Vice President, Neuroscience & Molecular Biology
"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."
years at Genentech
awards & honors
I started at Genentech in September 2008. Prior to that, I spent 14 years in academia focused on molecular and cellular neuroscience - first at Massachusetts General Hospital/Harvard Medical School and then at Massachusetts Institute of Technology (MIT), where I was the Menicon Professor of Neuroscience and an Investigator of the Howard Hughes Medical Institute. Before I got into research I completed a residency in general medicine 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 potential 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.
I have mentored over 30 postdocs and PhD students at Harvard, MIT and Genentech. Many have gone on to successful careers in academia (MGH/Harvard, Broad Institute, UCSD, Vanderbilt, Georgetown, Wisconsin, Erasmus (Netherlands), International Institute of Molecular and Cell Biology in Warsaw (Poland), CNR, Milano (Italy), Univ Munich (Germany), London Univ (UK), KAIST (Korea), Academia Sinica (Taiwan) etc), and industry (Amgen, Biogen, Vertex, Otsuka, etc). Presently there are 5-6 postdocs and 1 Senior Research Associate in my lab.
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.
At Genentech, we have built a world-class Neuroscience Department and research program committed to understanding the mechanisms underlying major diseases of the nervous system and discovering drugs for these disorders.
My lab’s research is broadly divided into three areas: (i) the molecular mechanisms of synapse weakening and loss (which are characteristic of neurodegenerative disorders such as Alzheimer’s); (ii) the molecular regulation of synapses on inhibitory interneurons (dysfunction of which is implicated in schizophrenia and autism); (iii) uncovering fresh insights into the pathogenesis of Alzheimer’s disease, Parkinson’s disease and frontotemporal dementia, starting from identification of novel human gene mutations that increase the risk of these disorders. These directions of research should yield new mechanisms and pathways that are of wide scientific interest and that might be a strategy for neurodegenerative and neurodevelopmental diseases.
Activity-Induced Nr4a1 Regulates Spine Density and Distribution Pattern of Excitatory Synapses in Pyramidal NeuronsNeuron, 2014, ISSN: 0896-6273 (ISSNLinking) View on PubMed
The mitochondrial deubiquitinase USP30 opposes parkin-mediated mitophagyNature, 2014, ISSN: 0028-0836 View on PubMed
Local pruning of dendrites and spines by caspase-3-dependent and proteasome-limited mechanismsJournal of Neuroscience, 2014, ISSN: 0270-6474 View on PubMed
Long-term depression: a cell biological viewPhilosophical transactions of the Royal Society of London. Series B, Biological sciences, 2013, ISSN: 0962-8436 View on PubMed
GPR3 Stimulates Aβ Production via Interactions with APP and β-Arrestin2PLoS ONE, 2013, ISSN: 1932-6203 View on PubMed
NMDA receptors in nervous system diseasesNeuropharmacology, 2013, ISSN: 0028-3908 View on PubMed
Specific Trans-synaptic interaction with inhibitory interneuronal neurexin underlies differential ability of neuroligins to induce functional inhibitory synapsesJournal of Neuroscience, 2013, ISSN: 0270-6474 View on PubMed
Neuroscience: Strength in numbersNature, 2013, ISSN: 0028-0836 View on PubMed
GluN2B Antagonism Affects Interneurons and Leads to Immediate and Persistent Changes in Synaptic Plasticity, Oscillations and BehaviorNeuropsychopharmacology, 2013, ISSN: 0006-3223 View on PubMed
Caspase-3 in the central nervous system: Beyond apoptosisTrends in Neurosciences, 2012, ISSN: 0166-2236 View on PubMed
Three-dimensional imaging of solvent-cleared organs using 3DISCONature Protocols, 2012, ISSN: 1750-2799 View on PubMed
Childhood disorders of the synapse: Challenges and opportunitiesScience Translational Medicine, 2012, ISSN: 1946-6234 View on PubMed
Caspase-3 Activation via Mitochondria is Required for Long-Term Depression and AMPA Receptor Internalization.Cell, 2010, ISSN: 0092-8674
Autophosphorylated CaMKIIα Acts as a Scaffold to Recruit Proteasomes to Dendritic Spines.Cell, 2010, ISSN: 0092-8674
- Harvard University, Molecular Genetics, Ph.D. – 1990
- Harvard University, USA, Ph.D. – 1990
- Oxford University, UK, M.A. – 1984
- London University, U.K., Guys Hospital Medical School, Medicine, M.B.B.S. – 1982
- Oxford University, UK, B.A. – 1979
Awards & Honors
- Fellow of the Academy of Medical Sciences (UK) – 2009
- Fellow of the Royal Society (FRS), London, UK – 2007
- Fondation IPSEN Prize for Neuronal Plasticity – 2006
- Fellow of the American Association for the Advancement of Science (AAAS) – 2004
- Young Investigator Award, Society for Neuroscience – 1999
- Presidential Early Career Award for Scientists and Engineers – 1996