin M, Reddy SE, Paprocki AM, Schramm RD, Latham KE, The primate embryo gene expression resource: a novel resource to facilitate rapid analysis of gene expression patterns in non-human primate oocytes and preimplantation stage embryos. Biol Reprod 70:5(1411-8)2004 May
14695909. Latham KE, Wigglesworth K, McMenamin M, Eppig JJ, Stage-dependent effects of oocytes and growth differentiation factor 9 on mouse granulosa cell development: advance programming and subsequent control of the transition from preantral secondary follicles to early antral tertiary follicles. Biol Reprod 70:5(1253-62)2004 May
14681201. Gao S, Czirr E, Chung YG, Han Z, Latham KE, Genetic variation in oocyte phenotype revealed through parthenogenesis and cloning: correlation with differences in pronuclear epigenetic modification. Biol Reprod 70:4(1162-70)2004 Apr
12606377. Gao S, Chung YG, Williams JW, Riley J, Moley K, Latham KE, Somatic cell-like features of cloned mouse embryos prepared with cultured myoblast nuclei. Biol Reprod 69:1(48-56)2003 Jul
12606374. Chung YG, Ratnam S, Chaillet JR, Latham KE, Abnormal regulation of DNA methyltransferase expression in cloned mouse embryos. Biol Reprod 69:1(146-53)2003 Jul
12135871. Latham KE, Akutsu H, Patel B, Yanagimachi R, Comparison of gene expression during preimplantation development between diploid and haploid mouse embryos. Biol Reprod 67:2(386-92)2002 Aug
11906939. Chung YG, Mann MR, Bartolomei MS, Latham KE, Nuclear-cytoplasmic "tug of war" during cloning: effects of somatic cell nuclei on culture medium preferences of preimplantation cloned mouse embryos. Biol Reprod 66:4(1178-84)2002 Apr
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