BSc University of Western Ontario, Department of Zoology
Office: Dental Sciences Building, Room 2022
My interest in science began in high school, when I initially aspired to a career in dentistry. During my fourth year of undergraduate studies, my research project focused on using cattle embryos as a model for human preimplantation development. This undergraduate work inspired me to pursue my Masters, during which I continued my embryology work that led to a research opportunity in Australia with renowned Canadian scientist, Dr. David Armstrong, who encouraged me to pursue a research career. My PhD thesis was focused on evaluating the genetic age of cloned animals. The defining moment during my PhD degree was when I wrote a CIHR operating grant proposal that was awarded; this approval gave me the confidence to pursue research professionally. Following my PhD, I conducted my postdoctoral studies in the Department of Genetics at Case Western Reserve University in Cleveland. I joined the Ontario Veterinary College as an Assistant Professor in 2001 to study nuclear reprogramming events in somatic cell nuclear transfer clones and to develop stem cell technologies in domestic animals. I moved my research lab to Western in 2009 where I now focus my research on preimplantation embryos and pluripotent stem cells.
My current research focuses on understanding the various events of early embryo development and elucidating the functional pathways of pluripotent stem cells. Pluripotency refers to the ability of a stem cell to develop through all three germ layers, and pluripotent states are biologically different at different stages of development; studying these cells at various states of development allows for a better understanding of developmental processes at a molecular level. Another aspect of my research focuses on developing canine pluripotent stem cell-based therapies for dogs and as a clinically relevant animal model. Dogs and humans share the same environment and hundreds of similar genetic disorders that are often treated the same way, making them a good model for translating stem cell-based therapies to humans.
Specific Research Interests
1. p66Shc Regulation of Mitophagy-Driven Metabolic Switch That Reprograms Stem Cell State and Fate
Our research has shown that a protein called p66Shc regulates cellular metabolism and cell fate decisions in mammalian stem cells and embryos. We recently discovered that loss of p66Shc results in altered autophagy. Using established early embryo and embryonic stem cell models, we will define the autophagic/mitophagic functions of p66Shc in regulating stem cell behavior (state) and p66Shc’s capacity to regulate embryo stem cell differentiation into specialized cell types (fate). Our novel studies will establish p66Shc as a key metabolic switch that maintains a primitive stem cell state and regulates cell fate decisions during embryo development by regulating autophagy. We expect our results to reveal novel therapeutic options to enhance tissue rejuvenation and repair to treat various diseases such as infertility, cardiovascular disease, neurodegenerative disorders, and cancer.
2. Metabolic Reprogramming to Enhance the Generation of Canine Induced Pluripotent Stem Cells (ciPSCs)
My NSERC Discovery research program will direct dog fibroblasts towards specific metabolic states using defined fuel sources and metabolite exposure to enhance their induction towards a pluripotent state. Pluripotency will be assessed using appropriate molecular and cellular assays on putative ciPSCs and their differentiated derivatives, while interrogation of metabolism will be carried out by measuring live cell metabolism, assessing various markers of glycolysis and OXPHOS, and analyzing various metabolic signaling pathways. These studies will develop a simple and reliable culture protocol to modulate the metabolic state of somatic cells to efficiently generate high quality canine iPSCs for implementing stem cell technologies in the dog.
Most Rewarding Moments
The most exciting part of being a researcher and a scientist is the discovery that comes along with the work I do. To discover something new and be able to add to the scientific community is extremely gratifying. It’s also really encouraging to see my students get excited about the research they’re doing and to see their progress from the time they first step into the lab to when they leave the lab. My students are constantly forming new ideas and discovering new knowledge, and to be able to help them achieve their goals as the next generation of scientists and researchers is extremely rewarding. To see their spark and desire for research, to mentor them in a way that helps them grow as individuals, and to be able to guide them along their journeys are some of the highlights of my career.
See all my publications on PubMed.
Edwards NA, Watson AJ, Betts DH (2018). Loss of p66Shc promotes primitive endoderm identity in the inner cell mass of mouse blastocysts. Stem Cells and Development 27(21):1479-1493. Link to article
Edwards NA, Watson AJ, Betts DH (2016). P66Shc, a key regulator of metabolism and mitochondrial ROS production is dysregulated by mouse embryo culture. Mol Hum Reprod 22 (9): 634-647.
Teichroeb JH, Kim J, Betts DH (2016). The Role of Telomeres and Telomerase Reverse Transcriptase Isoforms in Pluripotency Induction and Maintenance. RNA Biol 13(8):707-719. Link to article
Tobias IC, Isaac RR, Dierolf J, Khazaee R, Cumming RC and Betts DH (2018). Metabolic plasticity during transition to naïve-like pluripotency in canine embryo-derived stem cells. Stem Cell Research30:22-33. Link to article
Tobias IC, Brooks CR, Teichroeb JH, Villagómez DA, Hess DA, Séguin CA, Betts DH (2016). Small molecule induction of canine embryonic stem cells towards naïve pluripotency. Stem Cells and Development 25(16): 1208-1222. Link to article