Photo of Stefan F. Pinter, Ph.D.

Stefan F. Pinter, Ph.D.

Assistant Professor, Genetics and Genome Sciences
Institute for Systems Genomics
Assistant Director, Graduate Program in Genetics and Developmental Biology
Academic Office Location:
Genetics & Genome Sciences
UConn Health
400 Farmington Avenue
Farmington, CT 06030-6403
Phone: 860-679-3657
Fax: 860-679-8345
Email: spinter@uchc.edu
Website(s):

Pinter Lab Website

Genetics and Developmental Biology Graduate Program

Education
DegreeInstitutionMajor
B.S.St. Michael’s CollegeBiology
Ph.D.Princeton UniversityMolecular Biology

Post-Graduate Training
TrainingInstitutionSpecialty
PostdoctoralMGH, Harvard Medical SchoolResearch Fellow in Molecular Biology

Awards
Name of Award/HonorAwarding Organization
Centennial Award for Molecular Genetics ArticleGenetics Society of America
Fund for Medical Discovery FellowshipMassachusetts General Hospital
Research FellowshipGerman Research Foundation (DFG)
Name & DescriptionCategoryRoleTypeScopeStart YearEnd Year
Trisomy 21 Research Society (T21RS)Professional/Scientific OrganizationMemberExternalInternational2019
Genetics & Developmental Biology Graduate ProgramEducation CommitteeAssistant DirectorUConn HealthUniversity2017
Biomedical Science Admissions CommitteeEducation CommitteeApplication review and interviewingUConn HealthUniversity20162019

Our primary research interest is to understand how chromosomal gene dosage impacts human development, specifically in two viable human aneuploidy conditions: Turner Syndrome (monosomy X) and Down syndrome (trisomy 21). To this end, we develop computational & molecular approaches to accurately distinguish parental alleles, and alter their expression across chromosomes X & 21 using long non-coding RNA and CRISPR-mounted tools. We apply these techniques in human induced pluripotent stem cells (hiPSCs) that we derived alongside isogenic euploid control lines to model developmental aspects of Turner & Down syndrome in vitro.

The mammalian X provides a unique perspective on chromosomal gene dosage, as a classic model of epigenetics: X chromosome inactivation (XCI), the process by which one X chromosome in females is silenced to achieve gene dosage parity with males. To establish XCI, the long non-coding RNA XIST accumulates on the X from which it is transcribed, and orchestrates a series of changes in subnuclear localization, chromosome topology, chromatin compaction and regulatory modifications to stably silence genes in cis. Some genes however, are skipped by XIST and remain active on the inactive X chromosome, thereby escaping XCI. Our long-term goal is understand the mechanisms that insulate such “escapee” genes against the spread of heterochromatin, and translate these lessons to X-linked genetic disorders that can manifest heterozygous females, including Rett’s syndrome and Duchenne’s muscular dystrophy.

Importantly, because many escapee genes have Y-linked homologs (X-Y pair or gametologs), they are expressed from two active copies in both XY males and XX females. Turner’s syndrome (TS, karyotype 45,X) is hypothesized to result from haploinsufficiency in some of these genes, but only its cardinal phenotype (short stature) has been conclusively mapped to an X-Y pair to-date. Yet, by far the most frequent outcome of XO karyotype, is failure to reach term (est. 10-15% of all spontaneous terminations), and life-span in TS patients is reduced (~15 years) due to progressive aortic defects. We aim to use our TS hiPSC models to determine which genes contribute to the (extra)-embryonic defects that underpin these TS phenotypes.

In contrast, excess gene dosage from chromosome 21 causes Down Syndrome (DS), the most frequent viable aneuploidy in humans (karyotype 47, +21 incidence of 1 in 700). DS encompasses a range of phenotypes including congenital heart disease, immunodeficiency, and intellectual disability. In concert with signs of accelerated aging, middle-aged individuals with DS tend to develop highly-penetrant, early-onset Alzheimer’s disease (AD), making DS the most frequent single genetic cause of AD overall. We are re-purposing XIST to silence one of the three copies of chromosome 21 in our DS hiPSCs learn how trisomy 21 impacts neural development. Using allele-specific CRISPR-mounted tools, we also aim to dissect which genes contribute to DS-relevant cellular phenotypes and to explore avenues to correct their dosage.


 

Accepting Lab Rotation Students: Summer 2021, Fall 2021, and Spring 2022

Journal Articles

Reviews

Title or AbstractTypeSponsor/EventDate/YearLocation
Silencing a Single Copy of Chromosome 21 in Down Syndrome Stem CellsTalkMassachusetts Down Syndrome Congress. 36th Annual Conference2020Virtual
Contiguous Erosion of the Inactive X in Human Pluripotency Concludes with Global DNA HypomethylationTalkNew Horizons in Genomics. QMUL Epigenetics Hub2020Virtual
Trisomy 21 Silencing: Towards a Dynamic In Vitro Model of Down SyndromeTalk New England Down Syndrome Symposium. Alana Center MIT2020Virtual
Resolving Chromosome Dosage in Stem Cell Models of Viable Human AneuploidyTalkFrom Stem Cells to Human Development. Company of Biologists2020Virtual
Gene Dosage in Cellular Models of Trisomy 21TalkAlexander's Angels / The Up of Down Conference2019NYU Langone Winthrop Hospital
(Epi)genetic approaches towards resolving trisomy 21 gene-dosage contributionsTalkTrisomy 21 Research Society / Biennial T21RS International Conference2019Barcelona, Spain
Chromosome dosage & compensation in stem cell models of viable human aneuploidyTalkDean's Faculty Research Seminar, UConn Health2018Farmington, CT
Of Megadomains and Superloops: How Tandem Repeats Shape the Inactive X ChromosomeTalkFusion Conference on Epigenetics2018Cancun, Mexico
Causes and Consequences of Allelic Dosage RegulationTalkFels Institute, Temple University2017Philadelphia, PA
Allelic imbalance is a prevalent and tissue-specific feature of autosomal and X-linked genes in F1 hybrid miceTalkThe Allied Genetics Conference (TAGC), Genetics Society of America (GSA)2016Orlando, FL
Tissue-specific Allelic Imbalance is Prevalent in Hybrid MiceTalkAbcam Epigenetics Conference2015Boston, MA
Tissue-specific Allelic Imbalance of Mouse Autosomal GenesTalkNE Regional Chromosome Pairing Conf.2014Boston, MA
Spreading of X-Chromosome InactivationTalkHMS Program in Genetics and Genomics2014Boston, MA
Mapping of Xist RNA and Polycomb Repressive Complex 2 across the inactive XTalkBerlin Summer Meeting, Max-Delbrück Centre for Molecular Medicine2013Berlin, Germany