Matt LaVoie, Ph.D.
Associate Professor of Neurology
Harvard Institutes of Medicine, room 762
77 Avenue Louis Pasteur
Boston, MA 02115
Visit my lab page here.
The overall goal of the LaVoie lab is to elucidate the underlying pathophysiology of Parkinson’s disease (PD). We consider not only the specific inherited gene mutations in familial forms of PD but also maintain a focus on the more common sporadic form of the disorder. Our study of familial PD is centered on pathogenic mutations in the Parkin and LRRK2 genes and our examination of idiopathic PD focuses on models of mitochondrial dysfunction.
Parkin is an ubiquitin E3 ligase that is highly expressed in neurons and loss-of-function mutations in Parkin are a common cause of autosomal recessive PD. The precise role of parkin within the neuron is not clear, however, data from multiple model organisms strongly support a homeostatic or pro-survival function of parkin influencing mitochondrial biology. We seek to understand how this cytosolic protein possesses such a potent influence on the mitochondria. Autosomal dominant, missense mutations in the multi-domain kinase, LRRK2, are the most common genetic cause of PD. Our recent work has shown that a highly active, dimeric conformation of LRRK2 resides on the cell membrane and ongoing work is directed towards the physiological implications of the unique subcellular distribution of LRRK2 and the impact of its pathogenic mutations.
Deficits in mitochondrial complex-1 have been widely reported in sporadic PD patients. Therefore, we have developed a series of in vitro and in vivo models of electron transport chain deficiency to elucidate the pathological impact of primary defects in mitochondrial function and their potential role in sporadic PD.
For a complete listing of publications click here.
Last Update: 10/30/2013