LESLIE MILLER

I have been involved in the field of advanced heart failure for over 35 years, including over 90 clinical trials focusing on all forms of oral and intravenous pharmacologic therapy, including all types of immunosuppression for organ transplantation, and use of mechanical assist devices. My career has evolved over the past 10 years to focus almost entirely on the field of regenerative medicine for organ and tissue regeneration.

I have had a leadership role in this field beginning with being the founder of the Working Group of Transplant Cardiologists that helped evolve the field into a cardiology-based discipline from purely surgical, and grew to becoming the Program Chair for the International Heart Transplant Society meeting, and eventually the President of this organization. I also took a leadership role in entire the field of transplantation, and became the first non-nephrologist to hold the office of President of the American Society of Transplant Physicians.
I have also had leadership positions throughout my career including being the Chief of Cardiology for a total of over 15 years at the Universities of Minnesota, Georgetown, and University of South Florida. I have been the Director of Heart Failure, Transplant, and Mechanical Support from my first job at St Louis University, and each of the subsequent programs at which I was Chief of Cardiology. While at the University of MN I created the Lillehei Heart Institute which became the focus of all cardiovascular basic and clinical research there. I have also served  as the Director of Fellowship training for over 20 years and mentored over 750 cardiology trainees in my career.

My academic accomplishments include publication of over 250 manuscripts, 12 book chapters, and lead editor for two major textbooks in the field; Mechanical Circulatory Support and Stem Cell and Gene Therapy for Cardiovascular Disease. I have been involved in clinical and basic research throughout my career, including being the Principle Investigator in 94 clinical trials, including trials funded by the NIH, AHA, as well as industry, as well as on the Steering Committee for over 20 trials and National PI for 4 sstudies. I have been a manuscript reviewer for most major journals in the field of cardiology, and on the editorial board for 3 journals. I have been an abstract reviewer for over 15 years for most major meetings in the field of heart failure and cardiology. I have presented at nearly every meeting of the major society in the field including AHA, ACC, ISHLT, HFSA for the past 20 years, and lectured at most of the major universities in the US and Europe on topics ranging from heart failure to regenerative medicine.

My basic research began during a 14 month sabbatical with Dr Phillip Halloran in Alberta, Canada studying molecular mechanisms of immunosuppressive drugs, and Dr Alexandra Lucas on vascular biology and the role of a class of peptides known as Serpins in the pathogenesis of cardiac transplant related allograft arteriopathy. I was recruited to be Chief of Cardiology at the U of MN and hired and worked closely with Dr Jennifer Hall on NIH funded research examining the molecular basis of remodeling of patients with end stage heart failure who had an LVAD placed, using microarray analysis of pre and post implant tissue specimens to identify gene expression patterns associated with recovery. We identified the stem cell homing gene, Stromal Derived Factor(SDF-1) as the gene most upregulated in responders vs down regulated in non-responders. I also worked with Dr Jay Zhong on early investigation on the use of scaffolds of matrix imbedded with stem cells, as a superior alternative to intramuscular injection, and retrograde delivery versus intracoronary to develop a cheaper and easier method of delivery of cells or genes. I have collaborated with Dr Doris Taylor on her work on use of stem cells for cardiac regeneration, which spawned my evolution to regenerative medicine becoming the focus of my career and research interests. I became the site PI for the NHLBI SCOR grant on the first use of allogeneic mesenchymal stem cells in patients with heart failure at the time of implant of a ventricular assist device in 2008. Since that time I have been involved as the site or national PI for 12 trials of stem cell of gene therapy for cardiovascular disease, including not only heart failure but also acute MI, Peripheral Arterial Disease in addition to heart failure, using adipose derived and bone marrow cells, as well as currently the allogeneic MSCs in the DREAM trial, but also five different genes including SERCA-2A, Neuregulin, SDF-1, as well as a combination of S100A, SDF, and VEGF.

My intense interest in regenerative medicine led to me creating the outline for a textbook on this topic and became the lead editor for what is currently one of the leading textbooks in the field entitled, Stem Cells and Gene Therapy for Cardiovascular Disease. This led to extensive research on all areas of this field including tissue engineering, and a detailed grasp of nearly all the current and future strategies to enhance cell retention and harness native organ and tissue regeneration.

During the research for this book I became aware of the unique approach of using bioelectric stimulation to stimulate the upregulation in the local tissue of a variety of very pro-regenerative proteins, including SDF to enhance homing of stem cells to the target area, but also the unique signaling to enhance differentiation and proliferation of these stem cells. This interest led to collaboration with Howard Leonhardt, who is a pioneer in this concept and becoming the PI on a grant funded at the University of Utah to study cardiac regeneration with the use of Biolecrtric Stimulation(BES). We first examined iPSC-derived cardiomyocytes to prove the efficacy of the stimulation in upregulation of a set of 15 target protein expression by QPCR analysis, and will use his very novel approach to use deliver BES plus stem cells and a combination of most individual agents shown to play a role in stem cell function and organ regeneration including exosomes, mRNA, matrix, as well as amniotic fluid. I have become the Chief Medical Officer for Leonhardt Ventures and in this role I am involved in all of the research with the use of the combinatorial approach to organ and tissue regeneration across nearly all organs and diseases, including collaboration and grant applications with many universities and research labs. We have worked to identify genes that are uniquely important in specific conditions, such as IGF for brain injury and recovery, as well as liver regeneration. We are focusing on GDF-10,11 as potentially important in aging and regeneration in most organs.

This broad interest and background in basic science and molecular biology has led to the collaboration in this grant to study molecular mechanisms of erectile dysfunction using bioelectric stimulation.

1. Positions and Honors

1982-1996  Saint Louis University: Assistant Professor Medicine and Surgery;

1982-1996: Director of the Coronary Care Unit

1986-1989: Associate Professor of Medicine and Surgery; Director of the Heart Transplant and  Mechanical Support Program

1989-1996: Professor of Medicine and Surgery

1996-1997: Sabbatical leave: University of Alberta, CA with Dr Phiillp Halloran focused in  immunology and immunosuppression, and Dr Alexandra Lucas on vascular biology

1997-2007: Professor and Chair of the Division of Cardiology, Univ of Minnesota;

Director of the Heart Transplant and Mechanical Assist Program, and

Director of the Cardiology Fellowship Program

2005-2007: Founding Director of the Lillehei Heart Institute, U of MN

2007-2010: Chair of the combined Division of Cardiology Georgetown University

and Washington Hospital Center

Proctor Harvey Distinguished Professor of Cardiology, Georgetown Univ

Director of the Heart Transplant and Mechanical Support Program

Director of the Cardiology Fellowship Program

2010-2013: Chairman the Department of Cardiology Univ South Florida

Edward C. Wright Professor of Cardiovascular Medicine

Director of the Cardiology Fellowship Program

2012-2013: Director of the Cardiovascular Institute

2013-2016: Director of Heart Failure Morton Plant Hospital

2016-current: Chief Medical Officer, Leonhardt Ventures

1988-2009: Founder and Chair: Working Group of Transplant Cardiologists

1995-1997: President of American Society of Transplant Physicians

1997-1998: President of International Society of Heart and Lung Transplantation

1999:          Citation of Merit: University of Missouri, Outstanding Alumnus

1999-2006: Board of Directors of Cardiovascular Translational Research Society

2014-       : Chairman of the Board of the Alliance for the Advancement of Stem Cell Research

2013-  :       Board of Directors International Congress of Cardiology

1. Contributions to Science:

I began my career in 1982 at St Louis University when it was one of only three institutions using mechanical ventricular assist devices and only a very few doing heart transplantation. I helped evolve the field from purely surgical management, to now the majority of care being directed by cardiologists. Following my sabbatical on immunosuppression with Dr Phillip Halloran, I helped develop novel strategies for transplant immunosuppression, including withdrawal of corticosteroids in maintainance immunosuppression. This included collaboration with the development of the first molecular based test for rejection based on microarray analysis of both renal and cardiac allografts. I was a part of the first use of intravascular ultrasound to study the allograft coronary disease in heart transplant patients and was the founder of the first federally funded national database to study outcomes with heart transplantation, that evolved to become the REMATCH database, which remains the standard in the field.

I helped advance the field of mechanical circulatory support by establishing milestones such as the first patient discharged from the hospital with a VAD, and was the national PI on the first device in the field to change from pulsatile to continuous physiology. I have been an advisor to nearly every device manufacturer and personally managed patients supported with every VAD brought into clinical trials for 30 years.

I have mentored over 750 cardiology fellows during my career, many of whom have authored countless abstracts and made presentations at national meetings, as well as several who were awardees of grant funding from both the NIH and AHA, as well as industry.

1. Additional Information: Research Support and/or Scholastic Performance

I have had research support as Co-PI from the NHLBI, ranging from SCOR grants to RO-1, the Am Heart Association, as well as an extensive list of industry funded research from nearly all companies involved in the pharmacologic or biologic agents as well as mechanical devices for the treatment of  heart failure or heart transplantation.

I served as a reviewer for SBIR grants for the NIH for four years (199-2003)

Current Research Support:

I am currently the site PI for the following clinical trials in stem cell or gene therapy for CV Disease:

1. Mesoblast Phase III DREAM study of allogeneic MSCs for patients with HF
2. Athersys Phase II study of Bone Marrow derived Multi-potent Allogeneic Progenitor cells for NSTEMI
3. Juventas Phase II STOP-PAD study of SDF gene therapy for Peripheral Arterial Disease
4. Renova Phase II study of Adenyl Cyclase gene for patients with heart failure
5. Biocardia CARDI-AMP Phase III study of bone marrow MNCs for heart failure
6. Intrexon study of multi-gene therapy, SDF, S100A, and VEGF, for patients with heart failure

Industry Collaborative Roles past 5 years:

1. Steering Committee Intrexon Pharmaceuticals (2017-)
2. Steering Committee Juventas Pharmaceuticals (2011-)
3. Chair of the Steering Committee TargaCell Inc, (2016-)
4. Steering Committee Black Beret Lifesciences (2017-)

Society Memberships:

American Heart Association

American College of Cardiology

International Society of Heart and Lung Transplanation

International Congress of Cardiology

Heart Failure Society of America

American Society of Transplant Physicians

Society for Cardiovascular and Translational Research

Alliance for the Advancement of Cell Therapy

Journal Reviewer:

New England J of Medicine

Circulation, Heart Failure

Journal Am Coll of Cardiology

Journal of Heart Failure of JACC

Journal of Heart Failure

Journal of Heart and Lung Transplantation

European Journal of Heart Failure

Cochrane Database