Cell Communication
in Aging & Disease Lab.
ABOUT OUR RESEARCH
Our lab has been interested in understanding biogenesis of the primary cilium and its role in diverse cellular processes and human diseases. The primary cilium, distinct from the motile cilia, is a cellular organelle that protrudes from the cellular membrane. The primary cilium is non-motile and solely exists in most types of eukaryote cells. In the past, we identified novel genes from patients or focus on unknown genes to investigate the association of the primary cilium with diseases. Currently, our lab is focusing on dissecting the role of primary cilium in aging/age-associated diseases, including Sarcopenia, metabolic disorders, degenerative neuropathy, Alzheimer's disease, and also the role of primary cilium in intercellular communication.
SPECIFIC RESEARCH INTERESTS
Adipocyte primary cilium as a novel therapeutic target in MASLD
Our laboratory is currently investigating the role of primary cilia in adipocytes under conditions of metabolic disease. This project specifically focuses on the intercellular communication between adipocytes and hepatocytes mediated by adipocyte primary cilia during the progression of metabolic dysfunction-associated liver disease (MASLD). We aim to elucidate how adipocyte cilia sense inflammatory stimuli and regulate the secretion of exosomes and adipokines, which are subsequently delivered to hepatocytes and influence liver pathology. Through this research, we aim to establish a novel therapeutic strategy for metabolic liver diseases by targeting adipose tissue.
[ Diagram courtesy of Soo Mi Ki ]
Myocyte primary cilium as a novel therapeutic target in Sarcopenia
This project investigates the role of primary cilia in enhancing myogenic fusion as a potential therapeutic approach for sarcopenia. Myogenic fusion involves two sequential steps: first, the fusion of mononucleated myocytes (primary fusion) forming nascent myotubes, followed by additional myocytes fusing with these nascent myotubes (secondary fusion) to generate mature myotubes. We hypothesize that primary cilia on myocytes actively secrete extracellular vesicles (EVs) enriched with membrane receptors and signaling proteins. In the muscle microenvironment, inflammation creates a barrier to efficient myogenic fusion. These cilia-derived EVs suppress inflammatory signaling, thereby alleviating this inhibitory environment and facilitating myocyte fusion. By elucidating how primary cilia regulate inflammatory signals and enhance fusion efficiency, this research aims to provide novel insights into ciliary control of muscle regeneration and highlight its therapeutic potential for combating sarcopenia.
[ Diagram courtesy of So Yeon Won ]
Schwann cell primary cilium as a novel therapeutic target in Peripheral Neuropathy
This project focuses on terminal Schwann cells located at the neuromuscular junction (NMJ). We hypothesize that the primary cilia of Schwann cells release ectosomes into the extracellular space, promoting neural regeneration. However, chronic inflammation impairs this beneficial process. Our lab is currently investigating key proteins within Schwann cell-derived ectosomes that facilitate regeneration. Ultimately, we aim to develop a therapeutic strategy targeting the chronic inflammation-mediated impairment in peripheral neuropathy.
[ Diagram courtesy of Hui Su Jeong ]
Myocyte primary cilium as a novel therapeutic target in Alzheimer's disease
As aging progresses, impaired myocyte differentiation contributes to muscle loss, leading to sarcopenia. In parallel, ciliogenesis-deficient myocytes exhibit reduced secretion of ciliary exosomes, disrupting critical intercellular communication. This decline in exosome-mediated signaling exacerbates the activation of disease-associated microglia (DAM), driving chronic neuroinflammation observed in Alzheimer’s disease. Our research aims to elucidate this novel mechanistic link between muscle-derived vesicle dysfunction and neuroinflammatory processes in the aging brain, with the goal of identifying new therapeutic targets for both sarcopenia and neurodegenerative diseases.
[ Diagram courtesy of Seonok Kim ]
Myocyte primary cilium as a novel therapeutic target in Sarcopenic obesity
This project aims to elucidate the role of primary cilia in age-related sarcopenic obesity, a condition increasingly defined by chronic inflammatory crosstalk between skeletal muscle and adipose tissue. During aging, adipose tissue demonstrates reduced energy expenditure and increased lipid accumulation, contributing to adipocyte hypertrophy and ectopic lipid infiltration into skeletal muscle. This process promotes the production of pro-inflammatory myokines, further amplifying systemic inflammation. We hypothesize that primary cilia-derived ectosomes from muscle may exert regulatory effects by suppressing inflammation within adipose tissue, thereby modulating the pathological interaction between muscle and fat in sarcopenic obesity.
[ Diagram courtesy of Min Seon Kim ]
Adipocyte primary cilium as a novel therapeutic target in Sarcopenic obesity
Under normal conditions (top panel), acute inflammation in adipose tissue triggers the release of ciliary ectosomes from preadipocytes via the primary cilium. These ectosomes positively regulate muscle homeostasis, supporting normal muscle maintenance and regeneration.
In sarcopenic obesity (bottom panel), chronic inflammation either enhances the release of altered ciliary ectosomes or suppresses their release from preadipocytes. These dysfunctional ectosomes negatively impact muscle tissue, impairing muscle maintenance and regeneration, thereby contributing to the progression of sarcopenia.
[ Diagram courtesy of Shin Ji Oh ]