THE BETTS LAB
Early Embryo and Pluripotent Stem Cell Laboratory
Our research program aims to understand the cellular and molecular pathways that regulate preimplantation embryo development and pluripotent stem cell function. The lab focuses on training the next generation of scientists, biotechnologists, and entrepreneurs.
ABOUT THE BETTS LAB
The Betts Lab utilizes unique stem 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.
Stem Cells, Inked Episode 5 (Metabolism & Cell Fate)
CURRENT 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) - Completed
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 (PI: Watson) - Completed
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.
LAB MEMBERS
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
Daniel Kawa
MSC Candidate
BMSc Honours Biochemistry and Pathology of Human Diseases, Western
Project: Evaluating the capacity of p66Shc-deficient mouse embryonic stem cells
ALEX KOZLOV
PhD Candidate (Co-supervisor Robert Cumming)
BSc Honours Biology, Western
Project: Examining the relationship between lactate and cell fate
ANDREW POWELL
PhD Candidate (Co-supervisor Robert Cumming)
BASc Engineering Chemistry, Queen's
MASc Chemical Engineering, Queen's
Project: The role of p66Shc in neural stem cell maintenance and differentiation.
ALLISON TSE
MSc Candidate
BMSc Honours Physiology and Pharmacology, Western
Project: miRNAs as markers of embryo developmental competence
STEFAN GRAHOVAC
MSc Candidate
BSc Honours Specialization Biology, Western
Project: Genome-wide CRISPR-Cas9 screen to discover novel functional interactions of the p66Shc adaptor protein in regulating pluripotency
YARA AND MADDEN
Co-operative Students
London Central Secondary
PUBLICATIONS
EVALUATING AUTOPHAGY IN PREIMPLANTATION EMBRYOS
July 21, 2022
Leung ZCL, Hunter H, Abu Rafea B, Watson AJ, and Betts DH (2022). Evaluating Autophagy in Preimplantation Embryos. Autophagy Reports 1(1): 309-337.
MODULATION OF PKM1/2 LEVELS BY STERIC BLOCKING MORPHOLINOS ALTERS THE METABOLIC AND PLURIPOTENT STATE OF MURINE PLURIPOTENT STEM CELLS
June 8, 2022
Dierolf JG, Hunter HLM, Watson AJ, Betts DH (2022). Modulation of PKM1/2 levels by steric blocking morpholinos alters the metabolic and pluripotent state of murine pluripotent stem cells. Stem Cells and Development 31 (11-12): 278-295.
FREE FATTY ACID TREATMENT OF MOUSE PREIMPLANTATION EMBRYOS DEMONSTRATES CONTRASTING EFFECTS OF PALMITIC ACID AND OLEIC ACID ON AUTOPHAGY
May 1, 2022
Leung ZCL, Calder MD, Abu-Rafea B, Watson AJ, Betts DH (2022). Free fatty acid treatment of mouse preimplantation embryos demonstrates contrasting effects of palmitic acid and oleic acid on autophagy. Am J Physiol Cell Physiol. 322(5): C833-C848.
THE EFFECTS OF OBESITY AND NON-ESTERIFIED FATTY ACIDS ON PREIMPLANTATION EMBRYO DEVELOPMENT
2022
Leung ZCL, Betts DH, Watson AJ (2022). The effects of obesity and non-esterified fatty acids on preimplantation embryo development. Trends Dev Biol 14: 19-31.
3D IMMUNOFLUORESCENT IMAGE COLOCALIZATION QUANTIFICATION IN MOUSE EPIBLAST STEM CELLS
April 29, 2022
Dierolf JG, Watson AJ, Betts DH (2022). 3D immunofluorescent image colocalization quantification in mouse epiblast stem cells. Methods in Molecular Biology 2490: 69-79.
FLOW CYTOMETRIC CHARACTERIZATION OF PLURIPOTENT CELL PROTEIN MARKERS IN NAÏVE, FORMATIVE, AND PRIMED PLURIPOTENT STEM CELLS
April 29, 2022
Dierolf JG, Chadwick K, Brooks CR, Watson AJ, Betts DH (2022). Flow Cytometric Characterization of Pluripotent Cell Protein Markers in Naïve, Formative, and Primed Pluripotent Stem Cells. Methods in Molecular Biology 2490: 81-92.
EFFECTS OF PALMITIC ACID ON LOCALIZATION OF EMBRYO CELL FATE AND BLASTOCYST FORMATION GENE PRODUCTS
February 14, 2022
Calder MD, Chen R, MacDonald A, MacNeily Z, Leung ZCL, Adus A, Cui S, Betts DH, Abu-Rafea B, and Watson AJ (2022). Effects of palmitic acid on localization of embryo cell fate and blastocyst formation gene products. Reproduction 163(3): 133-143.
CELL THERAPY IN VETERINARY MEDICINE AS A PROOF-OF CONCEPT FOR HUMAN THERAPIES: PERSPECTIVES FROM THE NORTH AMERICAN VETERINARY MEDICINE ASSOCIATION
November 30, 2021
Arzi B, Webb TL, Koch TG, Volk SW, Betts DH, Watts A, Goodrich L, Kallos MS, Kol A (2021). Cell Therapy in Veterinary medicine as a Proof-of Concept for Human Therapies: Perspectives from the North American Veterinary Medicine Association. Front. Vet. Sci. doi: 10.3389/fvets.2021.779109.
DIFFERENTIAL LOCALIZATION PATTERNS OF PYRUVATE KINASE ISOFORMS IN MURINE NAÏVE, FORMATIVE AND PRIMED PLURIPOTENT STATES
June 26, 2021
Dierolf JG, Watson AJ, Betts DH (2021). Differential localization patterns of pyruvate kinase isoforms in murine naïve, formative and primed pluripotent states. Experimental Cell Research 405(2):112714.
MURINE BLASTOCYSTS RELEASE MATURE MICRORNAS INTO CULTURE MEDIA THAT REFLECT DEVELOPMENTAL STATUS
May 28, 2021
Hawke DC, Watson AJ, Betts DH (2021). Murine blastocysts release mature microRNAs into culture media that reflect developmental status. Frontiers in Genetics 12:655882.
ANALYSIS OF TERT ISOFORMS ACROSS TCGA, GTEX AND CCLE DATASETS
April 13, 2021
Subasri M, Shooshtari P, Watson AJ, Betts DH (2021). Analysis of TERT Isoforms Across TCGA, GTEx and CCLE Datasets. Cancers 13(8):1853.
PANNEXIN 1 BINDS Β-CATENIN TO MODULATE MELANOMA CELL GROWTH AND METABOLISM
February 26, 2021
Sayedyahossein S, Huang K, Li Z, Zhang C, Kozlov AM, Johnston D, Nouri-Nejad D, Dagnino L, Betts DH, Sacks DB and Penuela S (2021). Pannexin 1 binds β-catenin to modulate melanoma cell growth and metabolism. J Biol Chem 296:100478.
EXTRACELLULAR VESICLES, MICRORNA AND THE PREIMPLANTATION EMBRYO: NON-INVASIVE CLUES OF EMBRYO WELL-BEING
January 1, 2021
Hawke DC, Watson AJ, Betts DH (2021). Extracellular Vesicles, MicroRNA and the Preimplantation Embryo: Non-Invasive Clues of Embryo Well-Being. Reproductive BioMedicine Online 41(1): 39-54.
TARGETED EXPRESSION PROFILING REVEALS DISTINCT STAGES OF EARLY CANINE FIBROBLAST REPROGRAMMING ARE REGULATED BY 2-OXOGLUTARATE HYDROXYLASES
December 9, 2020
Tobias IC, Kao MC, Parmentier T, Hunter H, LaMarre J and Betts DH (2020). Targeted expression profiling reveals distinct stages of early canine fibroblast reprogramming are regulated by 2-oxoglutarate hydroxylases. Stem Cell Res Ther 11(1):528.
THE USE OF INDUCED PLURIPOTENT STEM CELLS IN DOMESTIC ANIMALS: A NARRATIVE REVIEW
December 8, 2020
Scarfone RA, Pena SM, Russell KA, Betts DH and Koch TG (2020). The Use of Induced Pluripotent Stem Cells in Domestic Animals: A Narrative Review. BMC Veterinary Research 16(1):477.
OLEIC ACID COUNTERS IMPAIRED BLASTOCYST DEVELOPMENT INDUCED BY PALMITIC ACID DURING MOUSE PREIMPLANTATION DEVELOPMENT: UNDERSTANDING OBESITY RELATED DECLINES IN FERTILITY
June 10, 2020
Yousif MD, Calder MD, Du JT, Ruetz KN, Crocker K, Urquhart BL, Betts DH, Rafea BA, Watson AJ (2020). Oleic Acid Counters Impaired Blastocyst Development Induced by Palmitic Acid during Mouse Preimplantation Development: Understanding Obesity Related Declines in Fertility. Reproductive Sciences 27(11):2038-2051.
LACTATE PRECONDITIONING PROMOTES A HIF-1-ALPHA-MEDIATED METABOLIC SHIFT FROM OXPHOS TO GLYCOLYSIS IN NORMAL HUMAN DIPLOID FIBROBLASTS
May 20, 2020
Kozlov AM, Lone A, Betts DH*, Cumming RC* (2020). Lactate preconditioning promotes a HIF-1-alpha-mediated metabolic shift from OXPHOS to glycolysis in normal human diploid fibroblasts. Scientific Reports 10: 8388. *Co-senior authors.
DYNAMIC REGULATION OF CONNEXINS IN STEM CELL PLURIPOTENCY
October 28, 2019
Esseltine JL, Brooks C, Edwards NA, Subasri M, Sampson J, Seguin C, Betts DH and Laird DW (2020). Dynamic regulation of connexins in stem cell pluripotency. Stem Cells 38(1):52-66.
TRAPPING AND SERS IDENTIFICATION OF EXTRACELLULAR VESICLES USING NANOHOLE ARRAYS.
March 7, 2019
Kaufman LH, Cooper T, Wallace GQ, Hawke DC, Betts D, Hess D, Lagugné-Labarthet F (2019). Trapping and SERS identification of extracellular vesicles using nanohole arrays. Proc. SPIE 10894, Plasmonics in Biology and Medicine XVI, 108940B.
P66SHC ACTIVATION PROMOTES INCREASED OXIDATIVE PHOSPHORYLATION AND RENDERS CNS CELLS MORE VULNERABLE TO AMYLOID BETA TOXICITY
November 20, 2018
Lone A, Harris R, Singh O, Betts DH, Cumming RC. (2018). p66Shc activation promotes increased oxidative phosphorylation and renders CNS cells more vulnerable to amyloid beta toxicity. Scientific Reports 8(1):17081.
LOSS OF P66SHC PROMOTES PRIMITIVE ENDODERM IDENTITY IN THE INNER CELL MASS OF MOUSE BLASTOCYSTS
November 1, 2018
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.
ANALYSIS OF MITOCHONDRIAL DIMENSIONS AND CRYSTAL STRUCTURE IN PLURIPOTENT STEM CELLS USING TRANSMISSION ELECTRON MICROSCOPY
November 2018
Tobias IC, Khazaee R, Betts DH (2018). Analysis of mitochondrial dimensions and crystal structure in pluripotent stem cells using transmission electron microscopy. Current Protocols in Stem Cell Biology 47(1):e67.
https://currentprotocols.onlinelibrary.wiley.com/doi/abs/10.1002/cpsc.67
METABOLIC PLASTICITY DURING TRANSITION TO NAÏVE-LIKE PLURIPOTENCY IN CANINE EMBRYO-DERIVED STEM CELLS
May 17, 2018
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 Research 30:22-33.
https://www.sciencedirect.com/science/article/pii/S1873506118301235?via%3Dihub
CD-1 MOUSE FERTILITY RAPIDLY DECLINES AND IS ACCOMPANIED WITH EARLY PREGNANCY LOSS UNDER CONVENTIONAL HOUSING CONDITIONS
March 1, 2018
Crocker K, Calder MD, Edwards NA, Betts DH, Watson AJ. CD-1 mouse fertility rapidly declines and is accompanied with early pregnancy loss under conventional housing conditions. Theriogenology. 2018 Mar 1;108:245-254.
TREATMENT WITH AICAR INHIBITS BLASTOCYST DEVELOPMENT, TROPHECTODERM DIFFERENTIATION AND TIGHT JUNCTION FORMATION AND FUNCTION IN MICE
November 1, 2017
Calder MD, Edwards NA, Betts DH, Watson AJ. Treatment with AICAR inhibits blastocyst development, trophectoderm differentiation and tight junction formation and function in mice. Mol Hum Reprod. 2017 Nov 1;23(11):771-785.
CONNEXIN43 MUTANT PATIENT-DERIVED INDUCED PLURIPOTENT STEM CELLS EXHIBIT ALTERED DIFFERENTIATION POTENTIAL
June 2016
Esseltine JL, Shao Q, Brooks C, Sampson J, Betts DH, Séguin CA, Laird DW. Connexin43 Mutant Patient-Derived Induced Pluripotent Stem Cells Exhibit Altered Differentiation Potential. J Bone Miner Res. 2017 Jun;32(6):1368-1385.
CHARACTERIZATION AND IMMUNOMODULATORY EFFECTS OF CANINE ADIPOSE TISSUE- AND BONE MARROW-DERIVED MESENCHYMAL STROMAL CELLS
December 1, 2016
Russell KA, Chow NH, Dukoff D, Gibson TW, LaMarre J, Betts DH, Koch TG. Characterization and Immunomodulatory Effects of Canine Adipose Tissue- and Bone Marrow-Derived Mesenchymal Stromal Cells. PLoS One. 2016 Dec 1;11(12):e0167442.
SMALL MOLECULE INDUCTION OF CANINE EMBRYONIC STEM CELLS TOWARDS NAIVE PLURIPOTENCY
August 15, 2016
Tobias IC, Brooks CR, Teichroeb JH, Villagómez DA, Hess DA, Séguin CA, Betts DH. Small-Molecule Induction of Canine Embryonic Stem Cells Toward Naïve Pluripotency. Stem Cells Dev. 2016 Aug 15;25(16):1208-22.
P66SHC, A KEY REGULATOR OF METABOLISM AND MITOCHONDRIAL ROS PRODUCTION, IS DYSREGULATED BY MOUSE EMBRYO CULTURE
September 2016
Edwards NA, Watson AJ, Betts DH. P66Shc, a key regulator of metabolism and mitochondrial ROS production, is dysregulated by mouse embryo culture. Mol Hum Reprod. 2016 Sep;22(9):634-47.
THE ROLE OF TELOMERES AND TELOMERASE REVERSE TRANSCRIPTASE ISOFORMS IN PLURIPOTENCY INDUCTION AND MAINTENANCE
August 2, 2016
Teichroeb JH, Kim J, Betts DH. The role of telomeres and telomerase reverse transcriptase isoforms in pluripotency induction and maintenance. RNA Biol. 2016 Aug 2;13(8):707-19.
CANINE PLURIPOTENT STEM CELLS: ARE THEY READY FOR CLINICAL APPLICATIONS?
October 7, 2015
Betts DH, Tobias IC. Canine Pluripotent Stem Cells: Are They Ready for Clinical Applications? Front Vet Sci. 2015 Oct 7;2:41.
DELIVERING ANTISENSE MORPHOLINO OLIGONUCLEOTIDES TO TARGET TELOMERASE SPLICE VARIANTS IN HUMAN EMBRYONIC STEM CELLS
2016
Radan L, Hughes CS, Teichroeb JH, Postovit LM, Betts DH. Delivering Antisense Morpholino Oligonucleotides to Target Telomerase Splice Variants in Human Embryonic Stem Cells. Methods Mol Biol. 2016;1341:133-42.
MICROENVIRONMENTAL REGULATION OF TELOMERASE ISOFORMS IN HUMAN EMBRYONIC STEM CELLS
September 1, 2014
Radan L, Hughes CS, Teichroeb JH, Vieira Zamora FM, Jewer M, Postovit LM, Betts DH. Microenvironmental regulation of telomerase isoforms in human embryonic stem cells. Stem Cells Dev. 2014 Sep 1;23(17):2046-66.
THE P66(SHC) ADAPTOR PROTEIN CONTROLS OXIDATIVE STRESS RESPONSE IN EARLY BOVINE EMBRYOS
January 24, 2014
Betts DH, Bain NT, Madan P. The p66(Shc) adaptor protein controls oxidative stress response in early bovine embryos. PLoS One. 2014 Jan 24;9(1):e86978.
DERIVATION AND CULTURE OF CANINE EMBRYONIC STEM CELLS
2013
Tobias IC, Brooks CR, Teichroeb JH, Betts DH. Derivation and culture of canine embryonic stem cells. Methods Mol Biol. 2013;1074:69-83.
EARLY EMBRYONIC DEVELOPMENT, ASSISTED REPRODUCTIVE TECHNOLOGIES, AND PLURIPOTENT STEM CELL BIOLOGY IN DOMESTIC MAMMALS
August 2013
Hall V, Hinrichs K, Lazzari G, Betts DH, Hyttel P. Early embryonic development, assisted reproductive technologies, and pluripotent stem cell biology in domestic mammals. Vet J. 2013 Aug;197(2):128-42.
STRESS-INDUCIBLE PHOSPHOPROTEIN 1 HAS UNIQUE COCHAPERONE ACTIVITY DURING DEVELOPMENT AND REGULATES CELLULAR RESPONSE TO ISCHEMIA VIA THE PRION PROTEIN
September 2013
Beraldo FH, Soares IN, Goncalves DF, Fan J, Thomas AA, Santos TG, Mohammad AH, Roffé M, Calder MD, Nikolova S, Hajj GN, Guimaraes AL, Massensini AR, Welch I, Betts DH, Gros R, Drangova M, Watson AJ, Bartha R, Prado VF, Martins VR, Prado MA. Stress-inducible phosphoprotein 1 has unique cochaperone activity during development and regulates cellular response to ischemia via the prion protein. FASEB J. 2013 Sep;27(9):3594-607.
ELEVATED P66SHC IS ASSOCIATED WITH INTRACELLULAR REDOX IMBALANCE IN DEVELOPMENTALLY COMPROMISED BOVINE EMBRYOS
January 2013
Bain NT, Madan P, Betts DH. Elevated p66Shc is associated with intracellular redox imbalance in developmentally compromised bovine embryos. Mol Reprod Dev. 2013 Jan;80(1):22-34.
THE LONG AND SHORT OF IT: THE ROLE OF TELOMERES IN FETAL ORIGINS OF ADULT DISEASE
October 3, 2012
Hallows SE, Regnault TR, Betts DH. The long and short of it: the role of telomeres in fetal origins of adult disease. J Pregnancy. 2012;2012:638476.
MASS SPECTROMETRY-BASED PROTEOMIC ANALYSIS OF THE MATRIX MICROENVIRONMENT IN PLURIPOTENT STEM CELL CULTURE
December 2012
Hughes C, Radan L, Chang WY, Stanford WL, Betts DH, Postovit LM, Lajoie GA. Mass spectrometry-based proteomic analysis of the matrix microenvironment in pluripotent stem cell culture. Mol Cell Proteomics. 2012 Dec;11(12):1924-36.
LONG TELOMERES BYPASS THE REQUIREMENT FOR TELOMERE MAINTENANCE IN HUMAN TUMORIGENESIS
February 23, 2012
Taboski MA, Sealey DC, Dorrens J, Tayade C, Betts DH*, Harrington L*. Long telomeres bypass the requirement for telomere maintenance in human tumorigenesis. Cell Rep. 2012 Feb 23;1(2):91-8. *Co-senior authors.
LOW LEVELS OF X-INACTIVE SPECIFIC TRANSCRIPT IN SOMATIC CELL NUCLEAR TRANSFER EMBRYOS DERIVED FROM FEMALE BOVINE FREEMARTIN DONOR CELLS
2012
Jeon BG, Rho GJ, Betts DH, Petrik JJ, Favetta LA, King WA. Low levels of X-inactive specific transcript in somatic cell nuclear transfer embryos derived from female bovine freemartin donor cells. Sex Dev. 2012;6(1-3):151-9.
SUPPRESSION OF THE IMPRINTED GENE NNAT AND X-CHROMOSOME GENE ACTIVATION IN ISOGENIC HUMAN IPS CELLS
October 2011
Teichroeb JH, Betts DH, Vaziri H. Suppression of the imprinted gene NNAT and X-chromosome gene activation in isogenic human iPS cells. PLoS One. 2011;6(10):e23436.
PROTEOMIC ANALYSIS OF EXTRACELLULAR MATRICES USED IN STEM CELL CULTURE
October 2011
Hughes CS, Radan L, Betts D, Postovit LM, Lajoie GA. Proteomic analysis of extracellular matrices used in stem cell culture. Proteomics. 2011 Oct;11(20):3983-91.
OSTEOGENIC DIFFERENTIATION OF EQUINE CORD BLOOD MULTIPOTENT MESENCHYMAL STROMAL CELLS WITHIN CORALLINE HYDROXYAPATITE SCAFFOLDS IN VITRO
2011
Figueroa RJ, Koch TG, Betts DH. Osteogenic differentiation of equine cord blood multipotent mesenchymal stromal cells within coralline hydroxyapatite scaffolds in vitro. Vet Comp Orthop Traumatol. 2011;24(5):354-62.
IN VITRO AND IN VIVO GERM LINE POTENTIAL OF STEM CELLS DERIVED FROM NEWBORN MOUSE SKIN
2011
Dyce PW, Liu J, Tayade C, Kidder GM, Betts DH, Li J. In vitro and in vivo germ line potential of stem cells derived from newborn mouse skin. PLoS One. 2011;6(5):e20339.
SYNAPTICALLY-COMPETENT NEURONS DERIVED FROM CANINE EMBRYONIC STEM CELLS BY LINEAGE SELECTION WITH EGF AND NOGGIN.
2011
Wilcox JT, Lai JK, Semple E, Brisson BA, Gartley C, Armstrong JN, Betts DH. Synaptically-competent neurons derived from canine embryonic stem cells by lineage selection with EGF and Noggin. PLoS One. 2011;6(5):e19768.
THE EARLY EMBRYO RESPONSE TO INTRACELLULAR REACTIVE OXYGEN SPECIES IS DEVELOPMENTALLY REGULATED
2011
Bain NT, Madan P, Betts DH. The early embryo response to intracellular reactive oxygen species is developmentally regulated. Reprod Fertil Dev. 2011;23(4):561-75.
IN VITRO DEVELOPMENTAL POTENTIAL OF NUCLEAR TRANSFER EMBRYOS CLONED WITH ENUCLEATION METHODS USING PRE-DENUDED BOVINE OOCYTES
December 2011
Jeon BG, Betts DH, King WA, Rho GJ. In vitro developmental potential of nuclear transfer embryos cloned with enucleation methods using pre-denuded bovine oocytes. Reprod Domest Anim. 2011 Dec;46(6):1035-42.
STEM CELL ROLES IN REPRODUCTION: WHAT IS THE BASIC SCIENCE?
November 2010
Betts DH, Kalionis B, Hillier SG. Stem cell roles in reproduction: what is the basic science? Mol Hum Reprod. 2010 Nov;16(11):791-2.
VIABLE IPSC MICE: A STEP CLOSER TO THERAPEUTIC APPLICATIONS IN HUMANS?
February 2010
Betts DH, Kalionis B. Viable iPSC mice: a step closer to therapeutic applications in humans? Mol Hum Reprod. 2010 Feb;16(2):57-62.
IMPROVED ISOLATION PROTOCOL FOR EQUINE CORD BLOOD-DERIVED MESENCHYMAL STROMAL CELLS
2009
Koch TG, Thomsen PD, Betts DH. Improved isolation protocol for equine cord blood-derived mesenchymal stromal cells. Cytotherapy. 2009;11(4):443-7.
CURRENT AND FUTURE REGENERATIVE MEDICINE - PRINCIPLES, CONCEPTS, AND THERAPEUTIC USE OF STEM CELL THERAPY AND TISSUE ENGINEERING IN EQUINE MEDICINE
February 2009
Koch TG, Berg LC, Betts DH. Current and future regenerative medicine - principles, concepts, and therapeutic use of stem cell therapy and tissue engineering in equine medicine. Can Vet J. 2009 Feb;50(2):155-65.
CHARACTERIZATION OF CANINE EMBRYONIC STEM CELL LINES DERIVED FROM DIFFERENT NICHE MICROENVIRONMENTS
October 2009
Wilcox JT, Semple E, Gartley C, Brisson BA, Perrault SD, Villagómez DA, Tayade C, Becker S, Lanza R, Betts DH. Characterization of canine embryonic stem cell lines derived from different niche microenvironments. Stem Cells Dev. 2009 Oct;18(8):1167-78.
CONCEPTS FOR THE CLINICAL USE OF STEM CELLS IN EQUINE MEDICINE
October 2008
Koch TG, Berg LC, Betts DH. Concepts for the clinical use of stem cells in equine medicine. Can Vet J. 2008 Oct;49(10):1009-17.
PERMANENT EMBRYO ARREST: MOLECULAR AND CELLULAR CONCEPTS
August 2008
Betts DH, Madan P. Permanent embryo arrest: molecular and cellular concepts. Mol Hum Reprod. 2008 Aug;14(8):445-53.
S-ADENOSYLHOMOCYSTEINE TREATMENT OF ADULT FEMALE FIBROBLASTS ALTERS X-CHROMOSOME INACTIVATION AND IMPROVES IN VITRO EMBRYO DEVELOPMENT AFTER SOMATIC CELL NUCLEAR TRANSFER
June 2008
Jeon BG, Coppola G, Perrault SD, Rho GJ, Betts DH, King WA. S-adenosylhomocysteine treatment of adult female fibroblasts alters X-chromosome inactivation and improves in vitro embryo development after somatic cell nuclear transfer. Reproduction. 2008 Jun;135(6):815-28.
ALTERNATIVE SPLICING AND EXPRESSION ANALYSIS OF BOVINE DNA METHYLTRANSFERASE 1
April 2008
Russell DF, Betts DH. Alternative splicing and expression analysis of bovine DNA methyltransferase 1. Dev Dyn. 2008 Apr;237(4):1051-9.
THE OXIDATIVE STRESS ADAPTOR P66SHC IS REQUIRED FOR PERMANENT EMBRYO ARREST IN VITRO
November 29, 2007
Favetta LA, Madan P, Mastromonaco GF, St John EJ, King WA, Betts DH. The oxidative stress adaptor p66Shc is required for permanent embryo arrest in vitro. BMC Dev Biol. 2007 Nov 29;7:132.
EARLY PREGNANCY DIAGNOSIS BY SERUM PROGESTERONE AND ULTRASOUND IN SHEEP CARRYING SOMATIC CELL NUCLEAR TRANSFER-DERIVED PREGNANCIES
April 2008
Alexander B, Coppola G, Mastromonaco GF, St John E, Reyes ER, Betts DH, King WA. Early pregnancy diagnosis by serum progesterone and ultrasound in sheep carrying somatic cell nuclear transfer-derived pregnancies. Reprod Domest Anim. 2008 Apr;43(2):207-11.
STEM CELL THERAPY FOR JOINT PROBLEMS USING THE HORSE AS A CLINICALLY RELEVANT ANIMAL MODEL
November 2007
Koch TG, Betts DH. Stem cell therapy for joint problems using the horse as a clinically relevant animal model. Expert Opin Biol Ther. 2007 Nov;7(11):1621-6.
LOW OXYGEN DELAYS FIBROBLAST SENESCENCE DESPITE SHORTER TELOMERES
February 2008
Betts DH, Perrault SD, King WA. Low oxygen delays fibroblast senescence despite shorter telomeres. Biogerontology. 2008 Feb;9(1):19-31.
ISOLATION OF MESENCHYMAL STEM CELLS FROM EQUINE UMBILICAL CORD BLOOD
May 30, 200
Koch TG, Heerkens T, Thomsen PD, Betts DH. Isolation of mesenchymal stem cells from equine umbilical cord blood. BMC Biotechnol. 2007 May 30;7:26.
TELOMERE LENGTH STATUS OF SOMATIC CELL SHEEP CLONES AND THEIR OFFSPRING
December 2007
Alexander B, Coppola G, Perrault SD, Peura TT, Betts DH, King WA. Telomere length status of somatic cell sheep clones and their offspring. Mol Reprod Dev. 2007 Dec;74(12):1525-37.
USE OF SOMATIC CELL NUCLEAR TRANSFER TO STUDY MEIOSIS IN FEMALE CATTLE CARRYING A SEX-DEPENDENT FERTILITY-IMPAIRING X-CHROMOSOME ABNORMALITY
Spring 2007
Rho GJ, Coppola G, Sosnowski J, Kasimanickam R, Johnson WH, Semple E, Mastromonaco GF, Betts DH, Koch TG, Weese S, Hewson J, Hayes MA, Kenney DG, Basrur PK, King WA. Use of somatic cell nuclear transfer to study meiosis in female cattle carrying a sex-dependent fertility-impairing X-chromosome abnormality. Cloning Stem Cells. 2007 Spring;9(1):118-29.
HIGH LEVELS OF P66SHC AND INTRACELLULAR ROS IN PERMANENTLY ARRESTED EARLY EMBRYOS
April 15, 2007
Favetta LA, St John EJ, King WA, Betts DH. High levels of p66shc and intracellular ROS in permanently arrested early embryos. Free Radic Biol Med. 2007 Apr 15;42(8):1201-10.
GENOMIC STABILITY AND PHYSIOLOGICAL ASSESSMENTS OF LIVE OFFSPRING SIRED BY A BULL CLONE, STARBUCK II
January 1, 2007
Ortegon H, Betts DH, Lin L, Coppola G, Perrault SD, Blondin P, King WA. Genomic stability and physiological assessments of live offspring sired by a bull clone, Starbuck II. Theriogenology. 2007 Jan 1;67(1):116-26.
ROLE OF CHROMOSOME STABILITY AND TELOMERE LENGTH IN THE PRODUCTION OF VIABLE CELL LINES FOR SOMATIC CELL NUCLEAR TRANSFER
August 9, 2006
Mastromonaco GF, Perrault SD, Betts DH, King WA. Role of chromosome stability and telomere length in the production of viable cell lines for somatic cell nuclear transfer. BMC Dev Biol. 2006 Aug 9;6:41.
THE IMPACT OF OOCYTE MATURATION MEDIA ON EARLY BOVINE EMBRYONIC DEVELOPMENT
October 2006
Russell DF, Baqir S, Bordignon J, Betts DH. The impact of oocyte maturation media on early bovine embryonic development. Mol Reprod Dev. 2006 Oct;73(10):1255-70.
QUANTITATIVE ANALYSIS OF TELOMERASE ACTIVITY AND TELOMERE LENGTH IN DOMESTIC ANIMAL CLONES
2006
Betts DH, Perrault S, Harrington L, King WA. Quantitative analysis of telomerase activity and telomere length in domestic animal clones. Methods Mol Biol. 2006;325:149-80.
THE IMPACT OF CHROMOSOMAL ALTERATION ON EMBRYO DEVELOPMENT
January 7, 2006
King WA, Coppola G, Alexander B, Mastromonaco G, Perrault S, Nino-Soto MI, Pinton A, Joudrey EM, Betts DH. The impact of chromosomal alteration on embryo development. Theriogenology. 2006 Jan 7;65(1):166-77.
THE EFFECT OF 6-DIMETHYLAMINOPURINE (6-DMAP) AND CYCLOHEXIMIDE (CHX) ON THE DEVELOPMENT AND CHROMOSOMAL COMPLEMENT OF SHEEP PARTHENOGENETIC AND NUCLEAR TRANSFER EMBRYOS
January 2006
Alexander B, Coppola G, Di Berardino D, Rho GJ, St John E, Betts DH, King WA. The effect of 6-dimethylaminopurine (6-DMAP) and cycloheximide (CHX) on the development and chromosomal complement of sheep parthenogenetic and nuclear transfer embryos. Mol Reprod Dev. 2006 Jan;73(1):20-30.
TELOMERE LENGTH ANALYSIS IN GOAT CLONES AND THEIR OFFSPRING
December 2005
Betts DH, Perrault SD, Petrik J, Lin L, Favetta LA, Keefer CL, King WA. Telomere length analysis in goat clones and their offspring. Mol Reprod Dev. 2005 Dec;72(4):461-70.
GLOBAL GENE EXPRESSION RESPONSE TO TELOMERASE IN BOVINE ADRENOCORTICAL CELLS
September 2005
Perrault SD, Hornsby PJ, Betts DH. Global gene expression response to telomerase in bovine adrenocortical cells. Biochem Biophys Res Commun. 2005 Sep 30;335(3):925-36.
DIFFERENT CULTURE MEDIA REQUIREMENTS OF IVF AND NUCLEAR TRANSFER BOVINE EMBRYOS
December 2004
Mastromonaco GF, Semple E, Robert C, Rho GJ, Betts DH, King WA. Different culture media requirements of IVF and nuclear transfer bovine embryos. Reprod Domest Anim. 2004 Dec;39(6):462-7.
EXPRESSION PROFILES OF P53 AND P66SHC DURING OXIDATIVE STRESS-INDUCED SENESCENCE IN FETAL BOVINE FIBROBLASTS
September 10, 2004
Favetta LA, Robert C, King WA, Betts DH. Expression profiles of p53 and p66shc during oxidative stress-induced senescence in fetal bovine fibroblasts. Exp Cell Res. 2004 Sep 10;299(1):36-48.
P66SHC, BUT NOT P53, IS INVOLVED IN EARLY ARREST OF IN VITRO-PRODUCED BOVINE EMBRYOS
June 2004
Favetta LA, Robert C, St John EJ, Betts DH, King WA. p66shc, but not p53, is involved in early arrest of in vitro-produced bovine embryos. Mol Hum Reprod. 2004 Jun;10(6):383-92.
TELOMERASE ACTIVITY IN CLINICALLY NORMAL DOGS AND DOGS WITH MALIGNANT LYMPHOMA
September 2001
Carioto LM, Kruth SA, Betts DH, King WA. Telomerase activity in clinically normal dogs and dogs with malignant lymphoma. Am J Vet Res. 2001 Sep;62(9):1442-6.
THE EFFECTS OF ANTIBODIES TO HEAT SHOCK PROTEIN 70 IN FERTILIZATION AND EMBRYO DEVELOPMENT
September 2001
Matwee C, Kamaruddin M, Betts DH, Basrur PK, King WA. The effects of antibodies to heat shock protein 70 in fertilization and embryo development. Mol Hum Reprod. 2001 Sep;7(9):829-37.
REPROGRAMMING OF TELOMERASE ACTIVITY AND REBUILDING OF TELOMERE LENGTH IN CLONED CATTLE
January 30, 2001
Betts D, Bordignon V, Hill J, Winger Q, Westhusin M, Smith L, King W. Reprogramming of telomerase activity and rebuilding of telomere length in cloned cattle. Proc Natl Acad Sci U S A. 2001 Jan 30;98(3):1077-82.
GENETIC REGULATION OF EMBRYO DEATH AND SENESCENCE
January 1, 2001
Betts DH, King WA. Genetic regulation of embryo death and senescence. Theriogenology. 2001 Jan 1;55(1):171-91.
APOPTOSIS IN THE EARLY BOVINE EMBRYO
February 2000
Matwee C, Betts DH, King WA. Apoptosis in the early bovine embryo. Zygote. 2000 Feb;8(1):57-68.
DIFFERENTIAL INVOLVEMENT OF NA(+),K(+)-ATPASE ISOZYMES IN PREIMPLANTATION DEVELOPMENT OF THE MOUSE
June 15, 2000
MacPhee DJ, Jones DH, Barr KJ, Betts DH, Watson AJ, Kidder GM. Differential involvement of Na(+),K(+)-ATPase isozymes in preimplantation development of the mouse. Dev Biol. 2000 Jun 15;222(2):486-98.
GENE EXPRESSION REGULATING BLASTOCYST FORMATION
January 1, 1999
Watson AJ, Westhusin ME, De Sousa PA, Betts DH, Barcroft LC. Gene expression regulating blastocyst formation. Theriogenology. 1999 Jan 1;51(1):117-33.
TELOMERASE ACTIVITY AND TELOMERE DETECTION DURING EARLY BOVINE DEVELOPMENT
1999
Betts DH, King WA. Telomerase activity and telomere detection during early bovine development. Dev Genet. 1999;25(4):397-403.
NA/K-ATPASE-MEDIATED 86RB+ UPTAKE AND ASYMMETRICAL TROPHECTODERM LOCALIZATION OF ALPHA1 AND ALPHA3 NA/K-ATPASE ISOFORMS DURING BOVINE PREATTACHMENT DEVELOPMENT
May 1, 1998
Betts DH, Barcroft LC, Watson AJ. Na/K-ATPase-mediated 86Rb+ uptake and asymmetrical trophectoderm localization of alpha1 and alpha3 Na/K-ATPase isoforms during bovine preattachment development. Dev Biol. 1998 May 1;197(1):77-92.
OUABAIN SENSITIVITY AND EXPRESSION OF NA/K-ATPASE ALPHA- AND BETA-SUBUNIT ISOFORM GENES DURING BOVINE EARLY DEVELOPMENT
February 1997
Betts DH, MacPhee DJ, Kidder GM, Watson AJ. Ouabain sensitivity and expression of Na/K-ATPase alpha- and beta-subunit isoform genes during bovine early development. Mol Reprod Dev. 1997 Feb;46(2):114-26.
MATERNAL AND EMBRYONIC CONTROL OF BOVINE PRE-ATTACHMENT DEVELOPMENT: EXPRESSION OF OVIDUCTAL AND EMBRYONIC GENES
1996
Watson AJ, Barcroft LC, Betts DH, De Sousa PA, Gilfoyle E, Looye J, Pierre-Louis J, and Winger QA (1996). Maternal and embryonic control of bovine pre-attachment development: Expression of oviductal and embryonic genes. Archiv fur Tierzucht (Archives of Animal Breeding) 39: 55-69.
FORMER TRAINEES
JOOHWAN KIM
MSc Student
Thesis: Alternative splicing and extra-telomeric role of telomerase reverse transcriptase isoforms in human embryonic stem cells.
Present position: Research Associate
JONATHAN TEICHROEB
Postdoctoral Fellow
Project: Extra-telomeric functions of telomerase reverse transcriptase (TERT) isoforms in human pluripotent stem cells.
STEPHANIE HALLOWS
MSc Student
Thesis: Telomerase inhibition causes premature senescence of fetal guinea pig muscle cells.
Present position: Higher Education Professional.
THOMAS KOCH
PhD Student
Thesis: Evaluation of Equine Cord Blood Multipotent Stromal Cells.
Present position: Associate Professor, University of Guelph.
STEVEN PERRAULT
MSc Student
Thesis: Global gene expression response to telomerase in bovine adrenocortical cells.
Present position: Senior Research Scientist at Rea
PAVNEESH MADAN
Postdoctoral Fellow
Project: Knockdown of telomerase reverse transcriptase (TERT) during bovine pre-attachment embryo development.
Present position: Associate Professor, University of Guelph.
RYAN FIGUEROA
MSc Student (Guelph)
Thesis: Tissue engineered bone from equine umbilical cord blood-derived mesenchymal stem
cells.
Present Position: Family Physician, Toronto
LIDA RADAN
MSc Student
Thesis: Post-transcriptional regulation of telomerase reverse transcriptase (TERT) in human embryonic stem cells cultured under varying oxygen microenvironments.
Present position: Research Associate, Toronto.
HEATHER MULHOLLAND
MSc Student
Thesis: Characterization of pluripotency factors in human umbilical cord blood derived multi-lineage progenitor cells treated with small molecules.
Present position: Account Manager with MilliporeSigma.
DANIELA FISCHER RUSSELL
PhD Student
Thesis: The role of DNMT1 and DNA methylation during early bovine development.
Present position: Associate Dean, Faculty of Science and Technology, Vancouver Island University.
NATHAN BAIN
PhD Student
Thesis: P66Shc regulates oxidative stress-induced developmental failure in the early bovine embryo.
Present position: Canadian military.
LAURA RODGER
MD Student Researcher
Project: Telomerase therapy for premature aging of the stem cell niche in intrauterine growth restriction (IUGR).
Present position: Resident, Internal Medicine, LHSC.
IAN TOBIAS
PhD Student
Thesis:
Present Position:
NICOLE EDWARDS
PhD Student
Thesis:
Present Position:
MAISOON YOUSIF
MSc Student
Thesis:
Present Position:
JOSHUA DIEROLF
PhD Student
Thesis:
Present Position:
MATHUSHAN SUBASRI
MSc Student
Thesis: Pan-Cancer Analysis of Telomerase Reverse Transcriptase (TERT) Isoforms
GRACE DIONNE
MSc Student
Thesis: Investigating the impact of free fatty acids on Nrf2 signalling in the early embryo
SUKHDEEP BHANGAL
4th Year Thesis
Thesis: The role of exogenous lactate treatment on histone lactylation levels in human embryonic stem cells
Present Position: Medical school, McMaster University
VIRGINA WOLFE
MSc Student
Thesis: The role of p66Shc in regulating preimplantation embryo metabolism
DAVID HAWKE
Thesis: Exosome-derived miRNAs as non-invasive predictors of preimplantation embryo competence
Present Position: Postdoctoral fellow at Standford University
OVERVIEW OF COURSES
PHYSIOLOGY 4510A
Understanding pluripotency: The physiology of stem cell fate and function
This undergraduate course examines a variety of current topics within the field of pluripotent stem cell physiology. In particular, we focus on the basic biology of embryo-derived stem cells and their potency. We briefly cover pre- and post-implantation embryo development, focusing on cell fate determination and the cell lines derived from these developmental stages. We will discuss how these embryo-derived cell lines are isolated and tested, what factors allow for their expansion, how they can be genetically manipulated and what intrinsic and extrinsic factors regulate their self-renewal and cellular differentiation characteristics. We will also discuss pluripotent stem cells derived by somatic cell nuclear transfer and cellular reprogramming technologies. An understanding of this physiology will enable students a thorough understanding of stem cell function and cell fate determination to assess whether regenerative medicine is feasible with pluripotent cells along with gaining the ability to critically evaluate the ethical issues that surround this field.
PHYSIOLOGY 4440B
Animal and cell modeling of development and disease
This course examines the use of established and emerging cell and animal models to study developmental and disease processes. From transgenic mice, to CRISPR-Cas9, to rapid screening of drugs for pharmaceutical testing, the understanding of how model systems can be utilized to evaluate normal development and physiology as well as pathologies.
PHYSIOLOGY 9553
Special Topics in Developmental Biology
This is a summary of your course. Include an overall description of the class, significant concepts that are taught and any other relevant information that would be helpful for a potential student. It’s also a good idea to mention any specific requirements for materials or time commitment outside of class.