McKee Research

A man in a lab coat examines a specimen through a microscope in a laboratory setting.Edward McKee’s laboratory was involved for many years in NIH supported research in mitochondrial bioenergetics, biogenesis, and drug toxicity. He moved away from research from 2015 to 2021 to serve as Senior Associate Dean of Research at CMED. He has stepped down from this position and has re-entered the laboratory to study mitochondrial DNA depletion diseases caused by interference with the synthesis of deoxynucleotide triphosphates (dNTPs) required for mitochondrial DNA replication, particularly in non-mitotic tissues. In conjunction with Dr. Demireva at Michigan State University they have generated several transgenic rat models that have deficiencies in two mitochondrial deoxynucleoside kinases, deoxyguanosine kinase or thymidine kinase 2. In humans deficiencies in either of these kinases are severe and are often fatal before the age of 5. While the condition can be improved by deoxynucleoside supplementation, the patients remain quite sick. They are now breeding these animals and beginning to collect preliminary data on the homozygous affected animals. They have two major goals. The first is to use radiolabeled precursors to understand how deoxynucleoside supplementation improves the condition.  The second is to use novel delivery systems of dNTPs to potentially provide a better treatment. We hope to submit a grant proposal early summer.

View Edward McKee's recent publications

Techniques used

  Techniques used in the laboratory include:

  1. *Isolation and measurement of transgenic rat tissue mitochondrial DNA to nuclear DNA using RT-PCR as a function of age and condition.
  2. *Isolation of transgenic tissue mitochondria to measure mitochondrial respiration using the Oroboros oxygraph as a function of age and condition.
  3. *Measurement of transgenic rat tissue levels of dNTPs using a primer extension assay as a function of age and condition.
  4. *Isolation of transgenic rat tissue mitochondria to measure the conversion of radiolabeled deoxynucleosides to dNTPs followed by extraction and quantitation by UPLC as a function of age and condition.
  5. *Growth and maintenance of cell-cultures used to test novel deliver systems.
  6. Rat heart perfusion of transgenic rat hearts to measure the conversion of radiolabeled deoxynucleosides to dNTPs followed by extraction and quantitation by UPLC as a function of age and condition.
  7. Development of novel delivery systems of dNTPs or precursors.
  8. Rat heart perfusion to test novel delivery systems.

McKee lab staff and volunteers

Paid staff: Avery Ward – technician.

Volunteers: Kayleigh Crane, second-year medical student, and Logan Nauts, first-year medical student.

McKee lab location

The McKee lab is housed in the Research Laboratory building at 2630 Denison Drive, south of the main campus.