Peter J Peters

Prof. Dr. Peter J Peters

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Academic Career Length

36Years (1991-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

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3 July 2020 in Science
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MLMart M. Lamers
Mart M. Lamers
JBJoep Beumer
Joep Beumer
JVJelte van der Vaart
Jelte van der Vaart
KKKèvin Knoops
Kèvin Knoops
JPJens Puschhof
Jens Puschhof
Hans CleversHans Clevers
Hans Clevers
Intestinal organoids as an infection model: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes an influenza-like disease with a respiratory transmission route; however, patients often present with gastrointestinal symptoms such as diarrhea, vomiting, and abdominal pain. Moreover, the virus has been detected in anal swabs, and cells in the inner-gut lining express the receptor that SARS-CoV-2 uses to gain entry to cells. Lamers et al. used human intestinal organoids, a “mini-gut” cultured in a dish, to demonstrate that SARS-CoV-2 readily replicates in an abundant cell type in the gut lining—the enterocyte—resulting in the production of large amounts of infective virus particles in the intestine. This work demonstrates that intestinal organoids can serve as a model to understand SARS-CoV-2 biology and infectivity in the gut. Science , this issue p. 50
1 February 1991 in Journal of Biological Chemistry
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Journal Article
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MMM J Metzelaar
M J Metzelaar
PWP L Wijngaard
P L Wijngaard
PPPeter J Peters
Peter J Peters
JSJ J Sixma
J J Sixma
HNH K Nieuwenhuis
H K Nieuwenhuis
Hans CleversHans Clevers
Hans Clevers
To clone the CD63 antigen, originally described as a blood platelet activation marker, we adapted the expression cloning procedure of Seed and Aruffo (Seed, B., and Aruffo, A. (1987) Proc. Natl. Acad. Sci. U.S. A. 84, 3365-3369) to allow cloning of intracellular antigens. A megakaryocyte expression cDNA library was transiently transfected into MOP-8 mouse fibroblasts cultured on polyvinylidene difluoride membranes. Individual cells expressing intracellular CD63 were identified by autoradiography. cDNA was extracted from positive spots and reintroduced into Escherichia coli. After two screening rounds, a CD63 cDNA clone was isolated as assessed by immunofluorescence and Western blot analysis. The single long open reading frame of 238 amino acids contained four putative transmembrane regions and three N-glycosylation sites. The CD63 gene was expressed in a wide variety of cells. Surprisingly, CD63 was identical to ME491, an antigen reported as a melanoma-associated antigen (Hotta, H., Ross, A. H., Huebner, K., Isobe, M., Wendeborn, S., Chao, M. V., Ricciardi, R. P., Tsujimoto, Y., Croce, C. M., and Koprowski, H. (1988) Cancer Res. 48, 2955-2962). By immunoelectron microscopy, co-localization with the lysosomal glycoproteins lamp-1 and -2 identified CD63 as a novel lysosomal membrane glycoprotein. CD63 was not related to the lysosomal glycoprotein family but contained the putative lysosomal targeting signal Gly-Tyr in its short cytoplasmic tail.
23 February 2023 in Nature Biotechnology
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DHDelilah Hendriks
Delilah Hendriks
JBJos F. Brouwers
Jos F. Brouwers
KHKarien Hamer
Karien Hamer
MGMaarten H. Geurts
Maarten H. Geurts
LLLéa Luciana
Léa Luciana
Hans CleversHans Clevers
Hans Clevers
The lack of registered drugs for nonalcoholic fatty liver disease (NAFLD) is partly due to the paucity of human-relevant models for target discovery and compound screening. Here we use human fetal hepatocyte organoids to model the first stage of NAFLD, steatosis, representing three different triggers: free fatty acid loading, interindividual genetic variability (PNPLA3 I148M) and monogenic lipid disorders (APOB and MTTP mutations). Screening of drug candidates revealed compounds effective at resolving steatosis. Mechanistic evaluation of effective drugs uncovered repression of de novo lipogenesis as the convergent molecular pathway. We present FatTracer, a CRISPR screening platform to identify steatosis modulators and putative targets using APOB−/− and MTTP−/− organoids. From a screen targeting 35 genes implicated in lipid metabolism and/or NAFLD risk, FADS2 (fatty acid desaturase 2) emerged as an important determinant of hepatic steatosis. Enhancement of FADS2 expression increases polyunsaturated fatty acid abundancy which, in turn, reduces de novo lipogenesis. These organoid models facilitate study of steatosis etiology and drug targets.
7 May 2021 in Nature Methods
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GWGiulia Weissenberger
Giulia Weissenberger
RHRene J. M. Henderikx
Rene J. M. Henderikx
PPPeter J Peters
Peter J Peters
22 May 2020 in Nature Communications
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Journal Article
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RRRaimond Ravelli
Raimond Ravelli
FNFrank J. T. Nijpels
Frank J. T. Nijpels
RHRene J. M. Henderikx
Rene J. M. Henderikx
GWGiulia Weissenberger
Giulia Weissenberger
STSanne Thewessem
Sanne Thewessem
PPPeter J Peters
Peter J Peters
: The increasing demand for cryo-electron microscopy (cryo-EM) reveals drawbacks in current sample preparation protocols, such as sample waste and lack of reproducibility. Here, we present several technical developments that provide efficient sample preparation for cryo-EM studies. Pin printing substantially reduces sample waste by depositing only a sub-nanoliter volume of sample on the carrier surface. Sample evaporation is mitigated by dewpoint control feedback loops. The deposited sample is vitrified by jets of cryogen followed by submersion into a cryogen bath. Because the cryogen jets cool the sample from the center, premounted autogrids can be used and loaded directly into automated cryo-EMs. We integrated these steps into a single device, named VitroJet. The device’s performance was validated by resolving four standard proteins (apoferritin, GroEL, worm hemoglobin, beta-galactosidase) to ~3 Å resolution using a 200-kV electron microscope. The VitroJet offers a promising solution for improved automated sample preparation in cryo-EM studies.
15 March 2017 in Development
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NSNorman Sachs
Norman Sachs
YTYoshiyuki Tsukamoto
Yoshiyuki Tsukamoto
PKPekka Kujala
Pekka Kujala
PPPeter J Peters
Peter J Peters
Hans CleversHans Clevers
Hans Clevers
Multiple recent examples highlight how stem cells can self-organize in vitro to establish organoids that closely resemble their in vivo counterparts. Single Lgr5+ mouse intestinal stem cells can be cultured under defined conditions forming ever-expanding epithelial organoids that retain cell polarization, cell type diversity and anatomical organization of the in vivo epithelium. Although exhibiting a remarkable level of self-organization, the so called ‘mini-guts’ have a closed cystic structure of microscopic size. Here, we describe a simple protocol to generate macroscopic intestinal tubes from small cystic organoids. Embedding proliferating organoids within a contracting floating collagen gel allows them to align and fuse to generate macroscopic hollow structures (‘tubes’) that are lined with a simple epithelium containing all major cell types (including functional stem cells) of the small intestine. Cells lining the central contiguous lumen closely resemble the epithelial cells on luminal villi in vivo, whereas buds that protrude from the main tube into the surrounding matrix closely resemble crypts. Thus, the remarkable self-organizing properties of Lgr5+ stem cells extend beyond the level of the microscopic cystic organoid to the next, macroscopic, level of tube formation.