Debbie McKenzie

Debbie McKenzie

PhD: University of Calgary

Post-doctoral Physiological Chemistry, University of Wisconsin at Madison

Position: Professor Emaritus 

Department of Biological Sciences Faculty of Science
Centre for Prions and Protein folding diseases

E-mail: debbie.mckenzie@ualberta.ca

Background

My research interests encompass two major areas: prion disease and biology of aging. My interest in prion diseases has focused elucidating the properties of this unusual infectious agent as well as its biology and transmission properties. The major foci of my prion research are 1) etiological, biological and biochemical characterization of chronic wasting disease and 2) mechanisms of prion strain cell tropism. An additional focus of my laboratory is age-related changes in tissues defining the role of age-dependent accumulation of mitochondrial DNA deletion mutations on aging processes

Current 91ÒùĸÊÓƵ

Chronic Wasting Disease (CWD) Strains:

CWD affects deer, elk, moose, and caribou across North America. We have demonstrated that polymorphisms in PRNP (the gene encoding the prion protein) affect susceptibility to disease and can result in the generation of novel strains. We characterized a new CWD strain, H95+ (Duque Velasquez et al., 2015). This novel strain has different biological (host range) and biochemical properties than more common cervid CWD strains. Ongoing studies include:

  • Characterization of CWD strains at the biological and biochemical levels (Gilch, University of Calgary).
  • Delineating interactions of CWD prions with soil and plants (Aiken, CPPFD)

Innate Immune Responses and Prion Infection

Activation of innate immunity in primary cultures of mixed neuronal and glial cells results in a reduction of PrP-res accumulation (the misfolded conformer) while inhibition of specific immune pathways enhances prion accumulation (Kang et al., 2016). 

Metabolic dysfunction in cells containing mitochondrial DNA deletions

The age-dependent loss of cells in the brain, muscle, heart and other terminally differentiated tissues is an integral component of the aging process, yet the molecular basis is not yet understood. We have, in collaboration with Aiken (CPPFD) and Wanagat (UCLA), demonstrated that age-dependent muscle fiber loss is a result of the accumulation of mitochondrial DNA deletion mutations. These deletion mutations occur focally and segmentally, cause abnormalities in the electron transport chain with subsequent fiber loss due to apoptotic and necrotic events (Cheema et al., 2015). 

Selected publications

Otero, A., Velásquez, C.D., Aiken, J. et al. Vet Res 52, 115 (2021).

Otero A, Duque Velásquez C, Aiken J, McKenzie D. Sci Rep. 2021 May 27;11(1):11193. doi: 10.1038/s41598-021-90606-8. PubMed PMID: 34045540; PubMed Central PMCID: PMC8160261.

Silva, C.J., M.L. Erickson-Beltran, C. Duque Velasquez, J.M. Aiken and D. McKenzie. 2019. Analytical Chemistry. Dec 9. doi: 10.1021/acs.analchem.9b04449. [Epub ahead of print]

Herbst, A., A.N. Hoang, W. Woo, D. McKenzie, J.M. Aiken, R.A. Miller, D.B. Allison, N. Liu and J. Wanagat. Mitochondrial DNA alterations in aged macrophage migration inhibitory factor-knockout mice Mechanisms in Ageing and Development. 82:111126. IF: 3.603. Ranking: (Aging) Q2.

Otero, A., C.D. Velasquez, C. Johnson, A. Herbst, R. Bolea, J.J. Badiola, J. Aiken and D. McKenzie. 2019. BMC Veterinary 91ÒùĸÊÓƵ 15: 50. IF: 1.98 Ranking: 20/140 (Veterinary Science) Q1.

Kuznetsova, A., C. Cullingham, D. McKenzie and J.M. Aiken. 2018. PLoS Pathogens 14: e1007414. IF: 6.158 Ranking: 14/126 (Microbiology) Q1.

Herbst, A., C.D. Velasquez, E. Triscott, J.M. Aiken and D. McKenzie. 2018. Emerging Infectious Diseases 23: 1598-1600. IF: 7.422 Ranking: 4/88 (Infectious Disease) Q1.

Bielas, J., A. Herbst, K. Widjaja, J. Hui, J.M. Aiken, D. McKenzie, R.A. Miller, S.V. Brooks and J. Wanagat. 2018. Experimental Gerontology 106: 125-131. IF: 3.224 Ranking: 19/53 (Geriatics and Gerontology) Q2.

Herbst, A., K. Widjaja, B. Nguy, E.B. Lushaj, T.M. Moore, A.L. Hevener, D. McKenzie, J. Aiken and J. Wanagat. 2018. Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences 72: 1327-1333. IF: 4.902 Ranking: 7/53 (Geriatics and Gerontology) Q1.

Gushue, D., A. Herbst, V. Sim, D. McKenzie and J.M. Aiken. 2018. Prion 12: 253-260. IF: 2.011 Ranking: 209/293 (Biochemistry and Molecular Biology) Q3.

Kang, S.G., C. Kim, J. Aiken, H.S. Yoo and D. McKenzie. 2017. . Molecular Neurobiology 55: 2384-2396. IF: 5.076 Ranking: 44/261 (Neurosciences) Q1.