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.
Reversing a genetic cause of poor stress responses in mice
April 7, 2021
CSHL researchers discovered how a gene prevents mice from coping with stressful situations. They found several ways to reverse its effects.
How chandelier cells light up the brain
June 18, 2020
Until now, chandelier cells were largely enigmatic, but new technology makes them accessible to researchers.
Historic building—groundbreaking science
October 29, 2019
The Demerec building has been monumental in scientific history. Now, a $75 million renovation of this celebrated labspace will define CSHL’s future.
Chandelier neuron requires ‘Velcro-like’ molecule to form connections
March 4, 2019
How do brain cells network? Researchers have discovered an essential ingredient that facilitates one type of neuron’s many neighborly connections.
Portrait of a Neuroscience Powerhouse
April 27, 2018
A relatively small neuroscience group at CSHL is having an outsized impact on a dynamic and highly competitive field
Watch a baby neuron crawl its way along a brain
November 2, 2017
"Adult neurogenesis" is the process in which new neurons replace old. But how do newborn neurons reach the part of the brain they need to rebuild?
Fantastic journey: how newborn neurons find their proper place in the brain
November 2, 2017
Neuroscientists have clarified the mechanism used by newly born neurons in mice to migrate to very specific areas.
Neuroscientists explain how mutated X-linked mental retardation protein impairs neuronal function
June 24, 2014
There are new clues about malfunctions in brain cells that contribute to intellectual disability and possibly other developmental brain disorders.
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
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.