Linda Van Aelst
Professor
Harold and Florence & Ethel McNeill Professor of Cancer Research
Ph.D., Catholic University of Leuven, 1991
vanaelst@cshl.edu | (516) 367-6829
Normal cell function relies on coordinated communication between all the different parts of the cell. These communication signals control what a cell does, what shape it takes, and how it interacts with other cells. I study these signaling networks to understand how they guard against cancer and neurological disorders.
Linda Van Aelst’s lab studies how aberrations in intracellular signaling involving enzymes called small GTPases can result in disease. They are particularly interested in Ras and Rho GTPases, which help control cellular growth, differentiation, and morphogenesis. Alterations affecting Ras and Rho functions are involved in cancer and various neurodevelopmental disorders. Van Aelst’s team has extended its prior study of mutations in a Rho-linked gene called oligophrenin-1 (OPHN1), part of an effort to connect the genetic abnormalities associated with mental retardation to biological processes that establish and modify the function of neuronal circuits. In addition to a role for OPHN1 in activity-driven glutamatergic synapse development, lab members have obtained evidence that OPHN1 has a critical role in mediating mGluR-LTD (long-term depression), a form of long-term synaptic plasticity, in CA1 hippocampal neurons. Their findings provide novel insight not only into the mechanism and function of mGluR-dependent LTD, but also into the cellular basis by which mutations in OPHN1 could contribute to the cognitive deficits observed in patients. Defects in cortical neurogenesis have been associated with cerebral malformations and disorders of cortical organization. The Van Aelst team discovered that interfering with the function of the Rho activator DOCK7 in neuronal progenitors in embryonic cerebral cortices results in an increase in the number of proliferating neuronal progenitors and defects in the genesis of neurons. In an extension of these studies, the Van Aelst team this year showed that DOCK7 has a central regulatory role in the process that determines how and when a radial glial cell progenitor “decides” to either proliferate, i.e., make more progenitor cells like itself, or give rise to cells that will mature, or “differentiate,” into pyramidal neurons. These lines of research provide novel insight into mechanisms that coordinate the maintenance of the neural progenitor pool and neurogenesis.
Chandelier neuron requires ‘Velcro-like’ molecule to form connections
March 4, 2019
Cold Spring Harbor, NY — As a brain grows, the neurons within it establish themselves, forming lasting connections with their neighbors. They’re creating the vast cell networks that ensure a mind and body run smoothly. Now, researchers have determined how a crucial kind of neuron called a chandelier cell (ChC) forms connections with other neurons,...
Portrait of a Neuroscience Powerhouse
April 27, 2018
At noon every Tuesday from September through June, scenes from a revolution in neuroscience are playing out at Cold Spring Harbor Laboratory. Week after week, over 100 scientists cram themselves into a ground-floor meeting room in the Beckman Laboratory. It’s standing-room only as everyone in the Neuroscience Program settles in to hear details of the...
Fantastic journey: how newborn neurons find their proper place in the brain
November 2, 2017
Cold Spring Harbor, NY — One of the most hopeful discoveries of modern neuroscience is firm proof that the human brain is not static following birth. Rather, it is continually renewing itself, via a process called postnatal neurogenesis—literally, the birth of new neurons. It begins not long after birth and continues into old age. There is...
Neuroscientists explain how mutated X-linked mental retardation protein impairs neuronal function
June 24, 2014
Cold Spring Harbor, NY — There are new clues about malfunctions in brain cells that contribute to intellectual disability and possibly other developmental brain disorders. Professor Linda Van Aelst of Cold Spring Harbor Laboratory (CSHL) has been scrutinizing how the normal version of a protein called OPHN1 helps enable excitatory nerve transmission in the brain,...
Scientists discover two proteins that control chandelier cell architecture
January 16, 2014
Chandelier cells, a group of powerful inhibitory neurons, are important in epilepsy and schizophrenia Cold Spring Harbor, NY — Chandelier cells are neurons that use their unique shape to act like master circuit breakers in the brain’s cerebral cortex. These cells have dozens, often hundreds, of branching axonal projections—output channels from the cell body of...
Christina Renna Foundation raises $20,000 for pediatric cancer research at CSHL
January 25, 2013
Foundation started by Long Island family raises funds for CSHL at sixth annual Angel’s Wish Gala Cold Spring Harbor, NY — The Christina Renna Foundation raised $20,000 at their sixth annual Angel’s Wish Gala on January 11, 2013. The funds will be used to support cancer research in the laboratory of Dr. Linda Van Aelst...
Research identifies protein that regulates key ‘fate’ decision in cortical progenitor cells
September 20, 2012
DOCK7 expression determines if radial glial cells will proliferate or differentiate Cold Spring Harbor, NY — Researchers at Cold Spring Harbor Laboratory (CSHL) have solved an important piece of one of neuroscience’s outstanding puzzles: how progenitor cells in the developing mammalian brain reproduce themselves while also giving birth to neurons that will populate the emerging...
X-linked mental retardation protein is found to mediate synaptic plasticity in hippocampus
October 19, 2011
Cold Spring Harbor, NY — Scientists at Cold Spring Harbor Laboratory (CSHL) have solved part of a puzzle concerning the relationship between changes in the strength of synapses—the tiny gaps across which nerve cells in the brain communicate—and dysfunctions in neural circuits that have been linked with drug addiction, mental retardation and other cognitive disorders....
CSHL researchers unravel how a protein helps nerve cells recycle neurotransmitter-containing vesicles
June 3, 2009
Oligophrenin-1, faulty in mental retardation, plays a vital pre-synaptic role in normal neural signaling Cold Spring Harbor, NY — Brain cells, or neurons, transmit electrical signals efficiently only when they recycle tiny cellular sacs that store signaling chemicals called neurotransmitters. When a neuron is stimulated, the sacs are expelled into the synapse—the tiny junction between...
Protein linked to mental retardation is found to control synapse maturation, plasticity by CSHL neuroscientists
June 1, 2009
Oligophrenin-1, a Rho-GTPase-activating protein, stabilizes postsynaptic AMPA receptors Cold Spring Harbor, NY — A team of neuroscientists at Cold Spring Harbor Laboratory (CSHL) has demonstrated the mechanism by which a signaling protein found throughout the brain controls the maturation and strength of excitatory synapses, the tiny gaps across which the majority of neurons communicate. The...
Yang, Y. T. and Wang, C. L. and Van Aelst, L. (2012) DOCK7 interacts with TACC3 to regulate interkinetic nuclear migration and cortical neurogenesis. Nature Neuroscience, 15(9) pp. 1201-10.
Nadif Kasri, N. and Nakano-Kobayashi, A. and Van Aelst, L. (2011) Rapid Synthesis of the X-Linked Mental Retardation Protein OPHN1 Mediates mGluR-Dependent LTD through Interaction with the Endocytic Machinery. Neuron, 72(2) pp. 300-315.
Janas, J. A. and Van Aelst, L. (2011) Oncogenic tyrosine kinases target Dok-1 for ubiquitin-mediated proteasomal degradation to promote cell transformation. Molecular and Cellular Biology, 31(13) pp. 2552-2565.
Nakano-Kobayashi, A. and Nadif Kasri, N. and Newey, S. E. and Van Aelst, L. (2009) The Rho-Linked Mental Retardation Protein OPHN1 Controls Synaptic Vesicle Endocytosis via Endophilin A1. Curr Biol, 19(13) pp. 1133-1139 .
Watabe-Uchida, M. and John, K. A. and Janas, J. A. and Newey, S. E. and Van Aelst, L. (2006) The Rac activator DOCK7 regulates neuronal polarity through local phosphorylation of stathmin/Op18. Neuron, 51(6) pp. 727-39.
Additional materials of the author atCSHL Institutional Repository