Jan, Yuh-Nung, Ph.D.

Professor & Investigator Emeritus of Howard Hughes Medical Institute, UCSF School of Medicine 

Ph.D. in Biology, California Institute of Technology B.S. in Physics, National Taiwan University 

Jan Lab 

Our lab is interested in various aspects of developmental neurobiology, ranging from neurogenesis, asymmetric cell division and more recently to neuronal morphogenesis and its functional implications. In the past 40 years, we have elucidated (1) how neurons acquire their identity, by discovering the role of the homeodomain protein Cut, the zinc finger protein Hamlet and the basic-helix-loop-helix (bHLH) protein Atonal, which is the founding member of an important family of proneural genes including Neurogenin, Math 1 and Math 5, (2) how two daughters of a neural progenitor acquire different cell fates, by identifying the first known asymmetrically segregated protein Numb that is essential as a cell fate determinant for imparting different daughter cell fates, (3) how a differential reliance on the secretory pathway contributes to the differentiation of axons and dendrites, (4) how neurons with distinctive dendrite morphologies depend on their level of Cut expression for diverse dendrite branching complexities, (5) how certain types of neurons exhibit homotypic repulsion of their dendrites to allow tiling of the dendritic field for maximal coverage without ambiguity, by revealing the essential role of the NDR family kinase Tricornered, (6) how tiling and dendrite maintenance can be differentially regulated by the upstream NDR family kinase and tumor suppressor Hippo, (7) how sensory neurons scale their dendrite expansion to precisely match the growing epidermis, owing to the critical role of the microRNA bantam in epithelial cells for signaling to adjacent neurons, (8) how the neuronal morphology affect neuronal function including mechano-sensation. Recently, we have also begun to gain insights about the control of axon and dendrite regeneration.

Current Projects

1. Control of dendrite morphogenesis remains one of our lab’s main interests including the molecular mechanism for dendritic tiling. 
2. Mechano-sensitive channels. As sensory neurons, most of the da neurons are involved in mechano-sensation. They turn out to be a good system to study mechano-sensing. (a) We found the class III da neurons can sense gentle touch via NompC and we established that NompC is a bona fide mechanotransduction channel. Our subsequent study of the mechanotransduction channel NompC reveals a tether mechanism of mechanogating in which the N-terminal Ankyrin repeats of NompC form a tether linking the channel and the microtubules that convey force exerted via cell deformation to gate the channel and activate touch-sensitive neurons. (b) More recently, we found that dPiezo inhibits axon regeneration via the CamKII-Nos-PKG pathway---this is exciting to us because it is a confluence of our two interests: axon regeneration and mechano-sensitive channels. (c) Whereas extensive studies focus on mechano-transduction at the plasma membrane, little is known about whether and how intracellular organelles sense mechanical force and the physiological functions of organellar mechano-sensing. Recently, we identified the Drosophila TMEM63 (DmTMEM63) ion channel as an intrinsic mechano-sensor of the lysosome, a major degradative organelle. Loss of function mutations of DmTMEM63 exhibit phenotypes including impaired lysosomal degradation, synaptic loss, progressive motor deficits and early death. This provides a molecular basis to explore the mechanosensitive process in subcellular organelles.
3. Continuing with our interest in the function of peptides in the nervous system, we recently discovered a novel peptide we named as Vulnusin, which functions as an acute wound signal in Drosophila. We are studying how Vulnusin activates its receptor and elicits nocifensive response.

 Featured publications

1. Yadav, S., Oses-Prieto, J.A., Peters, C.J., Zhou, J., Pleasure, S.J., Burlingame, A.L., Jan, L., and Jan, Y.N. (2017) TAOK2 kinase mediates PSD95 stability and dendritic spine maturation through Septin7 phosphorylation. Neuron 93:379-393. PMCID: PMC5267388.
2. Jin, P., Bulkley, D., Guo, Y., Zhang, W., Guo, Z., Huynh, W., Wu, S., Meltzer, S., Chang, T., Jan, L.Y., Jan, Y.N., and Cheng, Y. (2017) Electron cryo-microscopy structure of the mechanotransduction channel NOMPC. Nature 547:118-122. PMCID: PMC5669069.
3. DeVault, L., Li, T., Izabel, S., Thompson-Peer, K.L., Jan, L.Y., and Jan, Y.N. (2018). Dendrite regeneration of adult Drosophila sensory neurons diminishes with aging and is inhibited by epidermal-derived matrix-metalloproteinase 2. Genes Dev. 32:402-414. PMCID: PMC5900713.
4. Song, Y., Li, D., Farrelly, O., Miles, L., Li, F., Kim, S.E., Lo, T.Y., Wang, F., Li, T., Thompson-Peer, K.L., Gong, J., Murthy, S.E., Coste, B., Yakubovich, N., Patapoutian, A., Xiang, Y., Rompolas, P., Jan, L.Y., and Jan, Y.N. (2019). The Mechanosensitive Ion Channel Piezo Inhibits Axon Regeneration. Neuron. 102:373-389. PMCID: PMC6487666.
5. Jin, P., Jan, L.Y., and Jan, Y.N. (2020). Mechanosensitive Ion Channels: Structural Features Relevant to Mechanotransduction Mechanisms. Annu Rev Neurosci. 2020 Feb 21. doi: 10.1146/annurev-neuro-070918-050509. PMID: 32084327.
6. Petkovic, M., Oses-Prieto, J., Burlingame, A., Jan, L.Y., and Jan, Y.N. (2020). TMEM16K is an interorganelle regulator of endosomal sorting. Nat Commun. 11:3298. PMCID: PMC7335067.
7. Wang, P., Jia, Y., Liu, T., Jan, Y.N., and Zhang, W. (2020). Visceral Mechano-sensing Neurons Control Drosophila Feeding by Using Piezo as a Sensor. Neuron 2020 Sep 8; S0896-6273(20)30648-6. doi: 10.1016/j.neuron.2020.08.017.  PMID: 32910893.
8. O’Brien, C.E., Younger, S.H., Jan, L.Y., and Jan, Y.N. (2023). The GARP complex prevents sterol accumulation at the trans-Golgi network during dendrite remodeling. J Cell Biol 222:e202112108. PMCID: PMC9577387.
9. Li, K., Guo, Y., Wang, Y., Zhu, R., Chen, W., Cheng, T., Zhang, X., Jia, Y., Liu, T., Zhang, W., Jan, L.Y., Jan, Y.N. (2024) Drosophila TMEM63 and mouse TMEM63A are lysosomal mechanosensory ion channels. Nature Cell Biology 26, https://doi.org:10.1038/s41556-024-01353-7 PMID: 388853
10. Guo, Y., Li, T., Tuomivaara, S.T., Teo, C.F., Feng, S., Chalkley, R.J., Zhu, R., Cheng, T., Li, K.H., Chen, W., Simon, A., Jin, P., Younger, S., Yong, A.J.H., Li, K., Li, K., Burlingame, A.L., Jan, L.Y., Jan, Y.N. (2025) Identificatioin of the peptide volnusin, a wound signal that mediates mechanical-injury-induced nociception in Drosophila. Neuron 113, 3352-3362.e5 PMID: 41045928.