Dr. Patrick Zeeuwen
Dr. P.L.J.M. Zeeuwen
Research focuses on cellular differentiation programs that regulate the formation and homeostasis of the epidermis. Experimental approaches include genetics, mouse models, and in vitro model systems for skin barrier function/dysfunction. This work aims to get fundamental insights into the biology of skin barrier formation and cutaneous host defense mechanisms. From a clinical perspective, this work is relevant for elucidation of monogenic diseases and the proposed role of compromised skin barrier function in development of inflammatory skin diseases like psoriasis and atopic dermatitis.
In current projects we aim to develop and characterize an in vitro reconstructed skin model for normal human skin and lesional psoriatic skin, using keratinocytes and autologous immunocompetent cells from genetically characterized donors, and to identify ligands and pathways that control the vicious circle of keratinocyte and T-cell activation. Furthermore, a new project has been started to make a complete analysis of the microbiome of human skin in health and disease (psoriasis, atopic dermatitis). This will be performed by the latest DNA sequencing technology (454 "deep" sequencing). We will study the dynamics of the bacterial flora on human skin and perform functional studies on the interaction between bacteria and human epidermal cells.
Recent key publications
de Koning,H.D., Rodijk-Olthuis,D., van Vlijmen-Willems,I.M., Jooste,L.A., Netea,M.G., Schalkwijk,J. and Zeeuwen,P.L. (2010) A comprehensive analysis of pattern recognition receptors in normal and inflamed human epidermis: upregulation of dectin-1 in psoriasis. J. Invest. Dermatol. Jul 15. [Epub ahead of print]
Zeeuwen,P.L., van Vlijmen-Willems,I.M., Rodijk-Olthuis,D., Cheng,T., Hitomi,K., Hara-Nishimura,I., John,S., Smyth,N., Reinheckel,T., Hendriks,W.J., and Schalkwijk,J. (2010) The cystatin M/E - cathepsin L balance is essential for tissue homeostasis in epidermis, hair follicles and cornea. FASEB J May 21. [Epub ahead of print]
Zeeuwen,P.L., Cheng,T., and Schalkwijk,J. (2009) The biological role of cystatin M/E and its cognate target proteases. J.Invest.Dermatol. 129:1327-1338.
Cheng,T., van Vlijmen-Willems,I.M., Hitomi,K., Pash,M.C., van Erp,P.E., Schalkwijk,J., and Zeeuwen,P.L. (2009) 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. 129:1232-1242. Figure 2a-c of this paper was used as cover for this issue.
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. 41:211-215.*shared first-authorship.
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.
Hollox,E.J., Huffmeier,U., Zeeuwen,P.L., Palla,R., Lascorz,J., Rodijk-Olthuis,D., van de Kerkhof,P.C., Traupe,H., de Jongh,G.J., den Heijer,M., Reis,A., Armour,J.A., and Schalkwijk,J. (2008) Psoriasis is associated with increased beta-defensin genomic copy number. Nat. Genet. 40:23-25.
Zeeuwen,P.L., Ishida-Yamamoto,A., van Vlijmen-Willems,I.M., Cheng,T., Bergers,M., Iizuka,H., and Schalkwijk,J. (2007) Co-localization 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. Figure 3f of this paper was used as cover for this issue.
Cheng,T., Hitomi,K., van Vlijmen-Willems,I.M., 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.
