Mark Kotter Explained

Mark Kotter
Birth Name:Mark Reinhard Kotter
Birth Date:14 February 1971
Birth Place:Calgary, Canada
Nationality:Austrian, Canadian
Fields:Biology, Neurosciences, Medicine
Workplaces:University of Cambridge, bit.bio, clock.bio, Myelopathy.org, Meatable
Alma Mater:University of Graz, University of Cambridge
Thesis Title:Macrophages and CNS Remyelination
Doctoral Advisor:Robin Franklin
Known For:cell programming, degenerative cervical myelopathy
Website:https://www.stemcells.cam.ac.uk/people/affiliates/kotter

Mark Kotter (born 1971) is a neurosurgeon, biologist, and entrepreneur.

Kotter made contributions to the importance of macrophages for brain regeneration,[1] His work on cell programming includes the development of opti-ox (optimized inducible overexpression).[2] [3] It has become the scientific basis of bit.bio, and Meatable, which he co-founded. Kotter's scientific contributions to the field of degenerative cervical myelopathy (DCM) range from the diagnosis to the aetiology, pathophysiology, and treatment of DCM.[4]

Kotter is the founder and CEO of cell coding company bit.bio,[5] which is devoted to "democratising human cells"[6] and cell therapy. Additionally, he co-founded Meatable, a company focused on cultured meat production, and is the scientific founder of clock.bio, a rejuvenation company. He also co-founded Myelopathy.org, a charity supporting individuals with degenerative cervical myelopathy.[7]

Early life and education

Kotter was born in Canada and raised in Austria, Germany, and Australia.[8] He studied medicine in Graz and earned a PhD in stem cell biology from the University of Cambridge. He completed postgraduate medical training in Berlin and Vienna and later led a research group at the Max Planck Institute for Experimental Medicine. In 2009, he returned to Cambridge to complete his neurosurgery residency and joined the Stem Cell Institute as a principal investigator. Following sub-specialist training in complex spinal neurosurgery at the University of Toronto with Michael Fehlings, he established his neurosurgery practice and research laboratory at the University of Cambridge's Department of Clinical Neurosciences.[9]

Research

Kotter was among the first to recognise the role of macrophages in brain regeneration, a discovery that led to the first regenerative medicine trial for Degenerative cervical myelopathy.[10] [11] [12] [13] [14] [15] [16] [17]

Over the past decade, he has developed opti-ox,[18] a gene targeting approach that enables the faithful execution of genetic information in cells. His discoveries refute the theory that stochastically determined permissive states are required for cellular reprogramming[19] and have opened up the possibility of producing any human cell, within days, at purities approaching 100%.[20] Inspired by Marius Wernig[21] 's[21] and Thomas Südhof's work, he focussed on applying a synthetic biology[22] approach and developed a protocol for reprogramming pluripotent stem cells into oligodendrocytes.[23] In 2012, he succeeded in creating a batch of oligodendrocytes. He and his colleagues ultimately found a way to circumvent the gene silencing, by introducing the genetic instructions into "safe harbors" in the genome.[18] Their patented technique is known as opti-ox,[2] which stands for "optimised inducible over-expression[24] ".

Other activities

In 2016, Kotter founded it as Elpis Biomed, the company's name later changed to bit.bio to give a clearer indication of its function in cell coding: "bit" refers to the smallest building block in coding, while "bio" refers to the live cells that are being reprogrammed.[25] bit.bio leverages the opti-ox technology to program human cells from induced pluripotent stem cells (iPSCs).[26] [27] The company aims to transition biology into engineering,[28] addressing significant medical needs.[29] Notable board members include Hermann Hauser and Sir Gregory Winter, with Dr. Roger Pedersen[30] serving as the chief scientific advisor. In 2023, bit.bio partnered with BlueRock Therapeutics,[31] a Bayer subsidiary, to develop regulatory T cell therapies.

In 2015, Kotter co-founded Myelopathy.org[7] with neurosurgeon Ben Davies[32] and patient Iwan Sadler.[33] The charity is dedicated to supporting individuals with Degenerative cervical myelopathy[10] by enhancing patient advocacy and clinical practices. Myelopathy.org received the Points of Light Award from the British Prime Minister in February 2020.[34] Dr. Kotter is also a member of the AOSpine Knowledge Forum Spinal Cord Injury[35] and leads several international initiatives, including the RECODE-DCM project.[36]

In 2018, Kotter co-founded Meatable with Daan Luining.[37] The company develops cultured meat using porcine and bovine pluripotent stem cells, addressing environmental concerns associated with traditional agriculture.

Kotter launched clock.bio[38] in 2023, a rejuvenation company[39] that aims to extend and improve quality of life by reversing the harmful effects of time in our cells, harnessing the regenerative capabilities of human pluripotent stem cells. The company is founded on the insight that hiPSCs can be force-aged to display the hallmarks of ageing.[40] This triggers self-rejuvenation mechanisms which can be interrogated for the identification of gene candidates that are causally relevant for cell rejuvenation. Comprehensive genome-wide CRISPR screens result in a comprehensive 'atlas of rejuvenation genes'.[40]

Awards

References

  1. Macrophage depletion impairs oligodendrocyte remyelination following lysolecithin-induced demyelination . 2001 . 10.1002/glia.1085 . Kotter . Mark R. . Setzu . Anna . Sim . Fraser J. . Van Rooijen . Nico . Franklin . Robin J.M. . Glia . 35 . 3 . 204–212 . 11494411.
  2. Web site: bit.bio secures foundational US patent for opti-ox. Diana. Spencer. August 1, 2023. Drug Discovery World (DDW).
  3. Web site: Forbes Meet The Company Democratizing Access To Human Cells . .
  4. Web site: Mark Kotter. scholar.google.com.
  5. Web site: Synthetic Biology for Human Health | Cells Reprogrammed | bit.bio. www.bit.bio.
  6. Web site: Elpis BioMed: Mastering the art of reprogramming human cells . July 19, 2019 .
  7. Web site: Degenerative Cervical Myelopathy (DCM). MYELOPATHY.ORG.
  8. Fast-Forwarding Cellular Reprogramming An Interview with Dr. Mark Kotter . 2024 . 10.1089/cell.2024.29111.mk . 38381404 . Kotter . M. R. . Pereira . C. F. . Cellular Reprogramming . 26 . 1 . 2–7.
  9. Web site: Author: Mark Kotter. Cambridge Neuroscience.
  10. https://www.nhsinform.scot/illnesses-and-conditions/muscle-bone-and-joints/conditions/degenerative-cervical-myelopathy/
  11. Macrophage depletion impairs oligodendrocyte remyelination following lysolecithin-induced demyelination . 2001 . 10.1002/glia.1085 . Kotter . Mark R. . Setzu . Anna . Sim . Fraser J. . Van Rooijen . Nico . Franklin . Robin J.M. . Glia . 35 . 3 . 204–212 . 11494411.
  12. Macrophage-depletion induced impairment of experimental CNS remyelination is associated with a reduced oligodendrocyte progenitor cell response and altered growth factor expression . 2005 . 10.1016/j.nbd.2004.09.019 . 15649707 . Kotter . M. R. . Zhao . C. . Van Rooijen . N. . Franklin . R. J. . Neurobiology of Disease . 18 . 1 . 166–175.
  13. Myelin Impairs CNS Remyelination by Inhibiting Oligodendrocyte Precursor Cell Differentiation . 2006 . 16399703 . Kotter . M. R. . Li . W. W. . Zhao . C. . Franklin . R. J. . The Journal of Neuroscience . 26 . 1 . 328–332 . 10.1523/JNEUROSCI.2615-05.2006 . 6674302.
  14. Web site: Myelin-mediated inhibition of oligodendrocyte precursor differentiation can be overcome by pharmacological modulation of Fyn-RhoA and protein kinase C signalling.
  15. Antibody-mediated neutralization of myelin-associated EphrinB3 accelerates CNS remyelination . 2016 . 10.1007/s00401-015-1521-1 . Syed . Yasir A. . Zhao . Chao . Mahad . Don . Möbius . Wiebke . Altmann . Friedrich . Foss . Franziska . Sentürk . Aycan . Acker-Palmer . Amparo . Lubec . Gert . Lilley . Kathryn . Franklin . Robin J. M. . Nave . Klaus-A. . Kotter . Mark R. N. . Kotter MRN . Acta Neuropathologica . 131 . 2 . 281–298 . 26687980 . 4713754.
  16. Targeting patient recovery priorities in degenerative cervical myelopathy: design and rationale for the RECEDE-Myelopathy trial-study protocol . 2023 . 36882259 . Davies . B. . Mowforth . O. D. . Yordanov . S. . Alvarez-Berdugo . D. . Bond . S. . Nodale . M. . Kareclas . P. . Whitehead . L. . Bishop . J. . Chandran . S. . Lamb . S. . Bacon . M. . Papadopoulos . M. C. . Starkey . M. . Sadler . I. . Smith . L. . Kalsi-Ryan . S. . Carpenter . A. . Trivedi . R. A. . Wilby . M. . Choi . D. . Wilkinson . I. B. . Fehlings . M. G. . Hutchinson . P. J. . Kotter MRN . BMJ Open . 13 . 3 . e061294 . 10.1136/bmjopen-2022-061294 . 10008337.
  17. Web site: Regeneration in Cervical Degenerative Myelopathy (RECEDE) . December 24, 2021 . Kotter . Mark R..
  18. Inducible and Deterministic Forward Programming of Human Pluripotent Stem Cells into Neurons, Skeletal Myocytes, and Oligodendrocytes . 2017 . 5390118 . Pawlowski . M. . Ortmann . D. . Bertero . A. . Tavares . J. M. . Pedersen . R. A. . Vallier . L. . Kotter . M. R. . Stem Cell Reports . 8 . 4 . 803–812 . 10.1016/j.stemcr.2017.02.016 . 28344001.
  19. Web site: Controllable transcription.
  20. Web site: Introducing bit bio — coding cells, the building blocks of life . October 15, 2019 .
  21. Web site: Marius Wernig | Stanford Medicine. CAP Profiles.
  22. News: Synthetic Biology Matures, Promising Affordable And Personalized Treatments .
  23. Direct conversion of fibroblasts to functional neurons by defined factors . 2010 . 10.1038/nature08797 . Vierbuchen . Thomas . Ostermeier . Austin . Pang . Zhiping P. . Kokubu . Yuko . Südhof . Thomas C. . Wernig . Marius . Nature . 463 . 7284 . 1035–1041 . 20107439 . 2829121 . 2010Natur.463.1035V.
  24. Web site: Meet The Company Democratizing Access To Human Cells. John. Cumbers. Forbes.
  25. Web site: Proactive - Proactive financial news: fast, accessible, and actionable articles and videos for the global investment audience. - Companies. Proactiveinvestors UK.
  26. Web site: Cambridge Independent: Elpis BioMed: Mastering the art of reprogramming human cells . July 19, 2019 .
  27. Web site: Innovations in Pharmaceutical Technology (IPT) Coding of Cell Identity .
  28. Web site: Forbes Meet The Company Reprogramming The Future Of Synthetic Biology . .
  29. News: European Biotechnology feature: Biology as Software .
  30. Web site: Professor Roger Pedersen. Professor Roger. Pedersen. May 7, 2014. www.cardiovascular.cam.ac.uk.
  31. Web site: Home. May 30, 2024. BlueRock Therapeutics LP.
  32. https://www.researchgate.net/profile/Benjamin-Davies-11#:~:text=About&text=Benjamin%20Marshall%20Davies%20currently%20works,in%20particular%20Degenerative%20Cervical%20Myelopathy.
  33. Web site: Interview with Iwan Sadler. Iwan. Sadler. October 24, 2022.
  34. Web site: Myelopathy. Jake. McBride. February 26, 2020. Points of Light.
  35. Web site: AO Spine Knowledge Forum Spinal Cord Injury (SCI). www.aofoundation.org.
  36. Web site: AO Spine RECODE-DCM. www.aofoundation.org.
  37. Web site: Daan Luining. Kind Earth.Tech.
  38. Web site: clock.bio | Home. clock.bio.
  39. Web site: clock.bio Launches to Decode Rejuvenation Biology Across the Human Genome | Business Wire.
  40. Web site: A white paper for rejuvenation therapies and blueprint for clock.bio. Mark. Kotter. August 30, 2023.
  41. Web site: bit.bio CEO wins in 2 categories at Great British Entrepreneur Awards. www.bit.bio.
  42. Web site: bit.bio named Emerging Star at European Mediscience Awards 2022. www.bit.bio.
  43. Web site: EY Entrepreneur Of The Year™ Finalists. www.ey.com.
  44. Web site: bit.bio wins twice at cambridge independent science and technology awards. www.bit.bio.

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