The overall goal of research in this laboratory is to understand the mechanisms whereby neuronal precursors differentiate into mature functional neurons. To this end, we use the rat PC12 pheochromocytoma cell line developed in this laboratory as a model system to study the mechanism of action of nerve growth factor (NGF) and the steps that lead to neuronal differentiation. Among current projects in the laboratory are those addressing the following questions: 1) What is the essential property of the high-affinity NGF receptor that permits it to mediate the functional activities of NGF and how is this receptor different from the low-affinity, non-functional NGF receptor? 2) What is the transductional mechanism by which NGF receptor occupancy leads to subsequent response? 3) What are the steps beyond immediate transduction that lead to NGF mechanisms? 4) What is the mechanism by which NGF regulates growth cone motility? What are the molecules involved in this effect? 5) What genes are regulated by NGF? By what pathways are they regulated? 6) What are the mechanism by which NGF promotes the initiation and regeneration of neurites; specifically, what is the role of specific cytoskeleton proteins in this process? 7) How do NGF and other neuronotrophic substances maintain cell survival? 8) How do such agents regulate cell proliferation?
1. Sproul AA, Xu Z, Wilhelm M, Gire S, Greene LA
. Cbl negatively regulates JNK activation and cell death. Cell Res. 2009 Aug;19(8):950-61.
2. Li G, Li W, Angelastro JM, Greene LA
, Liu DX. Identification of a novel DNA binding site and a transcriptional target for activating transcription factor 5 in c6 glioma and mcf-7 breast cancer cells. Mol Cancer Res. 2009 Jun;7(6):933-43. Epub 2009 Jun 16.
3. Zareen N, Greene LA
. Protocol for culturing sympathetic neurons from rat superior cervical ganglia (SCG). J Vis Exp. 2009 Jan 30;(23). pii: 988. doi: 10.3791/988.
4. Lee HY, Greene LA
, Mason CA, Manzini MC. Isolation and culture of post-natal mouse cerebellar granule neuron progenitor cells and neurons. J Vis Exp. 2009 Jan 16;(23). pii: 990. doi: 10.3791/990.
5. Levy OA, Malagelada C, Greene LA
. Cell death pathways in Parkinson's disease: proximal triggers, distal effectors, and final steps. Apoptosis. 2009 Apr;14(4):478-500. Review.
6. Malagelada C, Jin ZH, Greene LA
. RTP801 is induced in Parkinson's disease and mediates neuron death by inhibiting Akt phosphorylation/activation. J Neurosci. 2008 Dec 31;28(53):14363-71.
7. Greene LA
, Lee HY, Angelastro JM. The transcription factor ATF5: role in neurodevelopment and neural tumors. J Neurochem. 2009 Jan;108(1):11-22. Epub 2008 Nov 15. Review.
8. Biswas SC, Buteau J, Greene LA
. Glucagon-like peptide-1 (GLP-1) diminishes neuronal degeneration and death caused by NGF deprivation by suppressing Bim induction. Neurochem Res. 2008 Sep;33(9):1845-51. Epub 2008 Mar 20.
9. Greene LA
, Isaac I, Gray DE, Schwartz SA. Streamlining plant sample preparation: the use of high-throughput robotics to process echinacea samples for biomarker profiling by MALDI-TOF mass spectrometry. J Biomol Tech. 2007 Sep;18(4):238-44.
10. Wilhelm M, Kukekov NV, Xu Z, Greene LA
. Identification of POSH2, a novel homologue of the c-Jun N-terminal kinase scaffold protein POSH. Dev Neurosci. 2007;29(4-5):355-62.
Honors and Awards
B.S. with general and special honors 1975-1979
Sloan Foundation Fellowship in the Neurosciences 1981-1986
Career Development Award from the Irma T. Hirschl Trust 1986-1993
Javits Award (NIH-NINDS) 1987
Medal of Excellence for Contributions to Neuroscience Research CNR (Italy) 1994
Adele Blank Award for Research in Neurodegenerative Disease 2000
Dean's Distinguished Lecturer in Basic Sciences, Columbia University
apoptosis, neurogenetics, neuron, neurotrophic factor, JUN kinase, cyclin, cyclin dependent kinase, phosphorylation, protein structure function, protooncogene, transcription factor, PC12 cell, SDS polyacrylamide gel electrophoresis, laboratory rat, microar