University of Exeter Medical School

Yu Hsuan Carol Yang

Yu Hsuan Carol Yang

Lecturer in Cell Biology (E&R)

 Y.C.Yang@exeter.ac.uk

 RILD Building 

 

University of Exeter Medical School, RILD Building, RD&E Hospital Wonford, Barrack Road, Exeter, EX2 5DW, UK

Overview

Dr. Yang received a BSc (Hons) in Biochemistry and Chemistry from the University of British Columbia (UBC) in Vancouver, Canada. She completed a PhD in Cell and Developmental Biology at UBC in the lab of Prof. Jim Johnson, studying pancreatic beta cell death in diabetic settings and characterizing factors that can promote beta cell survival. Her studies led to the discovery of unexpected roles for axon guidance cues in the survival and function of pancreatic beta cells.

Subsequently, Dr. Yang joined the Max Planck Institute in Bad Nauheim, Germany, as a postdoctoral fellow in the lab of Prof. Didier Stainier. With fellowship support from the Human Frontier Science Program, the Canadian Institutes of Health Research and the European Molecular Biology Organization, she investigated the in vivo interplay between autonomic innervation and pancreatic endocrine cells, which has potential implications in diabetes progression. She took advantage of the zebrafish model to conduct in vivo imaging, targeted-cell ablation, optogenetic-mediated neuromodulation and genetic analyses to uncover insights into pancreatic nerve-endocrine interactions during development and physiological adaptations.

In 2020, Dr. Yang moved to the University of Exeter to continue her research on the interplay between the nervous system and the endocrine pancreas during development and maintenance of energy homeostasis.  Her research interests are in molecular and cell biology of diabetes initiation and progression and she continues use zebrafish as a complementary model for interrogating the effects of neural perturbances on pancreas physiology. 

Qualifications

PhD Cell and Developmental Biology – University of British Columbia, Canada

BSc (Hons) Biochemistry and Chemistry – University of British Columbia, Canada

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Research

Research interests

The balanced interplay between pancreatic islets, liver, fat, muscle, kidney, gut and the brain is crucial for energy homeostasis. Activity coordination in these key tissues by the central and peripheral nervous system remains understudied, despite their fundamental importance.  Islet cells respond to physiological stimuli including glucose, fatty acids, hormones and neurotransmitters. Failure to tightly regulate hormone release from islet cells leads to diabetes and its many co-morbidities.

The endocrine pancreas is innervated by autonomic and sensory nerves, but the role of innervation in pancreas development, hormone secretion and diabetes progression remains under-explored because of limited tools/methods for assessing cause from effect and providing precise molecular mechanisms. New approaches, including emerging optogenetic and chemogenetic tools, are required for understanding peripheral neurobiology with precision on physiological time scales. The zebrafish, with organs and signalling/metabolic pathways that are evolutionarily conserved and similar to mammals, is ideal for studying innervation during organ development and environmental adaptation. By combining its advantages of rapid embryogenesis and optical transparency with genetic tools, pancreatic-neuro-endocrine crosstalk can be studied dynamically.

Research projects

  1. Elucidate the pathways that modulate neural-endocrine interactions
  2. Determine how specific neural perturbances alter pancreatic islet cell development, function and regeneration and contribute to diabetes etiology
  3. Explore changes in the neural network during islet cell dysfunction

Grants/Funding

  • Diabetes Research & Wellness Foundation Pump Priming Grant (2021-2023)
  • JDRF UK Small Grant Award (2021-2022)
  • Society for Endocrinology Equipment Grant (2021-2022)
  • Human Frontier Science Program Postdoctoral Fellowship (2015-2020)
  • Canadian Institutes of Health Research Postdoctoral Fellowship (2017-2019)
  • National Institute of Genetics Collaborative Research Grant (2016)
  • European Molecular Biology Organization Long-Term Fellowship (2014-2015)
  • Canadian Institutes of Health Research Postdoctoral Fellowship (2014-2015)

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Publications

Journal articles

Yang YHC, Briant LJB, Raab CA, Mullapudi ST, Maischein H-M, Kawakami K, Stainier DYR (2022). Innervation modulates the functional connectivity between pancreatic endocrine cells. Elife, 11 Abstract.  Author URL.
MacDonald AJ, Yang YHC, Cruz AM, Beall C, Ellacott KLJ (2021). Brain-Body Control of Glucose Homeostasis—Insights from Model Organisms. Frontiers in Endocrinology, 12 Abstract.
White SA, Zhang LS, Pasula DJ, Yang YHC, Luciani DS (2020). Bax and Bak jointly control survival and dampen the early unfolded protein response in pancreatic β-cells under glucolipotoxic stress. Sci Rep, 10(1). Abstract.  Author URL.
Yang YHC, Briant LJB, Raab C, Mullapudi ST, Maischein H-M, Kawakami K, Stainier DYR (2020). Innervation modulates the functional connectivity between pancreatic endocrine cells. Abstract.
Mullapudi ST, Boezio GLM, Rossi A, Marass M, Matsuoka RL, Matsuda H, Helker CSM, Yang YHC, Stainier DYR (2019). Disruption of the pancreatic vasculature in zebrafish affects islet architecture and function. Development, 146(21). Abstract.  Author URL.
Yang YHC, Kawakami K, Stainier DYR (2018). A new mode of pancreatic islet innervation revealed by live imaging in zebrafish. eLife, 7 Abstract.
Mullapudi ST, Helker CS, Boezio GL, Maischein H-M, Sokol AM, Guenther S, Matsuda H, Kubicek S, Graumann J, Yang YHC, et al (2018). Screening for insulin-independent pathways that modulate glucose homeostasis identifies androgen receptor antagonists. Elife, 7 Abstract.  Author URL.
Matsuda H, Mullapudi ST, Yang YHC, Masaki H, Hesselson D, Stainier DYR (2018). Whole-Organism Chemical Screening Identifies Modulators of Pancreatic β-Cell Function. Diabetes, 67(11), 2268-2279. Abstract.
Yang YHC, Wills QF, Johnson JD (2015). A live-cell, high-content imaging survey of 206 endogenous factors across five stress conditions reveals context-dependent survival effects in mouse primary beta cells. Diabetologia, 58(6), 1239-1249.
Szabat M, Modi H, Ramracheya R, Girbinger V, Chan F, Lee JTC, Piske M, Kamal S, Carol Yang YH, Welling A, et al (2015). High-content screening identifies a role for Na. <sup>+</sup>. channels in insulin production. Royal Society Open Science, 2(12), 150306-150306. Abstract.
Chan MT, Lim GE, Skovsø S, Yang YHC, Albrecht T, Alejandro EU, Hoesli CA, Piret JM, Warnock GL, Johnson JD, et al (2014). Effects of insulin on human pancreatic cancer progression modeled in vitro. BMC Cancer, 14(1).
Yang YHC, Vilin YY, Roberge M, Kurata HT, Johnson JD (2014). Multiparameter Screening Reveals a Role for Na+ Channels in Cytokine-Induced β-Cell Death. Molecular Endocrinology, 28(3), 406-417.
Rezania A, Bruin JE, Arora P, Rubin A, Batushansky I, Asadi A, O'Dwyer S, Quiskamp N, Mojibian M, Albrecht T, et al (2014). Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells. Nature Biotechnology, 32(11), 1121-1133.
Yang YHC, Manning Fox JE, Zhang KL, MacDonald PE, Johnson JD (2013). Intraislet SLIT–ROBO signaling is required for beta-cell survival and potentiates insulin secretion. Proceedings of the National Academy of Sciences, 110(41), 16480-16485. Abstract.
Yang YHC, Johnson JD (2013). Multi-parameter, single-cell, kinetic analysis reveals multiple modes of cell death in primary pancreatic beta-cells. Journal of Cell Science Abstract.
Yang YHC, Johnson JD (2012). Multi-parameter Live Cell Tracking of Apoptotic and Non-apoptotic Beta-cell Death: High-content Screening for Factors that Prevent Beta-cell Apoptosis. Canadian Journal of Diabetes, 36(5).
Son E, Kim J-J, Lim YW, Au-Yeung TT, Yang CYH, Breuil C (2011). Diversity and decay ability of basidiomycetes isolated from lodgepole pines killed by the mountain pine beetle. Canadian Journal of Microbiology, 57(1), 33-41. Abstract.
Szabat M, Kalynyak TB, Lim GE, Chu KY, Yang YH, Asadi A, Gage BK, Ao Z, Warnock GL, Piret JM, et al (2011). Musashi expression in β-cells coordinates insulin expression, apoptosis and proliferation in response to endoplasmic reticulum stress in diabetes. Cell Death & Disease, 2(11), e232-e232.
Yang YHC, Szabat M, Bragagnini C, Kott K, Helgason CD, Hoffman BG, Johnson JD (2011). Paracrine signalling loops in adult human and mouse pancreatic islets: netrins modulate beta cell apoptosis signalling via dependence receptors. Diabetologia, 54(4), 828-842.
Hill JA, Szabat M, Hoesli CA, Gage BK, Yang YHC, Williams DE, Riedel MJ, Luciani DS, Kalynyak TB, Tsai K, et al (2010). A Multi-Parameter, High-Content, High-Throughput Screening Platform to Identify Natural Compounds that Modulate Insulin and Pdx1 Expression. PLoS ONE, 5(9), e12958-e12958.

Chapters

Johnson JD, Yang YHC, Luciani DS (2014). Mechanisms of Pancreatic β-Cell Apoptosis in Diabetes and its Therapies. In  (Ed) Islets of Langerhans, 2. ed, Springer Netherlands, 1-20.
Johnson JD, Yang YHC, Luciani DS (2014). Mechanisms of Pancreatic β-Cell Apoptosis in Diabetes and its Therapies. In  (Ed) Islets of Langerhans, Springer Nature, 873-894.

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External Engagement and Impact

Invited lectures & workshops

  • Yang YHC. 2022. Neural regulation of pancreatic islet physiology. Invited speaker: European Zebrafish PI Meeting. Dresden, Germany.
  • Yang YHC, Briant L, Raab C, Mullapudi ST, Maischein HM, Kawakami K, Stainier DYR. 2021. Communication between pancreatic endocrine cells is modulated by neural signalling. Diabetes UK Professional Conference. Virtual meeting.
  • Yang YHC, Briant L, Raab C, Mullapudi ST, Maischein HM, Kawakami K, Stainier DYR. 2020. Innervation modulates the functional connectivity between pancreatic endocrine cells. Keystone Symposia on Islet Biology: From Gene to Cell to Micro-Organ. Santa Fe, NM, USA.
  • Yang YHC, Briant L, Raab C, Mullapudi ST, Maischein HM, Kawakami K, Stainier DYR. 2019. Innervation modulates the functional connectivity between pancreatic endocrine cells. Cold Spring Harbor Meeting: Zebrafish Neural Circuits and Behavior. Cold Spring Harbor, NY, USA.
  • Yang YHC. 2019. In vivo assessment of endocrine pancreas function following perturbed autonomic innervation. Invited speaker: University of Birmingham. Birmingham, United Kingdom.
  • Yang YHC. 2019. In vivo assessment of endocrine pancreas function following perturbed autonomic innervation. Invited speaker: Islet Society Meeting. Maribor, Slovenia.
  • Yang YHC. 2019. Probing the role of innervation in endocrine pancreas development and function. Invited speaker: Centre de recherche du CHUM. Montreal, QC, Canada.
  • Yang YHC and Stainier DY. 2018. Unraveling the role of endocrine pancreas innervation through in vivo time-lapse imaging and optogenetic control of nerve activity. Keystone Symposia on Endoderm Development. Taos, NM, USA.
  • Yang YHC. 2016. The role of autonomic innervation in endocrine pancreas development and function: Insights from the zebrafish. Invited speaker: The Leading Edge in Cytometry Meeting. Bad Nauheim, Germany.
  • Yang YHC. 2015. A live-cell imaging survey of 206 biologic factors across 5 stress conditions reveals context-dependent survival effects in primary beta cells. Invited speaker. Invited speaker: 3rd HumEn GA Meeting. Bad Nauheim, Germany.

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Supervision / Group

Postgraduate researchers

  • Rebekah Boreham (Research Assistant)

Alumni

  • Jasmine Aldam (2021-2022, FYP Student)
  • Elizabeth Bright (2021-2022, FYP Student)
  • Anna Dickerson (2021-2022, PTY Student)

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