Collaborate 2 Cure
June 5, 2017



KU Clinical Research: Fairway Auditorium
4350 Shawnee Mission Parkway Fairway, KS 66205

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Relationships Between Mitochondria and Beta Amyloid


Existing data strongly suggest a relationship exists between mitochondria, bioenergetics, and APP processing. In particular, changes in mitochondrial respiratory flux appear to alter Aβ production. We predict that a cell’s bioenergetic state can alter APP amyloidogenic processing.  Under conditions of increased reactive oxygen species (ROS) production and hyperpolarized mitochondrial membrane potential, we observe increased APP amyloidogenic processing. Conversely, under conditions of decreased ROS production and depolarized mitochondrial membrane potential we observe decreased APP amyloidogenic processing. This presentation will review pertinent data to this relationship between mitochondria, bioenergetics, and Aβ production. If our hypothesis is correct, a better understanding of the relationship between mitochondrial function, cell bioenergetics, and Aβ could enhance our understanding of AD.

Speaker- Heather Wilkins, PhD

Dr. Heather Wilkins is a postdoctoral fellow at the University of Kansas Alzheimer’s Disease Center and department of Neurology. Dr. Wilkins’ area of expertise is mitochondria, bioenergetics, and amyloid precursor protein biology. The focus of her research is the intersection of bioenergetics and amyloid production pathways.

Next Generation Sequencing as a Molecular Diagnostic Tool for Infantile Mitochondrial Diseases


At least 270 mitochondrial-disease genes have been identified to date, with up to 20 new disease genes described every year. We anticipate the discovery of many more, since over 1000 nuclear genes are known to participate in mitochondrial biology. We have been offering Next-generation sequencing (NGS) since 2011 as part of an undiagnosed disease program at The Center for Pediatric Genomic Medicine (CPGM) at Children’s Mercy Hospital. Like many other centers, we have published diagnostic yields of ~50% for certain disease groups, including neurodevelopmental disabilities. However, challenges remain in diagnosing the remaining half of these patients with rare disorders, which may harbor variants refractory to standard diagnosis. An important adjunct to NGS (WES or WGS) is functional studies & transcriptomics (RNA-seq), which are emerging as powerful tools to examine the impact of genomic variants on transcript expression, identify the potential pathways involved in pathogenesis, and assess the impact of a disease-causing variant on protein complexes. NGS coupled with downstream functional studies will boost diagnostic rates for pediatric mitochondrial diseases. Characterization of the impact of variants by biochemical and/or functional studies will lead to a better understanding of the process of mitochondrial dysfunction, shedding light on potential therapeutic strategies that could potentially be applicable to the more common acquired mitochondrial anomalies such as in metabolic and other neurodegenerative diseases.

Speaker- Isabelle Thiffault, PhD

Dr Thiffault, who is originally from Canada, joined Children’s Mercy Hospital 3 years ago, as Assistant director for the clinical laboratory at the Center for Pediatric Genomic at Children’s Mercy Hospitals & Clinics. While conducting her postdoctoral studies at McGill University with renowned scientist Dr. Eric Shoubridge, Dr Thiffault employed induced stem cells (iPS) as a model for studying mitochondrial dysfunction. Her longstanding scientific interest is in elucidating the genetic nature of mitochondrial disorders by using traditional and genomic technologies and by establishing genotype-phenotype correlations.