Dr Dominik Froehlich

Dr Dominik Froehlich

Senior Lecturer

  • PhD (2014 - Summa cum laude; Johannes Gutenberg University Mainz). Thesis: Oligodendroglial Exosomes in Glia to Neuron Signaling
  • MSc (2009 - with distinction; Johannes Gutenberg University Mainz)

Medicine & Health
School of Biomedical Sciences

I am a neuroscientist with a broad background in genetics, neuroscience, and molecular cell biology. My research seeks to establish innovative new gene therapies for the group of devastating neurodegenerative disorders termed leukodystrophies - genetic diseases of the central nervous system white matter associated with an early onset, substantial mortality, and a lack of effective treatment options. My research has significantly advanced the understanding of these diseases and successfully utilised refined CNS-targeted gene therapy to rescue disease pathology in mice. I have over 14 years of experience in translational neuroscience including in vivo disease modelling and the development of targeted gene therapies.

Commencing in 2023, my group is supported through two new research grants from the NHMRC and MRFF. This funding will expand the spectrum of neurological diseases investigated by my research program to include dementias, specifically globular glial tauopathies, as well as hereditary spastic paraplegias. Employing the refined pre-clinical modelling and gene therapy platforms, developed through my leukodystrophy research, will help to uncover the pathophysiology underlying these currently incurable conditions and guide the development of tailored treatment strategies.

At UNSW Sydney, I lead the CNS Gene Therapy group, which is part of the Translational Neuroscience Facility in the School of Biomedical Sciences. I contribute to the discipline in my roles as committee member of the UNSW Animal Care and Ethics Committee and as editorial board member of the Rare Disease and Orphan Drugs journal and Frontiers in Neuroscience. I also engage with the non-scientific community through my work for two not-for-profit organisations. I am the Vice President and Scientific Advisor of Leukodystrophy Australia, an organisation that provides information, support, and advocacy to those affected by leukodystrophies. I am also Scientific Advisory Board Member to the Mission Massimo Foundation, aimed at accelerating the discovery of genetic variations responsible for childhood leukodystrophies and to translate these findings into clinical treatments.

  • Journal articles | 2023
    Kalotay E; Klugmann M; Housley GD; Fröhlich D, 2023, 'Dominant aminoacyl-tRNA synthetase disorders: lessons learned from in vivo disease models', Frontiers in Neuroscience, 17, http://dx.doi.org/10.3389/fnins.2023.1182845
    Journal articles | 2023
    Kalotay E; Klugmann M; Housley GD; Fröhlich D, 2023, 'Recessive aminoacyl-tRNA synthetase disorders: lessons learned from in vivo disease models', Frontiers in Neuroscience, 17, http://dx.doi.org/10.3389/fnins.2023.1182874
    Journal articles | 2023
    Klugmann M; Suchowerska AK; Housley GD; Fröhlich D, 2023, 'Histological and biochemical methods to assess aminoacyl-tRNA synthetase expression in human post-mortem brain tissue', Rare Disease and Orphan Drugs Journal, 2, pp. 8 - 8, http://dx.doi.org/10.20517/rdodj.2023.05
    Journal articles | 2022
    Fröhlich D; Gessler DJ; Klugmann M, 2022, 'Editorial: Myelin Repair: At the Crossing-Lines of Myelin Biology and Gene Therapy', Frontiers in Cellular Neuroscience, 16, http://dx.doi.org/10.3389/fncel.2022.853742
    Journal articles | 2022
    Fröhlich D; Kalotay E; von Jonquieres G; Bongers A; Lee B; Suchowerska AK; Housley GD; Klugmann M, 2022, 'Dual-function AAV gene therapy reverses late-stage Canavan disease pathology in mice', Frontiers in Molecular Neuroscience, 15, http://dx.doi.org/10.3389/fnmol.2022.1061257
    Journal articles | 2022
    Klugmann M; Kalotay E; Delerue F; Ittner LM; Bongers A; Yu J; Morris MJ; Housley GD; Fröhlich D, 2022, 'Correction to: Developmental delay and late onset HBSL pathology in hypomorphic Dars1 M256L mice (Neurochemical Research, (2022), 47, 7, (1972-1984), 10.1007/s11064-022-03582-4)', Neurochemical Research, 47, pp. 1985 - 1990, http://dx.doi.org/10.1007/s11064-022-03602-3
    Journal articles | 2022
    Klugmann M; Kalotay E; Delerue F; Ittner LM; Bongers A; Yu J; Morris MJ; Housley GD; Fröhlich D, 2022, 'Developmental delay and late onset HBSL pathology in hypomorphic Dars1 M256L mice', Neurochemical Research, 47, pp. 1972 - 1984, http://dx.doi.org/10.1007/s11064-022-03582-4
    Journal articles | 2021
    Fröhlich D; Mendes MI; Kueh AJ; Bongers A; Herold MJ; Salomons GS; Housley GD; Klugmann M, 2021, 'A Hypomorphic Dars1D367Y Model Recapitulates Key Aspects of the Leukodystrophy HBSL', Frontiers in Cellular Neuroscience, 14, http://dx.doi.org/10.3389/fncel.2020.625879
    Journal articles | 2021
    Muthiah A; Housley GD; Klugmann M; Fröhlich D, 2021, 'The Leukodystrophies HBSL and LBSL—Correlates and Distinctions', Frontiers in Cellular Neuroscience, 14, http://dx.doi.org/10.3389/fncel.2020.626610
    Journal articles | 2020
    Das A; Fröhlich D; Achanta LB; Rowlands BD; Housley GD; Klugmann M; Rae CD; Froehlich D, 2020, 'L-Aspartate, L-Ornithine and L-Ornithine-L-Aspartate (LOLA) and Their Impact on Brain Energy Metabolism', Neurochemical Research, 45, pp. 1438 - 1450, http://dx.doi.org/10.1007/s11064-020-03044-9
    Journal articles | 2020
    Das A; Fröhlich D; Achanta LB; Rowlands BD; Housley GD; Klugmann M; Rae CD, 2020, 'Correction to: L-Aspartate, L-Ornithine and L-Ornithine-L-Aspartate (LOLA) and Their Impact on Brain Energy Metabolism (Neurochemical Research, (2020), 45, 6, (1438-1450), 10.1007/s11064-020-03044-9)', Neurochemical Research, 45, pp. 2527, http://dx.doi.org/10.1007/s11064-020-03087-y
    Journal articles | 2020
    Frühbeis C; Kuo-Elsner WP; Müller C; Barth K; Peris L; Tenzer S; Möbius W; Werner HB; Nave KA; Fröhlich D; Krämer-Albers EM, 2020, 'Oligodendrocytes support axonal transport and maintenance via exosome secretion', PLoS Biology, 18, http://dx.doi.org/10.1371/journal.pbio.3000621
    Journal articles | 2019
    Auber M; Fröhlich D; Drechsel O; Karaulanov E; Krämer-Albers EM, 2019, 'Serum-free media supplements carry miRNAs that co-purify with extracellular vesicles', Journal of Extracellular Vesicles, 8, http://dx.doi.org/10.1080/20013078.2019.1656042
    Journal articles | 2018
    Fröhlich D; Suchowerska AK; Voss C; He R; Wolvetang E; Von Jonquieres G; Simons C; Fath T; Housley GD; Klugmann M; Froehlich D, 2018, 'Expression pattern of the aspartyl-tRNA synthetase DARS in the human brain', Frontiers in Molecular Neuroscience, 11, pp. 81, http://dx.doi.org/10.3389/fnmol.2018.00081
    Journal articles | 2018
    von Jonquieres G; Spencer ZHT; Rowlands BD; Klugmann CB; Bongers A; Harasta AE; Parley KE; Cederholm J; Teahan O; Pickford R; Delerue F; Ittner LM; Fröhlich D; McLean CA; Don AS; Schneider M; Housley GD; Rae CD; Klugmann M; Froehlich D, 2018, 'Uncoupling N-acetylaspartate from brain pathology: implications for Canavan disease gene therapy', Acta Neuropathologica, 135, pp. 95 - 113, http://dx.doi.org/10.1007/s00401-017-1784-9
    Journal articles | 2017
    Fröhlich D; Suchowerska AK; Spencer ZHT; von Jonquieres G; Klugmann CB; Bongers A; Delerue F; Stefen H; Ittner LM; Fath T; Housley GD; Klugmann M, 2017, 'In vivo characterization of the aspartyl-tRNA synthetase DARS: Homing in on the leukodystrophy HBSL', Neurobiology of Disease, 97, pp. 24 - 35, http://dx.doi.org/10.1016/j.nbd.2016.10.008
    Journal articles | 2016
    von Jonquieres G; Fröhlich D; Klugmann CB; Wen X; Harasta AE; Ramkumar R; Spencer ZHT; Housley GD; Klugmann M, 2016, 'Recombinant human myelin-associated glycoprotein promoter drives selective AAV-mediated transgene expression in oligodendrocytes', Frontiers in Molecular Neuroscience, 9, http://dx.doi.org/10.3389/fnmol.2016.00013
    Journal articles | 2014
    Froehlich D; Fruehbeis C; Kuo WP; Moebius W; Goebbels S; Nave K-A; Schneider A; Simons M; Klugmann M; Trotter J; Kraemer-Albers E-M, 2014, 'Transfer of exosomes from oligodendrocytes to neurons', ACTA PHYSIOLOGICA, 210, pp. 134 - 134, https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000332259900346&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=891bb5ab6ba270e68a29b250adbe88d1
    Journal articles | 2014
    Fröhlich D; Kuo WP; Frühbeis C; Sun JJ; Zehendner CM; Luhmann HJ; Pinto S; Toedling J; Trotter J; Krämer-Albers EM, 2014, 'Multifaceted effects of oligodendroglial exosomes on neurons: Impact on neuronal firing rate, signal transduction and gene regulation', Philosophical Transactions of the Royal Society B: Biological Sciences, 369, http://dx.doi.org/10.1098/rstb.2013.0510
    Journal articles | 2013
    Frühbeis C; Fröhlich D; Kuo WP; Amphornrat J; Thilemann S; Saab AS; Kirchhoff F; Möbius W; Goebbels S; Nave KA; Schneider A; Simons M; Klugmann M; Trotter J; Krämer-Albers EM, 2013, 'Neurotransmitter-Triggered Transfer of Exosomes Mediates Oligodendrocyte-Neuron Communication', PLoS Biology, 11, http://dx.doi.org/10.1371/journal.pbio.1001604
    Journal articles | 2013
    Frühbeis C; Fröhlich D; Kuo WP; Krämer-Albers EM, 2013, 'Extracellular vesicles as mediators of neuron-glia communication', Frontiers in Cellular Neuroscience, http://dx.doi.org/10.3389/fncel.2013.00182
    Journal articles | 2013
    Von Jonquieres G; Mersmann N; Klugmann CB; Harasta AE; Lutz B; Teahan O; Housley GD; Frohlich D; Kramer-Albers EM; Klugmann M, 2013, 'Glial Promoter Selectivity following AAV-Delivery to the Immature Brain', PLoS ONE, 8, pp. Article number e65646, http://dx.doi.org/10.1371/journal.pone.0065646
    Journal articles | 2012
    Frühbeis C; Fröhlich D; Krämer-Albers EM, 2012, 'Emerging roles of exosomes in neuron-glia communication', Frontiers in Physiology, 3 APR, http://dx.doi.org/10.3389/fphys.2012.00119
  • Preprints | 2019
    Frühbeis C; Kuo-Elsner WP; Müller C; Barth K; Peris L; Tenzer S; Möbius W; Werner HB; Nave K-A; Fröhlich D; Krämer-Albers E-M, 2019, Oligodendrocytes support axonal transport and maintenance via exosome secretion, http://dx.doi.org/10.1101/2019.12.20.884171
    Conference Abstracts | 2017
    von Jonquieres G; Klugmann C; Frohlich D; Housley GD; Klugmann M, 2017, 'NOVEL APPROACHES TO PREVENT THE NAASTY - TARGETED GENE THERAPY FOR LEUKODYSTROPHIES', in JOURNAL OF GENE MEDICINE, WILEY, AUSTRALIA, Univ Technol Sydney, Sydney, Vol. 20, presented at Joint 10th Annual Scientific Meeting of the Australian-Gene-and-Cell-Therapy-Society (AGCTS) and Australasian-Society-for-Stem-Cell-Research (ASSCR), AUSTRALIA, Univ Technol Sydney, Sydney, 24 May 2017 - 26 May 2017, https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000426528300030&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=891bb5ab6ba270e68a29b250adbe88d1
    Conference Abstracts | 2015
    Froehlich D; Klugmann M, 2015, 'Modeling and treatment of the novel white-matter disorder HBSL', in JOURNAL OF NEUROCHEMISTRY, WILEY-BLACKWELL, AUSTRALIA, Cairns, Vol. 134, pp. 284 - 285, presented at 25th Biennial Meeting of the International-Society-for-Neurochemistry Jointly with the 13th Meeting of the Asian-Pacific-Society-for-Neurochemistry in Conjunction with the 35th Meeting of the Australasian-Neuroscience-Society, AUSTRALIA, Cairns, 23 August 2015 - 27 August 2015, https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000360206300716&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=891bb5ab6ba270e68a29b250adbe88d1
    Conference Papers | 2013
    Froehlich D; Kuo WP; Fruehbeis C; Moebius W; Nave K-A; Schneider A; Simons M; Klugmann M; Pinto S; Kyewski B; Trotter J; Kraemer-Albers E-M, 2013, 'TRANSFER OF EXOSOMES FROM OLIGODENDROCYTES TO NEURONS', in GLIA, WILEY-BLACKWELL, GERMANY, Berlin, pp. S112 - S113, presented at 11th European Meeting on Glial Cell Function in Health and Disease, GERMANY, Berlin, 03 July 2013 - 06 July 2013, https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000320408400354&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=891bb5ab6ba270e68a29b250adbe88d1

  • Medical Research Future Fund (MRFF) Stem Cell Therapies Mission (2023 -2025)Moon's Mission: creating a replicable therapeutic framework for hereditary spastic paraplegias ($940,424)
  • National Health and Medical Research Council (NHMRC) Ideas Grant (2023 - 2026); Understanding neurodegeneration caused by oligodendroglial dysfunction ($1,025,253)
  • National Health and Medical Research Council (NHMRC) Ideas Grant (2021 - 2026); Bionic-array Directed Gene Electrotransfer for Treating Focal Brain Disorders ($1,941,000)
  • Medical Research Future Fund (MRFF) Accelerated Research (2019 -2023)Massimo’s Mission – The Leukodystrophy Flagship ($3,000,000)
  • European Leukodystrophy Association (ELA)project grant (2019 -2022); Towards preclinical proof-of-concept for HBSL gene therapy ($316,000)
  • European Leukodystrophy Association (ELA) pilot grant (2016); Modelling and treatment of the novel leukoencephalopathy HBSL ($69,000)
  • German Research Foundation DFG - Early Career Research Fellowship (2014 -2016)Exosome-mediated nanomedicine for the treatment of leukodystrophies ($126,000)

  • UNSW Sydney SoMS New Researcher of the Year (2019)                                                                                                                               
  • UNSW Sydney SoMS Paper of the Month award (2018)     

I have established a comprehensive research program focused on developing innovative new gene therapy strategies for a neurodegenerative disorders with a focus on leukodystrophies. My research program can be split into two main activities:

  • Creation and characterisation of novel disease models, which are integral in understanding the pathophysiology underlying leukodystrophies and other neurological diseases
  • Pre-clinical efficacy studies demonstrating the effectiveness of AAV-mediated gene therapy for the treatment of leukodystrophies and other brain disorders

Professional Engagement

  • UNSW Animal Care and Ethics Committee Member (since 2021)
  • Rare Disease and Orphan Drugs Journal (RDODJ) - Editorial Board Member (since 2021)                                                                                                               
  • Frontiers in Cellular Neuroscience - Guest Editor (2020); Topic: Myelin Repair: At the Crossing-Lines of Myelin Biology and Gene Therapy                                                                                                           

 

Social Engagement

  • Leukodystrophy Australia Foundation - Vice President and Scientific Advisor (since 2019)                                                                                                                                         
  • Mission Massimo Foundation – Scientific Advisor (since 2014)                                                                                                                                                       

 

Media

  • ABC Australian Story (2018) The Massimo Mission. https://www.abc.net.au/austory/the-massimo-mission/9771118                                                                                                                                                            

My Research Supervision

I currently supervise three PhD, one Medicine Honours, and one Neuroscience Honours students:

  • Elizabeth Kalotay (PhD): Developing a gene therapy for the leukodystrophy HBSL
  • Elena Venuti (PhD): Prenatal HBSL gene therapy in Dars1 transgenic mice
  • Connor Karozis (PhD): Spatiotemporal targeting of neurotrophin gene therapy for enhanced sensorimotor reinnervation
  • Richa Chaluvadi (MedHonours): Gene therapy proof-of-concept for hereditary spastic paraplegia SPG56
  • Kwannatee Morey-Hype (NeuroHonours): AAV-mediated HBSL gene therapy proof-of-concept in oligodendroglial Dars1-KO mice

My Teaching

I contribute to teaching and student supervision into Science and Medicine courses, including lecturing Current Trends in Biotechnology, facilitating in the phase 1 medicine program, tutoring, and demonstrating.