Dr. Patrick Zeeuwen
Laboratory
of Skin Biology and Experimental Dermatology
Radboud University Nijmegen Medical Centre
Nijmegen Centre for Molecular Life Sciences
PO Box 9101, 6500 HB Nijmegen
The Netherlands
phone: 31-24-3617245
fax: 31-24-3541184
p.zeeuwen@ncmls.ru.nl
www.ncmls.nl
Research
focus
- The role of proteases and protease inhibitors in epidermal differentiation
and desquamation
- The role of transglutaminases in epidermal cornification
- Mouse models (transgenic and knockout) to study the role of proteases,
protease inhibitors and transglutaminases in skin and other epithelia
Figure left: Phenotype
of ichq mice. Cystatin M/E deficient mice (9 days of age)
are covered with white scales which start to appear at day 5 on the
dorsal skin,
just behind the neck. The mice die between day 6 and 12 from dehydration.
Figure right: Cystatin M/E expression in normal human skin.
Formalin fixed section of normal human skin was stained by rabbit anti-cystatin
M/E antiserum.
Staining is limited to the stratum granulosum. Bar = 100 µm.
From Zeeuwen et al 2009 J Invest Dermatol doi:10.1038/jid.2009.40
Important publications
- Zeeuwen,P.L., Cheng,T., and Schalkwijk,J. (2009) The biological
role of cystatin M/E and its cognate target proteases (Review). J.Invest.Dermatol.
doi:10.1038/jid.2009.40
- de Cid,R.*, Riveira-Munoz,E*., Zeeuwen,P.L.*, Robarge,J.*, Liao,W.,
Dannhauser,E.N., Giardina,E., Stuart,P.E., Nair,R., Helms,S., Escaramis,G.,
Ballana,E., Martin-Ezquerra,G., den Heijer,M., Kamsteeg,M., Eichler,E.E.,
Lazara,C., Pujol,R.M., Armengol,L., Abecasis,G., Elder,J.T., Novelli,G.,
Armour,J.A., Kwok,P., Bowcock,A., Schalkwijk,J., and Estivill,X. (2009)
Deletion of the late cornified envelope (LCE) 3C and 3B genes as a
susceptibility factor for psoriasis. Nat Genet. 41(2):211-5.
*shared first-authorship
- Cheng,T., van Vlijmen-Willems,I.M., Hitomi,K., Pash,M.C., van Erp,P.E.,
Schalkwijk,J., and Zeeuwen,P.L. (2008) Colocalization of cystatin
M/E and its target proteases suggests a role in terminal differentiation
of the human hair follicle and nail. J.Invest.Dermatol. doi: 10.1038/jid.2008.353
- Zeeuwen,P.L., de Jongh,G.J., Rodijk-Olthuis,D., Kamsteeg,M., Verhoosel,R.M.,
van Rossum,M.M., Hiemstra,P.S., and Schalkwijk,J. (2008) Genetically
programmed differences in epidermal host defense between psoriasis
and atopic dermatitis. PLoS ONE 3(6): e2301
- Zeeuwen,P.L., Ishida-Yamamoto,A., van Vlijmen-Willems,I.M., Cheng,T.,
Bergers,M., Iizuka,H., and Schalkwijk,J. (2007) Colocalization of
cystatin M/E and cathepsin V in lamellar granules and corneodesmosomes
suggests a functional role in epidermal differentiation. J.Invest.Dermatol.
127:120-128
- Cheng,T., Hitomi,K., van Vlijmen-Willems,I.M., de Jongh,G.J., Yamamoto,K.,
Nishi,K., Watts,C., Reinheckel,T., Schalkwijk,J., and Zeeuwen,P.L.
(2006) Cystatin M/E is a high affinity inhibitor of cathepsin V and
cathepsin L by a reactive site that is distinct from the legumain-binding
site. A novel clue for the role of cystatin M/E in epidermal cornification.
J.Biol.Chem. 281:15893-15899
- Zeeuwen,P.L. (2004) Epidermal differentiation: The role of proteases
and their inhibitors (Review). Eur.J.Cell Biol. 83:761-773
- Zeeuwen,P.L., Vlijmen-Willems,I.M., Olthuis,D., Johanson,H.T., Hitomi,K.,
Hara-Nishimura,I., Powers,J.C., James,K.E., Op Den Camp,H.J., Lemmens,R.,
and Schalkwijk,J. (2004) Evidence that unrestricted legumain activity
is involved in disturbed epidermal cornification in cystatin M/E deficient
mice. Hum.Mol.Genet. 13:1069-1079