Deregulated signaling pathways are known drivers of human diseases, and identifying their key nodes defines the basis of targeted therapy approaches. The druggable genome encodes well-characterized kinases and proteases that have been directly implicated in processing pathogenic signaling, particularly in oncogenic settings. My research activities are currently focused on validating such key enzymatic drivers of inflammatory and immune diseases to develop novel small molecule inhibitors and provide innovative therapies.
Our laboratory work includes:
Validating target dependency in relevant cellular models by siRNA and well-characterized tool inhibitors specific for known signaling nodes,
Developing proximal and distal cellular assays monitoring target activity and functional implications, respectively,
Implementing disease-relevant animal models for in vivo validation of target dependency.
Genetic resistance to JAK2 enzymatic inhibitors is overcome by HSP90 inhibition. Weigert O, Lane AA, Bird L, Kopp N, Chapuy B, van Bodegom D, Toms AV, Marubayashi S, Christie AL, McKeown M, Paranal RM, Bradner JE, Yoda A, Gaul C, Vangrevelinghe E, Romanet V, Murakami M, Tiedt R, Ebel N, Evrot E, De Pover A, Régnier CH, Erdmann D, Hofmann F, Eck MJ, Sallan SE, Levine RL, Kung AL, Baffert F, Radimerski T, Weinstock DM. J Exp Med. 2012 Feb 13;209(2):259-73.