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The McEwen Institute is home to five internationally recognized scientists, each with expertise in stem cell and human developmental biology. Together, they push the boundaries of stem cell science to revolutionize healthcare and advance our mission of developing therapies of the future. Learn more about their work below.


Gordon Keller  
Dr. Gordon Keller, PhD

Senior Scientist, Princess Margaret Cancer Centre
Director, McEwen Stem Cell Institute


Dr. Gordon Keller is the Director of the McEwen Stem Cell Institute (formerly the McEwen Centre for Regenerative Medicine), a Senior Scientist at the Princess Margaret Cancer Centre and a Professor in the Department of Medical Biophysics at the University of Toronto. Dr. Keller is the premier researcher in the application of developmental biology-guided principles to the differentiation of pluripotent stem cells (PSCs) into therapeutically relevant cells, such as cardiomyocytes, hematopoietic cells and liver cells. Using developmentally guided approaches, his lab has successfully generated most of the cell types of the human heart and the human blood cell system from human pluripotent stem cells. His current research efforts are focused on translating these advances to the development of new cell therapies to treat cardiovascular and hematological diseases.

Dr. Keller earned his PhD in Immunology at the University of Alberta in 1979 and completed a Post-Doctoral Fellowship at the Ontario Cancer Institute in Toronto in 1983. Following his post-doctoral studies, he became a Member of the Basel Institute for Immunology in Switzerland where he worked for five years, then moved to Vienna, Austria where he accepted the post of Visiting Scientist at the Research Institute of Molecular Pathology. In 1990, Dr. Keller moved to the United States, working initially at the National Jewish Centre for Immunology and Respiratory Medicine in Denver, Colorado and then in the Department of Gene and Cell Medicine at the Mt. Sinai School of Medicine in New York where he was appointed Director of the Black Family Stem Cell Institute. He returned to Canada in 2006 to assume the position of Director of the McEwen Centre for Regenerative Medicine (now the McEwen Stem Cell Institute) at the University Health Network in Toronto.

Dr. Keller is also a founding Board member of the International Society of Stem Cell Research. In December 2016, Keller was named scientific co-founder of BlueRock Therapeutics, a biotechnology company that is developing pluripotent stem cell-based therapies to treat heart failure and Parkinson's disease. Dr. Keller received the Ogawa-Yamanaka Stem Cell prize in 2019 for his research on the differentiation of pluripotent stem cells and was a co-recipient of the 2021 Scientific Grand Prize from the Lefoulon-Delalande Foundation at the Institut de France for his contributions to our understanding of human cardiovascular development.

Learn more about Dr. Gordon Keller's work on UHN's Behind the Breakthrough podcast.

Notable Achievements

  • UHN Inventor of the Year, 2017
  • Ogawa-Yamanaka Award, Gladstone Institute, November 2019
  • Bloom Burton Award, November 2020
  • Scientific Grand Prize, Institut de France, Lefoulon-Delalande, June 2021

Modeling human multi-lineage heart field development with pluripotent stem cells
Cell Stem Cell. 2022 Sep 1;29(9):1382-1401.e8.
Yang D, Gomez-Garcia J, Funakoshi S, Tran T, Fernandes I, Bader GD, Laflamme MA, Keller G


Generation of mature compact ventricular cardiomyocytes from human pluripotent stem cells
Nature Communications. 2021 May 26;12(1):3155.
Funakoshi S, Fernandes I, Mastikhina O, Wilkinson D, Tran T, Dhahri W, Mazine A, Yang D, Burnett B, Lee J, Protze S, Bader GD, Nunes SS, Laflamme M, Keller G


Therapeutic correction of hemophilia A by transplantation of hPSC-derived liver sinusoidal endothelial cell progenitors
Cell Reports. 2022 Apr 5;39(1):110621.
Gage BK, Merlin S, Olgasi C, Follenzi A, Keller GM


Modeling human yolk sac hematopoiesis with pluripotent stem cells
Journal of Experimental Medicine. 2922 Mar 7; 219(3):e20211924
Atkins MH, Scarfò R, McGrath KE, Yang D, Palis J, Ditadi A, Keller GM


Director: Dr. Gordon Keller

Administrative Assistant: Jonelle Martineau

Technicians

  • Kelvin Chan Tung
  • Brenda Cohen

Scientific Associates

  • Jamie Kwan
  • Marion Kennedy
  • Mark Gagliardi

Postdoctoral Fellows

  • Blair Gage
  • Vladimir Manchev

Students

  • Nestor Fernandez, PhD Student
  • Ian Fernandes, PhD Student
  • Amine Mazine, PhD Student
  • Gregory Kent, MSc Student

Michael Laflamme 
Dr. Michael Laflamme, MD, PhD

Robert McEwen Chair in Cardiac Regenerative Medicine
Canada Research Chair, Cardiovascular Regenerative Medicine
Senior Scientist, McEwen Stem Cell Institute
Staff Pathologist, UHN Laboratory Medicine Program
Professor, Laboratory Medicine and Pathobiology, University of Toronto


Dr. Michael Laflamme is a Senior Scientist at the McEwen Stem Cell Institute (formerly the McEwen Centre for Regenerative Medicine) at the University Health Network (UHN), where he also holds the Robert McEwen Chair in Cardiac Regenerative Medicine and the Tier 1 Canada Research Chair in Cardiovascular Regenerative Medicine. His research program is aimed at developing novel cell therapies to regenerate injured hearts.

After obtaining an undergraduate degree in Physics at Georgetown University in 1991, Dr. Laflamme completed the Medical Scientist (MD/PhD) Training Program at Emory University in 1999. His PhD studies were focused on the regulation of calcium homeostasis by beta-adrenergic signalling in adult ventricular cardiomyocytes. After residency in Anatomic Pathology and subspecialty training in cardiovascular pathology at the University of Washington Medical Center, he completed a postdoctoral fellowship in the laboratory of Dr. Charles Murry investigating the role of exogenous and endogenous stem cells in myocardial repair. After his postdoctoral studies, he joined the faculty at the University of Washington, where he remained prior to relocating to UHN in 2015.

His independent research career has been largely focused on the development of cell therapies based on human pluripotent stem cells (hPSCs), and his laboratory has made a number of important contributions in this area including 1) widely-used protocols to guide the differentiation of hPSCs into cardiomyocytes and specialized cardiac subtypes, 2) the first proof-of-concept study showing that the transplantation of hPSC-derived cardiomyocytes (hPSC-CMs) can "remuscularize" scar tissue and improve left ventricular contractile function in rodent models of myocardial infarction (MI), and 3) the first direct demonstration that hPSC-CM grafts can electrically couple with host myocardium following transplantation in injured hearts. Among other active projects, his team has ongoing efforts to promote the scaled manufacturing of mature hPSC-CMs, improve the electrical function of hPSC-CMs post-transplantation, and test their efficacy in small- and large-animal models of post-MI heart failure.

Dr. Laflamme has been the recipient of several honours, including the Society for Cardiovascular Pathology Young Investigator Award, the American Society of Gene & Cell Therapy Outstanding New Investigator Award, and the UHN Inventor of the Year. In addition to his position at the McEwen Stem Cell Institute, Dr. Laflamme is a Professor in the Department of Laboratory Medicine & Pathobiology at the University of Toronto and a Staff Pathologist in the UHN Laboratory Medicine Program, practicing diagnostic cardiovascular and autopsy pathology. He is also a scientific co-founding investigator of BlueRock Therapeutics.


A complete list of Dr. Laflamme's publications can be found on UHN Research

In Vitro Matured Human Pluripotent Stem Cell-Derived Cardiomyocytes Form Grafts With Enhanced Structure and Function in Injured Hearts.
Circulation. 2022 May 3; 145(18):1412-1426.
Dhahri W, Sadikov Valdman T, Wilkinson D, Pereira E, Ceylan E, Andharia N, Qiang B, Masoudpour H, Wulkan F, Quesnel E, Jiang W, Funakoshi S, Mazine A, Gomez-Garcia JM, Latifi N, Jiang Y, Huszti E, Simmons CA, Keller G, Laflamme MA


Methods for Transepicardial Cell Transplantation in a Swine Myocardial Infarction Model
Methods in Molecular Biology. 2022; 2485:191-212.
Wulkan F, Romagnuolo R, Qiang B, Laflamme MA


Optical mapping of human embryonic stem cell-derived cardiomyocyte graft electrical activity in injured hearts
Stem Cell Research & Therapy. 2020 Sep 25;11(1):417.
Filice D, Dhahri W, Solan JL, Lampe PD, Steele E, Milani N, Van Biber B, Zhu W, Sadikov Valdman T, Romagnolo R, Otero-Cruz JD, Hauch KD, Kay MW, Sarvazyan N, Laflamme MA.


Human Embryonic Stem Cell-Derived Cardiomyocytes Regenerate the Infarcted Pig Heart but Induce Ventricular Tachyarrhythmias
Stem Cell Reports. 2019 May 14; 12(5): 967-981.
Romanguolo R, Masoudpour H, Porta-Sánchez A, Qiang B, Barry J, Laskary A, Qi X, Massé S, Magtibay K, Kawajiri H, Wu J, Valdman Sadikov T, Rothberg J, Panchalingam KM, Titus E, Li RK, Zandstra PW, Wright GA, Nanthakumar K, Ghugre NR, Keller G, Laflamme MA


Principal Investigator: Dr. Michael Laflamme

Administrative Assistant: Jonelle Martineau

Research Technicians

  • Tamilla Valdman Sadikov
  • Wenlei Jiang

Scientific Associate

  • Beiping Qiang

Postdoctoral Fellows

  • Fanny Wulkan
  • Rasha Al-Attar
  • Faisal Alibhai

Students

  • Maria (Juliana) Gomez, PhD Student
  • Christoph Haller, PhD Student
  • Elana Sefton, PhD Student
  • Amine Mazine, PhD Student (co-supervised)
  • Coulter Montague, PhD Student

Maria Cristina Nostro 
Dr. Maria Cristina Nostro, PhD

Harry Rosen Chair, Diabetes and Regenerative Medicine Research
Senior Scientist, McEwen Stem Cell Institute, UHN
Associate Professor, Department of Physiology, University of Toronto


Dr. Nostro joined the McEwen Stem Cell Institute (formerly the McEwen Centre for Regenerative Medicine) in September 2012 as Principal Investigator and currently holds the Harry Rosen Chair in Diabetes Regenerative Medicine Research. The objective of her research is to differentiate pluripotent stem cells into pancreatic cells, with the ultimate goal of generating functional insulin-producing β cells for transplantation in people living with type 1 diabetes, eliminating the need for daily insulin injections.

Dr. Nostro obtained a Laurea in Biology (BSc and MSc equivalent) from the University of Florence, Italy in 2000. As an undergraduate student, she participated in the Erasmus Exchange Program and joined Professor Chris Potten's laboratory at the Paterson Institute for Cancer Research, in Manchester, UK. Her stay in his laboratory sparked her interest in stem cell biology and her desire to pursue an academic career.

In 2000, with a Fellowship from the Italian National Research Council, she enrolled as a PhD student at The University of Manchester and under the supervision of Dr. Gerard Brady, studied blood stem cells and became an expert in gene expression profiling of these cells at the single cell level. After obtaining her PhD in 2004, she was drawn to study a new model system and applied for a postdoctoral position in the laboratory of Dr. Gordon Keller at Mount Sinai School of Medicine in NY, where she focused on understanding the earliest stages of blood cell formation using embryonic stem cells. After relocating to Toronto in 2007, she progressed to her scientific independency by initiating a project on pancreatic development.

Her group has defined critical pathways leading to the efficient generation and purification of stem cell-derived pancreatic progenitors. Since 2015, Dr. Nostro has been leading a multi-investigator team aimed at developing novel transplantation approaches for Type 1 Diabetes therapy.


GP2-enriched pancreatic progenitors give rise to functional beta cells in vivo and eliminate the risk of teratoma formation
Stem Cell Reports. 2022 Apr 12;17(4):964-978.
Aghazadeh Y, Sarangi F, Poon F, Nkennor B, McGaugh EC, Nunes SS, Nostro MC.


Microvessels support engraftment and functionality of human islets and hESC-derived pancreatic progenitors in diabetes models
Cell Stem Cell. 2021 Nov 4;28(11):1936-1949.
Aghazadeh Y, Poon F, Sarangi F, Wong FTM, Khan ST, Sun X, Hatkar R, Cox BJ, Nunes SS, Nostro MC.


Sufu- and Spop-mediated downregulation of hedgehog signaling promotes beta cell differentiation through organ-specific niche signals
Nat Commun. 2019 Oct 11;10(1):4647.
Yung T, Poon F, Liang M, Coquenlorge-Gallon S, McGaugh EC, Hui C-C, Wilson MD, Nostro MC, Kim TH.


Glycoprotein 2 is a specific cell surface marker of human pancreatic progenitors
Nat Commun. 2017 Aug 24;8(1):331.
Cogger KF, Sinha A, Sarangi F, McGaugh EC, Saunders D, Dorrell C, Mejia-Guerrero S, Aghazadeh Y, Rourke JL, Screaton RA, Grompe M, Streeter PR, Powers AC, Brissova M, Kislinger T, Nostro MC.


Principal Investigator: Dr. Cristina Nostro

Administrative Assistant: Jonelle Martineau

Lab Manager: Farida Sarangi

Postdoctoral Fellows

  • Rangarajan Sambathkumar (supported by Juvenile Diabetes Research Foundation)
  • Adriana Migliorini (supported by Juvenile Diabetes Research Foundation)
  • Amanda Oakie (supported by Juvenile Diabetes Research Foundation, Banting and Best Diabetes Centre and Canadian Islet Research and Training Network)

Students

  • Paraish Misra, MSc Candidate (supported by KRESCENT Foundation and CIHR)
  • Alex Cho, PhD Candidate
  • Haiyang Huang, MSc Candidate

One step closer to stem cell breakthrough for diabetes

Dr. Cristina Nostro, holder of the Harry Rosen Chair in Diabetes Regenerative Medicine Research at the McEwen Centre for Regenerative Medicine, is on a mission to find a cure for Type 1 diabetes. Bringing an international flair to her scientific background (she is from Italy and has done advanced training in England and the United States), Dr. Nostro joined the McEwen Centre in 2007 as a post-doctoral fellow.

Type 1 diabetes has long been considered to be an ideal candidate for stem cell-based therapy. Her discoveries made in the McEwen Centre labs now give her the ability to produce functioning, insulin-producing beta cells. Among stem cell scientists, there is a sense that they are getting closer to a cell therapy goal, effectively making the leap from bench to bedside.

In 2015, Dr. Nostro published a groundbreaking study in Stem Cell Reports showing methods to effectively generate larger populations of pancreatic progenitor cells (essentially, pancreatic cells that can produce beta cells) using a wide range of pluripotent stem cells. Her research has shown that when these cells are transplanted into Type 1 models, they have successfully reverted glucose to normal levels. This will enable more efficient testing of these cells across a larger number of laboratories, increasing the odds – and the speed – of obtaining a cure for Type 1 diabetes. Dr. Nostro is also using a technique that allows the insulin-producing cells that are destroyed by Type 1 diabetes to be re-created in our laboratories. This will help her understand how the disease develops and perhaps lead to more effective treatments for the condition.

"Our ultimate goal is to develop new drugs that will modify the immune system so that it ends its attack on the beta cells."

Shinichiro Ogawa 
Dr. Shinichiro Ogawa, MD, PhD

Affiliate Scientist, McEwen Stem Cell Institute
Assistant Professor, Department of Laboratory Medicine and Pathobiology, University of Toronto


Dr. Shinichiro Ogawa joined the McEwen Stem Cell Institute in 2019 as a Principal Investigator. His research program is focused on developing cell- and tissue-based replacement therapies that can provide an alternative therapy to liver transplant for patients with liver failure.

Dr. Ogawa completed his PhD at Shinshu University School of Medicine in Nagano, Japan and his MD at the Tokyo Medical University in Tokyo, Japan. He completed a post-doctoral fellowship in the laboratory of Dr. Gordon Keller at the McEwen Centre for Regenerative Medicine prior to his appointment. Dr. Ogawa also holds an appointment as Professor at the Department of Surgery at Shinshu University School of Medicine in Japan.

In his research, he has developed methods to use hPSCs to generate liver progenitors (hepatoblasts), which can generate functional liver cells. He has used these progenitors to develop mature liver cells and bile duct epithelial cells, both of which have the characteristic properties of functional cells in the liver. In his work with the McEwen Stem Cell Institute, Dr. Ogawa is using hPSC-derived liver cells and organoids to assess restoration of liver function in an experimental model with the goal of developing treatments for liver failure. He is also using hPSC-derived bile duct epithelial cells to develop models to study Cystic Fibrosis Liver Disease and screen drugs for treatment.


Generation of functional ciliated cholangiocytes from human pluripotent stem cells
Nature Communications. 2021 Nov 11;12(1):6504
Ogawa M, Jiang J-X, Xia S, Yang D, Ding A, Laselva O, Chin S, Hernandez M, Cui C, Higuchi Y, Suemizu H, Dorrell C, Grompe M, Bear CE, Keller G, Ogawa S. Nat Commun.


Directed differentiation of cholangiocytes from human pluripotent stem cells
Nature Biotechnology. 2015 Aug;33(8):853-61
Ogawa M, Ogawa S, Bear CE, Ahmadi S, Chin S, Li B, Grompe M, Keller G, Kamath BM, Ghanekar A.


Three-dimensional culture and cAMP signaling promote the maturation of human pluripotent stem cell-derived hepatocytes
Development. 2013 Aug;140(15):3285-96.
Ogawa S, Surapisitchat J, Virtanen C, Ogawa M, Niapour M, Sugamori KS, Wang S, Tamblyn L, Guillemette C, Hoffmann E, Zhao B, Strom S, Laposa RR, Tyndale RF, Grant DM, Keller G.


Principal Investigator: Dr. Shinichiro Ogawa

Administrative Assistant: Jonelle Martineau

Lab Manager: Dr. Mina Ogawa

Students

  • Nicole Zhao, PhD Student

Stephanie Protze 
Dr. Stephanie Protze, PhD

Scientist, McEwen Stem Cell Institute
Assistant Professor, Department of Molecular Genetics, University of Toronto


Dr. Protze joined the McEwen Stem Cell Institute in 2018 where she is currently a Principal Investigator. Her research program is focused on human heart development and disease with the overarching goal to develop new therapies to treat cardiovascular disease.

Dr. Stephanie Protze obtained her Bachelor of Science degree in 2007 in the Molecular Biotechnology program at Dresden University of Technology (Germany). She joined the International Max Planck Research School in Dresden for her PhD studies in the laboratory of Drs. Ursula Ravens and Elly Tanaka during which time she focused on transcription factor-based direct reprogramming of fibroblasts to cardiomyocytes and their electrophysiological characterization. Dr. Protze graduated with a PhD in Cell Biology and Biomedicine from the University of Dresden in 2012 with summa cum laude. For her Post-Doctoral Fellowship, Dr. Protze trained in the laboratory of Dr. Gordon Keller at the McEwen Centre for Regenerative Medicine at the University Health Network in Toronto (Canada) where she specialized in human heart development and the generation of biological pacemakers from human pluripotent stem cells. These biological pacemakers have the potential to provide improved treatment over current electronic pacemaker devices in the future.

Through her research, Dr. Protze established a method for generating pacemaker cells from pluripotent stem cells. In an international collaboration with scientists from Technion, Israel, Dr. Protze provided first proof of principle that these pacemaker cells can function as biological pacemaker, the first step in developing a cell therapy approach to treat patients. Dr. Protze also spearheaded a project on the development of human atrial and ventricular cardiomyocytes from pluripotent stem cells and demonstrated for the first time that these two lineages are pre-specified by mesoderm patterning during gastrulation. In her work with the McEwen Stem Cell Institute, Dr. Protze is applying the pluripotent stem cell model system to identify the signals that govern atrioventricular node pacemaker lineage commitment with the ultimate goal to decipher a complete lineage tree of the cardiac conduction system. She is also pursuing translational research by applying the hPSC-derived cardiomyocyte subtypes for disease modeling and drug development and by further exploring the application of hPSC-derived pacemaker cells as biological pacemakers in pre-clinical animal models.


A complete list of Dr. Protze's publications can be found on UHN Research

Generation of mature compact ventricular cardiomyocytes from human pluripotent stem cells.
Nat Commun. 2021 May 26; 12(1):3155.
Funakoshi S, Fernandes I, Mastikhina O, Wilkinson D, Tran T, Dhahri W, Mazine A, Yang D, Burnett B, Lee J, Protze S, Bader GD, Nunes SS, Laflamme M, Keller G.


Genome-wide analysis identifies an essential human TBX3 pacemaker enhancer.
Circ Res. 2020 Dec4;127(12):1522-1535 Impact Factor 14.467.
van Eif WW V, Protze S, Bosada FM, Yuan X, Sinha T, van Duijvenboden K, Ernault AC, Mohan RA, Wakker V, de Gier-de Vries C, Hooijkaas IB, Wison MD, Verkerk AO, Bakkers J, Boukens BJ, Black BL, Scott IC, Christoffels VM.


Human pluripotent stem cell-derived cardiovascular cells: from developmental biology to therapeutic applications.
Cell Stem Cell. 2019 Sep 5;25(3):311-32.
Protze S, Lee JH, Keller G.


Human Pluripotent Stem Cell-Derived Atrial and Ventricular Cardiomyocytes Develop from Distinct Mesoderm Populations
Cell Stem Cell. 2017 Aug 03;21(2):179-194.e4
Lee JH, Protze SI, Laksman Z, Backx PH, Keller GM


Sinoatrial node cardiomyocytes derived from human pluripotent cells function as a biological pacemaker
Nat Biotechnol. 2017 Jan;35(1):56-68
Protze SI, Liu J, Nussinovitch U, Ohana L, Backx PH, Gepstein L, Keller GM


Principal Investigator: Dr. Stephanie Protze

Administrative Assistant: Jonelle Martineau

Lab Manager: Maggie Kwan

Graduate Students

  • Michelle Lohbihler, PhD Student
  • Amos Lim, PhD Student
  • Matthew Chang, PhD Student
  • Brandon Murareanu, MSc Student

Q: For the past five years, you have focused your research on trying to create a specific cell in the heart called the pacemaker cell. The idea is that these cells could help a heart beat regularly and naturally on its own. Recently, your team was successful in creating functional pacemaker cells from stem cells in just 21 days. How did you do it?

A: It was tricky. You have to determine the right signalling molecules at the right concentration, at the right time, to stimulate the stem cells. We did it by replicating nature's way of making the pacemaker cells. Human trials are still some years away, but with our community support and the continued innovation of our team, we will get there.

Q: What impact does this breakthrough stand to have in the long term?

A: Our team is hoping to eventually develop a biological pacemaker to transplant into patients who need an electronic one. Since more than 18,000 electronic pacemakers are implanted every year into Canadian patients, this alternative therapy stands to change tens of thousands of lives. If we're successful, the biological pacemaker holds the promise of a lifelong cure. And it would be our committed donors, along with the world-class researchers who have devoted their careers to this work, who made that possible.

Q: You're a Principal Investigator at the newly established McEwen Institute. Why was the Institute created?

A: Over the last 15 years, incredible research has been done through the McEwen Centre for Regenerative Medicine. Due to this success, UHN transitioned the efforts at McEwen Centre on a broad range of research areas to the McEwen Institute, focusing primarily on translating stem cell research to patient care in four key areas including heart, liver, blood and diabetes. The naming of the Institute recognizes the longstanding generosity of Rob and Cheryl McEwen who, since 2003, have spearheaded support for regenerative medicine at UHN. And thanks to their support, and the support of donors like the McEwens, the Institute will develop even more effective and cutting-edge treatments for heart disease, cancers of the blood like leukemia, type 1 diabetes and liver diseases using regenerative medicine with the full weight of UHN behind it.

Learn more about Dr. Stephanie Protze's work on UHN's Behind the Breakthrough podcast.

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