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RICHARD STANLEY, Ph.D. Positions: Professor, Department of Developmental and Molecular Biology, Albert Einstein College of Medicine Research interests: We have defined the biological roles of colony stimulating factor-1 (CSF-1) and its receptor (CSF-1R) using biochemical, cell biological and mouse genetic approaches. We have elucidated the developmental and physiological roles of CSF-1 and CSF-1R, showing that they regulate the production of macrophages, osteoclasts, microglia, Langerhans and Paneth cells and play an important role in the development of leukemia and several inflammatory diseases and the tumor macrophage enhancement of tumor progression. We are also studying the novel CSF-1R ligand interleukin-34 (IL-34), recently showing that both IL-34 and CSF-1 act via the CSF-1R to regulate not only microglial development but also the differentiation of neural progenitor cells. Recently, focusing on the CNS, we have identified a mouse model of an adult-onset dementia caused by dominant inactivating mutations in the kinase domain of the Csf1r gene. Additionally, we have developed novel biochemical and genetic approaches to CSF-1R structure/function and signal transduction, identifying and elucidating the function of several downstream signaling molecules, including PSTPIP2, mutations in which lead to an autoinflammatory disease in mice involving macrophages and osteoclasts and microRNA-21, a novel CSF-1R–induced molecule that suppresses the macrophage M1 (inflammatory) phenotype and enhances the M2 (trophic, oncogenic) phenotype. We have also pioneered studies of the Shark tyrosine kinase in Drosophila, elucidating the pathways Shark regulates during the processes of epithelial sheet movement and the recognition and engulfment of dying cells. Current grant funding: P01 CA100324-10 (Condeelis) NIH/NCI Program 04/01/2014 – 03/31/2019 Project grant: Motility and invasion. E. R. Stanley, project leader, Project 2, CSF-1R signaling pathways regulating macrophage chemotaxis and angiogenic factor release Pending grant funding: R01NS091519-01A1 (9th percentile) 12/01/2015 – 11/30/2020 Analysis of a mouse model of adult-onset leucoencephalopathy with axonal spheroids and pigmented glia. Recent publications: 1. Nandi S, Gokhan S, Dai X-M, Wei S, Enikolopov G, Lin H, Mehler MF, Stanley E.R. The CSF-1 receptor ligands IL-34 and CSF-1 exhibit distinct developmental brain expression patterns and regulate neural progenitor cell maintenance and maturation. Dev. Biol. 2012, 367:100–13 PMID: 22542597. 2. Chitu V., Nacu, V., Charles, J.F., Henne, W.M., McMahon, H.T., Nandi, S., Ketchum, H., Harris, R., Nakamura, M.C., Stanley, E.R. (2012) PSTPIP2 deficiency in mice causes osteopenia and increased differentiation of multipotent myeloid precursors into osteoclasts. Blood. 120:3126-35 PMID: 22923495 3. Nandi, S., Cioce, M., Yeung, Y.G., Nieves, E., Tesfa, L., Lin, H., Hsu, A.W., Halenbeck R., Cheng, H.Y., Gokhan, S., Mehler, M.F. and Stanley, E.R. (2013). Receptor-type protein tyrosine phosphatase zeta is a functional receptor for interleukin-34. J. Biol. Chem., 288:21972-86 PMID: 23744080 4. Stanley, E.R. and Chitu, V. (2014). CSF-1 Receptor Signaling in Myeloid Cells. Cold Spring Harb Perspect Biol., 6(6):1-21 PMID: 24890514. 5. Chitu, V., Gokhan, S., Gulinello, M., Branch C.A., Patil, M., Basu, R., Stoddart C., Mehler M.F. and Stanley E.R. (2014). Phenotypic characterization of a Csf1r haploinsufficient mouse model of adult-onset leukodystrophy with axonal spheroids and pigmented glia (ALSP). Neurobiology of Disease, 74:219–228. PMID: 25497733 6. Caescu, C.I., Guo,X., Tesfa, L., Bhagat, T.D., Verma, A., Zheng, D. and Stanley, E.R. (2015). Colony stimulating factor-1 receptor signaling networks inhibit mouse macrophage inflammatory responses by induction of microRNA-21. Blood, 125:e1-13. PMID:25573988