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Harvard Medical School/Harvard School of Dental Medicine Curriculum Vitae

Date Prepared: January 20, 2014

Name: Annarosa Leri, M.D.

Office Address: Brigham and Women’s Hospital Departments of Anesthesia and Medicine, and Cardiovascular Division Laboratories for Regenerative Medicine Thorn 1317 Boston, MA 02115

Home Address: 160 Commonwealth Avenue Apt. 212 Boston, MA 02116

Work Phone: 617 525 8174

Work Email: aleri@partners.org

Work FAX: 617 264 6320

Place of Birth: Reggio Emilia, Italy

Education

1982 1990

Diploma di Maturita’ summa cum laude MD summa cum laude

Biology and Italian Literature Medicine

Liceo Scientifico, Castelnovo ne’ Monti, Italy University of Parma, Medical School, Parma, Italy

Postdoctoral Training

1990-1994 1996-1999

Resident/Fellow (summa cum laude) Fellow

Dermatology Molecular Biology

University of Parma, Medical School Cardiovascular Research Institute, Department of Medicine, New York Medical College, Valhalla, NY

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Faculty Academic Appointments

1994-1996 1999-2002 2002-2006 2002-2007 2006-2007 2006-2007 2007-2010 2007- 2010- 2013-

Instructor Assistant Professor Associate Professor with Tenure Associate Professor Associate Professor Professor with Tenure Lecturer Adjunct Professor Associate Professor Associate Professor

Department of Dermatology Department of Medicine Department of Medicine Department of Dermatology Department of Physiology Department of Medicine Department of Anesthesia Department of Medicine Department of Anesthesia Department of Medicine

University of Parma, Medical School New York Medical College New York Medical College New York Medical College New York Medical College New York Medical College Harvard Medical School, Boston, MA New York Medical College (no voting privileges) Harvard Medical School Harvard Medical School

Appointments at Hospitals/Affiliated Institutions

12/2007- Scientist, Research Staff

Department of Anesthesiology Brigham and Women’s Hospital, Boston, MA

Major Administrative Positions

2010-2012 2010-2012 2012-

Center for Regenerative Therapeutics, BWH Biomedical Research Institute Research Oversight Committee BWH Regenerative Center

Brigham and Women’s Hospital Co-Leader Brigham and Women’s Hospital Member Member Steering Committee

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Committee Service

Local

International

2011- Call for Scientific Projects Committee Ministry of Health, Rome, Italy Member

Professional Societies

1994-1996 1996-

Italian Society of Dermatology and Venereology American Heart Association

Member

1996- 2000- 2005-2008 2006-2009 2006-2011 2007 2010-2012

Fellow Member, Abstract Grading Committee Member, Marcus Young Investigator Award Committee Chair, Council on Basic Cardiovascular Sciences, Committee on Scientific Sessions Program Member, Leadership Committee, Council on Basic Cardiovascular Sciences Chair, First International Symposium on Myocardial Regeneration Member, Leadership Committee, Council on Functional Genomics and Translational Biology

2011 2013

Basic Science Research Task Force BWH Biomedical Research Institute B-BIC Technology Assessment and Development Group

Brigham and Women’s Hospital Member Brigham and Women’s Hospital Member

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2010-2012 2011

Nominating Committee, Council on Basic Cardiovascular Science Co-Chair, Organizing Committee for Basic Cardiovascular Science Scientific Sessions

1998- International Society for Heart Research Member

2000- 2009-

American Physiological Society Heart Failure Society of America 2009- 2009-2012

Member Member Member, Organizing Committee of the Annual Meeting

Grant Review Activities

2000-2002 Peer Review Group National Cardiovascular Pathophysiology Group 1

American Heart Association Member

2003 2003-2006 2004 2004 2004 2005 2005

Biology of Aging Review Committee Peer Review Group North East Consortium Cardiovascular Pathophysiology Group 2 Myocardial Ischemia and Metabolism Review Committee Special Emphasis Panel “Proteomics and Aging” Special Emphasis Panel for the Review of Program Project Grant Applications Special Emphasis Panel for the Review of R01 Grants Special Emphasis Panel “Centers of

Member American Heart Association Member NIH Ad Hoc Member NIH Member NIH Member NIH Member NIH

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2006-2010 2009 2010- 2011 2011 2011 2011 2011 2012 2012 2012

Excellence in Translational Human Stem Cell Research” Cardiac Contractility, Hypertrophy and Failure Study Section 2006-2007 2007-2010 Biology of Aging Review Committee Regenerative Cell Biology 2 Peer Review Committee BRI Seed Grant Review Committee Harvard Stem Cell Institute Seed Grants (Translational Research) Call for Scientific Projects Metabolism and Myocardial Ischemia Review Committee Developmental Biology 2 Study Section Call for Scientific Projects Post-doctoral fellowships Regione Marche ISSNAF Peer Review Group AHA Innovative Grants

Member NIH Ad Hoc Member Permanent Member NIH Ad Hoc Member American Heart association Co-Chair Biomedical Research Institute, Brigham and Women’s Hospital Member Harvard Medical School Member Italian Ministry of Health Reviewer Member, Executive Council Committee NIH Ad Hoc Member NIH Ad Hoc Member Italian Ministry of Health Reviewer Italian Ministry of Health Reviewer American Heart Association

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AHA Innovative Grants 2012-2016 Myocardial Ischemia and Reviewer NIH/National Heart Lung

Metabolism and Myocardial Ischemia Review Committee

Reviewer NIH Standing Member

2013 SEP NHLBI Review Committee Chairman

2014 Young Investigator Award Competition Ministry of Health, Italy

Reviewer Editorial Activities

Ad Hoc Reviewer

Circulation American Journal of Physiology Journal of Molecular and Cellular Cardiology American Journal of Pathology Gene Stem Cells Journal of Clinical Investigation

Other Editorial Roles

2004- 2008-2014

Editorial Board Member Academic Editor

Circulation Research PLoS One

Honors and Prizes

2001 2008-2009 2012 2014

Angiotensin II Young Investigators Award Mentorship as Sarnoff Preceptor Plaque of Appreciation George E. Brown Memorial Lecturer

Louisville, Young Investigators Angiotensin II Symposium Sarnoff Foundation Chonnam National University Medical School, Gwangju, South Korea AHA Scientific Session 2014

Research Teaching Research Research

Report of Funded and Unfunded Projects Funding Information

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Past

2000-2005 Myocyte Stem Cells in the Mammalian Heart NHLBI/R01-65577 PI ($875,000) The objective of this project was the documentation of the existence of a pool of resident

stem cells in the normal and diseased heart, regulating cardiac turnover and repair. 2005-2011

Aging and Homeostasis of Cardiac Stem Cell Niches

NIA/R01AG026107 PI ($1,025,000) The goal of this project was to establish whether myocyte apoptosis plays a positive role in

cardiac homeostasis, by promoting the activation and differentiation of cardiac stem cells within the niches.

2010-2012

Cardiac Progenitor Cell Therapy for Advanced Ischemic Cardiomyopathy

NHLBI/P20HL101866 Co-Investigator This application aims at the development of cell-based strategies in a pre-clinical model of

ischemic cardiomyopathy. 2004-2012

Aging of Cardiac Stem Cells NIA/P01-AG023071 Project Leader The objective of this project is to define the role of the telomere-telomerase system in

cardiac stem cell growth, death, differentiation, and senescence with aging. 2006-2012

Bone Marrow and Cardiac Progenitor Cells in Cardiac Repair

NHLBI/R01HL65577 PI ($1,125,000) The objective of this project is to compare the therapeutic efficacy of bone marrow and

cardiac progenitors in animal models of acute myocardial infarction. 2007-2012

Cardiac Stem Cells and Diabetic Cardiomyopathy

NHLBI/R01HL65573 Co-PI The objective of this application is to demonstrate that reactive oxygen species induce

death of cardiac stem cells leading to the development of a diabetic cardiomyopathy.

2007-2013 Identification of a Coronary Vasculature Progenitor Cell in Human Ischemic Heart Failure NHLBI/R01HL039902 PI (MultiPI) The objective of this application is to characterize a novel class of cardiac stem cells with

high vasculogenic potential and define their role in vessel homeostasis and repair.

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Current

2008-2015 Epigenetic Mechanisms Regulate Cardiac Progenitor Cell Function NHLBI/P01 HL092668 Project Leader ($1,330,000) The goal of this proposal is to identify the epigenetic regulation of the expression of

stemness (Oct3/4) and differentiation (Nkx2.5) genes in human cardiac stem cells. 2010-2016

Telomeric Shortening, p53 and miR-34a Condition Senescence of Cardiac Progenitors NIA/R01 AG37490 PI ($1,690,000)

The objective of this application is to establish whether miR-34a is an essential regulator of senescence in cardiac stem cells carrying short telomeres.

2011-2017

Redefining Human Cardiac Biology NHLBI/R01 HL114346

PI (MultiPI) ($2,690,000) The objective of this application is to define the origin of cardiac stem cells and the rate of

their activation and differentiation throughout life. 2013-2015 2013-2016 2013-2017

Cardiac Stem Cells and Angiomyogenesis NHLBI/R01 HL111183 PI ($1,259,646) The objective of this application is to establish whether c-kit-positive cardiac stem cells play a role in myocyte renewal throughout development and during adulthood and senescence in the mouse heart. Cardiomyogenesis in the Adult Heart NHLBI/R01HL114346 PI (MultiPI) $1,705,000 The objective of this application is to determine whether oscillations in intracellular Ca2+ occurring in cardiac stem cells and bone marrow stem cells are responsible for cell cycle entry and fate specification of these two progenitor cell classes. Hypoxic and Normoxic Niches in the Aging Mouse Heart NHLBI/P01 AG043353

Project Leader ($1,637,000) The objective of this application is to establish whether intracellular oxygen content

controls the functional properties of cardiac stem cells and whether the proportion of hypoxic and normoxic cardiac niches changes with aging.

Report of Local Teaching and Training Teaching of Students in Courses

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2000-2007 Stem Cells Department of Physiology, New York Medical College

2008

PhD Students

2-hr sessions per wk for 2 weeks

HST 521 Course Students Harvard Medical School Overview of Cardiac Regeneration and

Stem Cell Therapy 3-hr session

Formal Teaching of Residents, Clinical Fellows and Research Fellows (post-docs)

1994-1996 Skin Pharmacology Dermatology Fellows

Department of Dermatology, University of Parma Medical School

1999-2001

Cardiomyocyte Apoptosis

2-hr sessions per wk. for 16 weeks Cardiovascular Research Institute, New

Research Fellows York Medical College 2001-2007

Molecular Mechanisms of Cardiac Stem Cell Growth and Differentiation

Cardiovascular Research Institute, New York Medical College

Research Fellows 2-hr sessions per wk. 2007-

Molecular Mechanisms of Cardiac Stem Cell Growth and Differentiation

Center for Regenerative Medicine, Brigham and Women’s Hospital

2-hr sessions per wk

Laboratory and Other Research Supervisory and Training Responsibilities

1999-2007 Supervision of post-doctoral research fellows/Cardiovascular Research Institute, New York Medical College

Daily mentorship

1999-2007

Supervision of high school, college, and medical students/Cardiovascular Research Institute, New York Medical College

Daily mentorship

2007-

Supervision of post-doctoral research fellows/Center for Regenerative Medicine, Brigham and Women’s Hospital

Daily mentorship

2007-

Supervision of high school and college students/ Center for Regenerative Medicine, Brigham and Women’s Hospital

Daily mentorship

Formally Supervised Trainees and Faculty

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1999-2003 Antonio P. Beltrami, MD, PhD, Assistant Professor, Department of Hematology and Oncology, University of Udine, Medical School, Udine, Italy

Research mentor; Published 7 manuscripts, including one in Cell and one in The New England Journal of Medicine

1999-2003

Daniela Cesselli, MD, PhD, Assistant Professor, Department of Hematology and Oncology, University of Udine, Medical School, Udine, Italy

Research mentor; Published two manuscripts in Circulation Research and in The Proceedings of the National Academy of Sciences

2003-2007

Toru Hosoda, MD, PhD, Assistant Professor, Department of Anesthesia, Brigham and Women’s Hospital

Research mentor; Published several manuscripts, including two in The Proceedings of the National Academy of Sciences

2004-2007

Angelo Nascimbene, MD, Fellow in Cardiology, Texas Heart Institute, Houston, TX

Research mentor; Published six manuscripts, including two in The Proceedings of the National Academy of Sciences

2005-2007

Serena Vitale, PhD, Staff Scientist, Department of Medicine, University of Perugia, Perugia, Italy

Research mentor; Published seven manuscripts, including three in The Proceedings of the National Academy of Sciences

2005-2007

Arantxa Gonzalez, PhD, Assistant Professor, Department of Medicine, University of Navarra, Pamplona

Research mentor; Published five manuscripts, including one in Circulation Research and four in The Proceedings of the National Academy of Sciences

2005-2007

Alessandro Boni, PhD, Staff Scientist, University of Geneva, Geneva, Switzerland

Research mentor; Published six manuscripts, including two in The Proceedings of the National Academy of Sciences

2008-2009

Research co-mentor; Derin Tugal, BS, Resident, Cleveland Clinic, Cleveland, OH, Recipient, Sarnoff Fellowship

Manuscript in its final phase of completion 2008-2010

Polina Goihberg, PhD, Instructor, Center for Regenerative Medicine, Departments of Anesthesia and Medicine, and Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School.

Research mentor; Published five manuscripts in Circulation Research 2008-2010

Hanqiao Zheng, MD, PhD, Career in Clinical Medicine

Research mentor; Published ten manuscripts, including 2 in Circulation, 6 in Circulation Research and two in The Proceedings of the National Academy of Sciences

2009-2011

Mauricio Cabral-Da-Silva, PhD, Post-doctoral fellow, University of Sao Paulo, Brazil

Research mentor; Published four manuscripts, including two in Circulation, one in

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Circulation Research and one in The Proceedings of the National Academy of Sciences 2009-2012

Noriko Ide-Iwata, MD, Post-doctoral Fellow, Center for Regenerative Medicine, Departments of Anesthesia and Medicine, and Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School.

Research mentor; Published four manuscripts, including one in Circulation, two in Circulation Research and one in The Proceedings of the National Academy of Sciences

2010-2011

Narassiman Gurusamy, PhD, Instructor, Center for Regenerative Medicine, Departments of Anesthesia and Medicine, and Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School

Research mentor; Published one manuscript in Circulation Research 2010-2012

Ada Pesapane, PhD, Post-doctoral Fellow, Center for Regenerative Medicine, Departments of Anesthesia and Medicine, and Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School

Research mentor; Published one manuscript in Circulation Research 2011-2012

Emily Mangano, PhD, Post-doctoral Fellow, Center for Regenerative Medicine, Departments of Anesthesia and Medicine, and Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School

Research mentor; Published one manuscript in Circulation Research 2011-2012

Mario Ricciardi, PhD, Post-doctoral Fellow, Center for Regenerative Medicine, Departments of Anesthesia and Medicine, and Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School

Research mentor; Published one manuscript in Stem Cells Dev. 2011-2014

Giorgia Palano, PhD, Post-doctoral Fellow, Center for Regenerative Medicine, Departments of Anesthesia and Medicine, and Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School

Research mentor; Manuscript in preparation 2012-2013

Yang-Ki Chan, PhD, Post-doctoral Fellow, Center for Regenerative Medicine, Departments of Anesthesia and Medicine, and Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School

Research mentor; Manuscript published in Circulation Research

2009-2013 Fumihiro Sanada, MD, PhD, Post-doctoral Fellow, Center for Regenerative Medicine, Departments of Anesthesia and Medicine, and Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School

Research mentor; Published five manuscripts, including one in Circulation Research 2011-2014

Jung Kim, PhD, Post-doctoral Fellow, Center for Regenerative Medicine, Departments of Anesthesia and Medicine, and Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School

Research mentor; Published two manuscripts, including one in Circulation Research

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2012-2014 Manila Candiracci, PhD, Post-doctoral Fellow, Center for Regenerative Medicine, Departments of Anesthesia and Medicine, and Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School Research mentor; Manuscript in preparation

2012-2014 Fiorenza Valeriani, PhD, Post-doctoral Fellow, Center for Regenerative Medicine,

Departments of Anesthesia and Medicine, and Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School

Research mentor; Manuscript in preparation 2011-

Ramaswamy Kannappan, PhD, Post-doctoral Fellow, Center for Regenerative Medicine, Departments of Anesthesia and Medicine, and Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School

2012-

Laura Graciotti, PhD, Post-doctoral Fellow, Center for Regenerative Medicine, Departments of Anesthesia and Medicine, and Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School

Research Mentor; Manuscripts submitted and in preparation 2013-

Joao Pereira, PhD, Post-doctoral Fellow, Center for Regenerative Medicine, Departments of Anesthesia and Medicine, and Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School

Research Mentor; Manuscripts submitted and in preparation 2013-

Moises Di Sante, PhD, Post-doctoral Fellow, Center for Regenerative Medicine, Departments of Anesthesia and Medicine, and Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School

2013-

Research Mentor; Manuscripts submitted and in preparation Antonio Di Rocco, PhD, Post-doctoral Fellow, Center for Regenerative Medicine, Departments of Anesthesia and Medicine, and Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School

2013-

Research Mentor; Manuscripts in preparation Marco Luciani, MD, Post-doctoral Fellow, Center for Regenerative Medicine, Departments of Anesthesia and Medicine, and Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School

Research Mentor; Manuscripts in preparation Report of Regional, National and International Invited Teaching and Presentations Invited Presentations and Courses

Local Invited Presentations

2008 Progenitor Cells and Myocardial Regeneration/5th Annual Symposium

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of Cellular, Molecular, and Clinical Research in Surgery Department of Surgery, Children’s Hospital, Boston, MA 2009

Vascular Progenitor Cells/Vascular Biology Seminars

Department of Pathology, Brigham and Women’s Hospital 2011

Molecular Control of Cardiac Stem Cell Differentiation/Cardiovascular Research Seminar Series

Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA

National Those presentations below sponsored by outside entities are so noted and the sponsors are identified.

2001 Aging of the Heart (Lecture) Functional Aging Workshop, National Institute on Aging, Bethesda, MD 2001

p53, Hyperglycemia and Myocyte Apoptosis

Young Investigators Meeting for Angiotensin II Research, Louisville, KY 2002

IGF-1 and Cardiac Aging (Lecture)

IGF-1 and Cardiac Aging Workshop, National Institute on Aging, Bethesda, MD 2002

Stem Cell Therapy (Lecture)

First Annual Symposium on Genomics and Heart, GlaxoSmithKline Foundation, New York, NY 2002

Heart, Aging and Diabetes (Lecture)

Diabetes Workshop, National Institute on Aging, Bethesda, MD 2002

The Role of Telomerase in the Myocardium (Featured Research Lecture)

Scientific Sessions of the American Heart Association, Chicago, IL 2003

Myocyte Hypertrophy and Hyperplasia in Human Aortic Stenosis (Cardiovascular Grand Rounds)

Texas A&M Anderson Medical School, Temple, Texas 2003

Stem Cells and Myocardial Regeneration (Lecture)

Stem Cell Symposium, GlaxoSmithKline Foundation, New York, NY 2003

Telomerase, Cell Death and Cell Growth (Cardiovascular Seminar)

Scientific Sessions of the American Heart Association, Orlando, FL 2004

Cardiac Stem Cells and Aging of the Heart (Cardiovascular Seminar Series)

Tufts University, St. Elizabeth Center, Boston, MA 2004

Cardiac Stem Cells and Ischemic Cardiomyopathy in Humans (Cardiovascular Seminar Series)

Department of Physiology, Temple University, Philadelphia, PA 2004

Reverse Remodeling of the Aging Heart (Lecture)

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Cardiovascular Regulatory Mechanisms, Gordon Research Conference, New London, NH 2004

Cardiac Stem Cells (Featured Research Lecture)

Scientific Sessions of the American Heart Association, New Orleans, LA 2004

Cardiac Stem Cells and the IGF-1-IGF-1 Receptor System (Cardiovascular Research Seminar Series)

Genzyme, Cambridge, MA (Genzyme) 2004

Cardiac Stem Cell Niches and Myocardial Growth (Cardiovascular Research Seminar Series)

Department of Molecular Cardiology, Cleveland Clinic, Cleveland, OH 2005

Cardiac Niches (Lecture)

Microscopy and Microanalysis Meeting, Microscopy Society of America, Honolulu, Hawaii 2005

Tissue-Specific Stem Cells and Cardiac Repair (Featured Research Lecture)

Scientific Sessions of the American Heart Association, Orlando, FL 2005

Cardiac Stem Cells: the Transition to a New Paradigm (Cardiology Grand Rounds)

Department of Medicine, Vanderbilt University, Nashville, TN 2006

The Aging Myopathy as a Stem Cell Disease (Lecture)

Stem Cells and Aging Workshop, National Institute on Aging, Bethesda, MD 2006

Myocardial Homeostasis (Cardiovascular Branch Seminar)

National Institute Of Heart, Lung and Blood, Bethesda, MD 2006

Cell Therapy for the Failing Heart (Plenary Talk)

Scientific Sessions of the American Heart Association, Chicago, IL 2006

Notch Signaling in Cardiac Stem Cells (Cardiovascular Seminar)

Scientific Sessions of the American Heart Association, Chicago, IL 2007

Molecular Mechanisms of Stemness and Differentiation in the Adult Heart (Cardiovascular Research Seminar Series)

Department of Medicine, University of Chicago, Chicago, IL 2007

Molecular Control of Stemness in Cardiac Niches (Lecture)

Cardiovascular Repair and Regeneration, Annual Symposium of the Basic Cardiovascular Sciences Council, American Heart Association, Keystone, Colorado

2007

Success with Heart Failure: Perspective from the Big Apple (Lecture)

Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY 2007

Transit Amplifying Myocytes (Cardiovascular Seminar)

Scientific Sessions of the American Heart Association, Orlando, FL 2008

Molecular Control of Myocyte Hypertrophy and Differentiation (Cardiovascular Institute Visiting Professor)

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Stanford University, Stanford, CA 2008

Cardiac Progenitor Cells and Aging Myopathy (Lecture)

Design and Medical Devices Symposium, Minneapolis, MN 2008

Cardiac Stem Cells, Homeostasis and Repair (Cardiovascular Research Seminar Series)

Lillihei Heart Institute, Minneapolis, MN 2008

The Heart is a Self-Renewing Organ (Lecture)

NIH Symposium on the Challenges and Promise of Cell-Based Therapies, Bethesda, MD 2008

Transit Amplifying Myocytes (Cardiovascular Seminar)

Scientific Sessions of the American Heart Association, New Orleans, LA 2009

Notch and Postnatal Cardiac Development (Lecture)

Molecular Mechanisms of Cardiovascular Diseases, Annual Symposium of the Basic Cardiovascular Sciences Council, American Heart Association, Lake Las Vegas, Nevada

2009

Viral Tagging and Clonal Marking of Cardiac Stem Cells (Department of Pharmacology Lecture Series)

Department of Pharmacology, University of Miami, Miami, FL 2010

Physiological and Pathological Cardiac Hypertrophy (Feinberg Cardiovascular Research Institute Seminar Series)

Department of Medicine, Northwestern University, Chicago, IL 2010

Cardiac Stem Cells (Lecture)

Heart Failure Society of America Annual Meeting, San Diego, CA 2010

Cardiac Hypertrophy (Abstract Dialogue Session)

Scientific Sessions of the American Heart Association, Chicago, IL 2010

Mircrine Mechanisms of Cardiac Stem Cell Differentiation (Cardiovascular Seminar)

Scientific Sessions of the American Heart Association, Chicago, IL 2011

The Ephrin A1/EphA2 System in Cardiac Stem Cells (Lecture)

Cardiovascular Diseases and therapeutics, Annual Symposium of the Basic Cardiovascular Sciences Council Scientific Sessions, American Heart Association, New Orleans, LA

2011

Hypoxic and Normoxic Cardiac Niches (Featured Lecture)

Scientific Sessions of the American Heart Association, Orlando, FL 2011

Migration of Cardiac Stem cells and Myocardial Regeneration (Cardiovascular Seminar)

Scientific Sessions of the American Heart Association, Orlando, FL 2012

Age-Induced Dysfunction of Cardiac Stem Cells (Sunday Morning Program)

Scientific Sessions of the American Heart Association, Los Angeles, LA

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2012

Stem Cells and Clinical Trials (Special Session)

Scientific Sessions of the American Heart Association, Los Angeles, LA 2013

Functional Heterogeneity of Cardiac Stem Cell Niches in the Aging Heart (Department of Pharmacology Seminar Series)

Department of Pharmacology, RUSH University, Chicago, IL 2013

Capillary Structures and Niche Microenvironment (Cardiovascular Seminar Series)

Department of Medicine, University of Kentucky, Lexington, KY 2013

Cardiac Niches: A Novel Therapeutic Target

2013 2013 2013 2014 2014 2014 2015

8th Annual Wisconsin Stem Cell Symposium, “Cell-Based Therapy for Heart and Vascular Diseases: Pathways to Clinic”, Madison, WI George E. Brown Memorial Lecture Cardiomyogenesis in the Adult Heart Scientific Sessions of the American Heart Association, Dallas, TX Cardiac Aging (Cardiovascular Seminar) Scientific Sessions of the American Heart Association, Dallas, TX Stem Cell Niches and Cardiac Aging Northeast Ohio Medical University Rootstown, OH Lineage Tracing of c-kit-Positive Cardiac Stem Cells Scientific Sessions of the American Heart Association Chicago, IL Bone Marrow Cell Transdifferentiation Scientific Sessions of the American Heart Association Chicago, IL Hypoxia and Behavior of Cardiac Stem Cells 4th Meeting of the American College of Wound Healing and Tissue Repair Chicago, IL Fate Tracking of Cardiac Stem cells: Population Studies and Single-Cell Based Approaches Cardiology Grand Rounds University of California at Los Angeles, Los Angeles, CA

International

2000

The Diabetic Cardiomyopathy (Lecture)

International Society for Heart Research Meeting, North-American Section, Louisville, KY

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2002

Cardiac Chimerism (Lecture)

International Society for Heart Research Meeting, Madison, WI 2004

Cardiac Stem Cell Niches (Lecture)

International Society for Stem Cell Research, Toronto, Canada 2007

Acute Cellular Loss, Cell-Dependent Responses and Repair (Lecture)

Third International Conference on Cell Therapy for Cardiovascular Diseases, New York, NY 2008

The Future of Cell Therapy in Cardiovascular Diseases (Lecture)

International Society for Stem Cell Research, Miami, FL 2008

Cardiac Progenitors and Microenvironment (Lecture)

Lugano Stem Cell Meeting SCM 2008, Cardiocentro Ticino, Lugano, Switzerland 2010

Cardiac Stem Cells and Dilated Cardiomyopathy (Lecture)

Lugano Stem Cell Meeting SCM 2010, Cardiocentro Ticino, Lugano, Switzerland 2011

Cell Therapy for the Failing Heart (Lecture)

International Society for Heart Research Annual Meeting, Philadelphia, PA 2012

Cardiac Stem Cells: Egress from the Niches

Conference on Novel Drug Discovery, Joint Conference of WCU Program between CBNU & Harvard Medical School, Seoul, South Korea

2012

Oxygen and Cardiac Stem Cell Function 3rd Gwangju-Boston Joint Cardiology Symposium “New paradigm of Cardiovascular Therapeutics” Chonnam National University Medical School, Gwangju, South Korea

2014 The Aging Cardiomyopathy: Pathophysiology and Therapeutic Strategies

International Society for Heart Research Miami Beach, FL

2014 Cardiac Stem Cells and The Aging Myopathy (Lecture) Lugano Stem Cell Meeting “Cardiac Regeneration”,

Cardiocentro Ticino, Lugano, Switzerland

Report of Clinical Activities and Innovations Current Licensure and Certification

1990 Italian Medical License 1994 Italian Board in Clinical and Surgical Dermatology

Practice Activities

1990-1994 Inpatient and Outpatient Care Division of Dermatology, Ospedale Maggiore, Parma, Italy

11 months per year

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Report of Scholarship Peer reviewed publications in print or other media Research Investigations 1. Bassissi P, Leri A, Alinovi A. Mid-dermal elastolysis. Eur J Dermatol 1994;6:36-40. 2. Leri A, Alinovi A. Skin and ACE inhibitors. Italian J Dermatol 1997;132:33-8. 3. Li Q, Li B, Wang X, Leri A, Jana KP, Liu Y, Kajstura J, Baserga R, Anversa P. Overexpression of insulin like growth factor-1 in mice protects from myocyte death after infarction, attenuating ventricular dilation, wall stress and cardiac hypertrophy. J Clin Invest 1997;100:1991-9. 4. Anversa P, Liu Y, Leri A, Cheng W, Di Somma S, Kajstura J. Angiotensin II-mediated programmed myocyte cell death may contribute to ventricular remodeling in the post-infarcted heart. Cardiologia 1997;41:311-5. 5. Anversa P, Olivetti G, Leri A, Liu Y, Kajstura J. Myocyte cell death and ventricular remodeling. Curr Opin Nephrol Hypertension 1997;6:169-76. 6. Leri A, Liu Y, Malhotra A, Li Q, Kajstura J, Hintze TH, Anversa P. Pacing-induced heart failure in dogs enhances the expression of p53 and p53 dependent genes in ventricular myocytes. Circulation 1998;97:194-203. 7. Nitahara JA, Cheng W, Liu Y, Li B, Leri A, Li P, Mogul D, Gambert SR, Kajstura J, Anversa P. Intracellular calcium, DNase activity and myocyte apoptosis in aging Fischer 344 rats. J Mol Cell Cardiol 1998;30:519-35. 8. Leri A, Claudio PP, Li Q, Wang X, Reiss K, Wang S, Malhotra A, Kajstura J, Anversa P. Stretch-mediated release of angiotensin II induces myocyte apoptosis by activating p53 that enhances the local renin-angiotensin-system and decreases the Bcl-2-to-Bax protein ratio in the cell. J Clin Invest 1998;101:1326-42. 9. Liu Y, Leri A, Li B, Wang X, Cheng W, Kajstura J, Anversa P. Angiotensin II stimulation in vitro induces hypertrophy of normal and post-infarcted ventricular myocytes. Circ Res 1998;82:1145-59. 10. Kajstura J, Leri A, Finato N, Di Loreto C, Beltrami CA, Anversa P. Myocyte proliferation in end-stage cardiac failure in humans. Proc. Natl. Acad. Sci. USA 1998;95:8801-5. 11. Anversa P, Leri A, Beltrami CA, Guerra S, Kajstura J. Myocyte death and growth in the failing heart. Lab Invest 1998;78:767-85. 12. Kajstura J, Liu Y, Baldini A, Li B, Clark WA, Olivetti G, Leri A, Anversa P. Coronary artery constriction in rats: necrotic and apoptotic myocyte death. Am J Cardiol 1998;82:30K-42K. 13. Leri A, Liu Y, Claudio PP, Kajstura J, Wang X, Wang S, Kang P, Malhotra A, Anversa P. IGF-1 induces Mdm2 and downregulates p53, attenuating the myocyte renin-angiotensin system (RAS) and stretch-mediated apoptosis. Am J Pathol 1999;154:567-80. 14. Frustaci A, Chimenti C, Setoguchi M, Guerra S, Corsello S, Crea F, Leri A, Kajstura J, Anversa P, Maseri A. Cell death in acromegalic cardiomyopathy. Circulation 1999;99:426-34.

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15. Leri A, Liu Y, Wang X, Kajstura J, Malhotra A, Meggs LG, Anversa P. Overexpression of IGF-1 attenuates the myocyte renin-angiotensin system in transgenic mice. Circ Res 1999;84:752-62. 16. Li B, Setoguchi M, Wang X, Leri A, Andreoli AM, Malhotra A, Kajstura J, Anversa P. Insulin-like growth factor-1 attenuates the detrimental impact of non-occlusive coronary artery constriction on the heart. Circ Res 1999;84:1007-19. 17. Guerra S, Leri A, Wang X, Finato N, Di Loreto C, Beltrami CA, Kajstura J, Anversa P. Myocyte death in the failing human heart is gender-dependent. Circ Res 1999;85:856-66. 18. Setoguchi M, Leri A, Wang S, Liu Y, De Luca A, Giordano A, Hintze TH, Kajstura J, Anversa P. Activation of cyclin and cyclin dependent kinases, DNA synthesis, and myocyte mitotic division in pacing-induced heart failure in dogs. Lab Invest 1999;79:1545-58. 19. Kajstura J, Pertoldi B, Leri A, Beltrami CA, Deptala A, Darzynkiewicz Z, Anversa P. Telomeric shortening is an in vivo marker of myocytes replication and aging. Am J Pathol 2000;156:813-9. 20. Leri A, Kajstura J, Li B, Sonnenblick EH, Beltrami CA, Anversa P, Frishman WH. Cardiomyocyte aging is gender dependent. The IGF-1 – IGF-1R system. Heart Disease 2000;2:108-15. 21. Leri A, Fiordaliso F, Setoguchi M, Limana F, Bishopric NH, Kajstura J, Webster K, Anversa P. Inhibition of p53 function prevents renin-angiotensin system activation and stretch-mediated apoptosis. Am J Pathol 2000;157:843-57. 22. Leri A, Liu Y, Li B, Fiordaliso F, Malhotra A, Latini R, Kajstura J, Anversa P. Upregulation of AT1 and AT2 receptors in post-infarcted hypertrophied myocytes and stretch-mediated apoptotic cell death. Am J Pathol 2000;156:1663-72. 23. Fiordaliso F, Li B, Latini R, Sonnenblick EH, Anversa P, Leri A, Kajstura J. Myocyte death in streptozotocin-induced diabetes in rats is angiotensin II dependent. Lab Invest 2000;80:513-27. 24. Frustaci A, Kajstura J, Chimenti C, Jakoniuk I, Leri A, Maseri A, Nadal-Ginard B, Anversa P. Myocardial cell death in human diabetes. Circ Res 2000;87:1123-32. 25. Leri A, Malhotra A, Liew CC, Kajstura J, Anversa P. Telomerase activity in rat cardiac myocytes is age and gender dependent. J Mol Cell Cardiol 2000;32:385-90. 26. Barlucchi L, Leri A, Dostal DE, Fiordaliso F, Tada H, Kajstura J, Nadal-Ginard B, Hintze TH, Anversa P. Canine ventricular myocytes possess a renin-angiotensin system that is upregulated with heart failure. Circ Res 2001;88:298-304. 27. Orlic D, Kajstura J, Chimenti S, Anderson S, Pickel J, Nadal-Ginard B, Bodine D, McKay R, Leri A, Anversa P. Bone marrow cells regenerate infarcted myocardium. Nature 2001;410:701-5. 28. Beltrami A, Urbanek K, Kajstura J, Yao S-M, Finato N, Bussani R, Nadal-Ginard B, Silvestri F, Leri A, Beltrami CA, Anversa P. Evidence that human cardiac myocytes divide after myocardial infarction. N Engl J Med 2001;344:1750-7. 29. Kajstura J, Fiordaliso F, Andreoli A-M, Li B, Chimenti S, Medow MS, Nadal-Ginard B, Anversa P, Leri A. IGF-1 overexpression inhibits the development of diabetic cardiomyopathy and Ang II-mediated oxidative stress. Diabetes 2001;50:1414-24.

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30. Cesselli D, Jakoniuk I, Barlucchi L, Beltrami AP, Hintze TH, Nadal-Ginard B, Kajstura J, Leri A, Anversa P. Oxidative stress-mediated cardiac cell death is a major determinant of ventricular dysfunction and failure in dog dilated cardiomyopathy. Circ Res 2001;89:279-86. 31. Fiordaliso F, Leri A, Cesselli D, Safai B, Nadal-Ginard B, Anversa P, Kajstura J. Hyperglycemia activates p53 and p53-dependent genes leading to myocyte cell death. Diabetes 2001;50:2363-75. 32. Leri A, Barlucchi LM, Limana F, Deptala A, Darzynkiewicz Z, Hintze TH, Kajstura J, Anversa P. Telomerase expression and activity are coupled with myocyte proliferation and preservation of telomeric length in the failing heart. Proc Natl Acad Sci USA 2001;98:8626-31. 33. Orlic D, Kajstura J, Chimenti S, Limana F, Jakoniuk I, Quaini F, Nadal-Ginard B, Bodine DM, Leri A, Anversa P. Mobilized bone marrow cells repair the infarcted heart improving function and survival. Proc Natl Acad Sci USA 2001;98:10344-9. 34. Quaini F, Urbanek K, Beltrami AP, Finato N, Beltrami CA, Nadal-Ginard B, Kajstura J, Leri A, Anversa P. Chimerism of the transplanted heart. N Engl J Med 2002;346:5-15. 35. Welch S, Plank D, Witt S, Glascock B, Schaefer E, Chimenti S, Andreoli AM, Limana F, Leri A, Kajstura J, Anversa P, Sussman MA. Cardiac-specific IGF-1 expression attenuates dilated cardiomyopathy in tropomodulin overexpressing transgenic mice. Circ Res 2002;90:641-8. 36. Anversa P, Leri A, Kajstura J, Nadal-Ginard B. Myocyte growth and cardiac repair. J Mol Cell Cardiol 2002;34:91-105. 37. Limana F, Urbanek K, Chimenti S, Quaini F, Leri A, Kajstura J, Nadal-Ginard B, Izumo S, Anversa P. bcl-2 overexpression promotes myocyte proliferation. Proc Natl Acad Sci USA 2002;99:6257-62. 38. Leri A, Franco S, Zacheo A, Barlucchi L, Chimenti S, Limana F, Nadal-Ginard B, Kajstura J, Anversa P, Blasco M. Ablation of telomerase and telomere loss leads to cardiac dilation and heart failure. EMBO J 2003;22:131-9. 39. Nadal-Ginard B, Kajstura J, Leri A, Anversa P. Myocyte death, growth and regeneration in cardiac hypertrophy and failure. Circ Res 2003;92:139-50. 40. Calvillo L, Latini R, Kajstura J, Leri A, Anversa P, Ghezzi P, Cerami A, Brines M. Recombinant human erythropoietin protects the myocardium from ischemia-reperfusion injury and promotes beneficial remodeling. Proc Natl Acad Sci USA 2003;100:4802-6. 41. Urbanek K, Quaini F, Tasca G, Torella D, Castaldo C, Nadal-Ginard B, Leri A, Kajstura J, Quaini E, Anversa P. Intense myocyte formation from cardiac stem cells in human cardiac hypertrophy. Proc Natl Acad Sci USA 2003;100;10440-5. 42. Chimenti C, Kajstura J, Torella D, Urbanek K, Heleniak H, Colussi C, Di Meglio F, Nadal-Ginard B, Frustaci A, Leri A, Maseri A, Anversa P. Senescence and death of primitive cells and myocytes leads to premature cardiac aging and heart failure. Circ Res 2003;93;604-13. 43. Beltrami AP, Barlucchi L, Torella D, Baker M, Limana F, Chimenti S, Kasahara H, Rota M, Musso E, Urbanek K, Leri A, Kajstura J, Nadal-Ginard B, Anversa P. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 2003;114:763-76. 44. Lanza R, Moore MA, Wakayama T, Perry AC, Shieh JH, Hendrikx J, Leri A, Chimenti S, Monsen A, Nurzynska D, West MD, Kajstura J, Anversa P. Regeneration of the infarcted heart with stem cells derived by nuclear transplantation. Circ Res 2004;94;820-7.

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45. Shiraishi I, Melendez J, Ahn Y, Skavadal M, Murphy E, Welch S, Scaefer E, Walsh K, Rosenzweig A, Torella D, Nurzynska D, Kajstura J, Leri A, Anversa P, Sussman MA. Nuclear targeting of Akt enhances kinase activity and survival of cardiomyocytes. Circ Res 2004;94:884-91. 46. Torella D, Rota M, Nurzynska D, Musso E, Shiraishi I, Zias E, Walsh K, Rosenzweig A, Sussman MA, Urbanek K, Nadal-Ginard B, Kajstura J, Anversa P, Leri A. Stem cell and myocyte aging, heart failure and IGF-1 overexpression. Circ Res 2004;94:514-24. 47. Kajstura J, Whang B, Rota M, Cascapera S, Bearzi C, Kasahara H, Nurzynska D, Bonafe’ M, Torella D, Quaini F, Nadal-Ginard B, Urbanek K, Leri A, Anversa P. Bone marrow cells differentiate in cardiac cell lineages after infarction. Circ Res 2005;96:127-37. 48. Dawn B, Stein AB, Urbanek K, Rota M, Whang B, Rastaldo R, Torella D, Tang X-L, Rezazadeh A, Kajstura J, Leri A, Hunt G, Varma J, Prabhu SD, Anversa P, Bolli R. Cardiac stem cells delivered intravascularly traverse the vessel barrier, regenerate infarcted myocardium, and improve cardiac function. Proc Natl Acad Sci USA 2005;102:3766-71. 49. Urbanek K, Rota M, Nurzynska D, Chimenti S, Barlucchi L, Baker M, Cascapera S, Bearzi C, Musso E, Rastaldo R, Limana F, Leri A, Kajstura J, Anversa P. Local activation of cardiac stem cells repairs the infarcted heart and improves survival. Proc Natl Acad Sci USA 2005;102:8692-7. 50. Linke A, Muller P, Nurzynska D, Casarsa C, Torella D, Nascimbene A, Castaldo C, Cascapera S, Bohm M, Urbanek K, Leri A, Hintze TH, Kajstura J, Anversa P. Multipotent cardiac stem cells in the dog heart regenerate infarcted myocardium improving cardiac performance. Proc Natl Acad Sci USA 2005;102:8966-71. 51. Nagoshi T, Matsui T, Ayoama T, Leri A, Anversa P, Li L, Ogawa W, Del Monte F, Gwathmey JK, Grazette L, Hemmings B, Kass DA, Champion HC, Rosenzweig A. PI3K rescues the detrimental effects of chronic Akt activation in the heart during ischemia/reperfusion injury. J Clin Invest 2005;115:2128-38. 52. Urbanek K, Rota M, Cascapera S, Bearzi C, Nascimbene A, De Angelis A, Hosoda T, Chimenti S, Baker M, Limana F, Nurzynska D, Torella D, Rotatori F, Rastaldo R, Musso E, Quaini F, Leri A, Kajstura J, Anversa P. Cardiac stem cells possess growth factor-receptor systems that after activation regenerate the infarcted myocardium, improving ventricular function and long-term survival. Circ Res 2005;97:663-73. 53. Leri A, Kajstura J, Anversa P. Cardiac stem cells and mechanisms of myocardial regeneration. Physiol Rev 2005; 85:1373-416. 54. Rota M, Boni A, Urbanek K, Padin-Iruegas ME, Kajstura TJ, Fiore G, Sonnenblick EH, Musso E, Houser SR, Leri A, Sussman MA, Anversa P. Nuclear targeting of Akt enhances ventricular function and myocyte contractility. Circ Res 2005; 97:1332-41. 55. Anversa P, Kajstura J, Leri A, Bolli R. Life and death of cardiac stem cells: a paradigm shift. Circulation 2006;113:1451-63. 56. Rota M, LeCapitaine N, Hosoda T, Boni A, De Angelis A, Padin-Iruegas ME, Esposito G, Vitale S, Urbanek K, Casarsa C, Giorgio M, Luscher TF, Pelicci PG, Anversa P, Leri A, Kajstura J. Diabetes

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promotes cardiac stem cell aging and heart failure, which are prevented by deletion of the p66shc gene. Circ Res 2006;99:42-52. 57. Urbanek K, Cesselli D, Rota M, Nascimbene A, Bearzi C, Hosoda T, Boni A, Kajstura J, Anversa P, Leri A. Cardiac stem cell niches. Proc Natl Acad Sci USA 2006;103:9226-31. 58. Anversa P, Leri A, Rota M, Bearzi C, Urbanek K, Kajstura J, Bolli R. Stem cells, myocardial regeneration and methodological artifacts. Stem Cells 2006;25:589-601. 59. Chen X, Wilson RM, Kubo H, Beretta RM, Harris DM, Zhang X, Jaleel N, MacDonnell SM, Bearzi C, Tillmanns J, Trofimova I, Hosoda T, Mosna F, Cribbs L, Leri A, Kajstura J, Anversa P, Houser SR. The adolescent feline heart contains a population of small proliferative ventricular myocytes with immature physiological properties. Circ Res 2007;100:536-44. 60. Rota M, Hosoda T, De Angelis A, Arcarese ML, Esposito G, Rizzi R, Tillmanns J, Tugal D, Musso E, Rimoldi O, Bearzi C, Urbanek K, Anversa P, Leri A, Kajstura J. The young mouse heart is composed of myocytes heterogeneous in age and function. Circ Res 2007;101:387-99. 65. Bearzi C, Rota M, Hosoda T, Tillmanns J, Nascimbene A, De Angelis A, Yasuzawa-Amano S, Trofimova I, Siggins RW, Cascapera S, Beltrami AP, Zias E, Quaini F, Urbanek K, Michler RE, Bolli R, Kajstura J, Leri A, Anversa P. Human cardiac stem cells. Proc Natl Acad Sci USA 2007;104:14068-73, 2007. 66. Rota M, Kajstura J, Hosoda T, Bearzi C, Vitale S, Esposito G, Iaffaldano G, Padin-Iruegas ME, Gonzalez A, Rizzi R, Small N, Muraski J, Xiongwen C, Urbanek K, Bolli R, Houser SR, Leri A, Sussman MA, Anversa P. Bone marrow cells to adopt the cardiomyogenic fate in vivo: Proc Natl Acad Sci USA 2007;104:17783-8. 67. Ren J, Duan J, Thomas DP, Yang X, Sreejayan N, Sowers JR, Leri A, Kajstura J, Gao F, Anversa P. IGF-I alleviates diabetes-induced RhoA activation, eNOS uncoupling, and myocardial dysfunction. Am J Physiol 2008;294:793-802. 68. Muraski JA, Rota M, Misao Y, Fransioli J, Cottage C, Gude N, Esposito G, Delucchi F, Arcarese M, Alvarez R, Siddiqi S, Emmanuel GN, Wu W, Fischer K, Martindale JJ, Glembotski CC, Leri A, Kajstura J, Magnuson N, Berns A, Beretta RM, Houser SR, Schaefer EM, Anversa P, Sussman MA. Pim-1 regulates cardiomyocyte survival downstream of Akt. Nat Med 2007;13:1467-75. 69. Tillmanns J, Rota M, Hosoda T, Misao Y, Esposito G, Gonzalez A, Vitale S, Parolin C, Yasuzawa-Amano S, Muraski J, De Angelis A, LeCapitaine N, Siggins RW, Loredo M, Bearzi C, Bolli R, Urbanek K, Leri A, Kajstura J, Anversa P. Formation of large coronary arteries by cardiac progenitor cells. Proc Natl Acad Sci USA 2008;105:1668-73. 70. Gonzalez A, Rota M, Nurzynska D, Misao Y, Tillmanns J, Ojaimi C, Padin-Iruegas ME, Müller P, Esposito G, Bearzi C, Vitale S, Dawn B, Math S, Baker M, Hintze TH, Bolli R, Urbanek K, Hosoda T, Anversa P, Kajstura J, Leri A. Activation of cardiac progenitor cells reverses the failing heart senescent phenotype and prolongs lifespan. Circ Res 2008;102:597-606.

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71. Siddiqi S, Gude N, Hosoda T, Muraski J, Rubio M, Emmanuel G, Fransioli J, Vitale S, Parolin C, D’Amario D, Schaefer E, Kajstura J, Leri A, Anversa P, Sussman M. Myocardial induction of nucleostemin in response to postnatal growth and pathological challenge. Circ Res 2008;103:89-97. 72. Dimmeler S, Leri A. Aging and disease as modifiers of efficacy of cell therapy. Circ Res 2008;102:1319-30. 73. Rota M, Padin-Iruegas ME, Misao Y, De Angelis A, Maestroni S, Ferreira-Martins J, Fiumana E, Rastaldo R, Arcarese ML, Mitchell TS, Boni A, Bolli R, Urbanek K, Hosoda T, Anversa P, Leri A, Kajstura J. Local activation or implantation of cardiac progenitor cells rescues scarred infarcted myocardium improving cardiac function. Circ Res 2008;103:107-16. 74. Boni A, Urbanek K, Nascimbene A, Hosoda T, Zheng H, Delucchi F, Amano K, Gonzalez A, Vitale S, Ojaimi C, Rizzi R, Bolli R, Yutzey KE, Rota M, Kajstura J, Anversa P, Leri A. Notch1 regulates the fate of cardiac progenitor cells. Proc Natl Acad Sci USA 2008;105:15529-15534. 75. Liu X, Ramjiganesh T, Chen YH, Chung SW, Hall SR, Schissel SL, Padera RF Jr, Liao R, Ackerman KG, Kajstura J, Leri A, Anversa P, Yet SF, Layne MD, Perrella MA. Disruption of striated preferentially expressed gene locus leads to dilated cardiomyopathy in mice. Circulation 2008;119:261-8. 76. Cesselli D, Beltrami AP, Rigo S, Bergamin N, D'Aurizio F, Verardo R, Piazza S, Klaric E, Fanin R, Toffoletto B, Marzinotto S, Mariuzzi L, Finato N, Pandolfi M, Leri A, Schneider C, Beltrami CA, Anversa P. Multipotent progenitor cells are present in human peripheral blood. Circ Res 2009;104:1225-34. 77. Padin-Iruegas ME, Misao Y, Davis ME, Segers VF, Esposito G, Tokunou T, Urbanek K, Hosoda T, Rota M, Anversa P, Leri A, Lee RT, Kajstura J. Cardiac progenitor cells and biotinylated insulin-like growth factor-1 nanofibers improve endogenous and exogenous myocardial regeneration after infarction. Circulation 2009;120:876-87. 78. Bearzi C, Leri A, Lo Monaco F, Rota M, Gonzalez A, Hosoda T, Pepe M, Qanud K, Ojaimi C, Bardelli S, D'Amario D, D'Alessandro DA, Michler RE, Dimmeler S, Zeiher AM, Urbanek K, Hintze TH, Kajstura J, Anversa P. Identification of a coronary vascular progenitor cell in the human heart. Proc Natl Acad Sci USA 2009;106:15885-90. 79. D'Alessandro DA, Kajstura J, Hosoda T, Gatti A, Bello R, Mosna F, Bardelli S, Zheng H, D'Amario D, Padin-Iruegas ME, Carvalho AB, Rota M, Zembala MO, Stern D, Rimoldi O, Urbanek K, Michler RE, Leri A, Anversa P. Progenitor cells from the explanted heart generate immunocompatible myocardium within the transplanted donor heart. Circ Res 2009;105:1128-40. 80. Ferreira-Martins J, Rondon-Clavo C, Tugal D, Korn JA, Rizzi R, Padin-Iruegas ME, Ottolenghi S, De Angelis A, Urbanek K, Ide-Iwata N, D'Amario D, Hosoda T, Leri A, Kajstura J, Anversa P, Rota M. Spontaneous calcium oscillations regulate human cardiac progenitor cell growth. Circ Res 2009;105:764-74. 81. Hosoda T, D'Amario D, Cabral-Da-Silva MC, Zheng H, Padin-Iruegas ME, Ogorek B, Ferreira-Martins J, Yasuzawa-Amano S, Amano K, Ide-Iwata N, Cheng W, Rota M, Urbanek K, Kajstura J,

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Anversa P, Leri A. Clonality of mouse and human cardiomyogenesis in vivo. Proc Natl Acad Sci USA 2009;106:17169-74. 82. De Angelis A, Piegari E, Cappetta D, Marino L, Filippelli A, Berrino L, Martins-Ferreira J, Zheng H, Hosoda T, Rota M, Urbanek K, Kajstura J, Leri A, Rossi F, Anversa P. Anthracycline cardiomyopathy is mediated by depletion of the cardiac stem cell pool and is rescued by restoration of progenitor cell function. Circulation 2010;121:276-92. 83. Tang XL, Rokosh G, Sanganalmath SK, Yuan F, Sato H, Mu J, Dai S, Li C, Chen N, Peng Y, Dawn B, Hunt G, Leri A, Kajstura J, Tiwari S, Shirk G, Anversa P, Bolli R. Intracoronary administration of cardiac progenitor cells alleviates left ventricular dysfunction in rats with a 30-day-old infarction. Circulation 2010; 121:293-305. 84. Gianni D, Li A, Tesco G, McKay KM, Moore J, Raygor K, Rota M, Gwathmey JK, Dec GW, Aretz T, Leri A, Semigran MJ, Anversa P, Macgillivray TE, Tanzi RE, del Monte F. Protein aggregates and novel presenilin gene variants in idiopathic dilated cardiomyopathy. Circulation 2010;121:1216-26. 85. Kajstura J, Urbanek K, Perl S, Hosoda T, Zheng H, Ogórek B, Ferreira-Martins J, Goichberg P, Rondon-Clavo C, Sanada F, D'Amario D, Rota M, Del Monte F, Orlic D, Tisdale J, Leri A, Anversa P. Cardiomyogenesis in the adult human heart. Circ Res 2010; 107:305-15. 86. Kajstura J, Gurusamy N, Ogórek B, Goichberg P, Clavo-Rondon C, Hosoda T, D'Amario D, Bardelli S, Beltrami AP, Cesselli D, Bussani R, del Monte F, Quaini F, Rota M, Beltrami CA, Buchholz BA, Leri A, Anversa P. Myocyte turnover in the aging human heart. Circ Res 2010;107:1374-86. 87. Urbanek K, Cabral-da-Silva MC, Ide-Iwata N, Maestroni S, Delucchi F, Zheng H, Ferreira-Martins J, Ogórek B, D'Amario D, Bauer M, Zerbini G, Rota M, Hosoda T, Liao R, Anversa P, Kajstura J, Leri A. Inhibition of notch1-dependent cardiomyogenesis leads to a dilated myopathy in the neonatal heart. Circ Res. 2010;107:429-41. 88. D'Amario D, Fiorini C, Campbell PM, Goichberg P, Sanada F, Zheng H, Hosoda T, Rota M, Connell JM, Gallegos RP, Welt FG, Givertz MM, Mitchell RN, Leri A, Kajstura J, Pfeffer MA, Anversa P. Functionally competent cardiac stem cells can be isolated from endomyocardial biopsies of patients with advanced cardiomyopathies. Circ Res. 2011;108:857-61. 89. Kajstura J, Rota M, Hall SR, Hosoda T, D’Amario D, Sanada F, Zheng H, Ogórek B, Rondon-Clavo C, Ferreira-Martins J, Matsuda A, Arranto C, Goichberg P, Giordano G, Haley KJ, Bardelli S, Rayatzadeh H, Liu X, Quaini F, Liao R, Leri A, Perrella MA, Loscalzo J, Anversa P. Evidence for human lung stem cells. N Engl J Med. 2011;364:1795-806. 90. Hosoda T, Zheng H, Cabral-de-Silva M, Sanada F, Ide-Iwata N, Ogórek B, Ferreira-Martins J, Arranto C, D’Amario D, del Monte F, Urbanek K, D’Alessandro D, Michler RE, Anversa P, Rota M, Kajstura J, Leri A. Human cardiac stem cell differentiation is regulated by a mircrine mechanism. Circulation 2011;123:1287-96. 91. Goichberg P, Bai Y, D’Amario D, Ferreira-Martins J, Fiorini C, Zheng H, Signore S, del Monte F, Ottolenghi S, D’Alessandro D, Michler RE, Hosoda T, Piero Anversa, Kajstura J, Rota M, Leri A. The

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ephrin A1-EphA2 system promotes cardiac stem cell migration after infarction. Circ Res. 2011;108:1071-83. 92. D'Amario D, Cabral-Da-Silva M, Zheng H, Fiorini C, Goichberg P, Steadman E, Ferreira-Martins J, Sanada F, Piccoli M, Cappetta D, D'Alessandro DA, Michler RE, Hosoda T, Anastasia L, Rota M, Leri A, Anversa P, Kajstura J. Insulin-like growth factor-1 receptor identifies a pool of human cardiac stem cells with superior therapeutic potential for myocardial regeneration. Circ Res. 2011;108:857-61. 93. Cesselli D, Beltrami AP, D’Aurizio F, Marcon P, Bergamin N, Toffoletto B, Pandolfi M, Puppato E, Marino L, Signore S, Livi U, Verardo R, Piazza S, Marchionni L, Fiorini C, Schneider C, Hosoda T, Rota M, Kajstura J, Anversa P, Beltrami CA, Leri A. Effects of age and heart failure on human cardiac stem cell function. Am J Pathol. 2011;179:349-66. 94. Kajstura J, Rota M, Hall SR, Hosoda T, D'Amario D, Sanada F, Zheng H, Ogórek B, Rondon-Clavo C, Ferreira-Martins J, Matsuda A, Arranto C, Goichberg P, Giordano G, Haley KJ, Bardelli S, Rayatzadeh H, Liu X, Quaini F, Liao R, Leri A, Perrella MA, Loscalzo J, Anversa P. Evidence for human lung stem cells. N Engl J Med. 2011;364:1795-806. 95. Anversa P, Kajstura J, Leri A, Loscalzo J. Tissue-specific adult stem cells in the human lung. Nat Med. 2011;17:1038-9. 96. Leri A, Kajstura J, Anversa P. Role of cardiac stem cells in cardiac pathophysiology: a paradigm shift in human myocardial biology. Circ Res. 2011;109:941-61. 97. Bolli R, Chugh AR, D'Amario D, Loughran JH, Stoddard MF, Ikram S, Beache GM, Wagner SG, Leri A, Hosoda T, Sanada F, Elmore JB, Goichberg P, Cappetta D, Solankhi NK, Fahsah I, Rokosh DG, Slaughter MS, Kajstura J, Anversa P. Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trial. Lancet. 2011;378:1847-1857. 98. Ferreira-Martins J, Ogórek B, Cappetta D, Matsuda A, Signore S, D'Amario D, Kostyla J, Steadman E, Ide-Iwata N, Sanada F, Iaffaldano G, Ottolenghi S, Hosoda T, Leri A, Kajstura J, Anversa P, Rota M. Cardiomyogenesis in the developing heart is regulated by c-kit-positive cardiac stem cells. Circ Res. 2012;110:701-715. 99. Anversa P, Leri A, Kajstura J. Biased DNA segregation during stem cell division. Circ Res. 2012;110:1403-1407. 100. Kajstura J, Bai Y, Cappetta D, Kim J, Arranto C, Sanada F, D'Amario D, Matsuda A, Bardelli S, Ferreira-Martins J, Hosoda T, Leri A, Rota M, Loscalzo J, Anversa P. Tracking chromatid segregation to identify human cardiac stem cells that regenerate extensively the infarcted myocardium. Circ Res. 2012;111:894-906. 102. Anversa P, Kajstura J, Rota, M, Leri A. Regenerating new heart with stem Cells. J Clin Invest. 2013;123:62-70. 103. Welt FG, Gallegos R, Connell J, Kajstura J, D'Amario D, Kwong RY, Coelho-Filho O, Shah R, Mitchell R, Leri A, Foley L, Anversa P, Pfeffer MA. Effect of cardiac stem cells on left ventricular remodeling in a canine model of chronic myocardial infarction. Circ Heart Fail. 2013;6:99-106.

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104. Dey D, Han L, Bauer M, Sanada F, Oikonomopoulos A, Hosoda T, Unno K, De Almeida P, Leri A, Wu JC. Dissecting the molecular relationship among various cardiogenic progenitor cells. Circ Res. 2013;112:1253-1262. 105. Bolli R, Tang XL, Sanganalmath SK, Rimoldi O, Mosna F, Abdel-Latif A, Jneid H, Dawn B, Rota M, Leri A, Kajstura J. Intracoronary delivery of autologous cardiac stem cells improves cardiac function in a porcine model of chronic ischemic cardiomyopathy. Circulation, 2013;128:122-131. 106. Leri A, Anversa P. Stem cells and myocardial regeneration: cooperation wins over competition. Circulation. 2013;127:165-168. 107. Isobe K, Wybieralska E, Borghetti G, Pesapane A, Sorrentino A, Mangano E, Cappetta D, Mangiaracina C, Ricciardi M, Cimini M, Ifedigbo E, Perrella MA, Goichberg P, Choi AM, Kajstura J, Hosoda T, Rota M, Anversa P, Leri A. c-Kit-positive cardiac stem cells nested in hypoxic niches are activated by stem cell factor reversing the aging myopathy. Circ Res. 2014;114:41-55. 108. Goichberg P, Kannappan R, Cimini M, Bai Y, Sanada F, Sorrentino A, Signore S, Kajstura J, Rota M, Anversa P, Leri A. Age-associated defects in EphA2 signaling impair the migration of human cardiac progenitor cells. Circulation. 2013;128:2211-2223. 109. Signore S, Sorrentino A, Ferreira-Martins J, Kannappan R, Shafaie M, Del Ben F, Isobe K, Arranto C, Wybieralska E, Webster A, Sanada F, Ogórek B, Zheng H, Liu X, Del Monte F, D'Alessandro DA, Wunimenghe O, Michler RE, Hosoda T, Goichberg P, Leri A, Kajstura J, Anversa P, Rota M. Inositol 1, 4, 5-trisphosphate receptors and human left ventricular myocytes. Circulation. 2013;128:1286-1297. 110. Melpignano A, Mandurino-Mirizzi A, Besagni F, Leri A. Dermatologic manifestations and neuropathic symptoms in women with Fabry disease. Acta Biomed. 2014;85:81-84. 111. D'Amario D, Leone AM, Iaconelli A, Luciani N, Gaudino M, Kannappan R, Manchi M, Severino A, Shin SH, Graziani F, Biasillo G, Macchione A, Smaldone C, De Maria GL, Cellini C, Siracusano A, Ottaviani L, Massetti M, Goichberg P, Leri A, Anversa P, Crea F. Growth properties of cardiac stem cells are a novel biomarker of patients' outcome after coronary bypass surgery. Circulation. 2014;129:157-72. 112. Sanada F, Kim J, Czarna A, Chan NY, Signore S, Ogórek B, Isobe K, Wybieralska E, Borghetti G, Pesapane A, Sorrentino A, Mangano E, Cappetta D, Mangiaracina C, Ricciardi M, Cimini M, Ifedigbo E, Perrella MA, Goichberg P, Choi AM, Kajstura J, Hosoda T, Rota M, Anversa P, Leri A. c-Kit-positive cardiac stem cells nested in hypoxic niches are activated by stem cell factor reversing the aging myopathy. Circ Res. 2014;114:41-55. 113. Leri A, Rota M, Hosoda T, Goichberg P, Anversa P. Cardiac stem cell niches. Stem Cell Res. 2014;13:631-646. 114. Leri A, Rota M, Pasqualini FS, Goichberg P, Anversa P. Origin of cardiomyocytes in the adult heart. Circ Res. 2015;116:150-166. Other peer-reviewed publications

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1. Anversa P, Leri A, Malhotra A, Quaini F, Kajstura J. Myocyte cell loss in ischemic cardiomyopathy: role of apoptosis. Heart Failure Reviews 1998;3:63-78. 2. Anversa P, Cheng W, Liu Y, Leri A, Redaelli G, Kajstura J. Apoptosis and myocardial infarction. Basic Res Cardiol 1999;93 (suppl 3): 8-12. 3. Anversa P, Leri A, Li B, Liu Y, Di Somma S, Kajstura J. Ischemic cardiomyopathy and the cellular renin-angiotensin system. J Heart Lung Transpl 2000;19:S1-S11. 4. Orlic D, Kajstura J, Chimenti S, Bodine DM, Leri A, Anversa P. Transplanted adult bone marrow cells repair myocardial infarcts in mice. Ann NY Acad Sci 2001;938:221-9. 5. Anversa P, Torella D, Kajstura J, Nadal-Ginard B, Leri A. Myocardial regeneration. Eur Heart J 2002;Supplements 4 (Supplement G):G67-G71. 6. Leri A, Kajstura J, Anversa P. Myocyte proliferation and cardiac remodeling. J Cardiac Failure 2002;8:S518-S525. 7. Orlic D, Kajstura J, Chimenti S, Bodine DM, Leri A, Anversa P. Bone marrow cells regenerate infarcted myocardium. Pediatr Transplant 2003;7:86-8. 8. Kajstura J, Leri A, Castaldo C, Nadal-Ginard B, Anversa P. Myocyte growth in the failing heart. Surg Clin North Am 2004;84:161-77. 9. Leri A, Kajstura J, Anversa P. Identity deception: not a crime for a stem cell. Physiology (Bethesda) 2005;20:162-8. 10. Anversa P, Rota M, Urbanek K, Hosoda T, Sonnenblick EH, Leri A, Kajstura J, Bolli R. Myocardial aging: a stem cell problem. Bas Res Cardiol 2005;00, 482-93. 11. Leri A, Kajstura J, Anversa P. Regenerating the myocardium: a reality today. Can J Cardiol. 2005;21:361-2. 12. Leri A, Kajstura J. Endothelial progenitor cells: unexpected disclosures. Circ Res 2005;97:299-301. 13. Anversa P, Kajstura J, Leri A. Circulating progenitor cells: search for an identity. Circulation 2005;110:3158-60. 14. Kajstura J, Leri A, Bolli R, Anversa P. Endothelial progenitor cells: neovascularization or more? J Mol Cell Cardiol 2006;40:1-8. 15. Kajstura J, Bolli R, Sonnenblick EH, Anversa P, Leri A. Cause of death: suicide. J Mol Cell Cardiol 2006;40:425-37. 16. Leri A, Hosoda T, Kajstura J, Anversa P. Heart failure and regenerative cardiology. Regenerative Med. 2006;1:153-9. 17. Anversa P, Leri A, Kajstura J. Cardiac regeneration. J Am Coll Cardiol 2006;47:1769-76.

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18. Kajstura, Rota M, Urbanek K, Hosoda T, Bearzi C, Anversa P, Bolli R, Leri A. The telomere-telomerase axis and the heart. Antioxid Redox Signal 2006;8:2125-41. 19. Anversa P, Kajstura J, Leri A. If I can stop one heart from breaking. Circulation 2007;115:829-32. 20. Leri A, Kajstura J, Anversa P, Frishman WH. Myocardial regeneration and stem cell repair. Curr Probl Cardiol 2008;33:91-153. 21. Leri A, Hosoda T, Rota M, Kajstura J, Anversa P. Myocardial regeneration by exogenous and endogenous progenitor cells. Drug Discovery Today: Disease Mechanisms 2008;4:197-203 22. Kajstura J, Urbanek K, Rota M, Bearzi C, Hosoda T, Bolli R, Anversa P, Leri A. Cardiac stem cells and myocardial disease. J Mol Cell Cardiol 2008;45:505-13. 23. Leri A. Human cardiac stem cells: the heart of a truth? Circulation 2009;120:2515-8. 24. Hosoda T, Kajstura J, Leri A, Anversa P. Mechanisms of myocardial regeneration. Circ J 2010;74:13-17. 25. Hosoda T, Rota M, Kajstura J, Leri A, Anversa P. Role of stem cells in cardiovascular biology. J Thromb Haemost. 2011;9 Suppl 1:151-61. 26. Leri A, Hosoda T, Anversa P, Kajstura J, Rota M. Identification of a coronary stem cell in the human heart. J Mol Med. 2011;89:947-59.

27. Frati C, Savi M, Graiani G, Lagrasta C, Cavalli S, Prezioso L, Rossetti P, Mangiaracina C, Ferraro F, Madeddu D, Musso E, Stilli D, Rossini A, Falco A, Angelis AD, Rossi F, Urbanek K, Leri A, Kajstura J, Anversa P, Quaini E, Quaini F. Resident cardiac stem cells. Curr Pharm Des. 2011;17:3252-3257.

28. Leri A, Kajstura J. Created equal? The many facets of reprogramming. Circ Res. 2012;111:152-155.

29. Hajjar RJ, Leri A, Wang Y. BCVS scientific conference 2012 meeting report. Circ Res. 2012;111:1121-1124 102. Leri A, Anversa P. Stem cells and myocardial regeneration: Cooperation wins over competition. Circulation. 2012;127:165-168. 30. Schoenfeld M, Frishman WH, Leri A, Kajstura J, Anversa P. The existence of myocardial repair: mechanistic insights and enhancements. Cardiol Rev. 2013;21:111-120. 31. Anversa P, Leri A. Innate regeneration in the aging heart: healing from within. Mayo Clin Proc. 2013;88:871-883. 32. Rota M, Leri A, Anversa P. Human heart failure: is cell therapy a valid option? Biochem Pharmacol. 2014;88:129-138. 33. Leri A, Rota M. Diabetes gets on the nerves of the bone marrow niche. Diabetes. 2014;63:1185-1187.

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34. Goichberg P, Chang J, Liao R, Leri A. Cardiac stem cells: biology and clinical applications. Antioxid Redox Signal. 2014;21:2002-2017. Non peer-reviewed publications Reviews, chapters, monographs and editorials (Place of publication indicated when known) 1. Anversa P, Leri A, Redaelli G, Kajstura J. Ventricular remodeling in hypertensive cardiomyopathy. In: La Cardiopatia Ipertensiva. Nuovi Orientamenti Diagnostici e Terepeutici,. Editors: A. Boccanelli, C. Greco, E. Zanchi, editors. Rome, Italy: CEPI, 1998; p 61-71. 2. Anversa P, Leri A, Kajstura J. Myocardial Basis for Heart Failure: Role of Cell Death. In Heart Failure: A Companion to Braunwald’s Heart Disease. D.L. Mann, editor. Philadelphia, PA: Elsevier. 2003; p. 71-89. 3. Nadal-Ginard B, Anversa P, Kajstura J, Leri A. Prospect for autologous cardiac stem cell-based heart regeneration. Biothech Med. 2004;29:16-22. 4. Anversa P, Leri A, Nadal-Ginard B, Kajstura J. Stem cells and heart disease. In Handbook of Stem Cells. Adult and Fetal Stem Cells. Editor, R.P. Lanza. Burlington, MA: Academic Press, 2004; p. 711-720. 5 Anversa P, Leri A. Myocardial regeneration. In Braunwald’s Heart Disease, 7th edition. Editors, D. Zipes, P. Libby, R.O. Bonow, E. Braunwald. Philadelphia, PA: WB Saunders, 2004; p. 1911-1923. 6. Kajstura J, Leri A, Castaldo C, Nadal-Ginard B, Anversa P. Myocyte growth and the failing heart. Surg Clin North Am. 2004; 84(1): 161-177. 7 Quaini F, Urbanek K, Graiani G, Lagrasta C, Maestri R, Monica M, Boni A, Ferraro F, Delsignore R, Tasca G, Leri A, Kajstura J, Quaini E, Anversa P. The regenerative potential of the human heart. Int J Cardiol. 2004;95:S26-S28. 8. Nadal-Ginard B, Anversa P, Kajstura J, Leri A. Cardiac stem cells and myocardial regeneration. Novartis Found Symp. 2005;265:142-154. 9. Anversa P, Leri A, Kajstura J. Cardiac regeneration. J Am Coll Cardiol.2006; 47:1769-1776. 10. Leri A, Hosoda T, Kajstura J, Anversa P. Heart failure and regenerative cardiology. Regenerative Med. 2006;1:153-159. 11. Leri A, Anversa P, Frishman WH. Introduction. In: Cardiovascular Regeneration and Stem Cell Therapy. Leri A, Anversa P, Frishman WH, editors. Malden, Massachusetts: Blackwell Publishing; 2007. p.1-4. 12. Leri A, Boni A, Siggins R, Nascimbene A, Hosoda T. Cardiac stem cells niches. In: Cardiovascular Regeneration and Stem Cell Therapy., Leri A, Anversa P, Frishman WH, editors. Malden, Massachusetts: Blackwell Publishing; 2007. p. 87-94.

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13. Leri A, Hosoda T, Rota M, Kajstura J, Anversa P. Myocardial regeneration by exogenous and endogenous progenitor cells. Drug Discovery Today: Disease Mechanisms 2007; 4:197-203. 14. Leri A, Hosoda T, Rota M, Bearzi C, Urbanek K, Bolli R, Kajstura J, Anversa P. Progenitor cells and cardiac homeostasis. In: Principles of Tissue Engineering. 3rd Edition. R. Lanza, R. Langer, J. Vacanti. Burlington, MA: Elsevier Press, 2007. pp. 535-550. 15. Leri A, Kajstura J, Anversa P, Frishman WH: Myocardial regeneration and stem cell repair. Curr Probl Cardiol. 33:91-153, 2008. 16. Kajstura J, Urbanek K, Rota M, Bearzi C, Hosoda T, Bolli R, Anversa P, Leri A. Cardiac stem cells and myocardial disease. J Mol Cell Cardiol. 2008; 45:505-513. 17. Leri A, Kajstura J, Anversa P. Cardiac regeneration and aging. In: Heart Development and Regeneration. Volume 2. Rosenthal N, Harvey RP, editors. Burlington, MA: Academic Press Elsevier. 2010. pp. 951-980. 18. Anversa P, Kajstura J, Leri A. Cellular basis for myocardial repair and regeneration. In: Heart Failure: A Companion to Braunwald’s Heart Disease. D.L. Mann, editor. St. Louis, MO: Elsevier, 2010. p. 48-73. 19. Anversa P, Kajstura J, Leri A. Cardiovascular Regeneration In: Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine, 8th edition. D.L. Mann, D. Zipes, P. Libby, R.O. Bonow, E. Braunwald, editors. Philadelphia: Elsevier, 2010. p. 1911-1924. 20. Anversa P, Kajstura J, Leri A. Cardiovascular Regeneration and Tissue Engineering, In: Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine, 9th edition. R.O. Bonow, D. L. Mann, D. Zipes, P. Libby, E. Braunwald, editors. St. Louis, MO: Elsevier, 2012. p. 99-106. 21. Books/Textbooks for the medical or scientific community 1. Cardiovascular Regeneration and Stem Cell Therapy. Leri A, Anversa P, Frishman WH, editors. Malden, Massachusetts: Blackwell Publishing; 2007. Letters to the Editor 1. Hosoda T, Zheng H, Cabral-de-Silva M, Sanada F, Ide-Iwata N, Ogórek B, Ferreira-Martins J, Arranto C, D’Amario D, del Monte F, Urbanek K, D’Alessandro D, Michler RE, Anversa P, Rota M, Kajstura J, Leri A. Response to letter regarding article “human cardiac stem cell differentiation is regulated by a mircrine mechanism.” Circulation 2011;124:e456. 2. Kajstura J, Rota M, Hosoda T, Anversa P, Leri A. Carbon 14 dating of human cardiomyocytes (letter). Circ Res. 2012;110:e19-21.

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3. Signore S, Sorrentino A, Ferreira-Martins J, Kannappan R, Shafaie M, Del Ben F, Isobe K, Arranto C, Wybieralska E, Webster A, Sanada F, Ogórek B, Zheng H, Liu X, del Monte F, D'Alessandro DA, Wunimenghe O, Michler RE, Hosoda T, Goichberg P, Leri A, Kajstura J, Anversa P, Rota M. Response to letter regarding article "Inositol 1,4,5-trisphosphate receptors and human left ventricular myocytes". Circulation. 2014;129:e510-511. 4. D'Amario D, Leone AM, Iaconelli A, Luciani N, Gaudino M, Kannappan R, Manchi M, Severino A, Shin SH, Graziani F, Biasillo G, Macchione A, Smaldone C, Cellini C, Siracusano A, Ottaviani L, Massetti M, Goichberg P, Leri A, Anversa P, Crea F. Response to letter regarding article, "growth properties of cardiac stem cells are a novel biomarker of patients' outcome after coronary bypass surgery". Circulation. 2014;130:e118-119.

Narrative Report My laboratory studies the molecular mechanisms that modulate the turnover and growth of cardiac stem cells (CSCs) and myocytes in the heart of humans and animals. Cardiac homeostasis is tightly regulated by the balance between cell regeneration and death. These processes are controlled by the myocardial niches, the anatomical compartment which integrates systemic and local cues for the maintenance of CSC self-renewal and cardiomyogenesis. My initial independent work led to the documentation that p53 is a transcriptional regulator of the renin-angiotensin-system (RAS) in cardiomyocytes. By utilizing transgenic mice that overexpress IGF-1, I showed that upregulation of IGF-1 results in the formation of Mdm2-p53 inactive complexes. This previously unknown molecular event decreases the transcriptional activity of p53, inhibiting the detrimental effects of RAS on cardiac performance and myocyte survival. Based on these observations, my next objective involved the recognition of the processes implicated in the replacement of dying myocytes with newly formed, better functioning cells. In telomerase-knockout mice, I documented that telomerase deficiency and telomere shortening impairs myocyte generation and promotes myocyte death, myocardial aging and heart failure. The unequivocal documentation that stem cells reside in the heart and generate cardiomyocytes has required the identification of cardiac niches and their cellular and extracellular components. Cardiac niches contain CSCs, which are connected to the supporting cells, myocytes and fibroblasts, by junctional proteins. Fibronectin and laminin occupy the niche area modulating the fate of CSCs, which, by dividing symmetrically and asymmetrically, ensure that the pool of primitive cells is preserved and that an adequate myocyte progeny is generated. With pulse-chase label assays and genetic tagging, I provided a functional demonstration that a lineage relationship exists in vivo between CSCs and their clonal myocyte progeny. In an attempt to understand the molecular control of niche homeostasis, I performed a series of studies to define the processes by which CSCs form cardiomyocytes. I documented that the Notch1 pathway regulates the early commitment of CSCs to the myocyte lineage. Notch1 activation in CSCs leads to the formation of a large number of highly proliferating myocytes. This cell pool constitutes the growth reserve of the myocardium and conditions the regenerative response in the presence of injury. I have found that the maturation of developing myocytes into functionally competent cells is largely regulated by the expression of miR-499. This small RNA traverses gap junction channels from cardiomyocytes to CSCs, repressing the gene program that controls stemness, favoring myocyte differentiation. My research efforts are tightly connected with teaching and education of graduate students and post-

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doctoral fellows working in my laboratory. Hours of formal teaching and daily interaction with the young components of my team constitute an essential part of my work. In summary, my research is testing whether abnormalities in the intrinsic properties of CSCs and their microenvironment are implicated in myocardial aging and heart failure. These findings have led to a Phase 1 clinical trial in which autologous CSCs were delivered to patients with chronic heart failure of ischemic origin. The beneficial effects of this cell therapy were documented, so that a Phase 2 clinical study is currently being developed.