Research Interests:Model-based molecular genetic analysis of trisomy 21 and other human genomic rearrangements
About Y. Eugene Yu
Dr. Yu received his PhD degree from the University of Texas at Austin. As a postdoctoral project investigator, he set up a transgenic mouse facility at MD Anderson Cancer Center Science Park. As a research associate in Marvin Meistrich’s laboratory at MD Anderson Cancer Center, he worked on generation and characterization of mouse mutants deficient in transition proteins. As a research associate/research assistant professor in Allan Bradley’s laboratory at Baylor College of Medicine, he generated chromosomal deletions and duplications to facilitate genetic analysis of mouse chromosome 11 and human chromosome 17. Currently, he is a faculty member of the Department of Cancer Genetics and Genomics, Genetics and Genomics Program, at Roswell Park Comprehensive Cancer Center, and Genetics, Genomics and Bioinformatics Program at the University at Buffalo. He directs the Children’s Guild Foundation Down Syndrome Research Program as well as the Gene Targeting and Transgenic Shared Resource at Roswell Park Comprehensive Cancer Center.
- Director, Gene Targeting and Transgenic Shared Resource
- Professor of Oncology
- Department of Cancer Genetics and Genomics
Education and Training:
- PhD - Biological Sciences, University of Texas at Austin
One of the current focuses of Dr. Yu's laboratory is the molecular genetic analysis of human trisomy 21 (Down syndrome). Trisomy 21 is the most frequent live-born human aneuploidy. In the United States, trisomy 21 occurs in approximately one in 691 newborns. Trisomy 21 is the most common genetic cause of congenital heart disease and cognitive deficits. It is a leading genetic cause of megakaryoblastic leukemia and early-onset Alzheimer-type neurodegeneration. The mouse is the premier model organism for Down syndrome because of the existence of highly conserved orthologous regions between human chromosome 21 and three segments of the mouse genome on mouse chromosomes 10, 16 and 17. Using recombinase-mediated chromosome engineering, Dr. Yu’s laboratory has developed the most complete Down syndrome model to date, which carries the duplications spanning the entire human chromosome 21 orthologous regions on three mouse chromosomes. The laboratory is currently in the process of generating and analyzing new mouse mutants that carry the desired duplications and deletions of the human chromosome 21 orthologous regions in order to narrow down the genomic regions associated with the trisomy 21 phenotypes. Their goal is to identify the dosage-sensitive genes underlying the phenotypes.
Dr. Yu's laboratory is also interested in the mouse-based genetic dissection of tumor-associated chromosomal rearrangements. Such efforts should facilitate the establishment of critical genetic alterations in the formation of various types of human tumors.
- Yu YE, Zhang Y, Unni E, Shirley CR, Deng JM, Russell LD, Weil MM, Behringer RR, Meistrich ML. Abnormal spermatogenesis and reduced fertility in transition nuclear protein 1-deficient mice. Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4683-8.
- Yu Y, Bradley A. Engineering chromosomal rearrangements in mice. Nat Rev Genet. 2001 Oct;2(10):780-90. PMID: 11584294.
- Adams DJ, Biggs PJ, Cox T, Davies R, van der Weyden L, Jonkers J, Smith J, Plumb B, Taylor R, Nishijima I, Yu Y, Rogers J, Bradley A. Mutagenic insertion and chromosome engineering resource (MICER). Nat Genet. 2004 Aug;36(8):867-71. PMID: 15235602.
- Li Z, Yu T, Morishima M, Pao A, LaDuca J, Conroy J, Nowak N, Matsui S, Shiraishi I, Yu YE. Duplication of the entire 22.9 Mb human chromosome 21 syntenic region on mouse chromosome 16 causes cardiovascular and gastrointestinal abnormalities. Hum Mol Genet. 2007 Jun 1;16(11):1359-66. PMID: 17412756.
- Yu T, Li Z, Jia Z, Clapcote SJ, Liu C, Li S, Asrar S, Pao A, Chen R, Fan N, Carattini-Rivera S, Bechard AR, Spring S, Henkelman RM, Stoica G, Matsui S, Nowak NJ, Roder JC, Chen C, Bradley A, Yu YE. A mouse model of Down syndrome trisomic for all human chromosome 21 syntenic regions. Hum Mol Genet. 2010 Jul 15;19(14):2780-91. PMCID: PMC2893810.
- Zhang L, Meng K, Jiang X, Liu C, Pao A, Belichenko PV, Kleschevnikov AM, Josselyn S, Liang P, Ye P, Mobley WC, Yu YE. Human chromosome 21 orthologous region on mouse chromosome 17 is a major determinant of Down syndrome-related developmental cognitive deficits. Hum Mol Genet. 2014 Feb 1;23(3):578-89. PMCID: PMC3888256.
- Grandi FC, Rosser JM, Newkirk SJ, Yin J, Jiang X, Xing Z, Whitmore L, Bashir S, Ivics Z, Izsvák Z, Ye P, Yu YE, An W Retrotransposition creates sloping shores: a graded influence of hypomethylated CpG islands on flanking CpG sites. Genome Res. 2015 Aug 25(8):1135-46. PMCID:PMC4509998.
- Jiang X, Liu C, Yu T, Zhang L, Meng K, Xing Z, Belichenko PV, Kleschevnikov AM, Pao A, Peresie J, Wie S, Mobley WC, Yu YE. Genetic dissection of the Down syndrome critical region. Hum Mol Genet. 2015 Nov 15;24(22):6540-51. PMCID:PMC4614710.
- Mendioroz M, Do C, Jiang X, Liu C, Darbary HK, Lang CF, Lin J, Thomas A, Abu-Amero S, Stanier P, Temkin A, Yale A, Liu M-M, Li Y, Salas M, Kerkel K, Capone G, Silverman W, Yu YE, Moore G, Wegiel J, Tycko B. Trans-effects of chromosome aneuploidies on DNA methylation patterns: mechanistic insights from analysis of human Down syndrome and mouse models. Genome Biol. 2015, Nov 25, 16:263. PMCID:PMC4659173.
- Do C, Xing Z, Yu YE*, Tycko B*. Trans-acting epigenetic effects of chromosomal aneuploidies: lessons from Down syndrome and mouse models. Epigenomics. 2017 Feb 9(2):189-207. PMCID:PMC5549717.
- Kleschevnikov AM, Yu J, Kim J, Lysenko LV, Zeng Z, Yu YE, Mobley WC. Evidence that increased Kcnj6 gene dose is necessary for deficits in behavior and dentate gyrus synaptic plasticity in the Ts65Dn mouse model of Down syndrome. Neurobiol Dis. 2017 Jul;103:1-10. doi: 10.1016/j.nbd.2017.03.009. Epub 2017 Mar 22. PubMed PMID: 28342823; PubMed Central PMCID: PMC5446050.
- Herault Y, Delabar JM, Fisher EMC, Tybulewicz VLJ, Yu E, Brault V. Rodent models in Down syndrome research: impact and future opportunities. Dis Model Mech. 2017 Oct 1;10(10):1165-1186. doi: 10.1242/dmm.029728. Review. PubMed PMID: 28993310; PubMed Central PMCID: PMC5665454.
- Liu C, Yu T, Xing Z, Jiang X, Li Y, Pao A, Mu J, Wallace PK, Stoica G, Bakin AV, Yu YE. Triplications of human chromosome 21 orthologous regions in mice result in expansion of megakaryocyte-erythroid progenitors and reduction of granulocyte-macrophage progenitors. Oncotarget. 2018 Jan 12;9(4):4773-4786. doi: 10.18632/oncotarget.23463. eCollection 2018 Jan 12. PubMed PMID: 29435140; PubMed Central PMCID: PMC5797011.
- Watson-Scales S, Kalmar B, Lana-Elola E, Gibbins D, La Russa F, Wiseman F, Williamson M, Saccon R, Slender A, Olerinyova A, Mahmood R, Nye E, Cater H, Wells S, Yu YE, Bennett DLH, Greensmith L, Fisher EMC, Tybulewicz VLJ. Analysis of motor dysfunction in Down Syndrome reveals motor neuron degeneration. PLoS Genet. 2018 May;14(5):e1007383. doi: 10.1371/journal.pgen.1007383. eCollection 2018 May. PubMed PMID: 29746474; PubMed Central PMCID: PMC5963810.
- Latour A, Gu Y, Kassis N, Daubigney F, Colin C, Gausserès B, Middendorp S, Paul JL, Hindié V, Rain JC, Delabar JM, Yu E, Arbones M, Mallat M, Janel N. LPS-Induced Inflammation Abolishes the Effect of DYRK1A on IkB Stability in the Brain of Mice. Mol Neurobiol. 2019 Feb;56(2):963-975. doi: 10.1007/s12035-018-1113-x. Epub 2018 May 30. PubMed PMID: 29850989.
- Souchet B, Duchon A, Gu Y, Dairou J, Chevalier C, Daubigney F, Nalesso V, Créau N, Yu Y, Janel N, Herault Y, Delabar JM. Prenatal treatment with EGCG enriched green tea extract rescues GAD67 related developmental and cognitive defects in Down syndrome mouse models. Sci Rep. 2019 Mar 8;9(1):3914. doi: 10.1038/s41598-019-40328-9. PubMed PMID: 30850713; PubMed Central PMCID: PMC6408590.
- Yu YE, Xing Z, Do C, Pao A, Lee EJ, Krinsky-McHale S, Silverman W, Schupf N, Tycko B. Genetic and epigenetic pathways in Down syndrome: Insights to the brain and immune system from humans and mouse models. Prog Brain Res. 2020;251:1-28. doi: 10.1016/bs.pbr.2019.09.002. Epub 2019 Oct 24. PubMed PMID: 32057305.
- Li Y, Xing Z, Yu T, Pao A, Daadi M, Yu YE. Coat Color-Facilitated Efficient Generation and Analysis of a Mouse Model of Down Syndrome Triplicated for All Human Chromosome 21 Orthologous Regions. Genes (Basel). 2021 August 6; 12(8): 1215. doi: 10.3390/genes12081215. PMCID: PMC8393392.
- Xing Z, Li Y, Cortes-Gomez E, Jiang X, Gao S, Pao A, Shan J, Song Y, Perez A, Yu T, Highsmith MR, Boadu F, Conroy JM, Singh PK, Bakin AV, Cheng J, Duan Z, Wang J, Liu S, Tycko B, Yu YE. Dissection of a Down syndrome-associated trisomy to separate the gene dosage-dependent and -independent effects of an extra chromosome. Hum Mol Genet. 2023 Jun 19;32(13):2205-2218. doi: 10.1093/hmg/ddad056. PubMed PMID: 37014740; PubMed Central PMCID: PMC10281752.