KU Clinical Research: Fairway Auditorium
4350 Shawnee Mission Parkway Fairway, KS 66205
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Speaker- Doug Wallace, PhD
Rescuing mtDNA-encoded Mitochondrial Diseases Through Import and Expression of Exogenous Transcripts in Mitochondria
The investigation of nuclear encoded mitochondrial proteins has been simplified due to an abundance of methods for manipulating the nuclear genome. However, methods for studying the effects of mutations found in mitochondrial DNA (mtDNA) are limited and indirect, resulting in a significant gap in our ability to address fundamental questions about mitochondrial contribution to disease. In an attempt to bridge this gap, we used an RNA localization sequence derived from H1 RNA, previously discovered by Koehler and Teitell to deliver mRNA of native mtCO2 and mtCO3 to mitochondria for translation in situ. Our results indicate successful import and translation of these mRNA’s within the mitochondrial matrix of SH-SY5Y human neuroblastoma cells. We are currently developing this method as a means for functional rescue of mtDNA-encoded neurological and mitochondrial defects in mtATP8 mutant mice and cells by targeting nucleus-transcribed mitochondrial mRNA transcripts to mitochondria for translation and functional incorporation into electron transport chain (ETC) holoenzymes. Our long-term goals are to study the functional consequences of disease-associated single nucleotide polymorphisms on mitochondrial function and brain aging.
Speaker: Hao Zhu, PhD
Dr. Zhu is currently a tenured Associate Professor. At KUMC, he is a recipient of institutional Faculty Research Award (2011) and Mentorship Award (2014 and 2016) from the Master of Science in Molecular Biotechnology Program. He has mentored 4 PhD students, 4 MS students and 5 visiting scholars, served on 18 doctoral dissertation and 12 MS thesis committees, and hosted more than 15 college and high-school students for summer research. Between January 1st and June 30th 2017, Dr. Zhu is on sabbatical leave at Washington University in St. Louis developing collaborative studies with Dr. Fumihiko Urano to further characterize how Ncb5or contributes to cell metabolism and stress response.