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Hans Bueler
Publisher:高雪  Time2019-02-20 View:36



  • Studies  in  Biology, University of Zurich, Switzerland, 1983-1988

  • M.Sc.  in  Molecular Biology, University of Zurich, 1987-1988

  • Ph.D.  in  Molecular Biology/Neuroscience, University of Zurich,     1989-1992

Positions and academic  appointments

  • Postdoc -  Institute of Molecular Life Sciences (formerly Molecular Biology), University of  Zurich, Switzerland, 1992-1993

  • Postdoctoral Fellow  - Whitehead Institute for Biomedical Research, Cambridge,   Massachusetts, 1993-1996

  • Assistant Professor  (START Fellow) - Institute of Molecular Life Sciences, University of  Zurich,  Switzerland, 1996-2006

  • Associate Professor  - Department of Anatomy and Neurobiology, University of Kentucky,  Lexington,  2006-2013

  • Professor -   School of Life Sciences and Technology, Harbin Institute of  Technology,  Harbin, China, since October 2013

Profile  and   research overview

Hans  Bueler  was trained as a molecular biologist and neuroscientist at the  University of  Zurich in Switzerland, where he received a M.S. degree in 1988   and Ph.D. in   1992. He developed the first prion protein (PrP)-deficient mice   and showed  that  they were resistant to contracting prion disease and failed to  replicate  the  infectious agent. This seminal finding established that PrP is   essential  for  prion disease pathogenesis and prion propagation. After   postdoctoral  research at  the Whitehead Institute for Biomedical Research and   Harvard  Medical School in  Boston in tumor immunotherapy, Dr. Bueler started  his  own  lab back at the  University of Zurich as an Assistant Professor,  focusing on   the development of viral vectors for gene therapy of  Parkinson’s  disease and amyotrophic laterals sclerosis. His group demonstrated  that  AAV-mediated overexpression of the chaperone Hsp70 and the  recessive  Parkinson’s disease-linked proteins DJ-1 and Parkin confer protection  against  dopaminergic system degeneration in a mouse model of sporadic  Parkinson’s  disease. As an Associate Professor at the University of Kentucky,  Dr. Bueler  studied the mechanisms of neuronal dysfunction in animal models of  familial  Parkinson’s disease. His lab has generated mice lacking PTEN-induced  kinase 1  (PINK1), a mitochondrial kinase linked to recessive inherited  Parkinson’s  disease. PINK1 plays an important role in mitochondrial quality  control by  regulating the selective degradation of depolarized mitochondria  through    mitophagy. Loss of PINK1 in mice leads to mitochondrial  abnormalities,  oxidative stress, alterations in autophagy/mitophagy, defects in  Akt signaling   and  abnormalities in neurogenesis. These mechanisms in  conjunction with other  stress factors may be involved in neurodegeneration and  neuropsychiatric disorders.  Dr. Bueler  has joined the School of Life Sciences and Technology of the Harbin  Institute  of Technology (HIT) in October 2013. At  HIT,  his lab has shown that lack of PINK1 leads to metabolic deficits of adult     neural stem cells and impaired dendritic differentiation of newborn neurons  in   the hippocampus of mice. In addition, the lab showed that PINK1  alters  glia  innate immune responses and enhances inflammation-induced,  nitric  oxide-mediated neuron death, suggesting a possible glial involvement  in  PINK1-related Parkinson’s disease. Current  projects  investigate the importance of PINK1 and mitochondrial function/dynamics  in the  vulnerability to stress-induced depression and  anxiety  (two frequent  human  mental disorders), and the function of  PINK1-regulated  cellular pathways   (such as mitophagy, mitochondrial dynamics  and mitochondrial  ROS signaling)  in  cell cycle regulation and tumor formation.  In the future, we  aim to  combine  viral vectors with CRISPR/Cas9 gene editing  technology to  knockout or  correct  neurodegeneration-linked genes directly in  the brain, in  order to  model specific  neurodegenerative disorders and develop  novel  therapeutic  approaches for these  devastating brain diseases.

Research  interests 

  • Molecular  genetics  and cellular mechanisms of neurodegeneration in Parkinson’s disease  and   related neurodegenerative disorders

  • Development  of  cell-based assays to screen small molecules, drugs and natural compounds  with   the potential to block neuronal loss  

  • Importance  of   PINK1-regulated mitochondrial quality control and mitochondrial dynamics  in neurodegeneration, neurogenesis and tumorigenesis

  • Viral  gene  transfer (AAV, retroviruses, lentiviruses) and CRISPR/Cas9 gene editing for  direct in  vivo modeling  and  gene therapy of neurodegenerative disorders (Parkinson’s, Huntington’s,     amyotrophic lateral sclerosis)

Publications (PubMed)

Selected   publications

  1. S. K.  Agnihotri, L. Sun, B. K. Yee, R. Shen, R. S. Akundi, L. Zhi, M. J. Duncan, W.  A. Cass, H. Bueler.  PINK1 deficiency  is associated with increased deficits of adult hippocampal  neurogenesis and  lowers the threshold for stress-induced depression in mice.  Behavioural  Brain  Research 363  (2019),  161-172.

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  2. L. Sun,  R. Shen, S.K. Agnihotri, Y. Chen, Z. Huang, H.  Bueler.  Lack  of PINK1 alters glia innate immune responses and enhances  inflammation-induced,  nitric oxide-mediated neuron death, Scientific  reports 8(1)     (2018) 383. 

  3. S.K. Agnihotri,  R. Shen, J. Li, X. Gao, H.  Bueler.  Loss of PINK1 leads to metabolic deficits in adult neural stem cells  and  impedes  differentiation of newborn neurons in the mouse  hippocampus,  FASEB  journal 31(7)     (2017) 2839-2853. 

  4. J.C.  Triplett,  Z. Zhang, R. Sultana, J. Cai, J.B. Klein, H.  Bueler,  D.A.  Butterfield. Quantitative expression proteomics and phosphoproteomics  profile  of brain from PINK1 knockout mice: insights into mechanisms of  familial    Parkinson's disease, Journal  of  neurochemistry 133(5)     (2015) 750-65. 

  5. G.I. Ellis,  L. Zhi, R. Akundi, H. Bueler,  F.  Marti. Mitochondrial and cytosolic roles of PINK1 shape induced  regulatory  T-cell development and function, European  journal of immunology 43(12)     (2013) 3355-60. 

  6. R.  Wang,  J.J. Li, S. Diao, Y.D. Kwak, L. Liu, L. Zhi, H.     Bueler,     N.R. Bhat, R.W. Williams, E.A. Park, F.F. Liao. Metabolic stress modulates     Alzheimer's beta-secretase gene transcription via SIRT1-PPARgamma-PGC-1  in  neurons, Cell  metabolism 17(5)  (2013) 685-94. 

  7. R.S.  Akundi,  L. Zhi, P.G. Sullivan, H. Bueler. Shared  and cell type-specific mitochondrial defects and metabolic adaptations   in   primary cells from PINK1-deficient mice, Neuro-degenerative  diseases 12(3)  (2013)  136-49. 

  8. R.S. Akundi,  L. Zhi, H.  Bueler. PINK1  enhances insulin-like growth factor-1-dependent Akt signaling and    protection  against apoptosis, Neurobiology  of  disease 45(1)  (2012) 469-78. 

  9. R.S. Akundi,  Z. Huang, J. Eason, J.D. Pandya, L. Zhi, W.A. Cass, P.G.  Sullivan, H. Bueler. Increased  mitochondrial calcium sensitivity and abnormal expression of innate immunity  genes precede dopaminergic defects in Pink1-deficient mice, PloS one 6(1) (2011)  e16038. 

  10. N. Saini,  S. Oelhafen, H. Hua, O. Georgiev, W. Schaffner, H. Bueler. Extended  lifespan of Drosophila parkin mutants through sequestration of    redox-active  metals and enhancement of anti-oxidative pathways, Neurobiology  of disease 40(1) (2010)  82-92. 

  11. H. Bueler. Impaired  mitochondrial dynamics and function in the pathogenesis of  Parkinson's    disease, Experimental  neurology 218(2)  (2009) 235-46. 

  12. J.C. Paterna,  A. Leng, E. Weber, J. Feldon, H. Bueler. DJ-1  and Parkin modulate dopamine-dependent behavior and inhibit MPTP-induced  nigral  dopamine neuron loss in mice, Molecular   therapy 15(4)   (2007) 698-704. 

  13. Z. Dong, D.P. Wolfer, H.P. Lipp, H. Bueler. Hsp70 gene transfer by adeno-associated virus inhibits MPTP-induced  nigrostriatal degeneration in the mouse model of Parkinson disease, Molecular therapy 11(1) (2005) 80-8. 

  14. J.C. Paterna,  J. Feldon, H.  Bueler.  Transduction  profiles of recombinant adeno-associated virus vectors derived  from  serotypes  2 and 5 in the nigrostriatal system of rats, Journal  of  virology 78(13) (2004)  6808-17. 

  15. Z. Dong,  B. Ferger, J.C. Paterna, D. Vogel, S. Furler, M. Osinde, J.  Feldon,  H. Bueler. Dopamine-dependent  neurodegeneration in rats induced by viral vector-mediated  overexpression of  the parkin target protein, CDCrel-1, Proceedings  of  the National Academy of Sciences of the United States  of  America 100(21) (2003)  12438-43. 

  16. K. Pajusola,  M. Gruchala, H. Joch, T.F. Luscher, S. Yla-Herttuala, H. Bueler. Cell-type-specific  characteristics modulate the transduction efficiency of    adeno-associated  virus type 2 and restrain infection of endothelial cells,    Journal of  virology 76(22) (2002)  11530-40. 

  17. S. Furler,  J.C. Paterna, M. Weibel, H.  Bueler. Recombinant  AAV vectors containing the foot and mouth disease virus 2A  sequence   confer  efficient bicistronic gene expression in cultured cells and  rat   substantia  nigra neurons, Gene     therapy 8(11)     (2001) 864-73. 

  18. J.C.  Paterna, T. Moccetti, A. Mura, J. Feldon, H. Bueler. Influence  of promoter and WHV post-transcriptional regulatory element on AAV-mediated  transgene expression in the rat brain, Gene therapy 7(15) (2000)  1304-11. 

  19. C.Klein,  H.   Bueler,   R.C. Mulligan. Comparative analysis of genetically modified dendritic cells   and   tumor cells as therapeutic cancer vaccines, The  Journal of experimental medicine 191(10)   (2000) 1699-708. 

  20. M.  Azzouz,  A. Hottinger, J.C. Paterna, A.D. Zurn, P. Aebischer,  H. Bueler. Increased  motoneuron survival and improved neuromuscular function in  transgenic  ALS mice  after intraspinal injection of an adeno-associated virus  encoding   Bcl-2,  Human     molecular genetics 9(5) (2000)  803-11. 

  21. M.  Glatzel,  E. Flechsig, B. Navarro, M.A. Klein, J.C. Paterna, H. Bueler,  A.  Aguzzi. Adenoviral and adeno-associated viral transfer of genes to the     peripheral nervous system, Proceedings  of  the National Academy of Sciences of the United States of     America 97(1) (2000)  442-7. 

  22. H.  Bueler, A.  Aguzzi, A. Sailer, R.A. Greiner, P. Autenried, M. Aguet, C. Weissmann.  Mice devoid of PrP are resistant to scrapie, Cell 73(7)  (1993)  1339-47. 

  23. H. Bueler,  M.  Fischer, Y. Lang, H. Bluethmann, H.P. Lipp, S.J. DeArmond, S.B. Prusiner,   M.  Aguet, C. Weissmann. Normal development and behaviour of mice lacking the     neuronal cell-surface PrP protein, Nature 356(6370)     (1992) 577-82.