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Linda Van Aelst

Linda Van Aelst

Professor
Harold and Florence & Ethel McNeill Professor of Cancer Research
Cancer Center Program Co-Leader

Ph.D., Catholic University of Leuven, 1991

vanaelst@cshl.edu | 516-367-6829

Faculty Profile

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.

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All Publications

Microglia regulate chandelier cell axo-axonic synaptogenesis

15 Mar 2022 | Proceedings of the National Academy of Sciences of USA | 119(11):e2114476119
Gallo, Nicholas, Berisha, Artan, Van Aelst, Linda

Connecting copper and cancer: from transition metal signalling to metalloplasia

11 Nov 2021 | Nature Reviews Cancer
Ge, Eva, Bush, Ashley, Casini, Angela, Cobine, Paul, Cross, Justin, DeNicola, Gina, Dou, Q, Franz, Katherine, Gohil, Vishal, Gupta, Sanjeev, Kaler, Stephen, Lutsenko, Svetlana, Mittal, Vivek, Petris, Michael, Polishchuk, Roman, Ralle, Martina, Schilsky, Michael, Tonks, Nicholas, Vahdat, Linda, Van Aelst, Linda, Xi, Dan, Yuan, Peng, Brady, Donita, Chang, Christopher

Oncogenic KRAS engages an RSK1/NF1 pathway to inhibit wild-type RAS signaling in pancreatic cancer.

25 May 2021 | Proceedings of the National Academy of Sciences of USA | 118(21):e2016904118
Cheng, Derek, Oni, Tobiloba, Thalappillil, Jennifer, Park, Youngkyu, Ting, Hsiu-Chi, Alagesan, Brinda, Prasad, Nadia, Addison, Kenneth, Rivera, Keith, Pappin, Darryl, Van Aelst, Linda, Tuveson, David

Molecular mechanisms of axo-axonic innervation.

13 Apr 2021 | Current Opinion in Neurobiology | 69:105-112
Ango, Fabrice, Gallo, Nicholas, Van Aelst, Linda

Oligophrenin-1 moderates behavioral responses to stress by regulating parvalbumin interneuron activity in the medial prefrontal cortex.

1 Apr 2021 | Neuron
Wang, Minghui, Gallo, Nicholas, Tai, Yilin, Li, Bo, Van Aelst, Linda

Cancer cell CCR2 orchestrates suppression of the adaptive immune response.

5 Oct 2020 | Journal of Experimental Medicine | 217(10)
Fein, Miriam, He, Xue-Yan, Almeida, Ana, Bružas, Emilis, Pommier, Arnaud, Yan, Ran, Eberhardt, Anaïs, Fearon, Douglas, Van Aelst, Linda, Wilkinson, John, Dos Santos, Camila, Egeblad, Mikala

Oncogenic KRAS engages an RSK1/NF1 complex in pancreatic cancer

14 Sep 2020 | bioRxiv
Cheng, D, Oni, T, Park, Y, Thalappillil, J, Ting, H-C, Alagesan, B, Prasad, N, Rivera, K, Pappin, D, Van Aelst, L, Tuveson, D

Shedding Light on Chandelier Cell Development, Connectivity, and Contribution to Neural Disorders

Jun 2020 | Trends in Neurosciences | 43(8):565-580
Gallo, N, Paul, A, Van Aelst, L

Stressing Out about Cancer Immunotherapy

11 Nov 2019 | Cancer Cell | 36(5):468-470
He, X, Ng, D, Van Aelst, L, Egeblad, M

Axo-axonic Innervation of Neocortical Pyramidal Neurons by GABAergic Chandelier Cells Requires AnkyrinG-Associated L1CAM

21 Feb 2019 | Neuron | 102(2):267-270
Tai, Y, Gallo, N, Wang, M, Yu, J, Van Aelst, L

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