Peter Michael Lansdorp

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Peter Michael Lansdorp
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Born (1952-12-16) December 16, 1952 (age 71)
Netherlands
NationalityNetherlands
Alma mater
  • Erasmus University
  • University of Amsterdam
Occupation

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.[1] His research has focused on the biology of blood-forming stem cells, telomeres and genome analysis. He is also known for the development of techniques including single cell Strand-seq and fluorescence in situ hybridization (FISH) techniques such as Q-FISH and flow FISH.[2]

Early Life & 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.[2][1] His early career included work on monoclonal antibodies at Sanquin and he obtained a PhD from the University of Amsterdam in 1985.[1] Between 2011 and 2017, he served as 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 Hematology and Medical Genetics at the University of British Columbia.[3]

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.[4] This method was patented and later licensed to StemCell Technologies in Vancouver.</ref> Lansdorp's early work in Vancouver predominantly focused on experimental hematology. He first demonstrated that the functional properties of purified "candidate" blood forming stem cells, including their self-renewal properties, change dramatically during development.[5] He subsequently showed that telomere repeats are lost in purified hematopoietic stem cells supporting the concept that blood stem cells do not truly "self-renew" but are mortal like most other somatic cells.[6][7]

Lansdorp also developed a novel fluorescent in situ hybridization (FISH) method to measure the length of telomere repeats using peptide nucleic acid (PNA) probes.[8] He subsequently showed that flow cytometry can be used to measure the average telomere length in individual nucleated blood cells.[9][10]

In 2002 Lansdorp provided compelling evidence for the formation of guanine quadruplex (G4) DNA structures in C. elegans.[11] He proposed that the dog-1 helicase gene is required to unwind G4 DNA structures that occasionally form during DNA synthesis.[12] The closest human homolog of the dog-1 gene is the BRIP1 gene. These studies provided the first genetic evidence that G4 structures occur in vivo and that specialized helicases are required to unwind G4 structures and thus prevent instability of guanine-rich DNA.[12]

Subsequently, Lansdorp and colleagues identified a previously unknown helicase gene as a major regulator of telomere length in the mouse.[13] He named the 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,[14] which has diverse applications in genome science, including the production of chromosome-length haplotypes[15] and the characterization of polymorphic inversions.[16][17] In 2022, Lansdorp proposed theories regarding the role of telomerase in cancer suppression in long-lived vertebrates and the impact of high telomerase levels in preimplantation embryos in determining telomere length and lifespan differences between sexes (20).[18][19]

References

  1. ↑ 1.0 1.1 1.2 Lansdorp, Peter M. (2008). "Telomeres, stem cells, and hematology". Blood. 111 (4): 1759–1766. doi:10.1182/blood-2007-09-084913. PMC 2234038. PMID 18263784.
  2. ↑ 2.0 2.1 "» Peter Lansdorp". neuroscience.umcg.nl. Retrieved 2023-12-31.
  3. ↑ "open.library.ubc.ca".
  4. ↑ 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.
  5. ↑ Lansdorp, P. M.; 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. Retrieved 2023-12-31.
  6. ↑ 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.
  7. ↑ Savage, Sharon A.; Stewart, Brian J.; Weksler, Babette B.; Baerlocher, Gabriela M.; Lansdorp, Peter M.; Chanock, Stephen J.; Alter, Blanche P. (2006). "Mutations in the reverse transcriptase component of telomerase (TERT) in patients with bone marrow failure". Blood Cells, Molecules & Diseases. 37 (2): 134–136. doi:10.1016/j.bcmd.2006.07.001. ISSN 1079-9796. PMID 16934504.
  8. ↑ 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.
  9. ↑ Baerlocher, Gabriela M.; Vulto, Irma; de Jong, Gary; Lansdorp, Peter M. (December 2006). "Flow cytometry and FISH to measure the average length of telomeres (flow FISH)". Nature Protocols. 1 (5): 2365–2376. doi:10.1038/nprot.2006.263. ISSN 1750-2799. PMID 17406480.
  10. ↑ "Our telomere testing team | RepeatDx". repeatdx.com. 2019-06-14. Retrieved 2023-12-31.
  11. ↑ 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.
  12. ↑ 12.0 12.1 Cheung, Iris; Schertzer, Michael; Rose, Ann; Lansdorp, Peter M. (2006). "High incidence of rapid telomere loss in telomerase-deficient Caenorhabditis elegans". Nucleic Acids Research. 34 (1): 96–103. doi:10.1093/nar/gkj417. ISSN 0305-1048. PMC 1326242. PMID 16407328.
  13. ↑ Sarek, Grzegorz; Vannier, Jean-Baptiste; Panier, Stephanie; Petrini, John H.J.; Boulton, Simon J. (2015). "TRF2 Recruits RTEL1 to Telomeres in S Phase to Promote T-Loop Unwinding". Molecular Cell. 57 (4): 622–635. doi:10.1016/j.molcel.2014.12.024. PMC 4339303. PMID 25620558.
  14. ↑ 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.
  15. ↑ 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.
  16. ↑ 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. ISSN 1088-9051. PMC 5088599. PMID 27472961.
  17. ↑ 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.
  18. ↑ Lansdorp, Peter M. (2022). "Telomeres, aging, and cancer: The big picture". Blood. 139 (6): 813–821. doi:10.1182/blood.2021014299. PMC 8832478. PMID 35142846.
  19. ↑ 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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