Scientist Profile

I started at Genentech in September 2008. Prior to that, I spent 14 years as a faculty member in the Boston area - first at Massachusetts General Hospital/Harvard Medical School and then at Massachusetts Institute of Technology (MIT), where I was Professor of Neuroscience. Before I got into research I was a practicing physician in London, U.K. So I have seen human disease from two sides - as a scientist investigating basic mechanisms and as a medical doctor treating patients.

I came to Genentech because I believe this company is best equipped to translate our increasing knowledge of the basic causes of disease into effective new treatments for serious brain disorders. I am energized by the people at Genentech, who have the right combination of know-how, creativity and motivation to make a difference for patients.

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My Focus

At Genentech we are committed to building a world-class Neuroscience Research program that will discover new drugs to treat major diseases of the nervous system. Not only are neurological and psychiatric conditions common and debilitating, but for many of them, there is no satisfactory treatment, a case in point being Alzheimer's disease. To meet these unmet needs, a current focus area of research is neurodegenerative disorders.

Much of my research is focused on brain "synapses," the tiny structures by which cells in the brain (neurons) contact and communicate with each other. Groups of neurons link together via synapses to form a functional "circuit." An emerging realization is that many diseases of the brain result from defective development or aberrant function of synapses, leading to circuit malfunction. For instance, Alzheimer's disease is characterized by severe loss of synapses in the brain as well as death of neurons. I believe that if we can understand the molecules that control the number, structure and function of synapses, we should be able to discover novel ways to treat many important neuropsychiatric illnesses.

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My Interests

Diseases of the nervous system have long afflicted large numbers of the world's population - in total, they inflict a terrible burden on patients, caregivers and society. Yet the treatment of most neurological and psychiatric disorders remains a huge unmet need. A big problem has been our ignorance of how the brain works normally and how it goes wrong in disease. In recent years, however, advances in neuroscience research are revealing the detailed mechanisms of neuronal and brain function, thus opening up promising new avenues for the treatment of neurodegeneration, psychosis, mood disorder, autism, pain and other conditions.

As a neuroscientist with a medical background, I am inspired to understand how the brain works from the level of molecule to cognitive behavior, and to tackle serious brain diseases based on understanding of biological mechanisms. These goals can only be achieved by the combined effort of many scientists, because neuroscience, perhaps more than any other branch of biology, is a multidisciplinary endeavor. Genentech - with its culture of scientific excellence, innovation and teamwork - offers a particularly stimulating and productive environment for realizing breakthrough drug discoveries. That is why I am excited to be here, working hard with my colleagues in Neuroscience Research.

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Publications & Recognition

• Caspase-3 activation via mitochondria is required for long-term depression and AMPA receptor internalization in hippocampal neurons.
• Cell 2010; (in press).
• Li Z, Jo J, Jia J-M, Lo S-C, Whitcomb DJ, Jiao S, Cho K, Sheng M.

• Autophosphorylated CaMKIIalpha acts as a scaffold to recruit proteasomes to dendritic spines.
• Cell 2010 Feb 19; 140(4): 567-78.
• Bingol B, Wang CF, Arnott D, Cheng D, Peng J, Sheng M.
• View Abstract on PubMed

• Regulation of synaptic structure and function by FMRP-associated microRNAs miR-125b and miR-132.
• Neuron 2010 Feb 11; 65(3): 373-84.
• Edbauer D, Neilson JR, Foster KA, Wang CF, Seeburg DP, Batterton MN, Tada T, Dolan BM, Sharp PA, Sheng M.
• View Abstract on PubMed