Judd Aiken

PhD: University of Calgary, Calgary, Alberta

Post-doctoral Veterinary Sciences, University of Wisconsin at Madison

Position: Professor

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

Biology and Etiology of Prions:

Prion diseases are slowly progressive, fatal neurodegenerative disorders with no effective treatment or vaccine available. Neuropathological changes include accumulation of abnormal prion protein aggregates, spongiform degeneration, neuronal loss and astrogliosis. These hallmarks are diagnostic for chronic wasting disease (CWD) in cervids as well as scrapie in sheep and goats, bovine spongiform encephalopathy (BSE) as well as Creutzfeld-Jakob disease (CJD) and variant CJD in humans. This research program has two primary areas of interest: i) 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; prions bound to soil particles remain infectious in the soils for many years) and, ii) Developing "omics" approaches to biomarker development to provide insights to the pathology and etiology of prion disease.

Mitochondrial DNA (mtDNA) mutations cause muscle fiber loss with age:

The loss of muscle mass and function with age is an inevitable component of the aging process. In humans, skeletal muscle fiber number in 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 a mtDNA deletion mutation, the concomitant development of electron transport chain, a subsequent triggering of apoptotic and necrotic events, a process resulting in muscle fiber atrophy, breakage, and ultimately fiber loss.

Current Research:

Environmental Contamination by Prions:

CWD is expanding both in terms of its geographic range; currently present in 24 US states, 2 Canadian provinces (Saskatchewan and Alberta), South Korea and Norway. Unlike other prion diseases, CWD affects free-ranging populations of deer, elk, moose and reindeer. Infected animals shed infectious agent in their saliva, urine, feces as well as from decaying carcasses. These prions in the environment are stable and can bind to both soil and plants. We are interested in determining the persistence and bioavailability of prions shed into the environment and developing methods to readily detect environmental CWD contamination.

An "omics" approach to Prion Biology:

We are using a combination of genomic, transcriptomic and proteomic approaches to identifying biomarkers of prion disease in laboratory models of disease as well as in humans and deer. These biomarkers will direct studies into the pathobiology of prion disease allowing us to determine critical pathways in disease. A long-term goal is to develop diagnostics with high sensitivity and specificity for prion disease, particularly for
ante-mortem diagnosis.

MtDNA deletion mutations and Aging:

We employ a variety of state-or-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. Using pharmacological interventions, we have been investigating the underlying mechanism driving the increase in mtDNA deletion mutations with age and the concomitant loss of electron transport activity and ultimately fiber loss.

Selected publications

Otero A, Duque Velásquez C, Aiken J, McKenzie D. White-tailed deer S96 prion protein does not support stable in vitro propagation of most common CWD strains. 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. A general mass spectrometry-based method of quantitating prion polymorphisms from heterozygous CWD-infected cervids. 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. Prion protein polymorphisms associated with reduced CWD susceptibility limit peripheral PrPCWD deposition in orally infected white-tailed deer. BMC Veterinary Research 15: 50. IF: 1.98 Ranking: 20/140 (Veterinary Science) Q1.

Kuznetsova, A., C. Cullingham, D. McKenzie and J.M. Aiken. 2018. Soil humic acids degrade CWD prions and reduce infectivity. 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. Chronic wasting disease prion protein strain emergence and host range expansion. 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. Long term rapamycin treatment improves mitochondrial DNA quality in aging mice. 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. Digital PCR quantitation of muscle mitochondrial DNA: age, fiber type and mutation induced changes. 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. 14-3-3 and enolase abundances in the CSF of prion diseased rats. 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. Dual microRNA to cellular prion protein inhibits propagation of pathogenic prion protein in cultured cells. Molecular Neurobiology 55: 2384-2396. IF: 5.076 Ranking: 44/261 (Neurosciences) Q1.