Yu, Eugene PHD

INCLUDE Grants​

Epigenetics of Down Syndrome

Tycko, BenjaminYu, Eugene

In this supplement/revision application, we are focused on three important co-occurring clinical phenotypes in Down syndrome (DS): age-related immune system alterations, age-dependent hearing loss, and age-dependent cognitive decline (independently of Alzheimer’s disease). Our long-term objectives are to ask whether measuring biological and molecular markers of aging in chromosomally engineered mouse models of DS can help to answer (i) what are the genes on chromosome 21 that cause early aging epigenetic aging in DS? (ii) what are the genes on this chromosome that cause early biological aging in DS (iii) does epigenetic aging influence biological aging? and (iv) do early epigenetic and biological aging contribute to the above listed medical conditions? To lay a foundation for achieving these goals, in our 2-year aims, we seek to determine whether the duplications of two chromosome 21 orthologous chromosomal regions in our mouse models affects epigenetic/transcriptomic/biological aging, thus contributing to the rate of development of the co-occurring conditions in DS, with implications for these same common age-related conditions in the general population.

Generation and analysis of new mouse models to determine novel therapeutic targets for Down syndrome-associated cognitive deficits

Yu, Eugene

Developmental delays and intellectual disabilities are common co-occurring conditions in Down syndrome, which is associated with an extra copy of human chromosome 21, and our proposed research aims to identify new target genes with therapeutic potential for improving cognitive function and thus the quality of life in people afflicted with this chromosomal alteration. These genes will be identified through the use of phenotype-based tests in mouse models tailor-made to facilitate genetic dissection of Down syndrome, and these models will be developed with the aid of CRISPR genome engineering technology. We will also test whether the characteristic features of Down syndrome are impacted by the gene-dosage-independent effects of trisomy 21, such as through alterations in the nuclear architecture, which could help to transform the current paradigm of understanding for Down syndrome-associated cognitive deficits.

Down Syndrome Publications​