1. OMB No. 0925-0001/0002 (Rev. 08/12 Approved Through 8/31/2015)
BIOGRAPHICAL SKETCH
Provide the following information for the Senior/key personnel and other significant contributors.
Follow this format for each person. DO NOT EXCEED FIVE PAGES.
NAME: Payne, Ronald Mark
eRA COMMONS USER NAME: XXXXX
POSITION TITLE: Professor of Pediatrics
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing,
include postdoctoral training and residency training if applicable. Add/delete rows as necessary.)
INSTITUTION AND LOCATION
DEGREE
(if
applicable)
Completion
Date
MM/YYYY
FIELD OF STUDY
Washington & Lee Univ., Lexington, VA
Univ. of Texas, Austin, TX
Univ. of Texas School of Medicine, Houston, TX
Washington University School of Medicine
Washington University School of Medicine
Washington University School of Medicine
Washington University School of Medicine
BS
n/a
MD
n/a
n/a
n/a
n/a
05/1977
05/1978
06/1983
06/1986
06/1987
06/1990
06/1993
Biology
Biology
Medicine
Pediatric Residency
Pediatric Chief Resident
Ped. Cardiology Fellow
Research Postdoc
A. Personal Statement
The goal of my research is to understand the mechanism(s) underlying metabolic cardiomyopathies of
childhood and young adults, and to develop therapies for them. The focus of my lab has been on Friedreich’s
Ataxia (FRDA), which is a mitochondrial disorder that causes a severe hypertrophic cardiomyopathy and heart
failure. In this regard, I have focused almost all of my efforts over past 2 yr on moving a novel invention out of
my lab as a therapy for FRDA. This was very time-consuming and resulted in a decrease of publications from
my lab. However, we were successful at advancing this novel therapy and the project has now been accepted
by the competitive Therapeutics for Rare and Neglected Diseases (TRND) program at NIH (NCATS) for
development as a drug. Thus, I have now re-focused my efforts on basic investigations and publishing again.
Relative to the grant at hand, we were the first to identify hyper-acetylation of mitochondrial proteins as a
feature of the hypertrophic cardiomyopathy in a mouse model of FRDA. In collaboration with Dr. Matt Hirschey
at Duke University, we will use this extreme of phenotype mouse model to determine the impact of
hyperacetylation on cardiac function, and determine the mechanism of metabolic disruption in these hearts.
We will also investigate if FRDA hearts from patients who died also have hyperacetylation. Because
hyperacetylation of mitochondrial proteins is being increasingly recognized in other metabolic disorders
affecting the heart, such as diabetes and metabolic syndrome (including obesity), we are anticipating that
findings from the rare disease, FRDA, will inform on more common heart disease, i.e., heart failure. We are
also collaborating on the identification of biochemical markers of mitochondrial dysfunction in blood from my
patients with FRDA. Matt will serve as Co-I on this multi-PI project, and will direct the work on metabolic and
proteomic analyses of these hearts, whereas I will direct the work on physiology and impact of acetylation on
cardiac function, including SIRT3 overexpression / ablation. This collaboration has already lead to novel
discovery and is exciting to me for it’s potential to advance the field of metabolic heart disease.
Most relevant to the current application
1. Vyas PM, Tomamichel WJ, Pride PM, Babbey CM, Wang Q, Mercier J, Martin EM, and Payne RM. A
TAT-Frataxin fusion protein increases lifespan and cardiac function in a conditional Friedreich's ataxia
mouse model. Human Molecular Genetics. 2012;21(6):1230-47. PMID: 22113996.
2. Payne RM, and Wagner GR. Cardiomyopathy in Friedreich Ataxia: Clinical Findings and Research. J
Child Neurol, 2012 Sep;27(9):1179-86. PMID: 22764179.

2. 3. Wagner GR, Pride PM, Babbey CM, and Payne RM. Friedreich's ataxia reveals a mechanism for
coordinate regulation of oxidative metabolism via feedback inhibition of the SIRT3 deacetylase. Human
Molecular Genetics. 2012;21(12):2688-97. PMID: 22394676.
4. Wagner GR and Payne RM. Widespread and enzyme-independent Nε
-acetylation and Nε
-succinylation
of proteins in the chemical conditions of the mitochondrial matrix. J Biol Chem. 2013, Oct
4;288(40):29036 – 045, PMID: 23946487. Note: selected by JBC as a feature paper.
B. Positions and Honors
Positions and Employment
1983-86 Pediatric Intern and Resident, Washington University Medical Center
1986-87 Chief Resident in Pediatrics, Washington University Medical Center (James P Keating)
1987-90 Fellow in Pediatric Cardiology, Washington University School of Medicine
1989-93 Research Fellow in Molecular Biology, Washington University School of Medicine (Arnold Strauss)
1991-93 Instructor in Pediatrics, Washington University School of Medicine
1993-97 Assistant Professor of Pediatrics, Washington University School of Medicine
1997-99 Assistant Professor of Pediatrics, Wake Forest Univ. School of Medicine
1997-05 Faculty Associate, Pharmacology and Physiology, Wake Forest Univ. School of Medicine
1997-05 Director, Pediatric Cardiac Catheterization Laboratory, Wake Forest Univ. School of Medicine
1999-05 Associate Professor of Pediatrics, Wake Forest Univ. School of Medicine
2005- Associate, Institute of Regenerative Medicine, Wake Forest Univ. School of Medicine
2005- Associate, Dept. of Medical and Molecular Genetics, Indiana Univ. School of Medicine
2005- Professor with Tenure, Department of Pediatrics (Cardiology), Indiana Univ. School of Medicine
2013- Chief Scientific Officer, Chondrial Therapeutics, LLC, Indianapolis, IN
2013- Associate, Dept. of Cellular & Integrative Physiology, Indiana Univ. School of Medicine
Other Experience and Professional Memberships
2000-05 Director, Graduate Program in Molecular Medicine, Wake Forest Univ. School of Medicine
2003-06 AHA molecular signaling study section (Chair 2005-06)
2004-10 Member and Chair, NIH BRT-A study section (basic research training) (Chair 2009-10)
2006-12 Director, Pediatric Cardiology Fellowship program, Indiana University School of Medicine
2007- Member, Friedreich’s Ataxia Research Alliance scientific board of directors
2008- Director, Translational Research Training Program, Indiana CTSA
2013 Ad hoc reviewer, NIH TAG study section.
2014-18 Member, NIH Institutional Training Mechanism study section (NITM), NHLBI
2016-19 Chair, Apixaban Study committee, Pediatric Heart Network (NHLBI)
Honors
1989-90 American Heart Association (AHA) Fellowship Award
1990-92 NIH NRSA individual fellowship award 1F32HL08332-01
1994 American Society for Biochemistry and Molecular Biology
1995- American Heart Association (Basic Science Council, and CV Disease in Young)
1997 Fellow of the American College of Cardiology (FACC)
1992-97 AHA Clinician Scientist Award
1998 Society of Pediatric Research
1999 AHA Established Investigator Award
2006 Fellow American Academy of Pediatrics (FAAP)
C. Contribution to Science:
Our initial work detailed the expression and regulation of the creatine kinase gene family in heart and other
tissues. This gene family is responsible for transfer of high energy phosphate groups from the mitochondria to
the site of utilization in the cell, and recycling of ADP - ATP. This work revealed the promoter based regulation
of the CK genes, and the switch in heart during stress or cardiomyopathy.
1. Payne RM, Haas RC, Strauss AW: Structural characterization and tissue-specific expression of the
mRNAs encoding isoenzymes from two rat mitochondrial creatine kinase genes. Biochim Biophys Acta
1991;1089:352-361.

3. 2. Payne RM, Friedman DL, Grant JW, Perryman B, Strauss AW: Creatine kinase isoenzymes are highly
regulated during pregnancy in rat uterus and placenta. Am J Physiol 1993;265:E624-E635.
Investigation of the mitochondrial import of sarcomeric and ubiquitous mitochondrial creatine kinase lead to our
second direction in which we determined the mechanism of mitochondrial protein import in mammalian tissues.
We made the novel discovery that Ribosomes with their nascent peptide chains can bind to receptors on the
mitochondrial outer membrane to cause co-translational import. Based on this work, we then made the novel
discovery that cell penetrant peptides could also cross the mitochondrial membranes independent of the native
import mechanisms to deliver a protein cargo to the matrix. This opened the possibility of developing therapies
for mitochondrial diseases. There are currently very poor (or no) therapies for mitochondrial disorders due to
the difficulties of cross the double mitochondrial membranes.
1. Crowley KS, and Payne RM. Ribosome Binding to Mitochondria is Regulated by GTP and the Transit
Peptide. J. Biol. Chem. 1998;273:17278-17285.
2. Del Gaizo V, and Payne RM. A Novel TAT-Mitochondrial Signal Sequence Fusion Protein is
Processed, Stays in Mitochondria, and Crosses the Placenta. Molecular Therapy, 2003;7:720-730.
3. Del Gaizo V, MacKenzie J, and Payne RM. Targeting proteins to mitochondria using TAT. Molecular
Genetics and Metabolism, 2003;80:170-180.
We have published multiple clinical and translational papers regarding cardiomyopathies in children, and are
now working on metabolism of the heart in FRDA patients.
1. Payne RM, The Heart in Friedreich’s Ataxia: Basic Findings and Clinical Implications. Progress in
Pediatric Cardiology 2011, May;31(2):103-109. PMID: 21691434.
2. Lynch DR, Pandolfo M, Schulz JB, Perlman S, Delatycki MB, Payne RM, Shaddy R, Fischbeck KH,
Farmer J, Kantor P, Raman SV, Hunegs L, Odenkirchen J, Miller K, Kaufmann P. Common Data
Elements for Clinical Research in Friedreich Ataxia. Mov Disord. 2013 Feb;28(2):190-5.
PMID:23239403.
3. Consensus clinical management guidelines for Friedreich ataxia. Corben LA, Lynch D, Pandolfo M,
Schulz JB, Delatycki MB; Clinical Management Guidelines Writing Group. Orphanet J Rare Dis. 2014
Nov 30;9:184. doi: 10.1186/s13023-014-0184-7. PMID: 25928624.
4. Summary of the 2015 International Paediatric Heart Failure Summit of Johns Hopkins All Children’s
Heart Institutie. Jacobs JP, Quintessenza JA, Karl TR, Asante-Korang A, Everett AD, Collins SB,
Ramirez-Correa GA, Burns KM, Cohen M, Colan SD, Costello JM, Daly KP, Franklin RC, Fraser CD,
Hill KD, Huhta JC, Kaushal S, Law YM, Lipshultz SE, Murphy AM, Pasquali SK, Payne MR, Rossano J,
Shirali G, Ware SM, Xu M, Jacobs ML. Cardiol Young. 2015 Aug;25 Suppl 2:8-30. doi:
10.1017/S1047951115001353. PMID 26377707.
Our most recent direction of investigation has been to understand the molecular basis of heart failure in
children, and to develop therapies for mitochondrial disorders in children that cause cardiomyopathy. This has
led to multiple collaborative and novel discoveries, and the development of a novel drug for treatment of the
cardiomyopathy (and neuropathy) of a mitochondrial disease, Friedreich’s Ataxia. The work on cardiomyopathy
in Friedreich’s Ataxia also led us to the novel finding that acetylation of mitochondrial proteins in heart is
upregulated in metabolic cardiomyopathy, and may play a role in mediating this cardiomyopathy.
1. Zhu W, Soonpaa MH, Chen H, Shey W, Liechty EA, Caldwell RL, Shou W, Payne RM, and Field LJ.
Acute Doxorubicin Cardiotoxicity is Associated with p53-Induced Inhibition of the Mammalian Target of
Rapamycin Pathway. Circ, 2009, Jan 6;119(1):99-106.
2. Vyas PM, Tomamichel WJ, Pride PP, Babbey CM, Wang Q, Mercier J, Martin EM, and Payne RM. A
TAT-Frataxin fusion protein increases lifespan and cardiac function in a conditional Friedreich’s Ataxia
mouse model. Hum Mol Genet, 2012 Mar 15;21(6):1230-1247. PMID: 22113996.
3. Wagner GR, and Payne RM. Mitochondrial acetylation and diseases of aging. J Aging Res.
2011;2011(234875. PMID 21437190.
4. Wagner GR and Payne RM. Widespread and enzyme-independent Nε-acetylation and Nε-succinylation
of proteins in the chemical conditions of the mitochondrial matrix. J Biol Chem. 2013, Oct
4;288(40):29036 – 045, PMID: 23946487. Note: selected by JBC as a feature paper.

4. Complete List of Published Work in MyBibliography: We have published over 67 peer reviewed articles,
reviews, and book chapters. Please see:
http://www.ncbi.nlm.nih.gov/sites/myncbi/1Nub6vxYjdzAr/bibliograpahy/47852834/public/?sort=date&direction=
ascending
D. Research Support
Ongoing Research Support
Mitochondrial Protein Acetylation and Heart Failure in Friedreich’s Ataxia
Friedreich’s Ataxia Research Alliance Payne, R. Mark (PI) 07/01/13-6/30/15
Sponsored Research Agreement
A pilot grant with Duke Univ. (Matt Hirschey, PhD) to understand protein acetylation in FRDA. No Cost
Extension to 12/31/2015.
Role: PI
Nrf2 activators in Friedreich’s Ataxia
GlaxoSmithKline Payne, R. Mark (PI) 09/15/15 – 0/14/16
Sponsored Research Agreement
A 1 year pilot project to understand gene expression changes in iPSC forced to cardiomyocyte lineage when
treated with Nrf2 activators.
Role: PI
TAT-Frataxin for Friedreich Ataxia
TRND Payne, R. Mark (PI) 8/2015 – 7/2017
NCATS (National Center for Advancement of Translational Sciences)
This is the Therapeutics for Rare and Neglected Diseases program to develop a protein replacement therapy
for FRDA that is being advanced to market by Chondrial Therapeutics, LLC.
Role: PI
Pediatric Heart Network, Prairieland Consortium
1U10HL109673-01 Cnota, James (PI) 09/01/11- 06/30/16
NIH/NHLBI
This is a collaborative grant to perform clinical studies in children with heart disease.
Role: Multi-PI (Co-I)
Indiana Clinical and Translational Sciences Institute
UL1TR001108-01 Shekhar, Anantha (PI) 09/26/13-04/30/18
NIH/NCRR
To establish a new institute that facilitates clinical and translational biomedical research across the state
of Indiana. This is an institute established by the CTSA to Indiana and Purdue Universities.
Role: Co-I
Indiana Clinical and Translational Sciences Institute – K12 Program
KL2TR001106-01
NIH/ NCRR Shekhar, Anantha (PI) 09/26/13-04/30/18
To establish a new training and career development program providing mentoring programs and
individual K08, K23, and K30 equivalent awards to junior investigators within the Indiana CTSI
Role: Mentor
Indiana Clinical and Translational Sciences Institute – T32 Program
TL1TR001107-01 Shekhar, Anantha (PI) 09/26/13-04/30/18
NIH/NCRR
To establish a new training program providing mentoring programs and individual training fellowships to
pre- and post-doctoral candidates in clinical and translational research programs within the Indiana CTSI
Role: Co-I

5. Pre-Clinical Development of TAT-FXN as a Treatment for Friedreich Ataxia
TRND (Therapeutics for Rare and Neglected Diseases)
NIH / NCATS Payne, RM (PI) 8/15/2015 – 7/2017
This is an NCATS program to collaboratively develop a drug, TAT-Frataxin, as a therapy for Friedreich’s
Ataxia. Award is to Chondrial Therapeutics, LLC.
Development of TAT-Frataxin therapy
Chondrial Therapeutics, LLC Payne, RM (PI) 10/01/15 – 09/30/17
An industry grant to develop a biologic therapy for treatment of Friedreich’s Ataxia.
Role: PI
Completed Recent Research Support
Genesis and Treatment of Heart Failure in the Young.
1 P01 HL085098-01A1 Field, Loren (PI) 04/01/07-03/30/13
NIH/NHLBI Role: Co-I Project 2
This was a Program Project Grant to study the molecular basis of the origins of heart failure in children.
Mechanism of Heart Failure in Friedreich’s Ataxia
Muscular Dystrophy Association Payne, R. Mark (PI) 02/01/13-10/30/15
This basic project investigated cardiac glucose and fatty acid metabolism in the FRDA mouse.
Role: PI
Cardiac Metabolism in Patients with Friedreich’s Ataxia
Indiana University Payne, R. Mark (PI) 11/01/12-10/30/15
Center of Excellence in Cardiovascular Research
Sponsored Research Agreement
This project investigates cardiac glucose and fatty acid metabolism in patients with Friedreich Ataxia.
Role: PI