What is your lab’s long-term/big-picture research goal?
The long-term goal of my research program is to understand how genetic mutations lead to brain diseases and find a cure for them.
DNA is our body’s blueprint. It contains the instruction for development, growth, and physiological activities. Hence, inherited mutations (deleterious changes) in DNA from parents often result in diseases in kids. The diseases caused by inherited mutations in DNA are called genetic diseases.
My lab has discovered five new genetic disorders caused by mutations in genes required for mitochondrial function. Mitochondria are one of the compartments inside most of our cells that convert food into energy to power our bodies. Mutations in the mitochondrial genes cause defective mitochondria (like defective engines) that burn fuel inefficiently and produce by-products that can be toxic to our cells and bodies. Children born with defective mitochondria caused by genetic mutations likewise suffer from profound neurological defects including intellectual disability, loss of full control of body movements, and stunted growth. However, how genetic mutations lead to neuron illness is not entirely understood. Using patient-derived stem cells, we aim to understand better the action of the mutations that would help find a way to cure the diseases.
What is your training/scientific background?
I obtained excellent training in academic as well as industrial environments. After completing my BS and MS degrees, I served duty as a research scientist at a pharmaceutical company in South Korea to fulfill a requirement for military service. Research experience in the industry benefited my research career as I developed unique molecular and biochemical biology skills, learned strategies to develop drug targets, and acquired communication skills that enabled me to work effectively with scientists from different fields and backgrounds. I also had an opportunity to research at the Pacific Northwest Research Institute in Seattle, where I became experienced with chemical genetics approaches. The important lesson I learned in industry is that successful drug development projects require knowledge of the gene functions at the organismal level. Thus, I decided to pursue a Ph.D. to learn how to study gene function in organisms.
During my Ph.D. course at the Johns Hopkins University School of Medicine, I was fascinated by the Drosophila model because of its genetic tractability and huge contributions to our understanding of biology. Under the guidance of Dr. Denise Montell, I equipped myself with the knowledge and skills to tackle complex questions for developmental biology using Drosophila genetics, enabling me to study gene function at organismal levels. During my postdoctoral training at the Howard Hughes Medical Institute at Baylor, I obtained the skills and knowledge to study neurobiology, mitochondrial biology, and metabolism. I built on my previous efforts to investigate mitochondrial diseases in humans under the guidance of Dr. Hugo Bellen. In collaboration with Dr. James Lupski, I identified novel mitochondrial disease genes and investigated the effects of pathogenic mutations in Drosophila and patient-derived cells.
After completing my postdoctoral training, I joined the Oklahoma Medical Research Foundation (OMRF). My faculty position is in the Aging & Metabolism Research Program at the OMRF. OMRF allows me to focus exclusively on my independent research programs to study human genetic and neurological diseases. In addition, my program colleagues look at various aspects of mitochondrial biology and metabolism in the context of human health, aging, and disease, providing me with an ideal environment to reach my research goals.
What is the goal of your OCASCR project?
My lab discovered a new human neurological disease that is caused by mutations in the OGDHL gene. OGDHL protein localizes in the mitochondria. Mitochondria are the compartments inside our cells that convert food (nutrition) into energy to power our bodies. Mitochondria need numerous enzymes that help food-energy conversion. OGDHL is one of the essential enzymes in the mitochondria for doing those jobs. We showed that the mutations in OGDHL identified in patients lead to impaired enzyme function. However, how mutations in OGDHL cause neurological problems and how the loss of OGDHL function impacts metabolism and cellular signaling in brain cells remain largely unknown. Our OCASCR project focuses on understanding how genetic mutations of OGDHL impact metabolism and damage brain cells called neurons. We utilized state-of-the-art genetic engineering to introduce mutations into OGDHL in human inducible pluripotent stem cells (iPSCs). Unlike embryonic stem cells, using iPSCs enables us to research tissues, including neurons, without damaging human embryos. This approach provides a powerful experimental system to determine how OGDHL mutations disrupt mitochondrial functions and identify a way that restores these functions and improves human health.
How might your research impact diseases related to obesity or smoking?
My research impacts understanding human diseases such as obesity because mitochondria play an essential role in fat metabolism. Obesity is a disease involving an excessive amount of body fat. Nutrition molecules, including fat, are digested in mitochondria to make cellular energy. However, excess energy molecules like fat overwhelm mitochondria function, causing mitochondrial dysfunction and damage. My research focuses on the study of defective metabolic enzymes in mitochondria. Hence, a better understanding of the impact of mitochondrial dysfunction could help to understand obesity biology.
5. What’s your most critical piece of research equipment in your lab? Why?
We have equipment that transfers genetic materials (i.e., DNA and RNA) into human cells using an electric pulse. This equipment is also called an electroporation machine. My lab can create human stem cells having mutations in target genes. Also, this equipment enables us to correct mutations in patient cells too. Hence, the equipment is essential for my research to study human genetic diseases.
What’s your favorite scientific meeting to attend? Why?
My favorite scientific meeting is an American Society of Human Genetics meeting. I could meet and communicate with my current collaborators. Also, I can learn new findings about human diseases by interacting with many scientists. The meeting often results in new collaboration too!
