Research

Neurons rely on precise molecular interactions at the cell surface to transmit signals, process information, and adapt to their environment. We study how membrane proteins such as ion channels and receptors contribute to neural function at the molecular level.

• Investigating biophysical and biochemical mechanisms of membrane protein signal transmission.
• Mapping protein-protein interactions that regulate cell surface signaling.
• Developing new techniques from structural and mechanistic insights.

Related publications

Kim YS*#, Gillespie SM*, Geraghty AC, Yalçın B, Ivec AE, Yang A, Mancusi R, Hysinger J, Reed J, Drexler R, Quezada M, Malacon K, Woo P, Byun YG, Mount C, Lam M, Pan Y, Zuchero JB, Trotter J, Monje M#, Neuroligin-3 interaction with CSPG4 regulates normal and malignant glial precursors through mechanotransduction, Nature Neuroscience (in press)

Tajima S*, Kim YS*, Fukuda M, Jo YJ, Wang PY, Paggi JM, Inoue M, Byrne EFX, Kishi KE, Nakamura S, Ramakrishnan C, Takaramoto S, Nagata T, Konno M, Sugiura M, Katayama K, Matsui TE, Yamashita K, Kim S, Ikeda H, Kim J, Kandori H, Dror RO, Inoue K, Deisseroth K#, Kato HE#, Structural basis for ion selectivity in potassium-selective channelrhodopsins, Cell, 186, 1-20 (2023)

Kishi KE*, Kim YS*, Fukuda M*, Inoue M*, Kusakizako T*, Wang PY*, Ramakrishnan C, Byrne EFX, Thadhani E, Paggi JM, Matsui TE, Yamashita K, Nagata T, Konno M, Quirin S, Lo M, Benster T, Uemura T, Liu K, Shibata M, Nomura N, Iwata S, Nureki O, Dror RO, Inoue K, Deisseroth K#, Kato HE#, Structural basis for channel conduction in the pump-like channelrhodopsin ChRmine, Cell, 185, 1-18 (2022)

Kim YS*, Kato HE*#, Yamashita K, Ito S, Inoue K, Ramakrishnan C, Fenno LE, Evans KE, Paggi JM, Dror RO, Kandori H, Kobilka BK and Deisseroth K#, Crystal structure of the natural anion-conducting channelrhodopsin GtACR1, Nature 561 (7723), 343-348 (2018)

Kato HE*#, Kim YS*, Paggi JM, Evans KE, Allen WE, Richardson C, Inoue K, Ito S, Ramakrishnan C, Fenno LE, Yamashita K, Hilger D, Lee SY, Berndt A, Shen K, Kandori H, Dror RO, Kobilka BK and Deisseroth K#, Structural mechanisms of selectivity and gating in anion channelrhodopsins, Nature 561 (7723), 349-354 (2018)

In our lab’s cancer research pillar, we investigate how biophysical and neuronal signals drive malignant progression in cancers in the brain. Our recent work identified a mechanosensitive signaling axis in which activity-dependent NLGN3 engages CSPG4 and PIEZO1, coupling the neural microenvironment to intracellular Ca²⁺ signaling, PI3K-AKT activation, and tumor growth. Building on these findings, our lab studies how membrane mechanics, lipid composition, and tumor–neuron interactions shape cancer cell state and therapeutic vulnerability in pediatric brain tumors.

Related publications

Kim YS*^#, Gillespie SM*, Geraghty AC, Yalçın B, Ivec AE, Yang A, Mancusi R, Hysinger J, Reed J, Drexler R, Quezada M, Malacon K, Woo P, Byun YG, Mount C, Lam M, Pan Y, Zuchero JB, Trotter J, Monje M^#, “Neuroligin-3 interaction with CSPG4 regulates normal and malignant glial precursors through mechanotransduction”, Nature Neuroscience (in press)

Savchuk S, Gentry KM, Wang W, Carleton E, Biagi-Junior CAO, Luthria K, Yalçın B, Ni L, Farnsworth HC, Davis RA, Drexler R, Melms JC, Liu Y, Acosta-Alvarez L, Hartmann GG, Pavarino EC, LaBelle J, Woo PJ, Toland AM, Qu F, Kim YS, Filbin MG, Krasnow MA, Ligon KL, Izar B, Sage J, Sabatini BL, Monje M, and Venkatesh HS, “Neuronal activity-dependent mechanisms of small cell lung cancer pathogenesis”, Nature, 1–11 (2025).

Drexler R, Drinnenberg A, Gavish A, Yalçın B, Shamardani K, Rogers AE, Mancusi R, Trivedi V, Taylor KR, Kim YS, Woo PJ, Soni N, Su M, Ravel A, Tatlock E, Midler A, Wu SH, Ramakrishnan C, Chen R, Ayala-Sarmiento AE, Rincon Fernandez Pacheco D, Siverts L, Daigle TL, Tasic B, Zeng H, Breunig JJ, Deisseroth K, Monje M#, “Cholinergic neuronal activity promotes diffuse midline glioma growth through muscarinic signaling”, Cell, 188, 1-18 (2025)

Barron T, Yalçın B, Su M, Byun YG, Gavish A, Shamardani K, Xu H, Ni L, Soni N, Mehta V, Maleki Jahan S, Kim YS, Taylor KR, Keough MB, Quezada MA, Geraghty AC, Mancusi R, Vo LT, Herrera Castañeda E, Woo PJ, Petritsch CK, Vogel H, Kaila K, Monje M#, “GABAergic neuron-to-glioma synapses in diffuse midline gliomas”, Nature, 639, 1060-1068 (2025)

Taylor KR, Barron T, Hui A, Spitzer A, Yalcin B, Ivec AE, Geraghty A, Zhang H, Hartmann G, Arzt M, Gillespie SM, Kim YS, Jahan SM, Shamardani K, Su M, Ni L, Du P, Woo PJ, Silva-Torres A, Venkatesh HS, Mancusi R, Ponnuswami A, Mulinyawe S, Keough MB, Chau I, Aziz-Bose R, Tirosh I, Suva ML, Monje M, “Glioma synapses recruit mechanisms of adaptive plasticity”, Nature, 623 (7986) (2023)

By leveraging synthetic biology and protein engineering, we develop molecular tools to control and manipulate neural activity with high precision.

• Developing novel biointerfaces for studying neural function in vitro and in vivo.
• Enhancing expression systems in the brain for better delivery.
• Applying synthetic evolution and computational methods to optimize neural tools.

Related publications

Fenno LE*, Ramakrishnan C*, Kim YS*, Evans KE, Lo M, Vesuna S, Inoue M, Cheung KYM, Yuen E, Pichamoorthy N, Hong A and Deisseroth K, Comprehensive dual- and triple-feature intersectional single-vector delivery of diverse functional payloads to cells of behaving mammals, Neuron, 107, 1-18 (2020)

Liu J*, Kim YS*, Richardson C*, Tom A*, Ramakrishnan C, Birey F, Katsumata T, Chen S, Wang C, Wang X, Joubert L, Jiang Y, Wang H, Fenno LE, Tok JBH, Pasca SP, Bao Z# and Deisseroth K#, Genetically-targeted Chemical Assembly of Functional Materials in Living Cells, Tissues and Animals, Science 367 (6484) (2020)

Marshel JH*, Kim YS*, Machado TA*, Quirin S*, Benson B, Kadmon J, Raja C, Chibukhchyan A, Ramakrishnan C, Inoue M, Shane JC, McKnight DJ, Yoshizawa S, Kato HE, Ganguli S and Deisseroth K, Cortical Layer-specific Critical Dynamics Triggering Perception, Science 365 (6453) (2019)