Research

1. Molecular control of synaptic vesicle cycle in neurotransmission
Robustness of the activity of the human brain relies on complicated yet extremely coordinated communications among tons of neurons. Neurons communicate via synapses in which fast exocytosis of tiny organelle called synaptic vesicle (SV) in response to nervous stimuli releases its content, namely chemical neurotransmitters, thereby governing all human behaviors. Repetitive SV exocytosis however would eventually deplete SVs and disorganize presynaptic plasma membrane architecture. To overcome such burdens, SV endocytosis immediately occurs after exocytosis. Clathrin-mediated endocytosis (CME) and activity-dependent bulk endocytosis (ADBE) are the major modes of endocytosis that are triggered separately under mild and strong stimulation conditions. We have focused on answering following questions. How is exocytosis tightly coupled with endocytosis? What initiates endocytosis? Since CME and ADBE are dependent on intracellular Ca2+ increase, where do Ca2+ ions come from? Our recent work showed that a SV-associated Ca2+ channel, called Flower, initiates SV endocytosis and therefore couples exocytosis and endocytosis, which has provided a conceptual breakthrough for the regulation of synaptic vesicle cycling. We keep on investigating spatiotemporal regulation of activity and localization of the Flower channel. These efforts will be expected to advance our knowledge of fast and efficient synaptic transmission behind brain computation.

2. Pathogenic role of dysregulated neurotransmission in human diseases
The human central nervous system establishes a complex neural circuit system to drive complex but rhythmic and coordinated behaviors such as walking, running and swimming by activating skeletal muscle contractions. The neural circuit system communicates with the muscles. If an imbalance occurs, it will cause serious illness. These systems consume more energy to function properly than other tissues in the human body. When the cell is productive, the reactive oxygen species (ROS) are known to be accompanied by release. When facing with aging or neurodegenerative diseases, excessive ROS (commonly known as oxidative stress) are often elicited, which in turn affects neuronal function and reduces overall nervous system function. Glutamate is the major excitatory neurotransmitter that controls most of the activity of the human nervous system. Therefore, the tight balance between its release and uptake is the key to the proper functioning of the nervous system. Excess glutamate accumulation is common in neurologically related diseases, which cause excessive nervous system activation and is therefore called glutamate excitotoxicity. It is worth mentioning that glutamate excitotoxicity is one of the main causes of increased oxidative stress. However, it has not yet been understood how oxidative stress interferes with the operation of neural networks. My lab has used the motor circuit of Drosophila larvae as a research system to solve this challenging problem in recent years. Drosophila larvae can use the rhythmic and coordinated crawling movements for feeding, which is similar to human walking, running and swimming. This behavior is controlled by the motor circuit. The motor circuit of Drosophila larvae is relatively simple compared to the human motor circuit, but has high functional conservation. Therefore, it is very suitable for studying the mechanism regulating the motor circuit. We found that glutamate excitotoxicity that can cause a neural circuit-dependent oxidative stress feedback loop to affect the normal functioning of the entire motor system. In the future, the key research direction is to clarify whether the abovementioned machine can be applied to age-dependent motor function decline and the pathogenesis of motor neuron diseases, such as amyotrophic lateral sclerosis (ALS). The results of this latest and follow-up study are expected to provide feasible preventive and therapeutic strategies to these urgent social health issues.

Degrees and Positions Held
Positions Held
  • 2020 – present   Associate research fellow, Institute of Biological Chemistry, Academia Sinica
  • 2011 – 2020   Assistant research fellow, Institute of Biological Chemistry, Academia Sinica
  • 2006 – 2011   Postdoctoral fellow, Department of Molecular and Human genetics, Baylor College of Medicine, TX, USA
  • 2005 – 2006   Postdoctoral fellow, Institute of Molecular Biology, Academia Sinica
Degrees
  • 2001 – 2005   Ph.D., Institute of Genetics, National Yang-Ming University, Taiwan R.O.C.
  • 1999 – 2001   M.S., nstitute of Genetics, National Yang-Ming University, Taiwan R.O.C.
  • 1995 – 1999   B.S., Department of Biology, National Cheng Kung Univeristy, Taiwan R.O.C.
Selected Publications
Peng JJ, Lin SH, Liu YT, Lin HC, Li TN, Yao CK
eLife (2019)
Yao CK, Liu YT, Lee IC, Wang YT, Wu PY
PLoS biology (2017)
Tsai YC, Grimm S, Chao JL, Wang SC, Hofmeyer K, Shen J, Eichinger F, Michalopoulou T, Yao CK, Chang CH, Lin SH, Sun YH, Pflugfelder GO
PloS one (2015)
Sandoval H, Yao CK, Chen K, Jaiswal M, Donti T, Lin YQ, Bayat V, Xiong B, Zhang K, David G, Charng WL, Yamamoto S, Duraine L, Graham BH, Bellen HJ
eLife (2014)
Yao CK, Lin YQ, Ly CV, Ohyama T, Haueter CM, Moiseenkova-Bell VY, Wensel TG, Bellen HJ
Cell (2009)
Giagtzoglou N, Mahoney T, Yao CK, Bellen HJ
Neuron (2009)
Yao JG, Weasner BM, Wang LH, Jang CC, Weasner B, Tang CY, Salzer CL, Chen CH, Hay B, Sun YH, Kumar JP
Developmental biology (2008)
Ly CV, Yao CK, Verstreken P, Ohyama T, Bellen HJ
The Journal of cell biology (2008)
Tsai YC, Yao JG, Chen PH, Posakony JW, Barolo S, Kim J, Sun YH
Developmental biology (2007)
Yao JG, Sun YH
The EMBO journal (2005)
Publications List
  1. Amartuvshin O, Lin CH, Hsu SC, Kao SH, Chen A, Tang WC, Chou HL, Chang DL, Hsu YY, Hsiao BS, Rastegari E, Lin KY, Wang YT, (Yao CK), Chen GC, Chen BC, Hsu HJ  (2020-08)  Aging cell  19(8), e13191  "Aging shifts mitochondrial dynamics toward fission to promote germline stem cell loss."
  2. Peng JJ, Lin SH, Liu YT, Lin HC, Li TN, (Yao CK)  (2019-07)  eLife  8, e47372  "A circuit-dependent ROS feedback loop mediates glutamate excitotoxicity to sculpt the Drosophila motor system."
  3. (Yao CK), Liu YT, Lee IC, Wang YT, Wu PY  (2017-04)  PLoS biology  15(4), e2000931  "A Ca2+ channel differentially regulates Clathrin-mediated and activity-dependent bulk endocytosis."
  4. Tsai YC, Grimm S, Chao JL, Wang SC, Hofmeyer K, Shen J, Eichinger F, Michalopoulou T, (Yao CK), Chang CH, Lin SH, Sun YH, Pflugfelder GO  (2015-03)  PloS one  10(3), e0120236  "Optomotor-blind negatively regulates Drosophila eye development by blocking Jak/STAT signaling."
  5. Sandoval H, (Yao CK), Chen K, Jaiswal M, Donti T, Lin YQ, Bayat V, Xiong B, Zhang K, David G, Charng WL, Yamamoto S, Duraine L, Graham BH, Bellen HJ  (2014-10)  eLife  3, e03558  "Mitochondrial fusion but not fission regulates larval growth and synaptic development through steroid hormone production."
  6. (Yao CK), Lin YQ, Ly CV, Ohyama T, Haueter CM, Moiseenkova-Bell VY, Wensel TG, Bellen HJ  (2009)  Cell  138(5), 947-960  "A synaptic vesicle-associated Ca2+ channel promotes endocytosis and couples exocytosis to endocytosis."
  7. Giagtzoglou N, Mahoney T, (Yao CK), Bellen HJ  (2009)  Neuron  64(5), 595-597  "Rab3 GTPase lands Bruchpilot."
  8. (Yao JG), Weasner BM, Wang LH, Jang CC, Weasner B, Tang CY, Salzer CL, Chen CH, Hay B, Sun YH, Kumar JP  (2008)  Developmental biology  315(2), 535-551  "Differential requirements for the Pax6(5a) genes eyegone and twin of eyegone during eye development in Drosophila."
  9. Ly CV, (Yao CK), Verstreken P, Ohyama T, Bellen HJ  (2008)  The Journal of cell biology  181(1), 157-170  "straightjacket is required for the synaptic stabilization of cacophony, a voltage-gated calcium channel alpha1 subunit."
  10. Tsai YC, (Yao JG), Chen PH, Posakony JW, Barolo S, Kim J, Sun YH  (2007)  Developmental biology  306(2), 760-771  "Upd/Jak/STAT signaling represses wg transcription to allow initiation of morphogenetic furrow in Drosophila eye development."
  11. (Yao JG), Sun YH  (2005)  The EMBO journal  24(14), 2602-2612  "Eyg and Ey Pax proteins act by distinct transcriptional mechanisms in Drosophila development."

1. Molecular control of synaptic vesicle cycle in neurotransmission
Robustness of the activity of the human brain relies on complicated yet extremely coordinated communications among tons of neurons. Neurons communicate via synapses in which fast exocytosis of tiny organelle called synaptic vesicle (SV) in response to nervous stimuli releases its content, namely chemical neurotransmitters, thereby governing all human behaviors. Repetitive SV exocytosis however would eventually deplete SVs and disorganize presynaptic plasma membrane architecture. To overcome such burdens, SV endocytosis immediately occurs after exocytosis. Clathrin-mediated endocytosis (CME) and activity-dependent bulk endocytosis (ADBE) are the major modes of endocytosis that are triggered separately under mild and strong stimulation conditions. We have focused on answering following questions. How is exocytosis tightly coupled with endocytosis? What initiates endocytosis? Since CME and ADBE are dependent on intracellular Ca2+ increase, where do Ca2+ ions come from? Our recent work showed that a SV-associated Ca2+ channel, called Flower, initiates SV endocytosis and therefore couples exocytosis and endocytosis, which has provided a conceptual breakthrough for the regulation of synaptic vesicle cycling. We keep on investigating spatiotemporal regulation of activity and localization of the Flower channel. These efforts will be expected to advance our knowledge of fast and efficient synaptic transmission behind brain computation.

2. Pathogenic role of dysregulated neurotransmission in human diseases
The human central nervous system establishes a complex neural circuit system to drive complex but rhythmic and coordinated behaviors such as walking, running and swimming by activating skeletal muscle contractions. The neural circuit system communicates with the muscles. If an imbalance occurs, it will cause serious illness. These systems consume more energy to function properly than other tissues in the human body. When the cell is productive, the reactive oxygen species (ROS) are known to be accompanied by release. When facing with aging or neurodegenerative diseases, excessive ROS (commonly known as oxidative stress) are often elicited, which in turn affects neuronal function and reduces overall nervous system function. Glutamate is the major excitatory neurotransmitter that controls most of the activity of the human nervous system. Therefore, the tight balance between its release and uptake is the key to the proper functioning of the nervous system. Excess glutamate accumulation is common in neurologically related diseases, which cause excessive nervous system activation and is therefore called glutamate excitotoxicity. It is worth mentioning that glutamate excitotoxicity is one of the main causes of increased oxidative stress. However, it has not yet been understood how oxidative stress interferes with the operation of neural networks. My lab has used the motor circuit of Drosophila larvae as a research system to solve this challenging problem in recent years. Drosophila larvae can use the rhythmic and coordinated crawling movements for feeding, which is similar to human walking, running and swimming. This behavior is controlled by the motor circuit. The motor circuit of Drosophila larvae is relatively simple compared to the human motor circuit, but has high functional conservation. Therefore, it is very suitable for studying the mechanism regulating the motor circuit. We found that glutamate excitotoxicity that can cause a neural circuit-dependent oxidative stress feedback loop to affect the normal functioning of the entire motor system. In the future, the key research direction is to clarify whether the abovementioned machine can be applied to age-dependent motor function decline and the pathogenesis of motor neuron diseases, such as amyotrophic lateral sclerosis (ALS). The results of this latest and follow-up study are expected to provide feasible preventive and therapeutic strategies to these urgent social health issues.

Positions Held
  • 2020 – present   Associate research fellow, Institute of Biological Chemistry, Academia Sinica
  • 2011 – 2020   Assistant research fellow, Institute of Biological Chemistry, Academia Sinica
  • 2006 – 2011   Postdoctoral fellow, Department of Molecular and Human genetics, Baylor College of Medicine, TX, USA
  • 2005 – 2006   Postdoctoral fellow, Institute of Molecular Biology, Academia Sinica
Degrees
  • 2001 – 2005   Ph.D., Institute of Genetics, National Yang-Ming University, Taiwan R.O.C.
  • 1999 – 2001   M.S., nstitute of Genetics, National Yang-Ming University, Taiwan R.O.C.
  • 1995 – 1999   B.S., Department of Biology, National Cheng Kung Univeristy, Taiwan R.O.C.
Peng JJ, Lin SH, Liu YT, Lin HC, Li TN, Yao CK
eLife (2019)
Yao CK, Liu YT, Lee IC, Wang YT, Wu PY
PLoS biology (2017)
Tsai YC, Grimm S, Chao JL, Wang SC, Hofmeyer K, Shen J, Eichinger F, Michalopoulou T, Yao CK, Chang CH, Lin SH, Sun YH, Pflugfelder GO
PloS one (2015)
Sandoval H, Yao CK, Chen K, Jaiswal M, Donti T, Lin YQ, Bayat V, Xiong B, Zhang K, David G, Charng WL, Yamamoto S, Duraine L, Graham BH, Bellen HJ
eLife (2014)
Yao CK, Lin YQ, Ly CV, Ohyama T, Haueter CM, Moiseenkova-Bell VY, Wensel TG, Bellen HJ
Cell (2009)
Giagtzoglou N, Mahoney T, Yao CK, Bellen HJ
Neuron (2009)
Yao JG, Weasner BM, Wang LH, Jang CC, Weasner B, Tang CY, Salzer CL, Chen CH, Hay B, Sun YH, Kumar JP
Developmental biology (2008)
Ly CV, Yao CK, Verstreken P, Ohyama T, Bellen HJ
The Journal of cell biology (2008)
Tsai YC, Yao JG, Chen PH, Posakony JW, Barolo S, Kim J, Sun YH
Developmental biology (2007)
Yao JG, Sun YH
The EMBO journal (2005)
  1. Amartuvshin O, Lin CH, Hsu SC, Kao SH, Chen A, Tang WC, Chou HL, Chang DL, Hsu YY, Hsiao BS, Rastegari E, Lin KY, Wang YT, (Yao CK), Chen GC, Chen BC, Hsu HJ  (2020-08)  Aging cell  19(8), e13191  "Aging shifts mitochondrial dynamics toward fission to promote germline stem cell loss."
  2. Peng JJ, Lin SH, Liu YT, Lin HC, Li TN, (Yao CK)  (2019-07)  eLife  8, e47372  "A circuit-dependent ROS feedback loop mediates glutamate excitotoxicity to sculpt the Drosophila motor system."
  3. (Yao CK), Liu YT, Lee IC, Wang YT, Wu PY  (2017-04)  PLoS biology  15(4), e2000931  "A Ca2+ channel differentially regulates Clathrin-mediated and activity-dependent bulk endocytosis."
  4. Tsai YC, Grimm S, Chao JL, Wang SC, Hofmeyer K, Shen J, Eichinger F, Michalopoulou T, (Yao CK), Chang CH, Lin SH, Sun YH, Pflugfelder GO  (2015-03)  PloS one  10(3), e0120236  "Optomotor-blind negatively regulates Drosophila eye development by blocking Jak/STAT signaling."
  5. Sandoval H, (Yao CK), Chen K, Jaiswal M, Donti T, Lin YQ, Bayat V, Xiong B, Zhang K, David G, Charng WL, Yamamoto S, Duraine L, Graham BH, Bellen HJ  (2014-10)  eLife  3, e03558  "Mitochondrial fusion but not fission regulates larval growth and synaptic development through steroid hormone production."
  6. (Yao CK), Lin YQ, Ly CV, Ohyama T, Haueter CM, Moiseenkova-Bell VY, Wensel TG, Bellen HJ  (2009)  Cell  138(5), 947-960  "A synaptic vesicle-associated Ca2+ channel promotes endocytosis and couples exocytosis to endocytosis."
  7. Giagtzoglou N, Mahoney T, (Yao CK), Bellen HJ  (2009)  Neuron  64(5), 595-597  "Rab3 GTPase lands Bruchpilot."
  8. (Yao JG), Weasner BM, Wang LH, Jang CC, Weasner B, Tang CY, Salzer CL, Chen CH, Hay B, Sun YH, Kumar JP  (2008)  Developmental biology  315(2), 535-551  "Differential requirements for the Pax6(5a) genes eyegone and twin of eyegone during eye development in Drosophila."
  9. Ly CV, (Yao CK), Verstreken P, Ohyama T, Bellen HJ  (2008)  The Journal of cell biology  181(1), 157-170  "straightjacket is required for the synaptic stabilization of cacophony, a voltage-gated calcium channel alpha1 subunit."
  10. Tsai YC, (Yao JG), Chen PH, Posakony JW, Barolo S, Kim J, Sun YH  (2007)  Developmental biology  306(2), 760-771  "Upd/Jak/STAT signaling represses wg transcription to allow initiation of morphogenetic furrow in Drosophila eye development."
  11. (Yao JG), Sun YH  (2005)  The EMBO journal  24(14), 2602-2612  "Eyg and Ey Pax proteins act by distinct transcriptional mechanisms in Drosophila development."