Lorraine Young

Contact

• workRoom A63 Wolfson Centre for Stem Cells, Tissue Engineering and Modelling (STEM), CBS
  University Park
  Nottingham
  NG7 2RD
  UK
• work0115 82 31238
• fax0115 82 31230
• lorraine.young@nottingham.ac.uk

Biography

Outline

My team investigates how, at the epigenetic level, cells acquire totipotency during normal embryonic development. Combined with our ongoing investigation of the nature of epigenetic reprogramming events a cell undergoes in an oocyte cytoplasm after somatic cell nuclear transfer, an exciting application of this work is to develop directed cellular transdifferentation ex ovo for the production of autologous stem cells.

We are investigating the effects of embryo technologies and maternal nutrition on developmental programming by epigenetic changes, especially DNA methylation. Phenotypic consequences (including Large Offspring syndrome) can arise in the fetus, after birth or in embryo-derived stem cells.

Our other main focus is in the epigenetic evaluation of human embryonic stem cells (hESC) and their derivatives, a vital pre-requisite for regenerative medicine applications. Since epigenetic disruptions in the embryo are likely to be transmitted to embryonic stem cells, tumorigenic potential or altered differentiation capacity may be inherent to derivatives. We are focussing on in changes in DNA methylation, part of the regulatory process that acts to stably silence transcription over many cell generations. By combining genome wide epigenetic screens for DNA and histone modifications with stem cell automation, we aim to extend current capacity to evaluate environmental effects on the developing epigenome.

A major application of human embryonic stem cells in Nottingham is to develop novel models for human disease. Our laboratory is particularly interested in the predisposition of adult cardiovascular disease by maternal nutrition, other wise known as "the developmental origins of adult health and disease".

We are investigating the hypothesis that nutrients which determine intracellular methyl group availability, such as folate, vitamin B12 and methionine, can affect DNA methylation at specific loci in the embryo or fetus and programme development by altering cellular proliferation or differentiation in specific tissues. Human embryonic stem cells provide a unique system to model early embryonic and later cardiac development and how these processes are affected by specific nutrients.

Expertise Summary

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•Nuclear reprogramming during normal fertilisation, somatic cell nuclear transfer and induced pluripotency

Molecular Regulation of Preimplantation Development • Large Offspring syndrome and the role of genomic imprinting • Effects of Embryo Technologies (IVF) on Preimplantation Epigenesis and later life health/disease • Embryonic Programming of Adult Disease by Maternal Nutrition and chemical exposure

Modelling systems biology of early human development using human pluripotent stem cells

Human pluripotent stem cell bioprocessing, quality control and automated culture

Developing human pluripotent stem cells and hepatocyte derivatives for automated screening applications • Epigenetic stability in cultured human pluripotent stem cells and consequences for cell differentiation and tumorigenic potential

Teaching Summary

I established the world's first taught MSc course in Stem Cell Technology in 2007 in order to meet a skills gap in students trained in the practical, multidisciplinary and regulatory aspects of stem… read more

Research Summary

My team investigates how, at the epigenetic level, cells acquire totipotency during normal embryonic development. Combined with our ongoing investigation of the nature of epigenetic reprogramming… read more

Selected Publications

• MALONEY, CHRISTOPHER A, HAY, SUSAN M, YOUNG, LORAINE E, SINCLAIR, KEVIN D and REES, WILLIAM D, 2011. A methyl-deficient diet fed to rat dams during the peri-conception period programs glucose homeostasis in adult male but not female offspring. The Journal of nutrition. 141(1), 95-100
• PRIDDLE, HELEN, ALLEGRUCCI, CINZIA, BURRIDGE, PAUL, MUNOZ, MARIA, SMITH, NIGEL M, DEVLIN, LYNDSEY, SJOBLOM, CECILIA, CHAMBERLAIN, SARAH, WATSON, SUE, YOUNG, LORRAINE E and DENNING, CHRIS, 2010. Derivation and characterisation of the human embryonic stem cell lines, NOTT1 and NOTT2. In vitro cellular & developmental biology. Animal. 46, 367-375
• PRIDDLE, HELEN, GRABOWSKA, ANNA, MORRIS, TERESA, CLARKE, PHILIP A, MCKENZIE, ANDREW J, SOTTILE, VIRGINIE, DENNING, CHRIS, YOUNG, LORRAINE and WATSON, SUE, 2009. Bioluminescence imaging of human embryonic stem cells transplanted in vivo in murine and chick models. Cloning and stem cells. 11(2), 259-67
• THOMAS, ROB J, ANDERSON, DAVID, CHANDRA, AMIT, SMITH, NIGEL M, YOUNG, LORRAINE E, WILLIAMS, DAVID and DENNING, CHRIS, 2009. Automated, scalable culture of human embryonic stem cells in feeder-free conditions. Biotechnology and bioengineering. 102(6), 1636-44

• View all publications

I established the world's first taught MSc course in Stem Cell Technology in 2007 in order to meet a skills gap in students trained in the practical, multidisciplinary and regulatory aspects of stem cells and regenerative medicine.

I enjoy developing small group teaching and tutorial style classes.

Current Research

My team investigates how, at the epigenetic level, cells acquire totipotency during normal embryonic development. Combined with our ongoing investigation of the nature of epigenetic reprogramming events a cell undergoes in an oocyte cytoplasm after somatic cell nuclear transfer, an exciting application of this work is to develop directed cellular transdifferentation ex ovo for the production of autologous stem cells . Our other main focus is in the epigenetic evaluation of human embryonic stem cells (hESC) and their derivatives, a vital pre-requisite for regenerative medicine applications. Since epigenetic disruptions in the embryo are likely to be transmitted to embryonic stem cells, tumorigenic potential or altered differentiation capacity may be inherent to derivatives. We are focussing on in changes in DNA methylation, part of the regulatory process that acts to stably silence transcription over many cell generations. A major application of human embryonic stem cells in Nottingham is to develop novel models for human disease. Our laboratory is particularly interested in the predisposition of adult cardiovascular disease by maternal nutrition, other wise known as "the fetal origins of adult disease".

We are investigating the effects of embryo technologies and maternal nutrition on developmental programming by epigenetic changes, especially DNA methylation. Phenotypic consequences can arise in the fetus, after birth or in embryo-derived stem cells.

• RIMPLE D. ALMEIDA, MATTHEW LOOSE, VIRGINIE SOTTILE, ELENA MATSA, CHRIS DENNING, LORRAINE YOUNG, ANDREW D. JOHNSON, MARTIN GERING and ALEXEY RUZOV, 2012. 5-hydroxymethyl-cytosine enrichment of non-committed cells is not a universal feature of vertebrate development Epigenics. 7(4), (In Press.)
• MATSA, ELENA, RAJAMOHAN, DIVYA, DICK, EMILY, YOUNG, LORRAINE, MELLOR, IAN, STANIFORTH, ANDREW and DENNING, CHRIS, 2011. Drug evaluation in cardiomyocytes derived from human induced pluripotent stem cells carrying a long QT syndrome type 2 mutation. Eur Heart J. 32(8), 952-62
• DICK, EMILY, MATSA, ELENA, BISPHAM, JAYSON, REZA, MOJGAN, GUGLIERI, MICHELA, STANIFORTH, ANDREW, WATSON, SUE, KUMARI, RAJENDRA, LOCHMÜLLER, HANNS, YOUNG, LORRAINE, DARLING, DAVID and DENNING, CHRIS, 2011. Two new protocols to enhance the production and isolation of human induced pluripotent stem cell lines. Stem cell research. 6(2), 158-67
• MALONEY, CHRISTOPHER A, HAY, SUSAN M, YOUNG, LORAINE E, SINCLAIR, KEVIN D and REES, WILLIAM D, 2011. A methyl-deficient diet fed to rat dams during the peri-conception period programs glucose homeostasis in adult male but not female offspring. The Journal of nutrition. 141(1), 95-100
• INTERNATIONAL STEM CELL INITIATIVE, AMPS K, ANDREWS PW, ANYFANTIS G, ARMSTRONG L, AVERY S, BAHARVAND H, BAKER J, BAKER D, MUNOZ MB, BEIL S, BENVENISTY N, BEN-YOSEF D, BIANCOTTI J, BOSMAN A, BRENA RM, BRISON D, CAISANDER G, CAMARASA MV, CHEN J, CHIAO E, CHOI YM, CHOO ABH, COLLINS D, COLMAN A, CROOK JM, DALEY GQ, DALTON A, DE SOUSA PA, DENNING C, DOWNIE J, DVORAK P, MONTGOMERY KD, FEKI A, FORD A, FOX V, FRAGA AM, FRUMKIN T, GE L, GOKHALE PJ, GOLAN-LEV T, GOURABI H, GROPP M, LU G, HAMPL A, HARRON K, HEALY L, HERATH W, HOLM F, HOVATTA O, HYLLNER J, INAMDAR MS, IRWANTO AK, ISHII T, JACONI M, JIN Y, KIMBER S, KISELEV S, KNOWLES BB, KOPPER O, KUKHARENKO V, KULIEV A, LAGARKOVA MA, LAIRD PW, LAKO M, LASLETT AL, LAVON N, LEE DR, LEE JE, LI C, LIM LS, LUDWIG TE, MA Y, MALTBY E, MATEIZEL I, MAYSHAR Y, MILEIKOVSKY M, MINGER SL, MIYAZAKI T, MOON SY, MOORE H, MUMMERY C, NAGY A, NAKATSUJI N, NARWANI K, OH SKW, OH SK, OLSON C, OTONKOSKI T, PAN F, PARK I, PELLS S, PERA MF, PEREIRA LV, QI O, RAJ GS, REUBINOFF B, ROBINS A, ROBSON P, ROSSANT J, SALEKDEH GH, SCHULZ TC, SERMON K, SHEIK MOHAMED J, SHEN H, SHERRER E, SIDHU K, SIVARAJAH S, SKOTTMAN H, SPITS C, STACEY GN, STREHL R, STRELCHENKO N, SUEMORI H, SUN B, SUURONEN R, TAKAHASHI K, TUURI T, VENU P, VERLINSKY Y, WARD-VAN OOSTWAARD D, WEISENBERGER DJ, WU Y, YAMANAKA S, YOUNG L and ZHOU Q, 2011. Screening Ethnically Diverse Human Embryonic Stem Cells Identifies A Chromosome 20 Minimal Amplicon Conferring Growth Advantage. Nature Biotechnology. 29(12), 1132-44
• DICK E, MATSA E, YOUNG LE, DARLING D and DENNING C, 2011. Faster Generation Of Hipscs By Coupling High-Titer Lentivirus And Column-Based Positive Selection. Nature Protocols. 6(6), 701-14
• PRIDDLE, HELEN, ALLEGRUCCI, CINZIA, BURRIDGE, PAUL, MUNOZ, MARIA, SMITH, NIGEL M, DEVLIN, LYNDSEY, SJOBLOM, CECILIA, CHAMBERLAIN, SARAH, WATSON, SUE, YOUNG, LORRAINE E and DENNING, CHRIS, 2010. Derivation and characterisation of the human embryonic stem cell lines, NOTT1 and NOTT2. In vitro cellular & developmental biology. Animal. 46, 367-375
• PRIDDLE, HELEN, GRABOWSKA, ANNA, MORRIS, TERESA, CLARKE, PHILIP A, MCKENZIE, ANDREW J, SOTTILE, VIRGINIE, DENNING, CHRIS, YOUNG, LORRAINE and WATSON, SUE, 2009. Bioluminescence imaging of human embryonic stem cells transplanted in vivo in murine and chick models. Cloning and stem cells. 11(2), 259-67
• THOMAS, ROB J, ANDERSON, DAVID, CHANDRA, AMIT, SMITH, NIGEL M, YOUNG, LORRAINE E, WILLIAMS, DAVID and DENNING, CHRIS, 2009. Automated, scalable culture of human embryonic stem cells in feeder-free conditions. Biotechnology and bioengineering. 102(6), 1636-44
• BRAAM, DENNING*, MATSA, YOUNG, PASSIER, MUMMERY, 2008. Feeder-free cultures of hESCs for efficient genetic modification. Nature Protocols.. 3, 1435-1443
• THURSTON, ALEXANDRA, TAYLOR, JANE, GARDNER, JOHN, SINCLAIR, KEVIN D and YOUNG, LORRAINE E, 2008. Monoallelic expression of nine imprinted genes in the sheep embryo occurs after the blastocyst stage. Reproduction. 135(1), 29-40
• ALLEGRUCCI, C., WU, Y-Z., THURSTON, A., DENNING, C.N., PRIDDLE, H., MUMMERY, C.L., WARD-VAN OOSTWAARD, D., ANDREWS, P.W., STOJKOVIC, M., SMITH, N., PARKIN, T., EDMONDSON-JONES, M., WARREN, G., YU, L., BRENA, R.M., PLASS, C. and YOUNG, L.E., 2007. Restriction landmark genome scanning identifies culture-induced DNA methylation instability in the human embryonic stem cell epigenome Human Molecular Genetics. 16(10), 1253-1268
• ALLEGRUCCI, C and YOUNG, LE, 2007. Differences between human embryonic stem cell lines. Human Reproduction Update. 16(10), 1253-68
• KIM, K-P., THURSTON, A., MUMMERY, C., WARD-VAN OOSTWAARD, D., PRIDDLE, H., ALLEGRUCCI, C., DENNING, C. and YOUNG, L., 2007. Gene-specific vulnerability to imprinting variability in human embryonic stem cell lines Genome Research. 17(12), 1731-1742
• ROOKE, JA, MCEVOY, TG, ASHWORTH,CJ, ROBINSON,JJ, WILMUT,I, YOUNG,LE and SINCLAIR,KD, 2007. Ovine fetal development is more sensitive to perturbation by the presence of serum in embryo culture before rather than after compaction. Theriogenology. 67(3), 639-647
• SINCLAIR,K.D, LEA,R.G, REES,W.D and YOUNG,L.E, 2007. The developmental origins of health and disease; current theories and epigenetic mechanisms Society for Reproduction and Fertility Supplement. 64, 425-443
• ALEXANDRA THURSTON, EMMA S. LUCAS, CINZIA ALLEGRUCCI, WILLIAM STEELE AND LORRAINE E. YOUNG, 2007. Region-Specific DNA Methylation in the Preimplantation Embryo as a Target for Genomic Plasticity Theriogenology. (In Press.)
• YOUNG, and DENNING,, 2007. Oct4 during the pluripotency differentiation transition: who is regulating the regulator. 2(2), 211-215
• BURRIDGE, P.W., ANDERSON, D., PRIDDLE, H., BARBADILLO MUÑOZ, M.D.B., CHAMBERLAIN, S., ALLEGRUCCI, C., YOUNG, L.E. and DENNING, C., 2006. Improved human embryonic stem cell embryoid body homogeneity and cardiomyocyte differentiation from a novel V-96 plate aggregation system highlights interline variability Stem Cells. 24(4), 929-938
• DENNING, C., ALLEGRUCCI, C., PRIDDLE, H., BARBADILLO-MUÑOZ, M.D., ANDERSON, D., SELF, T., SMITH, N.M., PARKIN, C.T. and YOUNG, L.E., 2006. Common culture conditions for maintenance and cardiomyocyte differentiation of the human embryonic stem cell lines, BG01 and HUES-7. International Journal of Developmental Biology. 50(1), 27-37
• POWELL, K, ROOKE, J A, MCEVOY, T G, ASHWORTH, C J, ROBINSON, J J, WILMUT, I, YOUNG, L E and SINCLAIR, K D, 2006. Zygote donor nitrogen metabolism and in vitro embryo culture perturbs in utero development and IGF2R expression in ovine fetal tissues. Theriogenology. 66(8), 1901-12
• MOORE, H. R., MEEHAN, R. R. and YOUNG, L. E., 2006. Methylation-Sensitive Polymerase Chain Reaction Methods in Molecular Biology. VOL 325, 239-250
• MOORE, HANNAH R, MEEHAN, RICHARD R and YOUNG, LORRAINE E, 2006. Methylation-sensitive polymerase chain reaction. Methods in Molecular Biology. 325, 239-49
• YOUNG, LORRAINE E, 2006. Focus on stem cells in reproduction. Reproduction. 132(5), 671-2
• STEELE, W, ALLEGRUCCI, C, SINGH, R, LUCAS, E, PRIDDLE, H, DENNING, C, SINCLAIR, K and YOUNG, L, 2005. Human embryonic stem cell methyl cycle enzyme expression: modelling epigenetic programming in assisted reproduction? Reproductive Biomedicine online. 10(6), 755-66
• ALLEGRUCCI, C., DENNING, C.N., BURRIDGE, P., STEELE, W., SINCLAIR, K.D. and YOUNG, L.E., 2005. Human embryonic stem cells as a model for nutritional programming: an evaluation Reproductive Toxicology. 20(3), 353-367
• ALLEGRUCCI, C, THURSTON, A, LUCAS, E and YOUNG, L, 2005. Epigenetics and the germline. Reproduction. 129(2), 137-49
• ALLEGRUCCI, C., DENNING, C., PRIDDLE, H. and YOUNG, L., 2004. Stem-cell consequences of embryo epigenetic defects. Lancet. 364(9429), 206-208
• BEAUJEAN, N., TAYLOR, J.E., MCGARRY, M., GARDNER, J.O., WILMUT, I., LOI, P., PTAK, G., GALLI, C., LAZZARI, G., BIRD, A., YOUNG, L.E. and MEEHAN, R.R., 2004. The effect of interspecific oocytes on demethylation of sperm DNA Proceedings of the National Academy of Sciences of the United States of America. 101(20), 7636-7640
• BEAUJEAN, N., HARTSHORNE, G., CAVILLA, J., TAYLOR, J., GARDNER, J., WILMUT, I., MEEHAN, R. and YOUNG, L., 2004. Non-conservation of mammalian preimplantation methylation dynamics Current Biology. 14(7), R266-R267
• BEAUJEAN, N., TAYLOR, J., GARDNER, J., WILMUT, I., MEEHAN, R. and YOUNG, L., 2004. Effect of limited DNA methylation reprogramming in the normal sheep embryo on somatic cell nuclear transfer Biology of Reproduction. 71(1), 185-193
• YOUNG,L.E., REES,W.D. and SINCLAIR,K.D, 2004. Programming in the pre-implantation embryo. In: Fetal nutrition and Adult Disease: Programming of chronic disease through fetal exposure to undernutrition CAB International, Oxford.
• YOUNG, L. E. and BEAUJEAN, N., 2004. DNA methylation in the preimplantation embryo: the differing stories of the mouse and sheep Animal Reproduction Science. VOL 82/83, 61-78
• YOUNG, L. E., SCHNIEKE, A. E., MCCREATH, K. J., WIECKOWSKI, S., KONFORTOVA, G., FERNANDES, K., PTAK, G., KIND, A. J., WILMUT, I. and LOI, P., 2003. Conservation of IGF2-H19 and IGF2R imprinting in sheep: effects of somatic cell nuclear transfer Mechanisms of Development. VOL 120(NUMBER 12), 1433-1442
• YOUNG,L.E., REES,W.D. and SINCLAIR,K.D, 2003. Nutritional programming of DNA methylation in the preimplantation embryo.. In: Frontiers in Nutritional Sciences: Fetal Nutrition and Adult Disease
• YOUNG, L. E., 2003. Scientific hazards of human reproductive `cloning' Human Fertility. VOL 6(PART 2), 59-63
• TAYLOR, J., FAIRBURN, H., BEAUJEAN, N., MEEHAN, R. and YOUNG, L., 2003. Gene expression in the developing embryo and fetus Reproduction. Supplement. ISSU 61, 151-165
• WILMUT, I, BEAUJEAN, N, DE SOUSA, P A, DINNYES, A, KING, T J, PATERSON, L A, WELLS, D N and YOUNG, L E, 2002. Somatic cell nuclear transfer. Nature. 419(6907), 583-6
• FAIRBURN, H. R., YOUNG, L. E. and HENDRICH, B. D., 2002. Epigenetic Reprogramming: How Now, Cloned Cow? Current Biology. VOL 12(NUMBER 2), R68-R70
• YOUNG, L.E., FERNANDES, K., MCEVOY, T.G., BUTTERWITH, S.C., GUTIERREZ, C.G., CAROLAN, C., BROADBENT, P.J., ROBINSON, J.J., WILMUT, I. and SINCLAIR, K.D., 2001. Epigenetic change in <i>IGF2R</i> is associated with fetal overgrowth after sheep embryo culture Nature Genetics. 27(2), 153-154
• YOUNG, L. E., 2001. Imprinting of Genes and the Barker Hypothesis Twin Research. VOL 4(PART 5), 307-317
• DE SOUSA, P A, KING, T, HARKNESS, L, YOUNG, L E, WALKER, S K and WILMUT, I, 2001. Evaluation of gestational deficiencies in cloned sheep fetuses and placentae. Biology of Reproduction. 65(1), 23-30
• MCEVOY, T. G., SINCLAIR, K. D., YOUNG, L. E., WILMUT, I. and ROBINSON, J. J., 2000. Large offspring syndrome and other consequences of ruminant embryo culture in vitro: relevance to blastocyst culture in human ART Human Fertility. VOL 3(PART 4), 238-246
• SINCLAIR, K. D., YOUNG, L. E., WILMUT, I. and MCEVOY, T. G., 2000. In-utero overgrowth in ruminants following embryo culture: lessons from mice and a warning to men Human Reproduction. VOL 15(SUPP/5), 68-86
• YOUNG, L. E. and FAIRBURN, H. R., 2000. IMPROVING THE SAFETY OF EMBRYO TECHNOLOGIES: POSSIBLE ROLE OF GENOMIC IMPRINTING Theriogenology. VOL 53(NO 2), 627-648
• WILMUT, I, YOUNG, L, DESOUSA, P and KING, T, 2000. New opportunities in animal breeding and production - an introductory remark. Animal Reproduction Science. 60-61, 5-14