Impact Story: David Jang, MD, MSc, FACMT

David H. Jang, MD, MSc, FACMT
2017 MTF Innovative Research and Teaching Award Recipient

Project Title: “Investigation of a cell-permeable mitochondrial prodrug (NV-118) on mitochondrial function in human blood cells from patients with CO poisoning.”

Award Amount: $10,000

About Dr. Jang

Dr. Jang is currently an Assistant Professor at the University of Pennsylvania in the Department of Emergency Medicine and Division of Medical Toxicology.

"The MTF Innovation and Research Award I received in 2017 for this project has had a significant impact on my overall research goals as a young investigator. My current research focus is at the intersection of mitochondrial medicine, therapeutics, and poisoning using a translational approach ranging from cell culture to both small and large animal models. Early on during the award, my project was focused primarily on in vitro cell culture work using blood cells as a biomarker in various critical care illnesses such as sepsis and carbon monoxide poisoning.

The foundation of this project was an interest in studying the use of a succinate prodrug (NV118 from Abliva) in the setting of poisoning. As our site is a major HBO site in the area, we get several CO patients who undergo treatment. I designed a study to use obtained blood cells from patients with CO poisoning to study alterations in mitochondrial function and to also see the treatment effect with the succinate prodrug. 

In order to continue to further develop the research beyond what our funding options at that time provided, I was hopeful when I became aware of the opportunity the MTF Innovation and Research Award offered. With the MTF award funding, we were able to complete a study demonstrating the beneficial effect of the succinate prodrug in our ex vivo study using blood cells from patients with CO poisoning entitled, “Ex vivo use of cell-permeable succinate prodrug attenuates mitochondrial dysfunction in blood cells obtained from carbon monoxide-poisoned individuals.” Our group was able to utilize this support to investigate this compound in a small animal model that was ultimately funded as an NIH R21 grant to examine the role of blood cells as a biomarker and the therapeutic in a rodent model. The research is still in progress.

Building on this work and the expertise of our lab, I was able to leverage these findings to obtain an R03 grant from NIH to develop a large animal model of CO poisoning to investigate alterations in cellular function. This allows us to study therapeutics for CO poisoning in a model that more closely mimics human physiology. You may access these findings in the publication in the Journal of Clinical Toxicology “Alterations in cerebral and cardiac mitochondrial function in a porcine model of acute carbon monoxide poisoning.”

In addition to my gratitude to MTF for providing this funding opportunity, I would like to acknowledge key collaborators on this project: Dr.Todd Kilbaugh, Dr. Sarah Piel, and Dr. Johannes Ehinger who were instrumental in making possible the work we have been able to accomplish on this project thus far."