Peter M. Lansdorp

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Peter Michael Lansdorp
Peter Lansdorp (2022).jpg
Born (1952-12-16) December 16, 1952 (age 72)
Terneuzen, the Netherlands
NationalityCanadian
Alma materErasmus University (MD), University of Amsterdam (PhD)
Known forDiscoveries in genome instability, aging and cancer, Development of single cell Strand-seq, Q-FISH, flow FISH techniques, Contributions to telomere biology
Scientific career
FieldsHematology, Medical Genetics, Cancer Research
InstitutionsTerr Fox Laboratory https://en.wikipedia.org/wiki/Terry_Fox_Laboratory, University of British Columbia, European Research Institute for the Biology of Aging, University of Groningen
Thesis  (1985)
Peter M Lansdorp Peter Lansdorp (2022).jpg
Peter M Lansdorp

Peter Michael Lansdorp (born December 16, 1952) is recognized for his contributions in the fields of hematology, medical genetics and cancer research. He has made significant contributions to the understanding of genome instability, particularly in relation to aging and cancer. His research has focused on the biology of blood-forming stem cells, telomeres and genome analysis. He is also known for developing techniques including single cell Strand-seq and fluorescence in situ hybridization (FISH) techniques such as Q-FISH and flow FISH. [1]

Contents

Early life and career

Peter Lansdorp grew up in the Netherlands (Den Haag and Wassenaar). He obtained a Medical Degree from the Erasmus University in Rotterdam in 1976 and a PhD from the University of Amsterdam 1985. His early career included work on monoclonal antibodies at Sanquin. [2] He moved to Canada in 1985 and became a Canadian citizen in 2002. Between 2011 and 2017, he was the Founding Scientific Director of the European Research Institute for the Biology of Aging at the University of Groningen, the Netherlands. He returned to Vancouver in 2017, resuming his role as a Distinguished Scientist at the Terry Fox Laboratory and a professor in Medical Genetics at the University of British Columbia. [3] [4]

Research

In 1984, Lansdorp made a significant contribution to the field of monoclonal antibodies with the discovery of a method to efficiently form bifunctional tetrameric antibody complexes. [5]

This method was patented and later licensed to StemCell Technologies in Vancouver. [6] Lansdorp's early work in Vancouver was predominantly focused on human stem cell biology. He first demonstrated that the functional properties of purified "candidate" blood forming stem cells, including their self-renewal properties, change dramatically during development. [7]

He subsequently showed that telomere repeats are lost in purified hematopoietic stem cells with replication and with age [8] supporting the concept that blood stem cells do not truly "self-renew" but are mortal like most other somatic cells. These results are increasingly being recognized worldwide, especially after Lansdorp showed, in collaboration with others, that telomere loss is linked to loss of stem cells in patients. [9] [10] [11] [12]

During a sabbatical in Leiden University in 1995, Lansdorp developed a novel fluorescent in situ hybridization (FISH) method to measure the length of telomere repeats using novel peptide nucleic acid probes [13] - a method which has since enabled numerous studies and observations in the telomere field. He subsequently showed that flow cytometry can be used to measure the average telomere length in nucleated blood cells. [14] This so-called flow FISH technique is now the method of choice to screen for possible telomere biology disorders in humans and such tests are offered by Repeat Diagnostics Inc., a biotech company founded by Lansdorp.

In 2002 Lansdorp provided compelling evidence for the formation of guanine quadruplex (G4) DNA structures in C. elegans. He proposed that a specialised helicase, "deletion of G-rich DNA" or dog-1, is required to unwind G4 DNA structures occasionally forming during replication. [15] The human homolog of the dog-1 gene is BRIP1/FANCJ. These studies provided the first genetic evidence that G4 DNA structures occur in vivo in multicellular organisms and that specialized helicases are required to prevent instability at guanine- rich DNA. [16]

Subsequently, Lansdorp and colleagues identified a previously unknown helicase gene as a major regulator of telomere length in the mouse. [17] He named this gene RTEL for Regulator of Telomere Length. In follow-up work, it was shown that mutations in the human RTEL1 gene result in telomere loss and bone marrow failure.

In 2012, his laboratory introduced the single cell Strand-seq technique, [18] which has diverse applications in genome science, including the production of chromosome-length haplotype information [19] and the characterization of polymorphic inversions. [20] [21]

Continuous refinements of Strand-seq technology [22] have enabled significant advancements in studies of human genome diversity and medical genetics. [23]

In 2022, Lansdorp proposed theories regarding the role of telomerase in suppressing cancer in long-lived animals [24] and levels of telomerase in preimplantation embryos in determining sex differences in average telomere length and lifespan. [25]

References

  1. ↑ "Peter M Lansdorp | Terry Fox Laboratory". www.bccrc.ca. Retrieved 2024-04-11.
  2. ↑ "sanquin.org".
  3. ↑ "open.library.ubc.ca".
  4. ↑ "Stem Cells & Gene Therapy". Department of Medical Genetics. Retrieved 2024-04-11.
  5. ↑ Lansdorp, Peter M.; Aalberse, Rob C.; Bos, Rogier; Schutter, Wilma G.; Van Bruggen, Ernst F. J. (January 1986). "Cyclic tetramolecular complexes of monoclonal antibodies: A new type of cross-linking reagent" . European Journal of Immunology. 16 (6): 679–683. doi:10.1002/eji.1830160615. ISSN   0014-2980. PMID   3459660.
  6. ↑ US4868109A,Lansdorp, Peter M.,"Immunological antibody complex, its preparation and its use",issued 1989-09-19
  7. ↑ Lansdorp PM; Dragowska W; Mayani H (1993). "Ontogeny-related changes in proliferative potential of human hematopoietic cells". The Journal of Experimental Medicine. 178 (3): 787–791. doi:10.1084/jem.178.3.787. PMC   2191172 . PMID   7688789.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  8. ↑ Vaziri, H; Dragowska, W; Allsopp, R C; Thomas, T E; Harley, C B; Lansdorp, P M (1994-10-11). "Evidence for a mitotic clock in human hematopoietic stem cells: loss of telomeric DNA with age". Proceedings of the National Academy of Sciences of the United States of America. 91 (21): 9857–9860. Bibcode:1994PNAS...91.9857V. doi: 10.1073/pnas.91.21.9857 . ISSN   0027-8424. PMC   44916 . PMID   7937905.
  9. ↑ Savage, Sharon A.; Stewart, Brian J.; Weksler, Babette B.; Baerlocher, Gabriela M.; Lansdorp, Peter M.; Chanock, Stephen J.; Alter, Blanche P. (2006-09-01). "Mutations in the reverse transcriptase component of telomerase (TERT) in patients with bone marrow failure" . Blood Cells, Molecules and Diseases. 37 (2): 134–136. doi:10.1016/j.bcmd.2006.07.001. ISSN   1079-9796. PMID   16934504.
  10. ↑ Alter, Blanche P.; Baerlocher, Gabriela M.; Savage, Sharon A.; Chanock, Stephen J.; Weksler, Babette B.; Willner, Judith P.; Peters, June A.; Giri, Neelam; Lansdorp, Peter M. (2007-09-01). "Very short telomere length by flow fluorescence in situ hybridization identifies patients with dyskeratosis congenita". Blood. 110 (5): 1439–1447. doi:10.1182/blood-2007-02-075598. ISSN   0006-4971. PMC   1975834 . PMID   17468339.
  11. ↑ Ly, Hinh; Calado, Rodrigo T.; Allard, Paulette; Baerlocher, Gabriela M.; Lansdorp, Peter M.; Young, Neal S.; Parslow, Tristram G. (2005-03-15). "Functional characterization of telomerase RNA variants found in patients with hematologic disorders". Blood. 105 (6): 2332–2339. doi:10.1182/blood-2004-09-3659. ISSN   0006-4971. PMID   15550482.
  12. ↑ Yamaguchi, Hiroki; Calado, Rodrigo T.; Ly, Hinh; Kajigaya, Sachiko; Baerlocher, Gabriela M.; Chanock, Stephen J.; Lansdorp, Peter M.; Young, Neal S. (2005-04-07). "Mutations in TERT, the Gene for Telomerase Reverse Transcriptase, in Aplastic Anemia". New England Journal of Medicine. 352 (14): 1413–1424. doi:10.1056/NEJMoa042980. ISSN   0028-4793. PMID   15814878.
  13. ↑ Lansdorp, P. (1996-05-01). "Heterogeneity in telomere length of human chromosomes". Human Molecular Genetics. 5 (5): 685–691. doi:10.1093/hmg/5.5.685. ISSN   1460-2083. PMID   8733138.
  14. ↑ Baerlocher, Gabriela M.; Vulto, Irma; De Jong, Gary; Lansdorp, Peter M. (December 2006). "nature.com" . Nature Protocols. 1 (5): 2365–2376. doi:10.1038/nprot.2006.263. PMID   17406480.
  15. ↑ Cheung I; Schertzer M; Rose A; Lansdorp PM (2002). "Disruption of dog-1 in Caenorhabditis elegans triggers deletions upstream of guanine-rich DNA". Nucleic Acids Research. 31 (4): 405–409. doi:10.1038/ng928. PMID   12101400.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  16. ↑ Lansdorp, Peter; van Wietmarschen, Niek (2019-10-31). "Helicases FANCJ, RTEL1 and BLM Act on Guanine Quadruplex DNA in Vivo". Genes. 10 (11): 870. doi: 10.3390/genes10110870 . ISSN   2073-4425. PMC   6896191 . PMID   31683575.
  17. ↑ Ding, Hao; Schertzer, Mike; Wu, Xiaoli; Gertsenstein, Marina; Selig, Sara; Kammori, Makoto; Pourvali, Reza; Poon, Steven; Vulto, Irma; Chavez, Elizabeth; Tam, Patrick P.L; Nagy, Andras; Lansdorp, Peter M (June 2004). "Regulation of Murine Telomere Length by Rtel". Cell. 117 (7): 873–886. doi: 10.1016/j.cell.2004.05.026 . ISSN   0092-8674. PMID   15210109.
  18. ↑ Falconer, Ester; Hills, Mark; Naumann, Ulrike; Poon, Steven S. S.; Chavez, Elizabeth A.; Sanders, Ashley D.; Zhao, Yongjun; Hirst, Martin; Lansdorp, Peter M. (November 2012). "DNA template strand sequencing of single-cells maps genomic rearrangements at high resolution". Nature Methods. 9 (11): 1107–1112. doi:10.1038/nmeth.2206. ISSN   1548-7105. PMC   3580294 . PMID   23042453.
  19. ↑ Porubský, David; Sanders, Ashley D.; Wietmarschen, Niek van; Falconer, Ester; Hills, Mark; Spierings, Diana C. J.; Bevova, Marianna R.; Guryev, Victor; Lansdorp, Peter M. (2016-11-01). "Direct chromosome-length haplotyping by single-cell sequencing". Genome Research. 26 (11): 1565–1574. doi:10.1101/gr.209841.116. ISSN   1088-9051. PMC   5088598 . PMID   27646535.
  20. ↑ Sanders, Ashley D.; Hills, Mark; Porubský, David; Guryev, Victor; Falconer, Ester; Lansdorp, Peter M. (November 2016). "Characterizing polymorphic inversions in human genomes by single-cell sequencing". Genome Research. 26 (11): 1575–1587. doi:10.1101/gr.201160.115. PMC   5088599 . PMID   27472961.
  21. ↑ Chaisson, Mark J. P.; Sanders, Ashley D.; Zhao, Xuefang; Malhotra, Ankit; Porubsky, David; Rausch, Tobias; Gardner, Eugene J.; Rodriguez, Oscar L.; Guo, Li; Collins, Ryan L.; Fan, Xian; Wen, Jia; Handsaker, Robert E.; Fairley, Susan; Kronenberg, Zev N. (2019-04-16). "Multi-platform discovery of haplotype-resolved structural variation in human genomes". Nature Communications. 10 (1): 1784. Bibcode:2019NatCo..10.1784C. doi:10.1038/s41467-018-08148-z. ISSN   2041-1723. PMC   6467913 . PMID   30992455.
  22. ↑ Hanlon, Vincent C.T.; Chan, Daniel D.; Hamadeh, Zeid; Wang, Yanni; Mattsson, Carl-Adam; Spierings, Diana C.J.; Coope, Robin J.N.; Lansdorp, Peter M. (January 2022). "Construction of Strand-seq libraries in open nanoliter arrays". Cell Reports Methods. 2 (1) 100150. doi:10.1016/j.crmeth.2021.100150. ISSN   2667-2375. PMC   9017222 . PMID   35474869.
  23. ↑ Akbari, Vahid; Hanlon, Vincent C.T.; O'Neill, Kieran; Lefebvre, Louis; Schrader, Kasmintan A.; Lansdorp, Peter M.; Jones, Steven J.M. (January 2023). "Parent-of-origin detection and chromosome-scale haplotyping using long-read DNA methylation sequencing and Strand-seq". Cell Genomics. 3 (1) 100233. doi:10.1016/j.xgen.2022.100233. ISSN   2666-979X. PMC   9903809 . PMID   36777186.
  24. ↑ Lansdorp, Peter M. (2022-02-10). "Telomeres, aging, and cancer: the big picture". Blood. 139 (6): 813–821. doi:10.1182/blood.2021014299. ISSN   0006-4971. PMC   8832478 . PMID   35142846.
  25. ↑ Lansdorp, Peter M. (May 2022). "Sex differences in telomere length, lifespan, and embryonic dyskerin levels". Aging Cell. 21 (5) e13614. doi:10.1111/acel.13614. ISSN   1474-9718. PMC   9124296 . PMID   35441417.
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