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Faculty Interests Database

Edward Grabczyk, PhD

School of Medicine
Genetics
egrabc@lsuhsc.edu

 
Research Website:
 http://www.medschool.lsuhsc.edu/genetics/faculty_detail.aspx?name=grabczyk_ed

Keywords Associated with Work DNA Repeat Expansion
Friedreich Ataxia
Huntington Disease
Neurodegenerative Diseases
Spinocerebellar Ataxias
Translational Research
Trinucleotide Repeat Expansion
Primary Research / Clinical / Teaching Interests DNA Mismatch Repair
DNA Repeat Expansion
Friedreich Ataxia
Huntington Disease
Secondary Research / Clinical / Teaching Interests MLH3 (MutL Protein Homolog 3) A minor mismatch repair protein subunit called MLH3 selectively cuts DNA in a way that causes DNA repeats to expand. MLH3 is expressed as two isoforms via alternative splicing in human tissue, isoform one causes DNA repeat expansion but isoform two does not.
Unique Equipment Used Oxford Nanopore MinION Molecular Sequencer The Oxford Nanopore MinION uses nanopores connected to sensor chips to measure disruption of current as a DNA or RNA molecule traverses the pore to determine the sequence. The molecular pore technique can sequence a DNA molecule over a million bases long. Whereas the short reads generated by "Next gen" sequencing are all but useless for tandem repeats. PCR-free sequencing of native DNA or RNA also provides base modification data such as DNA methylation.
Unique Techniques Used or Developed Therapeutic splice redirection of MLH3 isoforms MutL-gamma, a minor mismatch repair component comprised of MLH1-MLH3 heterodimers, is the active agent in DNA repeat expansion. We showed that MLH3 isoform 1 contributes to DNA repeat expansion, but that MLH3 isoform 2 does not. The two isoforms differ by one small exon, and exclusion of this exon by oligonucleotide mediated splice redirection can slow or stop DNA repeat expansion. As a therapeutic approach, MLH3 splice redirection has the potential to treat many if not all the DNA repeat expansion disorders.
Last Updated: 04/30/2024