Wan Hee Yoon, Ph.D.

Neurodegenerative and neurodevelopmental diseases affect millions of people around the globe. Scientists have thought many of these diseases may result from disruptions or failures in the mitochondria, a specialized cellular structure often referred to as the “powerhouse of the cell.”

Mitochondria play a key role in metabolism in cells. Metabolism is a series of biochemical reactions essential for all living organisms. It provides energy and the building blocks for healthy cells. As we age, we lose some of these capabilities of mitochondria, and the quality of our cells declines. This has been implicated in many diseases, including neurodegenerative diseases like Alzheimer’s and Parkinson’s and even cancer.

Our long-term goal is to learn how cells maintain mitochondrial structure and metabolism, how failures in that system may contribute to human pathologies and, ultimately, to find treatments for those diseases.

To do this, we use common fruit flies called Drosophila as a disease model. Because fruit flies share approximately 75 percent of a human’s disease genes, they are near-perfect tools for studying conditions that afflict people. We “humanize” these flies by using state-of-the-art gene editing tools. By studying how their mitochondrial dysfunction contributes to defects in flies, we can get hints into the root causes for human diseases.

My lab also focuses on identifying novel and previously unknown human diseases using the newest technologies in Drosophila. In collaboration with human geneticists, I discovered mitochondrial genes whose mutations cause neuronal and metabolic dysfunction in both flies and humans. This work shows that fruit flies serve as an excellent model system for discovering novel disease genes from human patient data. Using these tiny flies, we can continue to identify new human diseases, perform disease modeling in flies, and understand the mechanisms of their pathogenesis.

We are dedicated to understanding the molecular and cellular mechanisms underlying human neurological diseases caused by mutations in nuclear-encoded mitochondrial genes.

Our work integrates clinical genomics with functional studies in both Drosophila melanogaster and human cellular models, including neurons and brain organoids derived from patient-specific induced pluripotent stem cells (iPSCs). This multidisciplinary approach enables us to uncover how mitochondrial dysfunction impacts neural development and brain function.

Over the past few years, our lab has contributed to the discovery and molecular characterization of five distinct Mendelian mitochondrial disorders, including two novel syndromes—Harel-Yoon syndrome (MIM: #617183) and Yoon-Bellen neurodevelopmental syndrome (YOBELN, MIM: #619701). Most recently, we helped establish OGDH deficiency (OGDHD; OMIM #203740) as a new Mendelian condition caused by recessive variants in the OGDH gene.

We have developed a range of genetic tools and disease models in Drosophila and human iPSC-derived neural cells that allow us to investigate the biological functions of disease-associated mitochondrial genes, dissect their impact on metabolic and signaling pathways, and explore potential therapeutic strategies.

Our ultimate goal is to bridge the gap between gene discovery and clinical translation by advancing our understanding of mitochondrial biology in the context of neurodevelopment and disease
.

Education
B.Sc., Yonsei University, South Korea, 1997
M. Sc., Yonsei University, South Korea, 1999
Ph.D., Johns Hopkins University School of Medicine, 2011

Professional Activities
Visiting Research Scientist, Pacific Northwest Diabetes Research Institute, Seattle. Principal Investigator: Michael Kahn, Ph.D., 2001
Senior Research Scientist, Central Research Institute, Choongwae Pharmaceutical Company, South Korea, 1999-2004
Postdoctoral Research Fellow, Howard Hughes Medical Institute, Department of Molecular and Human Genetics, Baylor College of Medicine, Principal Investigator: Hugo J. Bellen, D.V.M., Ph.D., 2011-2016
Assistant Professor, Department of Molecular and Human Genetics, Baylor College of Medicine, 2016-2017

Honors and Awards
Korea Science and Engineering Foundation Fellowship, 2004
H.A. and Mary K. Chapman Young Investigator Fellowship, 2005
Best Oral Presentation Award, 14th Korean-American Biomedical Scientists Symposium, 2015
Oral Presentation Award, 15th Korean-American Biomedical Scientists Symposium, 2016
Best Postdoctoral Publication Award, Department of Molecular and Human Genetics, Baylor College of Medicine, 2017

Joined OMRF scientific staff in 2017

View more publications

Recent Publications

Muñoz-Oreja M, Sandoval A, Bruland O, Perez-Rodriguez D, Fernandez-Pelayo U, de Arbina AL, Villar-Fernandez M, Hernández-Eguiazu H, Hernández I, Park Y, Goicoechea L, Pascual-Frías N, Garcia-Ruiz C, Fernandez-Checa J, Martí-Carrera I, Gil-Bea FJ, Hasan MT, Gegg ME, Bredrup C, Knappskog PM, Gereñu-Lopetegui G, Varhaug KN, Bindoff LA, Spinazzola A, Yoon WH, Holt IJ. Elevated cholesterol in ATAD3 mutants is a compensatory mechanism that leads to membrane cholesterol aggregation. Brain, 2024 January, PMID: 38242545, PMCID: PMC11068212

Panda A, Suvakov M, Mariani J, Drucker KL, Park Y, Jang Y, Kollmeyer TM, Sarkar G, Bae T, Kim JJ, Yoon WH, Jenkins RB, Vaccarino FM, Abyzov A. Clonally Selected Lines After CRISPR-Cas Editing Are Not Isogenic. CRISPR J 6:176-182, 2023 April, PMID: 37071670, PMCID: PMC10123805

Whittle EF, Chilian M, Karimiani EG, Progri H, Buhas D, Kose M, Ganetzky RD, Toosi MB, Torbati PN, Badv RS, Shelihan I, Yang H, Elloumi HZ, Lee S, Jamshidi Y, Pittman AM, Houlden H, Ignatius E, Rahman S, Maroofian R, Yoon WH, Carroll CJ. Biallelic variants in OGDH encoding oxoglutarate dehydrogenase lead to a neurodevelopmental disorder characterized by global developmental delay, movement disorder, and metabolic abnormalities. Genet Med, 2022 December, PMID: 36520152, PMCID: PMC9905285

Selected Publications

Yoon WH, Sandoval H, Nagarkar-Jaiswal S, Jaiswal M, Yamamoto S, Haelterman NA, Putluri N, Putluri V, Sreekumar A, Tos T, Aksoy A, Donti T, Graham BH, Ohno M, Nishi E, Hunter J, Muzny DM, Carmichael J, Shen J, Arboleda VA, Nelson SF, Wangler MF, Karaca E, Lupski JR, Bellen HJ. Loss of Nardilysin, a Mitochondrial Co-chaperone for α-Ketoglutarate Dehydrogenase, Promotes mTORC1 Activation and Neurodegeneration. Neuron. 2017 Jan 4;93(1):115-131. Epub 2016 Dec 22. PMID: 28017472, PMCID: PMC5242142

Harel T, Yoon WH, Garone C, Gu S, Coban-Akdemir Z, Eldomery MK, Posey JE, Jhangiani SN, Rosenfeld JA, Cho MT, Fox S, Withers M, Brooks SM, Chiang T, Duraine L, Erdin S, Yuan B, Shao Y, Moussallem E, Lamperti C, Donati MA, Smith JD, McLaughlin HM, Eng CM, Walkiewicz M, Xia F, Pippucci T, Magini P, Seri M, Zeviani M, Hirano M, Hunter JV, Srour M, Zanigni S, Lewis RA, Muzny DM, Lotze TE, Boerwinkle E; Baylor-Hopkins Center for Mendelian Genomics; University of Washington Center for Mendelian Genomics, Gibbs RA, Hickey SE, Graham BH, Yang Y, Buhas D, Martin DM, Potocki L, Graziano C, Bellen HJ, Lupski JR. Recurrent De Novo and Biallelic Variation of ATAD3A, Encoding a Mitochondrial Membrane Protein, Results in Distinct Neurological Syndromes. Am J Hum Genet. 2016 Oct 6;99(4):831-845. Epub 2016 Sep 15. PMID: 27640307, PMCID: PMC5065660

Haelterman NA, Yoon WH, Sandoval H, Jaiswal M, Shulman JM, Bellen HJ. A mitocentric view of Parkinson's disease. Annu Rev Neurosci. 2014;37:137-59. Review. PMID: 24821430, PMCID: PMC4659514

Montell DJ, Yoon WH, Starz-Gaiano M. Group choreography: mechanisms orchestrating the collective movement of border cells. Nat Rev Mol Cell Biol. 2012 Oct;13(10):631-45. PMID: 23000794 PMCID: PMC4099007

Yoon WH, Meinhardt H, Montell DJ. miRNA-mediated feedback inhibition of JAK/STAT morphogen signalling establishes a cell fate threshold. Nat Cell Biol. 2011 Aug 21;13(9):1062-9. PMID: 21857668 PMCID: PMC3167036

Aging & Metabolism Research Program, MS 46
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, OK 73104

Phone: (405) 271-1574
Fax: (405) 271-3765
E-mail: wanhee-yoon@omrf.org

For media inquiries, please contact OMRF’s Office of Public Affairs at news@omrf.org.

Matt McDougal, Ph.D.
Postdoctoral Scientist

Abigail Sandoval
Research Technician II

Gyu Seung Lee
Research Technician I

Heather Spencer
Administrative Assistant III

News from the Yoon lab

OMRF receives grant to examine rare neurological disorder

October 10, 2024

Focus is disease named after OMRF scientist

OMRF scientist identifies genetic cause of rare disease

March 16, 2023

Genetic mutation pinpointed in severe neurological disorder

OMRF study reveals genetic cause of neurological disease

December 14, 2021

Dr. Wan Hee Yoon’s discovery links nine children who displayed an array of symptoms.

OMRF receives $2.19 million to study rare neurological condition

July 1, 2021

The National Institutes of Health has awarded OMRF $2.19 million to continue research on a rare neurological disease.

Federal grant brings $13.1 million to OMRF labs

July 12, 2018

The award is part of the Centers of Biomedical Research Excellence (COBRE) program.

OMRF hosts 2018 Loyal Donors reception

May 15, 2018

OMRF officials brought more than 110 long-time donors together from across the state to celebrate their dedicated supporters at the annual Loyal Donor Society reception.

Rapp Foundation gives $400,000 to OMRF for new researchers

December 27, 2017

The grant will help two new scientists establish labs at OMRF.