Stefan F. Pinter, Ph.D.Assistant Professor, Genetics and Genome Sciences
Institute for Systems Genomics
|B.S.||St. Michael’s College||Biology|
|Ph.D.||Princeton University||Molecular Biology|
|Postdoctoral||MGH, Harvard Medical School||Research Fellow in Molecular Biology|
|Name of Award/Honor||Awarding Organization|
|Centennial Award for Molecular Genetics Article||Genetics Society of America|
|Fund for Medical Discovery Fellowship||Massachusetts General Hospital|
|Research Fellowship||German Research Foundation (DFG)|
|Name & Description||Category||Role||Type||Scope||Start Year||End Year|
|Assistant Director, Genetics & Developmental Biology Graduate Program||Education Committee||Member of AoC executive committee||UConn Health||University||2017|
The primary research objective in my lab is to learn how chromosome topology, non-coding (nc)RNA and chromatin modifiers orchestrate gene expression. Over a decade of genome-wide association studies has revealed a common theme in a wide variety of conditions, namely, that the vast majority of risk/benefit conferring variants reside not in genes, but in non-coding regions of the genome that control gene expression. Yet, our mechanistic understanding of gene regulation is insufficient to predict the functional impact of these variants or to impose desired gene expression outcomes epigenetically. We therefore develop novel and scalable genomic methodology to explore several poorly-understood aspects of gene regulation, particularly at the intersection of genome architecture and transcription.
The mammalian X chromosome provides a unique and informative perspective on this problem, in 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. XCI combines changes in nuclear architecture, chromosome topology, chromatin compaction, and nucleosome/nucleotide-level modifications to silence the X chromosome, all driven initially by the cis-acting long ncRNA Xist. Some X-linked genes however, are skipped by Xist and remain active, escaping XCI on the otherwise inactive X chromosome (“escapees”).
We are interested in understanding the mechanisms that allow escapees to insulate themselves against an oncoming wave of heterochromatin. Translating these lessons to other X-linked genes that are subject to XCI, may allow us to address genetic disorders affecting heterozygous females, including Rett’s syndrome (MECP2) and Duchenne’s muscular dystrophy (DMD). Furthermore, because several escapees have Y-linked homologs, both XY males and XX females have two active copies. Turner’s syndrome (XO karyotype) is therefore likely the result of haploinsufficiency in one or more of these genes. By far the most frequent outcome of XO karyotype, is failure to reach term due to placental defects, accounting for an estimated 10-15% of all spontaneous terminations. We aim to dissect which genes contribute to this developmental disorder and explore avenues to correct their dosage in the relevant extra-embryonic cell types.
Accepting Lab Rotation Students: Summer '18, Fall '18, Spring '19
|Title or Abstract||Type||Sponsor/Event||Date/Year||Location|
|Of Megadomains and Superloops: How Tandem Repeats Shape the Inactive X Chromosome||Talk||Fusion Conference on Epigenetics||2018||Cancun, Mexico|
|Causes and Consequences of Allelic Dosage Regulation||Talk||Fels Institute, Temple University||2017||Philadelphia, PA|
|Allelic imbalance is a prevalent and tissue-specific feature of autosomal and X-linked genes in F1 hybrid mice||Talk||The Allied Genetics Conference (TAGC), Genetics Society of America (GSA)||2016||Orlando, FL|
|Tissue-specific Allelic Imbalance is Prevalent in Hybrid Mice||Talk||Abcam Epigenetics Conference||2015||Boston, MA|
|Tissue-specific Allelic Imbalance of Mouse Autosomal Genes||Talk||NE Regional Chromosome Pairing Conf.||2014||Boston, MA|
|Spreading of X-Chromosome Inactivation||Talk||HMS Program in Genetics and Genomics||2014||Boston, MA|
|Mapping of Xist RNA and Polycomb Repressive Complex 2 across the inactive X||Talk||Berlin Summer Meeting, Max-Delbrück Centre for Molecular Medicine||2013||Berlin, Germany|