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Lloyd A. Greene, Ph.D.
Professor of Pathology
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Research
Summary
Cell biology of differentiating neurons; mechanisms of action of nerve growth factor and other neurotropic factors.
The basic interests of this laboratory concern the mechanisms of neuronal differentiation and degeneration and the regulation thereof by external growth factors. A major model employed is a cell line (designated PC12) developed by this laboratory which, in response to the neurotrophic factor NGF, acquires a neuronal phenotype characterized by generation of neurites and the specific induction of neuronal genes. As in the case of neurons, NGF can also promote the survival of PC12 cells. Thus this system provides a convenient means to assess at the molecular level the mechanisms by which growth factors regulate neuronal differentiation as well as survival and death. This system is complemented with studies of cultured CNS and peripheral neurons.
Current studies are aimed at some of the following issues: 1) What are the intracellular signaling pathways that are stimulated by NGF? NGF sets in motion a number of signaling elements and we are involved in both dissecting these and defining the neuronal properties they regulate. 2) How do receptors for NGF activate intracellular signaling pathways? The surface receptor for NGF is a tyrosine kinase designated Trk. Mutational and structural analysis are being used to define the molecular mechanisms by which Trk signaling is activated by NGF. 3) What are the NGF-regulated genes that mediate neuronal differentiation? The SAGE (Serial Analysis of Gene Expression) technique is being employed to address this issue at high resolution and to maximally exploit current and upcoming genomic sequence information. 4) How do factors such as NGF prevent neuronal death, both during development and in the mature nervous system? Conversely, why do neurons die in neurodegenerative disorders and trauma and can this be prevented by exploiting our understanding of the molecular mechanisms governing neuronal survival and death?
http://www.cumc.columbia.edu/dept/ihn/faculty/greene.html
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Selected Publications:
1. Loeb DM, Tsao H, Cobb M, Greene LA (1992) NGF and other growth factors induce an association between extracellular signal regulated kinase I (ERK1) and the NGF receptor, gp 140 prototrk Neuron
9:1053-1065
2. Ferrari G, Batistatou A, Greene LA (1993) Gangliosides rescue neuronal cells from death after trophic factor deprivation J Neurosci
13:1879-1887
3. Sherr EH, Joyce MP, Greene LA (1993) Mammalian myosin l , l ß and l : New widely expressed genes of the Myosin I family J Cell Biol
120:1405-1416
4. Greene LA, Biswas SC, Liu DX. (2004) Cell cycle molecules and vertebrate neuron death: E2F at the hub. Cell Death Differ
11:49-60
5. Xu Z, Kukekov NV, Greene LA. (2003) POSH acts as a scaffold for a multiprotein complex that mediates JNK activation in apoptosis. EMBO J
22:252-261
6. Greene LA, Mount SL, Schned AR, Cooper K. (2003) Recurrent perivascular epithelioid cell tumor of the uterus (PEComa): an immunohistochemical study and review of the literature. Gynecol Oncol
90:677-681
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