THE BETTS LAB

Early Embryo and Pluripotent Stem Cell Laboratory

Our research program is aimed towards understanding the cellular and molecular pathways that regulate preimplantation embryo development and pluripotent stem cell function. A main focus of the lab is to train the next generation of scientists, biotechnologists and entrepreneurs.

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ABOUT THE BETTS LAB

The Betts Lab utilizes unique cell and animal models including cutting-edge molecular cell biology techniques to study preimplantation embryos, stem cell function and cellular reprogramming events during early embryonic development and during the generation of induced pluripotent stem cells.

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Stem Cells, Inked Episode 5 (Metabolism & Cell Fate)

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CURENT PROJECTS

THE P66SHC ADAPTOR PROTEIN MAINTAINS PLURIPOTENCY AND REGULATES CELL FATE DURING EMBRYO DEVELOPMENT

CIHR submitted (PI: Betts)

The P66Shc adaptor protein belongs to the Src homology 2 domain containing (Shc) family of adaptor proteins that mediates cellular response to oxidative stress by translocating into the mitochondrial intermembrane space where it regulates metabolism and ROS production. Using established embryo-derived stem cell populations and early mouse embryo models, we will define the metabolic functions of p66Shc in regulating stem cell behavior (state) and p66Shc’s capacity to regulate stem cell differentiation into specialized cell types (fate).

REDOX REGULATION OF CANINE PLURIPOTENT STEM CELLS

NSERC Discovery (PI: Betts)

These studies will identify redox-modified proteins that will begin to elucidate the redox signaling pathways responsible for regulating self-renewal and pluripotency and will enhance our understanding of the molecular mechanisms that regulate the transition from inner cell mass (ICM) to epiblast cell fate. Modulation of the redox state during the cellular reprogramming procedure will define specific mechanisms underlying redox regulation of pluripotency induction.

EXTRA-TELOMERIC FUNCTIONS OF TELOMERASE REVERSE TRANSCRIPTASE (TERT) ISOFORMS

CIHR Operating (PI: Betts)

Expression of specific TERT isoforms likely promotes stem cell function via extra-telomeric means. These studies will elucidate the extra-telomeric roles for TERT isoforms and define new mechanisms controlling pluripotent stem cell function. These studies may reveal novel therapeutic options to enhance tissue regeneration, differentiation and repair and to treat age-related diseases such as cancer.

NON-INVASIVE IDENTIFICATION OF CONDITIONED CULTURE MEDIA CONSTITUENTS TO DETERMINE EMBRYO DEVELOPMENTAL COMPETENCE

CHRI & OB/GYN TRGF (PI: Basim Rafea)

The proposed studies are directed at characterizing microRNAs and mRNAs that are released into culture medium by preimplantation embryos. We expect to define patterns of microRNA and mRNAs that are indicative of normal preimplantation development and allow for a molecular indication of embryonic developmental competence post embryo transfer.

UNDERSTANDING AND TREATING OBESITY RELATED LOSS OF EMBRYO DEVELOPMENTAL COMPETENCE

CIHR submitted (PI: Watson)

We will investigate the possible ways in which obesity may restrict early mouse and human development by treating early mouse and human embryos with non-esterified fatty acids (NEFAs) that are sharply elevated in the serum and ovarian fluids of obese patients. We will also investigate ways in which early embryos attempt to avoid and adapt to maternal obesity effects imposed on their development. Our experiments will advance effective embryo culture medium development and will initiate approaches that could result in the production of therapeutic culture medium. Our ultimate goal is to improve the developmental capacity of early embryos and the success of assisted reproductive technologies.

SOLE FUEL SOURCE SELECTION STRATEGY TO ENHANCE PLURIPOTENCY

OIRM New Ideas Grant (PIs: Betts and Cumming)

In this project we will direct fibroblasts towards a single and/or bivalent metabolic states using sole fuel source selection to determine if their induction towards multiple pluripotent states is enhanced. Pluripotency will be assessed using various molecular markers of general, naïve, and primed pluripotency, while interrogation of metabolic pathways will be carried out by metabolic measurements and assessing various markers of glycolysis and OXPHOS. These studies will develop a simple and reliable culture protocol to modulate the bioenergetic state of somatic cells to efficiently generate high quality naïve human iPSCs for future stem cell therapies.

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LAB MEMBERS

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DEAN H. BETTS, PHD

Professor

BSc Honours Cell Biology, Western
MSc Zoology, Western
PhD Biomedical Sciences, Guelph
PDF Genetics, CWRU

QUINN

Executive Assistant

PhD Best Doggo, Bett's School

Project: The lab's lab

ZULEIKA C. L. LEUNG

Research Assistant

BMSc Interdisciplinary Medical Sciences, Western

MSc Physiology and Pharmacology & Developmental Biology, Western

Project: The impact of free fatty acids on preimplantation embryo autophagy

ALEX KOZLOV

PhD Candidate (Co-supervisor Robert Cumming)

BSc Honors Biology, Western

Project: Examining the relationship between lactate and cell fate.

DAVID HAWKE

PhD Candidate

BSc Chemical Engineering, Queen's

MASc Chemical Engineering, Queen's

Project: Exosome-derived miRNAs as non-invasive predictors of preimplantation embryo competence.

ANDREW POWELL