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Appointments
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Attending Neurologist
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Professor of Neurology and Neuroscience
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ROSS, M. ELIZABETH
 (212) 746-5533  (212) 746-8226
Laboratory of Neurogenetics and Development
The research in my laboratory centers on discovery of gene mutations associated with brain malformations and investigation of how these genes direct the construction of brain. Three major projects encompass: 1) neural tube formation, 2) cell cycle regulation and its role in cellular patterning of brain, and 3) regulation of neuronal migration to establish brain architecture. These three areas of study, all NIH funded, are approached from both basic science and clinical genetic perspectives.
Neural tube closure -- This project examines primary neurogenesis and cell migration in a naturally occurring mouse model of neural tube defects (NTDs). This mouse mutant, Crooked tail (Cd), is prone to failed neural tube closure most similar to anencephaly in humans. We previously modeled human NTD prevention by folic acid supplementation in this Cd mouse strain and showed Cd to be a remarkably good paradigm for investigation of the vitamin's effects on brain development. We identified the Cd gene mutation as defect in the Lrp6 co-receptor that is required for Wnt signaling, a pathway important for early development and tumor formation. The cellular and molecular events leading to NTDs and cortical dysplasia in Cd are studied. This work is being extended to a multi-center clinical effort to examine complex genetic traits associated with NTDs, using folate pathway and other candidate genes to screen clinical populations.
Neurogenesis -- Primary genesis and differentiation of neurons are examined in the context of cell cycle regulation and its relationship to brain structure. We have previously shown that the G1 active protein, cyclin D2, is expressed in developing mammalian brain in highly specific and restricted brain regions. In addition, examination of animals lacking cyclin D2 expression demonstrated that this isoform is necessary for the emergence and survival of cerebellar stellate interneurons, half of the granule cell population, and specific cerebral interneurons. Ongoing work addresses how molecular components of the cell cycle are controlled to generate specific neurons and whether this activating subunit of cyclin dependent kinases has a direct role in the differentiation of selected neuronal precursors. The cyclin D2 is also being used as a candidate gene in the search for causes of microcephaly in humans, while the basic science work is turning to investigation of the regulation of brain size and function, especially in the areas of behavior and epilepsy.
Neuronal migration -- This project aims to identify and study genes responsible for human neuronal migration disorders causing brain malformation. This began with the linkage mapping and identification of a gene associated with an X-linked form of lissencephaly (XLIS/DCX). We have also produced several transgenic mouse lines for the investigation of the XLIS/DCX gene function that are being analyzed in vivo, in slice cultures and in dissociated cells. Using a mouse knockout model for a closely related neuronal migration gene, Lis1, we have used biochemical and in vitro cell culture systems to examine neuronal migration. Our studies have revealed that loss of Lis1 results in deregulated Rho-family GTPases and that Lis1 participates in molecular cascades that affect neuronal cytoskeletal dynamics to impact their movement and connections between neurons. In our emerging model, Lis1 is viewed as a signalling molecule required for the transduction of molecular cues presented to the neuronal surface to modulate migration and neuronal connectivity. Additional neuronal migration genes are being sought through investigation of patients with brain malformations and their families.
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http://www.weillcornellneuroscience.org
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| Education |
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M.D., Cornell University Medical College, 1979
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Ph.D., Cornell University Graduate School of Medical Sciences, 1982
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