뇌질환의 메커니즘을 동물모델로 이해하려는 시도가 많으나 환자의 여러 표현형을 모방하는 데에 한계가 있고, 모델에서 검증된 약물의 효능이 실제 환자에서는 미비한 경우가 빈번합니다. 인간의 뇌는 다른 동물과 매우 다른 구조적, 발생학적 차이를 가지고 있기 때문입니다. 따라서 인간에서 보이는 뇌발생원리를 파악하고, 이를 반영하는 대체 모델을 만들어 뇌질환을 이해하는 연구가 시급합니다. 저희 연구실은 기증자의 뇌에 새겨진 모자이크변이 정보를 이용해 발견한 ‘Dorsally-derived cortical inhibitory neuron’과 같이 기존 모델로는 발견하지 못했던 인간 뇌 발생과정을 규명하고 분자생물학적 분화원리를 밝히는 것을 목표로 하고 있습니다. 나아가 이 연구 결과를 바탕으로 인간 고유의 뇌 발달 특성을 더 정밀하게 반영하는 대체 오가노이드 및 생쥐 모델을 만들고자 합니다. 이 대체모델들은 인간 뇌 질환에 대한 이해와 효과적인 치료 전략 수립에 기여할 수 있을 것입니다.

Although animal models are widely used to study brain disorders, they often fail to replicate patient phenotypes or predict clinical drug efficacy since the human brain differs significantly from animal brains in both structure and development. This highlights the urgent need to uncover principles of human brain development to establish alternative models.
Our laboratory aims to identify human developmental processes—such as the dorsally-derived cortical inhibitory neuron, which we discovered using mosaic mutations imprinted in postmortem human brains and which could not be detected in conventional models. We further seek to elucidate the molecular mechanisms governing human brain cell differentiation.
Based on these findings, ultimately, we strive to create next-generation organoid and animal models that more precisely recapitulate the features of human brain development. These alternative models will contribute to a deeper understanding of brain disorders and facilitate the development of more effective therapeutic strategies.

• Changuk Chung, Xiaoxu Yang, Robert F. Hevner, Katie Kennedy, Keng Ioi Vong, Yang Liu, Arzoo Patel, Rahul Nedunuri, Scott T. Barton, Geoffroy Noel, Chelsea Barrows, Valentina Stanley, Swapnil Mittal, Martin W. Breuss, Johannes C. M. Schlachetzki, Stephen F. Kingsmore & Joseph G. Gleeson. Cell-type-resolved mosaicism reveals the clonal dynamics of the human forebrain.

  Nature (2024), 629:384-392

• Changuk Chung, Xiaoxu Yang, Taejeong Bae, Keng Ioi Vong, Swapnil Mittal, Catharina Donkels, H. Westley Phillips, Zhen Li, Ashley P. L. Marsh, Martin W. Breuss, Laurel L. Ball, Camila Araújo Bernardino Garcia, Renee D. George, Jing Gu, Mingchu Xu, Chelsea Barrows, Kiely N. James, Valentina Stanley, Anna S. Nidhiry, Sami Khoury, Gabrielle Howe, Emily Riley, Xin Xu, Brett Copeland, Yifan Wang, Se Hoon Kim, Hoon-Chul Kang, Andreas Schulze-Bonhage, Carola A. Haas, Horst Urbach, Marco Prinz, David D. Limbrick Jr., Christina A. Gurnett, Matthew D. Smyth, Shifteh Sattar, Mark Nespeca, David D. Gonda, Katsumi Imai, Yukitoshi Takahashi, Hsin-Hung Chen, Jin-Wu Tsai, Valerio Conti, Renzo Guerrini, Orrin Devinsky, Wilson A. Silva Jr., Helio R. Machado, Gary W. Mathern, Alexej Abyzov, Sara Baldassari, Stéphanie Baulac, Focal Cortical Dysplasia Neurogenetics Consortium, Brain Somatic Mosaicism Network & Joseph G. Gleeson. Comprehensive multi-omic profiling of somatic mutations in malformations of cortical development.

  Nature Genetics (2023), 55:209-220 (Cover selected)

• Changuk Chung, Seungmin Ha, Hyojin Kang, Jiseok Lee, Seung Min Um, Haidun Yan, Ye-Eun Yoo, Taesun Yoo, Hwajin Jung, Dongwon Lee, Eunee Lee, Seungjoon Lee, Jihye Kim, Ryunhee Kim, Yonghan Kwon, Woohyun Kim, Hyosang Kim, Lara Duffney, Doyoun Kim, Won Ma, Hyejung Won, Seojung Mo, Jin Yong Kim, Chae-Seok Lim, Bong-Kiun Kaang, Tobias M. Boeckers, Yeonseung Chung, Hyun Kim, Yong-hui Jiang, Eunjoon Kim. Early correction of NMDAR function improves autistic-like behaviors in adult Shank2–/– mice.

  Biological Psychiatry (2019). 85:534-543 (Selected as Priority Communications)