MAILMAN RESEARCH CENTER
Molecular Neurobiology Laboratory
Abnormal regulation/degeneration of midbrain dopamine neuron is associated with major neurological and psychiatric disorders such as Parkinson’s disease, schizophrenia, and substance abuse. We are interested in understanding the molecular mechanisms underlying the development and maintenance of dopamine neurons in healthy and diseased brains. This is accomplished through detailed mechanistic studies of the relationship between critical extrinsic signals and intrinsic transcription factors, leading to important genetic networks and their functional roles in orchestrating the development and maintenance of dopamine neurons. Based on this molecular information, we seek to translate our results to preclinical and clinical application for neurodegenerative disorders such as Parkinson’s disease. In particular, we identified several key transcription factors that are crucial for early development and long-term maintenance and protection of midbrain dopamine neurons, leading us to identify them as potential drug targets for neurodegenerative disorders. We established efficient in vitro and in vivo assay systems and are currently investigating the development of novel therapeutics that may have neuroprotective and disease-modifying effects on neurodegenerative disorders.
The Molecular Neurobiology Lab Staff
Another area of research interest is the study of stem cells. In particular, we have recently focused on the development of clinically feasible and safe induced pluripotent stem (iPS) cell technology, which has great potential to study and treat human diseases. At present, the majority of iPS cells are derived through the use of viral vectors, resulting in clinically unsafe stem cells. We are interested in developing clinically and biomedically ideal iPS cells by safe techniques such as protein-based reprogramming with the long-term goal of advancing future personalized regenerative medicine. Once this technology is fully optimized, it will open an era of ‘cellular alchemy’ and provide potential platforms for human disease mechanism studies and novel therapeutic developments.
- Kwang-Soo Kim, Ph.D. - Professor of Psychiatry and Neuroscience & Director, Molecular Neurobiology Laboratory
- Sangmi Chung, Ph.D. - Instructor
- Chun-Hyung Kim, Ph.D. - Instructor
- Dohoon Kim, Ph.D. - Instructor
- Young Cha, Ph.D. - Postdoctoral Fellow
- Debkanya Datta, Ph.D. - Postdoctoral Fellow
- Min-joon Han, Ph.D. - Postdoctoral Fellow
- Sanghyeok Ko, Ph.D. - Postdoctoral Fellow
- Minho Moon, Ph.D. - Postdoctoral Fellow
- Jisun Oh, Ph.D. - Postdoctoral Fellow
- Amanda Leung, B.A. - Lab Manager
- Inhye Jeong, M.E. – Technical Research Assistant
- Pierre Leblanc, Ph.D. - Consultant
- Susan Knapp - Administrative Assistant (e-mail)
- Kim, D., Kim, C.-H., Moon, J., Chung, Y.-G., Chang, M.-Y., Han, B.-S., Ko, S., Yang, E., Cha, K.Y., Lanza, R., Kim, K.S. (2009). Generation of Human Induced Pluripotent Stem Cells by Direct Delivery of Reprogramming Proteins. Cell Stem Cell 4(6):472-6. (selected as one of 2009 Research Highlights by Nature 2009, 462:960).
- Chung, S., Leung, A., Hong, S.H., Chang, M.Y., Pruszak, J., Han, B.-S., Isacson, O. and Kim, K.S. (2009) Wnt1 and Lmx1a form a novel autoregulatory loop and critically regulate midbrain dopaminergic development at multiple steps. Cell Stem Cell 5:646-58.
- Riccio, A., Li, Y., Moon, J., Kim, K.S., Gapon, S., Yao, G.L., Tsvetkov, E., Rodig, S.J., Meloni, E.G., Carlezon, W.A., Clapham, D.E., and Bolshakov, V.Y., (2009) Essential role for TRPC5 in amygdale function and fear-related behavior. Cell 137(4):761-72.
- Neveu, P., Kye, M.J., Qi, S., Buchholz, D.E., Clegg, D.O., Sahin, M., Park, I.-H., Kim, K.S., Daley, G.Q., Kornblum, H.I., Shraiman, B.I., and Kosik, K.S. (2010) MicroRNA profiling reveals two distinct p53-related human pluripotent stem cell states. Cell Stem Cell, 7:671-81 (Comment in Cell Stem Cell. 2010, 7(6):649-50).
- Chang, M.-Y., Kim, D., Kim, C.-H., Kang, H.-C., Yang, E., Moon, J-I., Ko, S., Park, J., Park, K.-S., Lee, K.A., Hwang, D.-Y., Chung, Y., Lanza, R., Kim, K.S. (2010) Direct Reprogramming of Rat Neural Precursor Cells and Fibroblasts into Pluripotent Stem Cells. PlosONE, 5(3): e9838.
- Kim, C.H., Leung, A., Huh, Y.H., Yang, E., Kim, D.J., Leblanc, P., Ryu, H., Kim, K., Kim, D.W., Garland, E.M., Raj, S.R., Biaggioni, I., Robertson, D., and Kim, K.S. (2011) Norepinephrine deficiency is caused by combined abnormal mRNA processing and defective protein trafficking of dopamine b-hydroxylase. J Biol Chem. 286(11):9196-204.
- Rhee, Y.-H., Ko, J.-Y., Chang, M.-Y., Yi, S.-H., Kim, D., Kim, C.-H., Shim, J.-W., Jo, A.-Y., Kim, B.-W., Lee, H., Lee, S.-H., Suh, W., Park, C.-H., Koh, H.-C., Lee, Lee, Y.-S., Lanza, R., Kim, K.S.* and Lee, S.-H.* (*co-corresponding authors) (2011) Protein-based human iPS cells efficiently generate functional dopamine neurons without abnormal phenotypes associated with genome integration. J. Clin. Invest. 121(6):2326-35. Epub 2011 May 16. (featured in Nature Review Neurology 14 June 2011, 7:357 and in Sciencedaily; http://www.sciencedaily.com/releases/2011/05/110516121419.htm).
- Chung, S., Moon, J.-I., Leung, A., Aldrich, D., Lukianov, S., Kitayama, Y., Park, S., Li, Y., Bolshakov, V.Y., Lamonerie, R., and Kim, K.S. (2011) ES cell-derived renewable and functional midbrain dopaminergic progenitors. P.N.A.S. 108(23):9703-8.