Scientist Profile

I joined Genentech for the opportunity to do cutting edge science in a truly collaborative research environment, and for the potential to translate basic science discoveries made in my lab to effective treatments for disease. I currently split my time between being a project team leader for a drug development program and directing a research group working to identify novel targets for the treatment of chronic neurodegenerative diseases such as Alzheimer's disease and Amyotrophic Lateral Sclerosis (ALS).

My Focus

Research in my lab is focused on understanding whether conserved pathways underlie neuronal degeneration in development and disease.

Synapse elimination, degeneration of neuronal processes, and neuronal loss occur in both of these contexts, and our hope is that defining the core mechanisms that regulate this degeneration will lead to attractive drug targets.

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My Interests

I am particularly interested is Amyotrophic Lateral Sclerosis, also known as Lou Gehrig's disease, which is a disorder characterized by muscle weakness, loss of coordination, and eventual paralysis. Though in most cases the exact cause of disease is not known, those who are afflicted by ALS are linked by common symptoms that result from degeneration of motor neurons. We hypothesize that common molecular mechanisms must underlie at least a portion of the degeneration observed in ALS, and these key points in the pathway provide the best opportunity for therapeutic intervention. We have been able to identify a number of candidate drug targets using this approach and are currently working to further define their role in disease.

Postdoctoral Mentor

I greatly enjoy being a postdoctoral mentor, and think it is one of the highlights doing research at Genentech. It allows the lab to really dive into the molecular mechanisms of neuronal development, degeneration, and regeneration. Our recent work has identified Dual Leucine zipper Kinase (DLK) as an essential upstream regulator axon degeneration and apoptosis in the developing nervous system, a function that appears conserved in multiple neuronal subtypes. Ongoing projects in the lab are looking to better define DLK dependent pathways, identify additional regulators of degeneration, and examine the relevance of these pathways to neurodegenerative disease.

Publications & Recognition

• A Whole Cell Assay to Measure Caspase-6 Activity by Detecting Cleavage of Lamin A/C
• (2012) PLOS One, ;7(1):e30376. Epub 2012 Jan 12.
• Mintzer R, Ramaswamy S, Shah K, Hannoush RN, Pozniak CD, Cohen F, Zhao X, Plise E, Lewcock JW, Heise CE

• DLK induces developmental neuronal degeneration via selective regulation of proapoptotic JNK activity.
• (2011) J Cell Biol. Sep 5;194(5):751-64.
• Ghosh AS, Wang B, Pozniak CD, Chen M, Watts RJ, Lewcock JW.

• Presenilin-dependent receptor processing is required for axon guidance
• (2011) Cell. Jan 7;144(1):106-18
• Bai G, Chivatakarn O, Bonanomi D, Lettieri K, Franco L, Xia C, Stein E, Ma L, Lewcock JW, Pfaff SL