Peter Lansdorp - Major research contributions#

A summary of the major research contributions by Peter Lansdorp is given below.

1. As a graduate student in Amsterdam, the Netherlands, Peter Lansdorp discovered a way to cross-link monoclonal antibodies into tetrameric antibody complexes. This discovery has found numerous applications and tetrameric antibody complexes are currently used worldwide in various cell separation techniques (commercialized by Stem Cell Technologies Inc in Vancouver).

2. As a Principal Investigator in the Terry Fox Laboratory in Vancouver, Lansdorp showed that the functional properties of purified blood stem cells, including their self-renewal properties, change dramatically during development. He subsequently found that the telomere length in these cells decreases with age. These findings support the concept that human blood stem cells do not truly "self-renew" but are mortal like most other somatic cells. These major contributions are increasingly being recognized worldwide especially now that Lansdorp has shown in more recent, collaborative, studies that telomerase deficiencies can result in bone marrow failure and other hypo-proliferative disorders.

3. In 1995, Lansdorp developed novel fluorescent in situ hybridization (FISH) methods to measure the length of telomere repeats using peptide nucleic acid (PNA) probes during a sabbatical at the Leiden University in the Netherlands. This method has enabled numerous studies and observations in the telomere field. Dr. Lansdorp was a co-author of a landmark paper in Cell (1997, 1221 citations, with a cover image from his lab) defining the molecular phenotype of a telomerase-deficient mouse which highlighted the advantages of PNA-FISH over conventional methods to measure telomere length. His laboratory subsequently showed that flow cytometry can also be used to measure the telomere length of individual nucleated blood cells. This so-called Flow-FISH technique is now the method of choice to screen for possible genetic defects in telomere maintenance in humans and is offered by Repeat Diagnostics Inc., a biotech start-up company founded by Lansdorp.

4. In collaboration with Dr. Ann Rose at UBC, Lansdorp’s laboratory published a landmark paper in 2002 that provides compelling evidence for the formation of guanine quadruplex (G4) DNA structures in C. elegans. In this paper, Dr. Lansdorp proposed that a gene that was called dog-1 is required to unwind G4 DNA structures that occasionally form during lagging strand DNA synthesis. The closest human homolog of the dog-1 gene is the FANC-J gene. These findings and the implications of this work for studies of patients with Fanconi anemia are now emerging. In collaboration with Dr. Andras Nagy in Toronto, Lansdorp’s laboratory cloned and characterized a novel gene in the mouse which he called Rtel (for "Regulator of Telomere Length"), the major regulator of telomere length in the mouse. This landmark paper implicates a previously unknown gene as a major regulator of telomere length.

5. One of the latest research interests of Lansdorp is to investigate the possibility that development of multi-cellular organisms is regulated in part by epigenetic differences between sister chromatids. For this purpose, Lansdorp framed the “silent sister” hypothesis. His laboratory recently described that DNA template strand sequences can be used to identify sister chromatids and his new group in Groningen is now using this approach to test the “silent sister” hypothesis, amongst others within the framework of the recently awarded ERC Advanced Grant entitled ‘Role of telomeres and stem cells in ageing’ (acronym: ROOTS). His laboratory developed novel single cell DNA template strand sequencing techniques to test the "silent sisiter" hypothesis. The Strand-seq method appears extremely powerful for a wide variety of applications including the detection of copy number variations, haplotyping, reference genome editing, sister chromatid exchange mapping and enumeration and analysis of chromosomal rearrangements.
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