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.

 

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.

 

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.

 

LAB MEMBERS

 

DEAN H. BETTS, PHD

Professor

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

MICHELE CALDER, PHD

Research Associate (Watson Lab)

Embryologist

BSc

PhD

PDF

IAN TOBIAS

PhD Candidate

BMSc, Honours Pharmacology

Project: Pluripotent state manipulation and metabolic plasticity in canine embryonic stem cells

NICOLE EDWARDS

PhD Candidate

BSc, Honours Physiology, McGill

Msc, Experimental Medicine, McGill

Project: The role of the p66Shc adapter protein during mouse blastocyst development.

DAVID HAWKE

PhD Student

BASc Chemical Engineering, Queen's

MASc Chemical Engineering, Queen's

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

JOSHUA DIEROLF

PhD Student

BSc Honors Biology, Western

Project: Delineating the metabolic role of pyruvate kinase muscle isoforms PKM1 and PKM2 in regulating pluripotent stem cell state conversion.

ALEX KOZLOV

PhD Student (Co-supervisor Robert Cumming)

BSc Honors Biology, Western

Project: Sole fuel source selection strategy to enhance pluripotency induction.

MATHUSHAN SUBASRI

MSc Student

BSc Honors Physiology, Western

Project: The role of telomerase reverse transcriptase (TERT) splice variants in ovarian cancer cell phenotype.

ANDREW POWELL

MSc Student (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.


MAISOON YOUSIF

MSc Student (Co-supervisor Andrew Watson)

BMSc, Honors Specialization in Physiology 


Project: The effects of elevated saturated fatty acid levels and endoplasmic reticulum stress in preimplantation embryos. 

FEATURED PUBLICATION

scd.2016.25.issue-16.largecover.jpg

SMALL-MOLECULE INDUCTION OF CANINE EMBRYONIC STEM CELLS TOWARD NAÏVE PLURIPOTENCY

Tobias et al. Stem Cells Dev. 2016 Aug 15;25(16):1208-22.

 

PUBLICATIONS

 

ANALYSIS OF MITOCHONDRIAL DIMENSIONS AND CRYSTAL STRUCTURE IN PLURIPOTENT STEM CELLS USING TRANSMISSION ELECTRON MICROSCOPY

November 2018

Tobias IC, Khazaee RBetts 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.

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.

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.

 

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 4640A

Organogenesis in Mammals

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PHYSIOLOGY 9553

Special Topics in Developmental Biology

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GRADUATE COURSE

January 5 - June 13, 2026

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GET IN TOUCH

 

519-661-3786

Department of Physiology and Pharmacology
Schulich London, ON, Canada

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