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Heads of Laboratories

Head shot of Marc Tessier-Lavigne
Marc Tessier-Lavigne, Ph.D.
President
Carson Family Professor
Laboratory of Brain Development and Repair
marctl@rockefeller.edu

Dr. Tessier-Lavigne’s laboratory investigates how neural circuits in the brain form during embryonic development. It also studies nerve cell responses to injury and the mechanisms underlying nerve cell death with the goal of developing therapies for brain injury and neurodegenerative disease.

The human brain comprises several hundred billion nerve cells or neurons, which are connected in an intricate and precise pattern to form the neural circuits that underlie all brain functions, including perception, memory, and the control of movement. These circuits form during embryonic development when each neuron sends out a slender extension, the axon, to connect to an appropriate set of target cells. Dr. Tessier-Lavigne’s laboratory is interested in how neuronal axons locate their targets and how inappropriate axon projections are refined or eliminated by selective axon pruning (or degeneration) during development. They also study how these pruning mechanisms may also mediate degeneration of axons in neurodegenerative diseases like Alzheimer’s and Parkinson’s diseases or following trauma, such as in stroke.

In the embryonic brain, developing axons are tipped by a specialized sensory structure called the growth cone, which senses chemical guidance cues that instruct it to migrate in particular directions. The lab has discovered a number of the chemical cues operating in the mammalian nervous system, including small protein families known as netrins and slits, as well as receptors on the growth cones that detect many of these cues. To understand how guidance cues collaborate to ensure that the axons are guided unerringly, Dr. Tessier-Lavigne’s lab is seeking to identify the full complement of cues guiding particular sets of axons, as well as the intracellular pathways they trigger to signal directed motion. As an axon progresses along its trajectory, its growth cone exhibits a remarkable plasticity, changing its response to guidance cues — losing responsiveness to those that directed it over the previous leg of its trajectory and acquiring responsiveness to those that will guide it over the next leg. A major focus in the lab is on understanding mechanisms that control this plasticity and their relation to other plastic changes, such as those occurring after injury and in learning.

In the embryo, too many axonal connections are initially formed, and many axons have to be selectively eliminated through a process of pruning or developmental degeneration. Dr. Tessier-Lavigne’s lab has shown that several of the cues that initially guide axons are later responsible for triggering axon degeneration in the embryo. The lab has also shown that some of the mechanisms that refine neuronal circuits during development are reutilized in pruning that occurs as part of adult plasticity. To assist in these studies, the lab has developed a method, iDISCO, for immunolabeling and clearing of the entire adult mouse that permits imaging of axonal projections and associated biochemical changes by volume imaging in three dimensions.

The lab has also found that pruning of neuronal circuits shares important mechanistic similarities with neurodegeneration that occurs in diseases like Alzheimer’s. To test the relevance of these mechanisms to human diseases, the lab has also begun using stem cell technology to reprogram nonneuronal cells obtained from patients with neurodegenerative diseases into neurons. This approach offers the opportunity to characterize the behavior of diseased human neurons and to examine the mechanisms that cause these diseased neurons to degenerate. Collectively, these studies have the potential to provide novel therapeutic entry points for treating these diseases.


EDUCATION

B.Sc. in physics, 1980
McGill University

B.A. in philosophy and physiology, 1982
Oxford University

Ph.D. in physiology, 1987
University College London

POSTDOC

University College London, 1987

Columbia University, 1987–1991

POSITIONS

Assistant Professor, 1991–1995
Associate Professor with Tenure, 1995–1997
Professor, 1997–2001
University of California, San Francisco

Professor, 2001–2005
Stanford University

Senior Vice President, Research Drug Discovery, 2003–2008
Executive Vice President, Research Drug Discovery, 2008–2009
Chief Scientific Officer, 2009–2011
Genentech, Inc.

Professor, 2011–
President, 2011–
The Rockefeller University

Assistant Investigator, 1994–1997
Investigator, 1997–2003
Howard Hughes Medical Institute

AWARDS

Ameritec Prize, 1995

Fondation IPSEN Prize in Neuronal Plasticity, 1996

Viktor Hamburger Award, 1997

Wakeman Award, 1998

Robert Dow Neuroscience Award, 2003

Reeve-Irvine Research Medal, 2007

Gill Distinguished Award in Neuroscience, 2010

W. Alden Spencer Award, 2010

Memorial Sloan Kettering Medal, 2011

Henry G. Friesen International Prize, 2012

Burke Award, Burke Rehabilitation Hospital, 2014

NY/NJ CEO Lifetime Achievement Award, 2014

MEMBERSHIPS

National Academy of Sciences
National Academy of Medicine
American Academy of Arts and Sciences
Fellow, American Association for the Advancement of Science
The Royal Society
UK Academy of Medical Sciences
The Royal Society of Canada

SELECTED PUBLICATIONS

Yang, J. et al. Pathological axonal death through a MAPK cascade that triggers a local energy deficit. Cell 160, 161-176 (2015).

Renier N. et al. iDISCO: A simple, rapid method to immunolabel large tissue samples for volume imaging. Cell 159, 896-910 (2014).

Xu, K. et al. Neural migration. Structures of netrin-1 bound to two receptors provide insight into its axon guidance mechanism. Science 344, 1275–1279 (2014).

Yang, J. et al. Regulation of axon degeneration after injury and in development by the endogenous calpain inhibitor calpastatin. Neuron 80, 1175–1189 (2013).

Jaworski, A. and Tessier-Lavigne, M. Autocrine/juxtaparacrine regulation of axon fasciculation by Slit-Robo signaling. Nat. Neurosci. 15,
367–369 (2012).


Dr. Tessier-Lavigne is a faculty member in the David Rockefeller Graduate Program and the Tri-Institutional M.D.-Ph.D. Program.