Indiana University School of Medicine

R. Mark Payne, MD

R. Mark Payne, M.D.
Professor Pediatrics


Department of Pediatrics
Indiana University School of Medicine


317-278-6239 office
317-274-1530 lab
317-278-9298 fax

  • Research Fellowship: Molecular Biology (1992), Washington University Medical Center, St. Louis, MO
  • Fellowship: Pediatric Cardiology (1989), Children's Hospital at Washington University Medical Center, St. Louis, MO
  • Residency: Pediatrics (1987), Children's Hospital at Washington University Medical School, St. Louis, MO
  • M.D.: (1983) University of Texas School of Medicine, Houston, TX
  • B.S.: (1977) Washington and Lee University, Lexington, VA
Academic and Professional
Roles and Appointments: Current
Academic and Professional
Roles and Appointments: Past
  • Associate Professor of Pediatrics (1999 - 2005), Assistant Professor of Pediatrics (1997 - 1999), Wake Forest University School of Medicine
  • Assistant Professor of Pediatrics (1993 - 1997), Instructor in Pediatrics (1991 - 1993), Washington University School of Medicine
Awards, Honors and Distinguished
Professional Activities
  • Study Sections: AHA molecular signaling, NIH BRT-A, NIGMS K12, NHLBI K99-00
  • American Heart Association: Clinician Scientist Award (1992-1997)
  • American Heart Association: Fellowship Award (1989-1990)
  • American Heart Association: Established Investigator
Research Interest

Mitochondria produce virtually all of the energy supply in tissues with high energy demands. Many inherited and acquired diseases have been described that are the result of impaired mitochondrial function and involve both the mitochondrial and nuclear genomes. In heart, mitochondria play two roles essential for myocyte survival: synthesis of ATP, and maintenance of calcium homeostasis. Disruption of normal mitochondrial function can thus lead to loss of adequate energy production, and possible initiation of apoptosis and cell death. Because mitochondria have a small genome that encodes only 13 proteins, most of the hundreds of proteins needed for normal mitochondrial function are encoded in the nucleus and imported from the cytosol after translation. This 'post-translational' model predicts a completely synthesized protein will be targeted to a mitochondrial receptor for import, and has been well established in yeast and Neurospora. However, our work has suggested that a different model, termed 'co-translational import', may be equally important in mammalian cells. We have shown that ribosomes are targeted to receptors on the surface of mitochondria and that GTP hydrolysis controls the specificity of this ribosome binding. In mammalian tissues, such as heart, this would provide increased efficiency for generating energy. However, it is not known if the process of protein import into mitochondria can be disrupted and contribute to the disease state of injured heart, and if this process participates in the recovery of the heart. We want to understand the role of protein targeting and import into mitochondria in order to design genetic therapies to repair or protect mitochondrial function in the heart. Ongoing projects include: 1) Gene replacement therapy for Sudden Infant Death Syndrome. Sometimes children inherit a defective ability for mitochondria to burn fats normally. In this case, the children can be at risk of SIDS and may die suddenly during episodes poor nutritional intake. These studies involve the development of protein transduction domains as a 'gene therapy' vehicle for delivering proteins associated with the beta-oxidation spiral into the matrix of mammalian mitochondria. We have used the Transactivator of Transcription (TAT) from HIV to develop TAT-fusion proteins that will deliver a therapeutic cargo to mitochondria when injected into the peritoneum. These studies use genetically modified mice that recapitulate the disease state of SIDS to test hypothesis of protein transduction into mitochondria. 2) Gene replacement therapy for Friedreich's Ataxia. This is the most common inherited form of ataxia in humans and results from a triplet expansion in intron 1 of the human Frataxin gene (FRDA). As a result, very little Frataxin is produced and children begin to show symptoms of cardiomyopathy and a staggering gait by early teen years. Frataxin appears to be an iron-binding protein that is targeted to the mitochondrial matrix and in its absence, mitochondrial function declines. These studies use genetically modified mice that recapitulate the disease state of Friedreich's Ataxia to test TAT-Frataxin fusion proteins as a mechanism for replacing the missing gene product. 3) Understanding signaling pathways that regulate apoptosis in the setting of childhood heart failure from inherited, or acquired, myocardial injuries leading to dilated cardiomyopathies. Heart failure is a common event in childhood with significant morbidity and mortality and this project seeks to understand the role of apoptosis in mediating this heart failure. Because mitochondria play a key role in regulation of apoptosis in heart, we want to understand how mitochondria signal this event and if it can be prevented. These studies will use genetically altered mice, and human cardiac cells, to address these questions. 4) Characterization of mitochondrial protein import in mammalian tissues. We have characterized the binding of ribosomes to mitochondria and now want to identify the ribosome receptor on the mitochondrial surface. Because GTP hydrolysis acts to confer specificity to this ribosome binding, we also want to characterize the GTP-binding proteins that are involved with protein import into mitochondria. These studies use cells in culture, as well as isolated mitochondria, to analyze these components.


1. Co-Investigator: "Early Intervention for Acute Kidney injury after Pediatric Cardiopulomonary Bypass", (NIH / CCHMC U10HL109673) [09/01/2011 - 06/30/2016] This project is part of the Pediatric Heart Network from the NHLBI. The goal of this clinical project is to understand and define clinical markers of acute kidney injury during and after open heart surgery in children.

2. Mentor: Indiana Clinical and Translational Sciences Institute - T32 Program. (TL 1RR025759-01) Dr. Anatha Shekhar (Indiana University) is the PI.

3. Mentor: Indiana Clinical and Translational Sciences Institute (UL1RR025761-01) Dr. Anatha Shekhar (Indiana University) is the PI.

4. Mentor: Indiana Clinical and Translational Sciences Institute - K12 Program (KL2RR025760-01) Dr. Anatha Shekhar (Indiana University) is the PI.

5. Principal Investigator: "Cardiac Metabolism in patients with Friedreich's Ataxia" (Indiana University School of Medicine Strategic Research Initiative, CECARE) [11/12 - 10/14] The goal of this project is to understand metabolism in the FRDA patient heart.

6. Principal Investigator: "Mechanism of Heart Failure in Friedreich Ataxia" (Muscular Dystrophy Association) [02/2013 - 01/2015] The goal of this project is to understand cardiac metabolism and biochemistry in the FRDA mouse. 

7. Co-Investigator: "Mitochondrial protein acetylation and heart failure in Friedreich's ataxia" (Friedreich's Ataxia Research Alliance, Keith Michael Andrus Cardiac Research Grant).  [2013 - 2015]. Co-Investigator with Dr. Matt Hirschey.

Dr. Payne's Laboratory

The Payne lab