Select Page

The Lefler Center

for the study of Neurodegenerative Diseases

Alban Ordureau

Research Fellow in Neurology, The Harper Lab, Department of Cell Biology, Harvard Medical School;

2016-2017 Lefler Fellow

1.  What motivated you to come to Harvard Medical School?

During my PhD, my research focused on using biochemistry and cell biology to study cellular signaling pathways that govern activation, regulation, localization or degradation of proteins in a cell. Specifically, I focused on how processes called phosphorylation and ubiquitylation, which add tags onto proteins, affect protein function. After my graduate training, I sought a lab that would allow me to further study these modifications, but from a different perspective. The strength of the mass spectrometry skills at Harvard Medical School directly drew me to Boston for my post-doctoral research. Mass spectrometry is a technology that enables precise and accurate measurement and identification of thousands of proteins in a sample, even detecting whether a protein has been modified by phosphorylation and ubiquitylation. I was really attracted here by the idea of learning more about what mass spectrometry can reveal about cellular signaling.

2. What is your current area of research?

I am particularly interested in what happens to phosphorylation and ubiquitylation of proteins when mitochondria, the energy supplier of the cell, are damaged. What we, and others, have found is that cells have a very precise and sophisticated process to get rid of damaged mitochondria, which is called mitophagy. This is very important process; if it is impaired then damaged mitochondria generate toxic species that can spread to other healthy mitochondria in the cell, and ultimately kill the cell. We and others have shown that once a mitochondrion is severely damaged it starts a cascade of phosphorylation and ubiquitylation events that lead to recycling of the damaged mitochondria to prevent the spread of toxic species. Two of the proteins I study are mutated in some early-onset form of Parkinson’s disease and are key players that get rid of damaged mitochondria. Therefore, our hypothesis is that Parkinson’s disease may be rooted in the way the cell deals, or fails to deal with, damaged mitochondria.

3. How does your research relate to diseases of the nervous system?

The proteins I focus on, called PINK1 and Parkin, are mutated in some early-onset form of Parkinson’s disease and are key players that help cells to get rid of damaged mitochondria.
More generally, a growing body of evidence suggests that defects in mitochondrial quality control may also be what underlies many other neurodegenerative diseases. For example, we have recently discovered two other proteins, called TBK1 and Optineurin, that are involved in the mitophagy pathway, and have also been linked directly to Amyotrophic Lateral Sclerosis, also known as Lou Gehrig’s disease.

4. What has your Lefler fellowship allowed you to do as a scientist?

The Lefler fellowship has allowed me to transpose what I had learned and developed over the years in biochemistry and cell signaling to neuronal cells so as to better understand the pathology underlying Parkinson’s disease. Our goal has been to use mass spectrometry approaches to address the mechanism of Parkin activation and mitophagy in cortical as well as dopaminergic neurons, which are the primary cells afflicted in Parkinson’s disease. To this end, I have developed a novel platform for quantitative analysis of PARKIN activity in vivo and in vitro using Parallel Reaction Monitoring, an approach that allows quantitative analysis of modified proteins with unprecedented sensitivity.

5. What are your research goals?

My aim is to be able to picture all of the cell signals, protein activity and interactions that when impaired can ultimately lead to the neurodegenerative disease. If we understand how everything works at a molecular level then we can understand how each pathogenic mutation affects a specific pathway or step in the process of disease.

Back to Fellows & Faculty >