News & Views 2014 Lucian Award Jeffrey Robbins Susan Ince The 37th Louis and Artur Lucian Award for research in circulatory disease has been presented to Jeffrey Robbins, PhD, of Cincinnati Children’s Hospital Medical Center. Robbins is being honored for 20 continuous years of exceptional cardiovascular research, bolstered by his openness in sharing his materials and findings. Since its beginnings with a $2 million bequest to McGill University in 1965, the Lucian Award has recognized the contributions of active investigators or teams whose work has already had a significant effect on the understanding of cardiovascular disease (Table). In her will, Olga Leibovici established the award to honor her brothers, both engineers, who had died prematurely. The $60 000 CAN prize, the largest given in any biomedical field in Canada, was first awarded in 1978. The Lucian Award places no restrictions on the nationality of recipients, and scientists working in 7 countries have received the honor. The McGill University community and awardees benefit from collaborations that are established or furthered during the 1 or 2 weeks each winner spends at McGill. “Through careful management, this single philanthropic donation from the 1960s has created an incredible legacy that just keeps on giving, and that is something that we will never forget and will protect for the future,” said Jacques Genest, MD, FRCP(C), Professor, Faculty of Medicine at McGill University, current Chair of the Lucian Selection Committee, and Novartis Chair in Medicine, McGill University. Recipients are selected by a volunteer committee of scientists, including many former awardees (see Box, Lucian Award Selection Committee), and each year about 15 topnotch applications make it to the last round. “Robbins has over 20 years of continuous stellar work and his career has led to many unexpected firsts in our understanding of cardiac disease. But what made our decision unanimous was his incredible openness to sharing his findings and materials. He has offered transgenic mice and the reagents used in creating them to other researchers without asking for money or even coauthorship in return, and that is a form of altruism that is extraordinary in science,” Genest said.
Jeffrey Robbins received his PhD in genetics and cell biology from the University of Connecticut. After a postdoctoral fellowship with Jerry Lingrel, PhD, at the University of Cincinnati, Robbins joined the faculty of the University of Missouri-Columbia. Seven years later, he gave up a comfortable, tenured position there to move to the University of Cincinnati College of Medicine. In 1993, Robbins was recruited to Cincinnati Children’s Hospital Medical Center to start a new division he named Molecular Cardiovascular Biology. In that position, Robbins excelled in his own research and proved gifted in hiring young faculty who would develop distinguished independent research careers. “He wants you to succeed and anticipates what you’re going to need next. The environment he created made it easy for me to move from studying early chicken heart development to working with mice and looking at human disease mechanisms,” said Katherine Yutzey, PhD, who was hired by Robbins in her first faculty position and is now a professor in the division. In 2009, Robbins founded the Heart Institute at Cincinnati Children’s. “At the Heart Institute, basic clinical translational and outcomes-based research and clinical practice and cardiothoracic surgery are all under one roof with a single strategic mission and a single budget. It removes the artificial barriers thrown up between research and clinical practice so that basic and other research can be seamlessly translated into clinical practice,” said Robbins. Robbins is currently Professor of Pediatrics, Chief of the Division of Molecular Cardiovascular Biology, and Executive Co-director of the Heart Institute at Children’s. In 1991, the local American Medical Students Association awarded Robbins the Golden Apple Award for Teaching Excellence. Among his many research awards are The national research achievement award from the American Heart Association (AHA, 2005); the presidential award for research from the International Society for Heart Research (2007); the distinguished scientist award from the Basic Cardiovascular Sciences Council of the AHA (2008); and the national distinguished scientist award from the AHA (2011). Since 2009, Robbins has served as senior associate editor for Circulation Research. “Circulation Research remains the premier journal for basic cardiovascular research and has become more important over the past 5 years. There has been an explosion in the scientific literature, so readers benefit from a rigorous and selective editorial board that can filter the papers so they are not inundated with a large volume of articles of uneven quality,” Robbins says.
The opinions expressed in News & Views are not necessarily those of the editors or of the American Heart Association. Correspondence to [email protected] (Circ Res. 2014;115:969-972.) © 2014 American Heart Association, Inc. Circulation Research is available at http://circres.ahajournals.org DOI: 10.1161/CIRCRESAHA.114.305558
969
970 Circulation Research December 5, 2014
Giving Away the Keys to Molecular Cardiology Jeffrey Robbins fundamentally changed the way cardiovascular research is performed by creating tools for altering the protein complement of the heart through transgenic manipulation. In a series of innovative papers, Robbins defined the promoter elements needed to spur cardiac-specific gene expression in the mammalian heart. His laboratory used those tools to direct the heart to synthesize normal and mutant proteins at specific times in development, conducting both gainand loss-of-function studies and establishing cause-and-effect relationships for normal proteins, as well as those involved in cardiovascular disease. “Robbins recognized early on that genetic manipulations in mice would provide important insights into the molecular basis of heart disease. Toward that end, he generated strains of mice with cardiac-specific overexpression of a variety of cardiac structural and signaling proteins. These mouse models, and especially the cardiac-specific gene regulatory elements he used to create them, served as key reagents for the field during the transition into the era of molecular cardiology. Robbins’ generosity in providing reagents to the field also provided a major boost to the field at a critical time,” says Eric Olson, PhD, professor and chair of molecular biology at the University of Texas Southwestern Medical Center at Dallas. Olson’s laboratory is one of >1500 over the years to have been given reagents or transgenic mice from Robbins. To scientists equipped to breed their own transgenic mice, Robbins supplies the reagents, and >400 different disease models have been created—a rapid pace of discovery that would not have been possible without his generosity. For those who want to use transgenic mice created in Robbins’ laboratory, he sends them—even to direct competitors—and until very recently without passing on shipping or mouse expenses. “I believe that there are really more open questions than there are scientists trying to answer them. Even if you’re a competitor, if you can find a better way to answer a question I’m asking, I say more power to you,” says Robbins. “Institutions have a habit of putting up so many barriers in terms of intellectual property that it makes it difficult for scientists. My belief is that for anything that’s published, if you haven’t already obtained the intellectual property rights, those are gone and those materials should be free for all to use. That’s what I’ve lived by, and I don’t feel that I’ve ever lost anything by giving it away.”
When Good Proteins Go Bad Although people might understandably consider Robbins’ primary contribution to cardiovascular research to be developing tools for manipulating the heart’s protein complement, he believes his ongoing exploration of the concept of proteotoxicity might turn out to be just as important. For normal function and adaptation to changing conditions, cardiomyocytes must be able to both synthesize and break down proteins efficiently. Errors in protein synthesis, whether from mutations or environmental stressors, can lead to a buildup of unneeded or mis-folded proteins in the cells. Robbins has described the multipronged quality-control mechanism needed to maintain proper protein conformation, repair misshapen proteins, and to remove those that are irreversibly
Table.
Previous Recipients of the Lucian Award
1978
Nicolae and Maya Simionescu
Bucharest and Yale University
1979
James Bassingthwaighte
University of Washington
1980
Solbert Permutt
Johns Hopkins University
1981
Gilbert Thompson
Hammersmith Hospital
1982
Christian Crone
University of Copenhagen
1983
Norman Staub
University of California
1984
James and Una Ryan
University of Miami
1985
Earl Wood
Mayo Clinic
1986
Dirk Brutsaert
University of Antwerp
1987
Daniel Steinberg
University of California
1988
Aubrey Taylor
University of South Alabama
1989
Francis Chinard
New Jersey Medical School
Ian Phillips
University of Florida
1990
Barbara Meyrick
Vanderbilt University
1991
José Jalife
State University of New York, Syracuse
1992
Judah Folkman
The Children’s Hospital, Boston
1993
Arthur Brown
Baylor College of Medicine
1994
John B. Barlow
University of Witwatersrand, South Africa
1995
Andrew and Avril Somlyo
University of Virginia, Charlottesville
Robert Furchgott
State University of New York
Salvador Moncada
University College, London
1996 1997
Russell Ross
University of Washington
1998
Eduardo Marban
Johns Hopkins University
1999
Victor J. Dzau
Harvard Medical School
2000
Robert J. Lefkowitz
Duke University Medical School
2001
Mark C. Fishman
Harvard Medical School
2002
Salim Yusuf
McMaster University
2003
Eric N. Olson
University of Texas Southwestern Medical Center
2004
Roberto Bolli
University of Louisville
2005
Michael A. Gimbrone, Jr
Harvard Medical School
2006
Peter Carmeliet
University of Leuven
2007 2008
Not Awarded Piero Anversa
Harvard Medical School
2009
Peter Libby
Harvard Medical School
2010
Marlene Rabinovitch
Stanford University School of Medicine
2011
Shaun R. Coughlin
University of California, San Francisco
2012
Garret A. FitzGerald
University of Pennsylvania
2013
David Ginsburg
University of Michigan
2014
Jeffrey Robbins
University of Cincinnati College of Medicine
damaged or have formed insoluble aggregates.1 Chaperones, a diverse family of proteins, mediate correct folding or refolding. Heat shock proteins, a class of chaperones that are
Ince 2014 Lucian Award 971
Figure. First demonstration of preamyloid oligomers in human heart failure. On the left, normal human ventricle tissue with healthy cardiomyocytes staining red. On the right, ventricle section from a randomly chosen patient with heart failure, a 33-year-old woman with nonobstructive hypertrophic cardiomyopathy. The muscle bundles are full of preamyloid oligomers staining green. Reprinted with permission from Sanbe et al.2 Copyright© 2004, The National Academy of Sciences.
plentiful in cardiomyocytes, are upregulated in cardiac stress and disease. When proteins are damaged or unneeded, they may be degraded through the ubiquitin–proteasome system (a series of enzymatic steps that primarily eliminates unneeded short-lived proteins) and the autophagy–lysosome system, which forms a membrane around damaged or aged proteins, large aggregates and organelles, and delivers them to the lysosomes for degradation. If synthesis and breakdown is not balanced, misfolded proteins may accumulate, causing harmful proteotoxicity. No matter what its primary cause, heart failure is preceded or accompanied by a failure of protein quality control, with enhanced synthesis and decreased removal of abnormal proteins. Robbins also saw commonalities with protein accumulation in neurons in several degenerative diseases. Robbins’ laboratory demonstrated that, in a genetically engineered mouse with a missense mutation in the heat shock protein α-B-crystallin (CryABR120G), which results in desminrelated cardiomyopathy and death from heart failure, ventricle sections were characterized by protein aggregates that were indistinguishable from aggresomes found in Alzheimer’s disease and Parkinson’s disease. The laboratory then showed that the aggresomes in these mice, as well as ventricle sections from randomly selected patients with various cardiomyopathies, contain soluble preamyloid oligomer (See Figure), which they think may represent the primary toxic species in Alzheimer’s and other neurodegenerative disorders, as well as in heart failure.2,3 “Alzheimer’s disease is characterized by plaques in the brain but those plaques are the end point of a long disease process rather than the cause. It’s like when you go to a graveyard and look at a tombstone. It’s not the tombstone that killed the person, it’s a marker of the process. We’re asking what that process was, and we believe that these pre-amyloid oligomers are an essential or even the essential part of the process,” Robbins says. In 2011, Robbins used gain- and loss-of-function approaches to determine that inducing basal autophagy, the process the cell uses to recycle its internal components could reverse the accumulation of proteins and aggregates in cultured cardiomyocytes.4 Recently, his laboratory demonstrated that by upregulating a rate-limiting enzyme in autophagy (autophagy-related 7, Atg7), the process could be enhanced in the intact heart, reducing the
cardiac intracellular aggregates in a transgenic mouse model of desmin-related cardiomyopathy in which autophagy is significantly reduced.5 Enhancing autophagy by crossing the desmin-related cardiomyopathy mice with an inducible transgenic mouse expressing Atg7, the resulting mice had decreased interstitial fibrosis, better ventricular function, decreased cardiac hypertrophy, and prolonged survival. In addition, the team found
Lucian Award Selection Committee Jacques Genest Jr., M.D. Chair, McGill University, Canada Roberto Bolli, M.D. University of Louisville, United States Dirk L. Brutsaert, M.D., Ph.D. Universiteit Antwerpen, Belgium José Jalife, M.D. University of Michigan, United States Richard J. Novick, M.D. University of Western Ontario, Canada Marlene Rabinovitch, M.D. Stanford University, United States Jean L. Rouleau, M.D. Université de Montréal, Canada Avril V. Somlyo, Ph.D. University of Virginia, United States Duncan J. Stewart, M.D. University of Ottawa, Canada Emeritus Members Yves Clermont, Ph.D. McGill University, Canada Anthony R.C. Dobell, M.D. McGill University, Canada Samuel O. Freedman, M.D. McGill University, Canada
972 Circulation Research December 5, 2014 that physical exercise, which increases autophagy via a different mechanism, had a synergistic effect. Desmin-related cardiomyopathy mice with upregulated Atg7 raised in cages with a running wheel lived longer than those with upregulated Atg7 but with no opportunity for voluntary exercise. The findings established proof of principle for autophagy as a therapeutic target, and multiple laboratories are already using the transgenic mice created for this study in their own investigations. “Some people have a flash of genius, but for Robbins it has been a continuous strobe light for 20 uninterrupted years and it’s difficult to keep up with his accomplishments. This fascinating paper involves basic cellular work that has an impact on the entire animal,” says Genest. Robbins is currently the North American coordinator for an international network to explore proteotoxicity as an unappreciated mechanism involved in many heart diseases and with a potential for novel therapeutics, an effort funded by the Fondation LeDucq. He is also taking steps to facilitate greater communication between neurological and cardiovascular
researchers who wish to share results and explore the unifying themes of proteotoxicity across various systems The next deadline to nominate a scientist for the Lucian Award is March 20, 2015. Further information is available on their website at http://www.mcgill.ca/lucianaward/.
Disclosures None.
References 1. Wang X, Robbins J. Heart failure and protein quality control. Circ Res. 2006;99:1315–1328. 2. Sanbe A, Osinska H, Saffitz JE, Glabe CG, Kayed R, Maloyan A, Robbins J. Desmin-related cardiomyopathy in transgenic mice: a cardiac amyloidosis. Proc Natl Acad Sci U S A. 2004;101:10132–10136. 3. Pattison JS, Robbins J. Protein misfolding and cardiac disease: establishing cause and effect. Autophagy. 2008;4:821–823. 4. Pattison JS, Robbins J. Autophagy and proteotoxicity in cardiomyocytes. Autophagy. 2011;7:1259–1260. 5. Bhuiyan MS, Pattison JS, Osinska H, James J, Gulick J, McLendon PM, Hill JA, Sadoshima J, Robbins J. Enhanced autophagy ameliorates cardiac proteinopathy. J Clin Invest. 2013;123:5284–5297.
Jeffrey Robbins received his PhD in genetics and cell biology from the University of Connecticut. After a postdoctoral fellowship with Jerry Lingrel, PhD, at the University of Cincinnati, Robbins joined the faculty of the University of Missouri-Columbia. Seven years later, he gave up a comfortable, tenured position there to move to the University of Cincinnati College of Medicine. In 1993, Robbins was recruited to Cincinnati Children’s Hospital Medical Center to start a new division he named Molecular Cardiovascular Biology. In that position, Robbins excelled in his own research and proved gifted in hiring young faculty who would develop distinguished independent research careers. “He wants you to succeed and anticipates what you’re going to need next. The environment he created made it easy for me to move from studying early chicken heart development to working with mice and looking at human disease mechanisms,” said Katherine Yutzey, PhD, who was hired by Robbins in her first faculty position and is now a professor in the division. In 2009, Robbins founded the Heart Institute at Cincinnati Children’s. “At the Heart Institute, basic clinical translational and outcomes-based research and clinical practice and cardiothoracic surgery are all under one roof with a single strategic mission and a single budget. It removes the artificial barriers thrown up between research and clinical practice so that basic and other research can be seamlessly translated into clinical practice,” said Robbins. Robbins is currently Professor of Pediatrics, Chief of the Division of Molecular Cardiovascular Biology, and Executive Co-director of the Heart Institute at Children’s. In 1991, the local American Medical Students Association awarded Robbins the Golden Apple Award for Teaching Excellence. Among his many research awards are The national research achievement award from the American Heart Association (AHA, 2005); the presidential award for research from the International Society for Heart Research (2007); the distinguished scientist award from the Basic Cardiovascular Sciences Council of the AHA (2008); and the national distinguished scientist award from the AHA (2011). Since 2009, Robbins has served as senior associate editor for Circulation Research. “Circulation Research remains the premier journal for basic cardiovascular research and has become more important over the past 5 years. There has been an explosion in the scientific literature, so readers benefit from a rigorous and selective editorial board that can filter the papers so they are not inundated with a large volume of articles of uneven quality,” Robbins says.
The opinions expressed in News & Views are not necessarily those of the editors or of the American Heart Association. Correspondence to [email protected] (Circ Res. 2014;115:969-972.) © 2014 American Heart Association, Inc. Circulation Research is available at http://circres.ahajournals.org DOI: 10.1161/CIRCRESAHA.114.305558
969
970 Circulation Research December 5, 2014
Giving Away the Keys to Molecular Cardiology Jeffrey Robbins fundamentally changed the way cardiovascular research is performed by creating tools for altering the protein complement of the heart through transgenic manipulation. In a series of innovative papers, Robbins defined the promoter elements needed to spur cardiac-specific gene expression in the mammalian heart. His laboratory used those tools to direct the heart to synthesize normal and mutant proteins at specific times in development, conducting both gainand loss-of-function studies and establishing cause-and-effect relationships for normal proteins, as well as those involved in cardiovascular disease. “Robbins recognized early on that genetic manipulations in mice would provide important insights into the molecular basis of heart disease. Toward that end, he generated strains of mice with cardiac-specific overexpression of a variety of cardiac structural and signaling proteins. These mouse models, and especially the cardiac-specific gene regulatory elements he used to create them, served as key reagents for the field during the transition into the era of molecular cardiology. Robbins’ generosity in providing reagents to the field also provided a major boost to the field at a critical time,” says Eric Olson, PhD, professor and chair of molecular biology at the University of Texas Southwestern Medical Center at Dallas. Olson’s laboratory is one of >1500 over the years to have been given reagents or transgenic mice from Robbins. To scientists equipped to breed their own transgenic mice, Robbins supplies the reagents, and >400 different disease models have been created—a rapid pace of discovery that would not have been possible without his generosity. For those who want to use transgenic mice created in Robbins’ laboratory, he sends them—even to direct competitors—and until very recently without passing on shipping or mouse expenses. “I believe that there are really more open questions than there are scientists trying to answer them. Even if you’re a competitor, if you can find a better way to answer a question I’m asking, I say more power to you,” says Robbins. “Institutions have a habit of putting up so many barriers in terms of intellectual property that it makes it difficult for scientists. My belief is that for anything that’s published, if you haven’t already obtained the intellectual property rights, those are gone and those materials should be free for all to use. That’s what I’ve lived by, and I don’t feel that I’ve ever lost anything by giving it away.”
When Good Proteins Go Bad Although people might understandably consider Robbins’ primary contribution to cardiovascular research to be developing tools for manipulating the heart’s protein complement, he believes his ongoing exploration of the concept of proteotoxicity might turn out to be just as important. For normal function and adaptation to changing conditions, cardiomyocytes must be able to both synthesize and break down proteins efficiently. Errors in protein synthesis, whether from mutations or environmental stressors, can lead to a buildup of unneeded or mis-folded proteins in the cells. Robbins has described the multipronged quality-control mechanism needed to maintain proper protein conformation, repair misshapen proteins, and to remove those that are irreversibly
Table.
Previous Recipients of the Lucian Award
1978
Nicolae and Maya Simionescu
Bucharest and Yale University
1979
James Bassingthwaighte
University of Washington
1980
Solbert Permutt
Johns Hopkins University
1981
Gilbert Thompson
Hammersmith Hospital
1982
Christian Crone
University of Copenhagen
1983
Norman Staub
University of California
1984
James and Una Ryan
University of Miami
1985
Earl Wood
Mayo Clinic
1986
Dirk Brutsaert
University of Antwerp
1987
Daniel Steinberg
University of California
1988
Aubrey Taylor
University of South Alabama
1989
Francis Chinard
New Jersey Medical School
Ian Phillips
University of Florida
1990
Barbara Meyrick
Vanderbilt University
1991
José Jalife
State University of New York, Syracuse
1992
Judah Folkman
The Children’s Hospital, Boston
1993
Arthur Brown
Baylor College of Medicine
1994
John B. Barlow
University of Witwatersrand, South Africa
1995
Andrew and Avril Somlyo
University of Virginia, Charlottesville
Robert Furchgott
State University of New York
Salvador Moncada
University College, London
1996 1997
Russell Ross
University of Washington
1998
Eduardo Marban
Johns Hopkins University
1999
Victor J. Dzau
Harvard Medical School
2000
Robert J. Lefkowitz
Duke University Medical School
2001
Mark C. Fishman
Harvard Medical School
2002
Salim Yusuf
McMaster University
2003
Eric N. Olson
University of Texas Southwestern Medical Center
2004
Roberto Bolli
University of Louisville
2005
Michael A. Gimbrone, Jr
Harvard Medical School
2006
Peter Carmeliet
University of Leuven
2007 2008
Not Awarded Piero Anversa
Harvard Medical School
2009
Peter Libby
Harvard Medical School
2010
Marlene Rabinovitch
Stanford University School of Medicine
2011
Shaun R. Coughlin
University of California, San Francisco
2012
Garret A. FitzGerald
University of Pennsylvania
2013
David Ginsburg
University of Michigan
2014
Jeffrey Robbins
University of Cincinnati College of Medicine
damaged or have formed insoluble aggregates.1 Chaperones, a diverse family of proteins, mediate correct folding or refolding. Heat shock proteins, a class of chaperones that are
Ince 2014 Lucian Award 971
Figure. First demonstration of preamyloid oligomers in human heart failure. On the left, normal human ventricle tissue with healthy cardiomyocytes staining red. On the right, ventricle section from a randomly chosen patient with heart failure, a 33-year-old woman with nonobstructive hypertrophic cardiomyopathy. The muscle bundles are full of preamyloid oligomers staining green. Reprinted with permission from Sanbe et al.2 Copyright© 2004, The National Academy of Sciences.
plentiful in cardiomyocytes, are upregulated in cardiac stress and disease. When proteins are damaged or unneeded, they may be degraded through the ubiquitin–proteasome system (a series of enzymatic steps that primarily eliminates unneeded short-lived proteins) and the autophagy–lysosome system, which forms a membrane around damaged or aged proteins, large aggregates and organelles, and delivers them to the lysosomes for degradation. If synthesis and breakdown is not balanced, misfolded proteins may accumulate, causing harmful proteotoxicity. No matter what its primary cause, heart failure is preceded or accompanied by a failure of protein quality control, with enhanced synthesis and decreased removal of abnormal proteins. Robbins also saw commonalities with protein accumulation in neurons in several degenerative diseases. Robbins’ laboratory demonstrated that, in a genetically engineered mouse with a missense mutation in the heat shock protein α-B-crystallin (CryABR120G), which results in desminrelated cardiomyopathy and death from heart failure, ventricle sections were characterized by protein aggregates that were indistinguishable from aggresomes found in Alzheimer’s disease and Parkinson’s disease. The laboratory then showed that the aggresomes in these mice, as well as ventricle sections from randomly selected patients with various cardiomyopathies, contain soluble preamyloid oligomer (See Figure), which they think may represent the primary toxic species in Alzheimer’s and other neurodegenerative disorders, as well as in heart failure.2,3 “Alzheimer’s disease is characterized by plaques in the brain but those plaques are the end point of a long disease process rather than the cause. It’s like when you go to a graveyard and look at a tombstone. It’s not the tombstone that killed the person, it’s a marker of the process. We’re asking what that process was, and we believe that these pre-amyloid oligomers are an essential or even the essential part of the process,” Robbins says. In 2011, Robbins used gain- and loss-of-function approaches to determine that inducing basal autophagy, the process the cell uses to recycle its internal components could reverse the accumulation of proteins and aggregates in cultured cardiomyocytes.4 Recently, his laboratory demonstrated that by upregulating a rate-limiting enzyme in autophagy (autophagy-related 7, Atg7), the process could be enhanced in the intact heart, reducing the
cardiac intracellular aggregates in a transgenic mouse model of desmin-related cardiomyopathy in which autophagy is significantly reduced.5 Enhancing autophagy by crossing the desmin-related cardiomyopathy mice with an inducible transgenic mouse expressing Atg7, the resulting mice had decreased interstitial fibrosis, better ventricular function, decreased cardiac hypertrophy, and prolonged survival. In addition, the team found
Lucian Award Selection Committee Jacques Genest Jr., M.D. Chair, McGill University, Canada Roberto Bolli, M.D. University of Louisville, United States Dirk L. Brutsaert, M.D., Ph.D. Universiteit Antwerpen, Belgium José Jalife, M.D. University of Michigan, United States Richard J. Novick, M.D. University of Western Ontario, Canada Marlene Rabinovitch, M.D. Stanford University, United States Jean L. Rouleau, M.D. Université de Montréal, Canada Avril V. Somlyo, Ph.D. University of Virginia, United States Duncan J. Stewart, M.D. University of Ottawa, Canada Emeritus Members Yves Clermont, Ph.D. McGill University, Canada Anthony R.C. Dobell, M.D. McGill University, Canada Samuel O. Freedman, M.D. McGill University, Canada
972 Circulation Research December 5, 2014 that physical exercise, which increases autophagy via a different mechanism, had a synergistic effect. Desmin-related cardiomyopathy mice with upregulated Atg7 raised in cages with a running wheel lived longer than those with upregulated Atg7 but with no opportunity for voluntary exercise. The findings established proof of principle for autophagy as a therapeutic target, and multiple laboratories are already using the transgenic mice created for this study in their own investigations. “Some people have a flash of genius, but for Robbins it has been a continuous strobe light for 20 uninterrupted years and it’s difficult to keep up with his accomplishments. This fascinating paper involves basic cellular work that has an impact on the entire animal,” says Genest. Robbins is currently the North American coordinator for an international network to explore proteotoxicity as an unappreciated mechanism involved in many heart diseases and with a potential for novel therapeutics, an effort funded by the Fondation LeDucq. He is also taking steps to facilitate greater communication between neurological and cardiovascular
researchers who wish to share results and explore the unifying themes of proteotoxicity across various systems The next deadline to nominate a scientist for the Lucian Award is March 20, 2015. Further information is available on their website at http://www.mcgill.ca/lucianaward/.
Disclosures None.
References 1. Wang X, Robbins J. Heart failure and protein quality control. Circ Res. 2006;99:1315–1328. 2. Sanbe A, Osinska H, Saffitz JE, Glabe CG, Kayed R, Maloyan A, Robbins J. Desmin-related cardiomyopathy in transgenic mice: a cardiac amyloidosis. Proc Natl Acad Sci U S A. 2004;101:10132–10136. 3. Pattison JS, Robbins J. Protein misfolding and cardiac disease: establishing cause and effect. Autophagy. 2008;4:821–823. 4. Pattison JS, Robbins J. Autophagy and proteotoxicity in cardiomyocytes. Autophagy. 2011;7:1259–1260. 5. Bhuiyan MS, Pattison JS, Osinska H, James J, Gulick J, McLendon PM, Hill JA, Sadoshima J, Robbins J. Enhanced autophagy ameliorates cardiac proteinopathy. J Clin Invest. 2013;123:5284–5297.
