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Transcript
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