91ÒùĸÊÓƵ

PhD: University of Calgary, Calgary, 91ÒùĸÊÓƵ

Post-doctoral Veterinary Sciences, University of Wisconsin at Madison

Position: Professor Emeritus

Department of Agriculture, Food and Nutritional Sciences Faculty of Agriculture, Life and Environmental Sciences Centre for Prions and Protein Folding Diseases

Environmental Contamination by Prions

Prion diseases are slowly progressive, fatal neurodegenerative disorders with no effective treatment or vaccine available. Neuropathological changes include the accumulation of abnormal prion protein aggregates, spongiform degeneration, neuronal loss, and astrogliosis. These hallmarks are diagnostic for chronic wasting disease (CWD) in cervids, scrapie in sheep and goats, bovine spongiform encephalopathy (BSE), and Creutzfeldt-Jakob disease (CJD) and variant CJD in humans.

My current research interests are:

1. Understanding the role of environmental contamination—including the binding of shed CWD prions to soils and plants—in the transmission of CWD in cervid populations. Soil can serve as a stable reservoir for infectious prion proteins, and prions bound to soil particles remain infectious in soils for many years.

2. Developing "omics" approaches to biomarker development to provide insights into the pathology and etiology of prion disease.

CWD is expanding in terms of its geographic range; it is currently present in 24 US states, 2 Canadian provinces (Saskatchewan and 91ÒùĸÊÓƵ), South Korea, and Norway. Unlike other prion diseases, CWD affects free-ranging populations of deer, elk, moose, and reindeer. Infected animals shed the infectious agent in their saliva, urine, and feces, as well as from decaying carcasses. These prions in the environment are stable and can bind to both soil and plants. Our collaborations with North Dakota Fish and Wildlife and the Norwegian Veterinary Institute, among others, are allowing us to determine the persistence and bioavailability of prions shed into the environment.

MtDNA Deletion Mutations + Aging

The loss of muscle mass and function with age is an inevitable component of the aging process. In humans, the skeletal muscle fiber number in the quadriceps declines from 600,000 at 50 years of age to 323,000 at 80 years. We have demonstrated that one cause of this decline in fiber number is the accumulation of mtDNA genomes containing large deletion mutations. Our studies suggest a progression of events beginning with the generation and accumulation of an mtDNA deletion mutation, the concomitant development of electron transport chain dysfunction, a subsequent triggering of apoptotic and necrotic events, and a process resulting in muscle fiber atrophy, breakage, and ultimately fiber loss.

We employ a variety of state-of-the-art molecular and histological methodologies to elucidate the mechanisms involved in age-dependent muscle fiber loss. Our studies also examine the accumulation and impact of mtDNA deletion mutations in aged cardiac and brain tissue. In collaboration with Jon Wanagat (UCLA), we have been using pharmacological interventions to investigate the underlying mechanism driving the increase in mtDNA deletion mutations with age, the concomitant loss of electron transport activity, and ultimately, fiber loss.

Selected publications

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.