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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 46:2(66-80)2014 Jan 15
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
23307892. Cheng Y, Gaughan J, Midic U, Han Z, Liang CG, Patel BG, Latham KE, Systems genetics implicates cytoskeletal genes in oocyte control of cloned embryo quality. Genetics 193:3(877-96)2013 Mar
23008515. Chaffin CL, Lee YS, VandeVoort CA, Patel BG, Latham KE, Rhesus monkey cumulus cells revert to a mural granulosa cell state after an ovulatory stimulus. Endocrinology 153:11(5535-45)2012 Nov
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
21645893. Vandevoort CA, Mtango NR, Latham KE, Stewart DR, Primate preimplantation embryo is a target for relaxin during early pregnancy. Fertil Steril 96:1(203-7)2011 Jul
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
21329766. Mtango NR, VandeVoort CA, Latham KE, Ontological aspects of pluripotency and stemness gene expression pattern in the rhesus monkey. Gene Expr Patterns 11:3-4(285-98)2011 Mar-Apr
21193554. Tripurani SK, Lee KB, Wang L, Wee G, Smith GW, Lee YS, Latham KE, Yao J, A novel functional role for the oocyte-specific transcription factor newborn ovary homeobox (NOBOX) during early embryonic development in cattle. Endocrinology 152:3(1013-23)2011 Mar
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
20107036. Han Z, Mtango NR, Zhong Z, Vassena R, Latham KE, Early transcription from the maternal genome controlling blastomere integrity in mouse two-cell-stage embryos. Am J Physiol Cell Physiol 298:5(C1235-44)2010 May
20043319. Nyholt de Prada JK, Kellam LD, Patel BG, Latham KE, Vandevoort CA, Growth hormone and gene expression of in vitro-matured rhesus macaque oocytes. Mol Reprod Dev 77:4(353-62)2010 Apr
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
19641179. VandeVoort CA, Mtango NR, Lee YS, Smith GW, Latham KE, Differential effects of follistatin on nonhuman primate oocyte maturation and pre-implantation embryo development in vitro. Biol Reprod 81:6(1139-46)2009 Dec
19276391. Nyholt de Prada JK, Lee YS, Latham KE, Chaffin CL, VandeVoort CA, Role for cumulus cell-produced EGF-like ligands during primate oocyte maturation in vitro. Am J Physiol Endocrinol Metab 296:5(E1049-58)2009 May
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
18614575. Wan LB, Pan H, Hannenhalli S, Cheng Y, Ma J, Fedoriw A, Lobanenkov V, Latham KE, Schultz RM, Bartolomei MS, Maternal depletion of CTCF reveals multiple functions during oocyte and preimplantation embryo development. Development 135:16(2729-38)2008 Aug
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
18024232. Kuzmin A, Han Z, Golding MC, Mann MR, Latham KE, Varmuza S, The PcG gene Sfmbt2 is paternally expressed in extraembryonic tissues. Gene Expr Patterns 8:2(107-16)2008 Jan
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
17176552. Latham KE, Gao S, Han Z, Somatic cell nuclei in cloning: strangers traveling in a foreign land. Adv Exp Med Biol 591:(14-29)2007
17147927. Latham KE, The Primate Embryo Gene Expression Resource in embryology and stem cell biology. Reprod Fertil Dev 18:8(807-10)2006
16988375. Chung YG, Gao S, Latham KE, Optimization of procedures for cloning by somatic cell nuclear transfer in mice. Methods Mol Biol 348:(111-24)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
15733677. Nolen LD, Gao S, Han Z, Mann MR, Gie Chung Y, Otte AP, Bartolomei MS, Latham KE, X chromosome reactivation and regulation in cloned embryos. Dev Biol 279:2(525-40)2005 Mar 15
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
15661341. Gao S, Han Z, Kihara M, Adashi E, Latham KE, Protease inhibitor MG132 in cloning: no end to the nightmare. Trends Biotechnol 23:2(66-8)2005 Feb
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