Research Summary

Taken together with our previous studies of the KCNK9 potassium channel upregulation in breast cancer (Mu et al., 2003, Cancer Cell 3, 297-302; Pei et al., 2003, PNAS 100, 7803-7807) and the EAG2 potassium channel upregulation in multiple subgroups of medulloblastoma (MB) that facilitates MB cell proliferation and migration (Huang et al., 2012, Genes & Development 26, 1780-1796; Huang et al., 2015, Nature Neuroscience 18, 1236-1246), our recent study of the TMEM16A calcium activated chloride channel upregulation in pancreatic cancer that is associated with the ligand-dependent EGF receptor signaling pathway and poor prognosis (Crottes et al., 2019, PNAS 116, 13026-13035) and our on-going studies of ion channels that are up- or down-regulated in various cancers support the notion that different types of cancer may involve different ion channels for their rapid proliferation, extensive migration and invasion.

Research Funding

  • May 1, 2021 - April 30, 2029 - The TMEM16 Family of Ion Channels and Lipid Scramblases , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R35NS122110
  • February 15, 2020 - January 31, 2025 - Molecular and Genetic Studies of TMEM16C Control of Thermoregulation and Neuronal Excitability , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01NS108946
  • September 15, 2017 - August 31, 2023 - Illuminating Druggable Dark Matter , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: U24DK116214
  • July 15, 2011 - April 30, 2023 - Molecular, genetic & physiological studies of calcium-activated chloride channels , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01NS069229

Education

National Taiwan University, Taipei, Taiwan, B.Sc., 06/1968, Physics
California Institute of Technology, Pasadena, CA, M.Sc., 06/1970, Physics
California Institute of Technology, Pasadena, CA, Ph.D., 06/1974, Biophysics & Physics
California Institute of Technology, Pasadena, CA, Postdoc, 06/1977, Neuroscience
Harvard Medical School, Boston, MA, Postdoc, 06/1979, Neuroscience

Honors & Awards

  • 1996-present
    Member, National Academy of Sciences
  • 1998-present
    Member, Academia Sinica
  • 2006
    NIMH MERIT Award
  • 2007-present
    Member, American Academy of Arts and Sciences
  • 2007
    Outstanding Mentorship Award form the Postdoctoral Scholar’s Association of UCSF
  • 2009
    Ralph W. Gerard Prize, Society for Neuroscience
  • 2010
    Edward M. Scolnick Prize in Neuroscience
  • 2010
    Grass Lecture at Society for Neuroscience Annual Meeting
  • 2011
    Wiley Prize in Biomedical Research
  • 2012
    Gruber Prize in Neuroscience

Selected Publications

  1. Lin King YH, Chen C, Lin King JV, Simms J, Glasscock E, Yang SB, Jan YN, Jan LY. Kv1.1 preserves the neural stem cell pool and facilitates neuron maturation during adult hippocampal neurogenesis. Proc Natl Acad Sci U S A. 2022 May 31; 119(22):e2118240119.  View on PubMed
  2. Ye W, Zhao H, Dai Y, Wang Y, Lo YH, Jan LY, Lee CH. Activation and closed-state inactivation mechanisms of the human voltage-gated KV4 channel complexes. Mol Cell. 2022 May 11.  View on PubMed
  3. Jaszczak JS, DeVault L, Jan LY, Jan YN. Steroid hormone signaling activates thermal nociception during Drosophila peripheral nervous system development. Elife. 2022 Mar 30; 11.  View on PubMed
  4. Cheng Y, Feng S, Puchades C, Ko J, Figueroa E, Chen Y, Wu H, Gu S, Han T, Li J, Ho B, Shoichet B, Jan YN, Jan L. Identification of a conserved drug binding pocket in TMEM16 proteins. Res Sq. 2022 Feb 10.  View on PubMed
  5. Cao C, Kang HJ, Singh I, Chen H, Zhang C, Ye W, Hayes BW, Liu J, Gumpper RH, Bender BJ, Slocum ST, Krumm BE, Lansu K, McCorvy JD, Kroeze WK, English JG, DiBerto JF, Olsen RHJ, Huang XP, Zhang S, Liu Y, Kim K, Karpiak J, Jan LY, Abraham SN, Jin J, Shoichet BK, Fay JF, Roth BL. Structure, function and pharmacology of human itch GPCRs. Nature. 2021 12; 600(7887):170-175.  View on PubMed
  6. Chou SM, Li KX, Huang MY, Chen C, Lin King YH, Li GG, Zhou W, Teo CF, Jan YN, Jan LY, Yang SB. Kv1.1 channels regulate early postnatal neurogenesis in mouse hippocampus via the TrkB signaling pathway. Elife. 2021 05 21; 10.  View on PubMed
  7. Wang TA, Chen C, Huang F, Feng S, Tien J, Braz JM, Basbaum AI, Jan YN, Jan LY. TMEM16C is involved in thermoregulation and protects rodent pups from febrile seizures. Proc Natl Acad Sci U S A. 2021 05 18; 118(20).  View on PubMed
  8. Petkovic M, Oses-Prieto J, Burlingame A, Jan LY, Jan YN. TMEM16K is an interorganelle regulator of endosomal sorting. Nat Commun. 2020 07 03; 11(1):3298.  View on PubMed
  9. He M, Wu B, Ye W, Le DD, Sinclair AW, Padovano V, Chen Y, Li KX, Sit R, Tan M, Caplan MJ, Neff N, Jan YN, Darmanis S, Jan LY. Chloride channels regulate differentiation and barrier functions of the mammalian airway. Elife. 2020 04 14; 9.  View on PubMed
  10. Jin P, Jan LY, Jan YN. Mechanosensitive Ion Channels: Structural Features Relevant to Mechanotransduction Mechanisms. Annu Rev Neurosci. 2020 07 08; 43:207-229.  View on PubMed
  11. Piggott BJ, Peters CJ, He Y, Huang X, Younger S, Jan LY, Jan YN. Paralytic, the Drosophila voltage-gated sodium channel, regulates proliferation of neural progenitors. Genes Dev. 2019 12 01; 33(23-24):1739-1750.  View on PubMed
  12. Li KX, He M, Ye W, Simms J, Gill M, Xiang X, Jan YN, Jan LY. TMEM16B regulates anxiety-related behavior and GABAergic neuronal signaling in the central lateral amygdala. Elife. 2019 09 04; 8.  View on PubMed
  13. Feng S, Dang S, Han TW, Ye W, Jin P, Cheng T, Li J, Jan YN, Jan LY, Cheng Y. Cryo-EM Studies of TMEM16F Calcium-Activated Ion Channel Suggest Features Important for Lipid Scrambling. Cell Rep. 2019 Jul 30; 28(5):1385.  View on PubMed
  14. Ye W, Han TW, He M, Jan YN, Jan LY. Dynamic change of electrostatic field in TMEM16F permeation pathway shifts its ion selectivity. Elife. 2019 07 18; 8.  View on PubMed
  15. Wang L, Simms J, Peters CJ, Tynan-La Fontaine M, Li K, Gill TM, Jan YN, Jan LY. TMEM16B Calcium-Activated Chloride Channels Regulate Action Potential Firing in Lateral Septum and Aggression in Male Mice. J Neurosci. 2019 09 04; 39(36):7102-7117.  View on PubMed
  16. Wang TA, Teo CF, Åkerblom M, Chen C, Tynan-La Fontaine M, Greiner VJ, Diaz A, McManus MT, Jan YN, Jan LY. Thermoregulation via Temperature-Dependent PGD2 Production in Mouse Preoptic Area. Neuron. 2019 Jul 17; 103(2):349.  View on PubMed
  17. Feng S, Dang S, Han TW, Ye W, Jin P, Cheng T, Li J, Jan YN, Jan LY, Cheng Y. Cryo-EM Studies of TMEM16F Calcium-Activated Ion Channel Suggest Features Important for Lipid Scrambling. Cell Rep. 2019 07 09; 28(2):567-579.e4.  View on PubMed
  18. Crottès D, Jan LY. The multifaceted role of TMEM16A in cancer. Cell Calcium. 2019 09; 82:102050.  View on PubMed
  19. Crottès D, Lin YT, Peters CJ, Gilchrist JM, Wiita AP, Jan YN, Jan LY. TMEM16A controls EGF-induced calcium signaling implicated in pancreatic cancer prognosis. Proc Natl Acad Sci U S A. 2019 06 25; 116(26):13026-13035.  View on PubMed
  20. Wang TA, Teo CF, Åkerblom M, Chen C, Tynan-La Fontaine M, Greiner VJ, Diaz A, McManus MT, Jan YN, Jan LY. Thermoregulation via Temperature-Dependent PGD2 Production in Mouse Preoptic Area. Neuron. 2019 07 17; 103(2):309-322.e7.  View on PubMed

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