Lucía Chávez-Gutiérrez (LCG) holds a PhD in Sciences with a major in Biochemistry from the National University of Mexico. Trained as an enzymologist with a strong background in structural biology, LCG explores proteolytic mechanisms and their (dys)regulation, under the premise that developing a solid mechanistic understanding of these processes will offer critical insights into how proteolytic switches control fundamental processes in physiology and disease.

Her fascination for proteases motivated her postdoctoral studies on γ-secretase intramembrane proteases in the laboratory of Bart De Strooper at the VIB-KU Leuven Center for Brain and Disease Research, Belgium. LCG’s studies on γ-secretase proteases and their pathogenic involvement in the familial form of Alzheimer‘s disease (AD) settled down a long-standing “loss-of-function vs. gain-of-function” debate on familial AD etiology (Chávez-Gutiérrez et al, EMBO 2012; Szaruga et al, JEM 2015 and Veugelen et al, Neuron 2016). In this work, she demonstrated that disease-linked mutations in Presenilin (catalytic subunit of the γ-secretase)and the amyloid precursor protein (APP) have no consistent inhibitory effects on the global activity of the protease-that controls key signalling cascades- but invariably lead to enhanced generation of longerand amyloidogenic Aβ peptides from APP.

Her recent mechanistic work depicts γ-secretases as metastable structures and AD-linked mutations as destabilizing variants that weaken γ-secretase and APP (enzyme and substrate) interactions during proteolysis and thereby lead to enhanced generation of amyloidogenic Aβs (Szaruga et al, Cell 2017).  These findings place Aβ at the core of ADpathogenesis and importantly, put forward a novel model for the sporadic and most common form of Alzheimer‘s disease, in which environmental factors (potentially linked to aging, diet or life style) modulating the stability of γ-secretase/APP interactions alter the risk for AD.

LCG lives in Belgium with her husband and two children. She is group leader at the VIB Center for Brain and Disease Research  and Assistant Professor at the University of Leuven.