Trisomy 21 Dosage Correction and Mapping Resource (T21DoCoMap) and XIST silencing in mature neurons.

University of Connecticut

Principal Investigator: 

  • Dr. Stefan Pinter, PhD

Experimental research

Dr. Stefan Pinter, PhD
Tackling the extra chromosomal material seen in Down syndrome

Dr. Pinter’s research is focused on understanding how chromosome arrangement and other genetic features orchestrate gene expression in Down syndrome (Ds). The presence of an additional full or partial chromosome 21 affects cellular health by impacting the important processes of DNA replication and cellular division. Research has indicated that altered expression of certain genes is seen throughout the entire genome.

More than a decade of association studies between portions of the genome and various diseases has revealed that much of the variety in gene characteristics that are either beneficial or detrimental, are not in the genes themselves, but actually in the portions of the genome that control gene expression. Therefore, a better understanding of the mechanisms that lead to altered gene expression may help in identifying targets for Ds-related gene therapies.

Dr. Pinter brings long-standing expertise on how chromosome arrangement and other contributors to gene expression, such as a type of non-coding RNA and chromatin modifiers, may be altered in individual’s with Ds. He is also an expert on diseases and conditions of the X-chromosome. Dr. Pinter has explored mechanisms that can inactivate sex-linked trisomies using the XIST promoter. In all typically-developing females, XIST plays a critical role in silencing one of the two copies of the X-chromosome. This is a natural silencing strategy used by the cells balances the gene dosage in males (since they only have one X-chromosome).

In theory, this same silencing mechanism could be applied to inactivate the extra chromosome 21 in Ds in order to balance the gene dosage and normalize the gene expression. Dr. Pinter is bringing his knowledge of gene expression regulation to the field of Ds to better develop this silencing therapy.





Target Life-stage

Ongoing stem cell work using skin cells
Several years until preclinical trials
Early translational research and deepening of genetic understanding
Life long