Peter Brouckaert
Molecular Pathophysiology and Experimental Therapy
VIB Department for Molecular Biomedical Research, UGent

MD: Univ. of Ghent, Ghent, Belgium, '84 VIB Group leader since 1996

e-mail phone +32 9 331 37 10 ADDRESS

Current team members
Group leader: Peter Brouckaert
Staff scientist: Anje Cauwels
Postdoctoral scientist: Leander Huyghe
Ph.D. Student: Ben Vandendriessche
Support personnel: Elke Rogge

Keywords
cytokines and anticancer therapy - mouse transgenesis - NO and guanylate cyclase in inflammation and shock - TNF - mouse models of inflammation

Science

Based upon previous research on the in vivo effects of cytokines, our group uses molecular technology (e.g. transgenesis) to study the molecular mechanisms of inflammatory and vascular reactions at the level of the organism (mouse models). The ultimate goal is to identify and validate new molecular targets, particularly those modulating the NO/sGC/cGMP pathway, and to establish new cancer treatments disrupting the neovasculature.
Our group provided proofs of principle that the remarkably effective antitumour activities of TNF (also observed in patients in locoregional treatment) are not inevitably linked to the shock-inducing effects. Currently, the molecular mechanisms of this in vivo antitumour activity, which is essentially a selective disruption of the tumour vasculature, are dissected in detail, in order to identify downstream targets enabling selective induction of these antitumour effects, without inducing shock. NO-related research includes a mouse transgenic approach for the target validation of sGC (cytosolic guanylate cyclase) and its isoforms. Target identification and validation in the NO-dependent and NO–independent pathways involved in various forms of shock is the second branch of this program. A third branch is the transcriptome profiling of macrophages.

Link to Group's website for more details.

Press releases
See also press release (15/12/2009): Septic shock: nitric oxide beneficial after all based on a publication Journal of Experimental Medicine (Cauwels et al.)

Buys E, Sips P, Vermeersch P, Raher M, Rogge E, Ichinose F, Dewerchin M, Bloch K, Janssens S, Brouckaert P
Gender-specific hypertension and responsiveness to nitric oxide in sGCalpha1 knockout mice
CARDIOVASC RES 79, 179-86, 2008



Vermeersch P, Buys E, Pokreisz P, Marsboom G, Ichinose F, Sips P, Pellens M, Gillijns H, Swinnen M, Graveline A, Collen D, Dewerchin M, Brouckaert P, Bloch K, Janssens S
Soluble guanylate cyclase-alpha1 deficiency selectively inhibits the pulmonary vasodilator response to nitric oxide and increases the pulmonary vascular remodeling response to chronic hypoxia
CIRCULATION 116, 936-43, 2007



Cauwels A, Janssen B, Buys E, Sips P, Brouckaert P
Anaphylactic shock depends on PI3K and eNOS-derived NO
J CLIN INVEST 116, 2244-51, 2006



Brouckaert P, Takahashi N, Van Tiel t, Hostens J, Eggermont A m, Seynhaeve A b, Fiers W, Ten Hagen T m
Tumor necrosis factor-alpha augmented tumor response in B16BL6 melanoma-bearing mice treated with stealth liposomal doxorubicin (Doxil(R)) correlates with altered Doxil(R) pharmacokinetics
INT J CANCER 109, 442-448, 2004



Cauwels A, Janssen B, Waeytens A, Cuvelier C, Brouckaert P
Caspase inhibition causes hyperacute tumor necrosis factor-induced shock via oxidative stress and phospholipase A2
NAT IMMUNOL 4, 387-393, 2003

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