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E. Richard Stanley

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Dr. Evan Richard Stanley is the Professor Emeritus at the Albert Einstein College of Medicine, New York in the departments of Developmental and Molecular Biology.[1] Stanley received the Marie T. Bonazinga Research Award of the Society for Leukocyte Biology in 1989 and the E. Donnall Thomas Prize from the American Society of Hematology in 2006. He is best known for his pioneering work on the identification and function of the macrophage growth factor, colony stimulating factor-1 (CSF-1) and its receptor (CSF-1R). He was Chair of the department of Developmental and Molecular Biology at Einstein from 1987-2010 and has been Interim Chair since 2018. He has held the Renee and Robert A. Belfer Professorship in Developmental Biology since 1987. He lives in Manhattan with his wife, Pamela Stanley, Ph.D., a Professor of Cell Biology at Einstein.[2][3][4]

Education[edit]

Dr. Stanley earned a bachelor's degree in science with honors in biochemistry from the University of Western Australia, followed by his doctorate in medical biology from the University of Melbourne.[5]

Research & Career[edit]

Dr. Stanley’s laboratory identified CSF-1 and its class III tyrosine kinase receptor (CSF-1R) and defined their developmental, physiological and disease-related roles, using biochemical, cell biological and mouse genetic approaches. They showed that CSF-1 and the CSF-1R regulate the production of macrophages, osteoclasts, microglia and Langerhans cells and play an important role in the development of some leukemias and of several inflammatory diseases.[6][7][8][9][10]

They identified and purified a novel cytokine, hemopoietin-1 (subsequently identified as interleukin-1α), that synergizes other hematopoietic cytokines, including CSF-1, permitting their action on more primitive hematopoietic cells.[11][12][13][14][15] His laboratory developed novel biochemical and genetic approaches to analyze CSF-1R structure/function[16] and signal transduction[17] in macrophages, identifying and elucidating the function of several downstream signaling molecules, including Cb[18] PSTPIP2[19] PTP-phi[20] and miR-21.[21]

In collaborative studies, they showed that circulating CSF-1 is elevated in multiple human neoplasms and have studied CSF-1 regulation of tumor-associated macrophages and the macrophage enhancement of tumor progression and metastasis.[22][23][24][25] Independent of their CSF-1R studies, his laboratory also identified the Shark tyrosine kinase in Drosophila, elucidating the regulation by Shark of the processes of embryonic dorsal closure (epithelial sheet movement) and the engulfment of dying neurons.[26][27]

Recently focusing on the nervous system, his team has shown that all microglial development and maintenance is dependent on the CSF-1R[28] that the novel CSF-1R ligand, interleukin-34 (IL-34) signals through the CSF-1R, like CSF-1, but differs in its cell and tissue expression pattern[29][30] and can also signal through an additional receptor. [23][24][25] They have further shown that the Csf1r heterozygous mouse is a model of CSF-1 receptor-related leukoencephalopathy (CRL), a dementia caused by dominant, inactivating mutations in the kinase domain of the CSF1R gene, or by CSF1R haploinsufficiency.[31][32] They are currently studying disease development in this model.

Awards and Honors[edit]

Dr. Stanley received the NIH Merit Award in the year 2002.[5] Additional awards include the E. Donnall Thomas Award, Marie T. Bonazinga Research Award, Frederick Stohlman Jr. Memorial Lecturer and Basic Science Prize, International Union Against Cancer - Roll of Honour, Commonwealth Scholarship, Swan Brewery Scholarship in Biochemistry, Commonwealth Postgraduate Award, Irma T. Hirschl Career Scientist Award, Leukemia Society of America Scholar, and Lucille P. Markey Charitable Trust Award.[2]

Research Contributions[edit]

  • Purification and gene cloning of a colony stimulating factor (CSF-1); demonstration of its mononuclear phagocyte lineage specificity.[33][34][35][36][37]
  • Demonstration that CSF-1 is required for macrophage survival and proliferation; development of a CSF-1-dependent macrophage cell line for signal transduction studies.[38][39]
  • Identification and purification of hemopoietin-1 (interleukin-1α) and demonstration of its action on primitive hematopoietic cells.[40][41][42]
  • Elucidation of the binding, internalization and destruction of CSF-1 by macrophages.[43]
  • Purification of the CSF-1R, demonstration that it possessed tyrosine kinase activity and is encoded by the c-fms protooncogene.[44][45]
  • Elucidation of role CSF-1R tyrosine phosphorylation in receptor activation and signaling and the Identification and mechanism of action of several CSF-1R downstream signaling molecules.[46][47][48][49][50]
  • Identification of a mouse mutation responsible for CSF-1 deficiency and inactivation the Csf1r gene in the mouse, demonstrating the requirement of CSF-1 and the CSF-1R osteoclastogenesis.[51][52]

Patents[edit]

Dr. Richard E. Stanley has obtained several patents and his patents include Csf-1r mutants (WO2008150383A1), and Il-34 receptor assays and uses thereof (US20160123962A1).[53][54]

References[edit]

  1. "E. Richard Stanley, Ph.D. | Faculty Directory | Albert Einstein College of Medicine". www.einsteinmed.edu. Retrieved 2022-03-31.
  2. 2.0 2.1 "Einstein's Dr. E. Richard Stanley receives 2006 E. Donnall Thomas Prize". EurekAlert!. Retrieved 2022-03-31.
  3. "Résumé - E. Richard Stanley". sites.google.com. Retrieved 2022-03-31.
  4. "Interview with the Faculty: Pamela Stanley". F1000 Blogs. 2014-03-24. Retrieved 2022-03-31.
  5. 5.0 5.1 "Einstein Researcher Receives Second Prestigious MERIT Award from the National Institutes of Health". Albert Einstein College of Medicine. Retrieved 2022-03-31.
  6. Stanley, E. Richard; Chitu, Violeta (2014-06-01). "CSF-1 Receptor Signaling in Myeloid Cells". Cold Spring Harbor Perspectives in Biology. 6 (6): a021857. doi:10.1101/cshperspect.a021857. ISSN 1943-0264. PMC 4031967. PMID 24890514.
  7. Stanley, E. R.; Chitu, V. (2014-06-01). "CSF-1 Receptor Signaling in Myeloid Cells". Cold Spring Harbor Perspectives in Biology. 6 (6): a021857. doi:10.1101/cshperspect.a021857. ISSN 1943-0264. PMC 4031967. PMID 24890514.
  8. Stanley, E. R.; Chitu, V. (2014-06-01). "CSF-1 Receptor Signaling in Myeloid Cells". Cold Spring Harbor Perspectives in Biology. 6 (6): a021857. doi:10.1101/cshperspect.a021857. ISSN 1943-0264. PMC 4031967. PMID 24890514.
  9. "Cold Spring Harbour Perspectives in Biology". Cold Spring Harbour Perspectives in Biology. 2009. OCLC 1076661719.
  10. Stanley, E. Richard; Chitu, Violeta (June 2014). "CSF-1 Receptor Signaling in Myeloid Cells". Cold Spring Harbor Perspectives in Biology. 6 (6): a021857. doi:10.1101/cshperspect.a021857. ISSN 1943-0264. PMC 4031967. PMID 24890514.
  11. Stanley, E. Richard; Bartocci, Anna; Patinkin, Deborah; Rosendaal, Martin; Bradley, T. Ray (1986-06-06). "Regulation of very primitive, multipotent, hemopoietic cells by hemopoietin-1". Cell. 45 (5): 667–674. doi:10.1016/0092-8674(86)90781-6. ISSN 0092-8674. PMID 3085956. Unknown parameter |s2cid= ignored (help)
  12. Stanley, E.Richard; Bartocci, Anna; Patinkin, Deborah; Rosendaal, Martin; Bradley, T.Ray (June 1986). "Regulation of very primitive, multipotent, hemopoietic cells by hemopoietin-1". Cell. 45 (5): 667–674. doi:10.1016/0092-8674(86)90781-6. PMID 3085956. Unknown parameter |s2cid= ignored (help)
  13. Stanley, E. Richard; Bartocci, Anna; Patinkin, Deborah; Rosendaal, Martin; Bradley, T. Ray (1986-06-06). "Regulation of very primitive, multipotent, hemopoietic cells by hemopoietin-1". Cell. 45 (5): 667–674. doi:10.1016/0092-8674(86)90781-6. ISSN 0092-8674. PMID 3085956. Unknown parameter |s2cid= ignored (help)
  14. ScienceDirect (Online service) (1974). Cell. Cambridge, Mass.: Elsevier Inc. OCLC 137343240. Search this book on
  15. Stanley, E. R.; Bartocci, A.; Patinkin, D.; Rosendaal, M.; Bradley, T. R. (1986-06-06). "Regulation of very primitive, multipotent, hemopoietic cells by hemopoietin-1". Cell. 45 (5): 667–674. doi:10.1016/0092-8674(86)90781-6. ISSN 0092-8674. PMID 3085956. Unknown parameter |s2cid= ignored (help)
  16. Yu, Wenfeng; Chen, Jian; Xiong, Ying; Pixley, Fiona J.; Yeung, Yee-Guide; Stanley, E. Richard (2012-04-20). "Macrophage proliferation is regulated through CSF-1 receptor tyrosines 544, 559, and 807". The Journal of Biological Chemistry. 287 (17): 13694–13704. doi:10.1074/jbc.M112.355610. ISSN 1083-351X. PMC 3340183. PMID 22375015.
  17. Yeung, Yee-Guide; Stanley, E. Richard (November 2003). "Proteomic approaches to the analysis of early events in colony-stimulating factor-1 signal transduction". Molecular & Cellular Proteomics: MCP. 2 (11): 1143–1155. doi:10.1074/mcp.R300009-MCP200. ISSN 1535-9476. PMID 12966146. Unknown parameter |s2cid= ignored (help)
  18. Lee, P. S.; Wang, Y.; Dominguez, M. G.; Yeung, Y. G.; Murphy, M. A.; Bowtell, D. D.; Stanley, E. R. (1999-07-01). "The Cbl protooncoprotein stimulates CSF-1 receptor multiubiquitination and endocytosis, and attenuates macrophage proliferation". The EMBO Journal. 18 (13): 3616–3628. doi:10.1093/emboj/18.13.3616. ISSN 0261-4189. PMC 1171440. PMID 10393178.
  19. Chitu, Violeta; Ferguson, Polly J.; de Bruijn, Rosalie; Schlueter, Annette J.; Ochoa, Luis A.; Waldschmidt, Thomas J.; Yeung, Yee-Guide; Stanley, E. Richard (2009-09-17). "Primed innate immunity leads to autoinflammatory disease in PSTPIP2-deficient cmo mice". Blood. 114 (12): 2497–2505. doi:10.1182/blood-2009-02-204925. ISSN 1528-0020. PMC 2746474. PMID 19608749.
  20. Pixley, F. J.; Lee, P. S.; Dominguez, M. G.; Einstein, D. B.; Stanley, E. R. (1995-11-10). "A heteromorphic protein-tyrosine phosphatase, PTP phi, is regulated by CSF-1 in macrophages". The Journal of Biological Chemistry. 270 (45): 27339–27347. doi:10.1074/jbc.270.45.27339. ISSN 0021-9258. PMID 7592997.
  21. Caescu, Cristina I.; Guo, Xingyi; Tesfa, Lydia; Bhagat, Tushar D.; Verma, Amit; Zheng, Deyou; Stanley, E. Richard (2015-02-19). "Colony stimulating factor-1 receptor signaling networks inhibit mouse macrophage inflammatory responses by induction of microRNA-21". Blood. 125 (8): e1–13. doi:10.1182/blood-2014-10-608000. ISSN 1528-0020. PMC 4335087. PMID 25573988.
  22. "Newsroom | Albert Einstein College of Medicine". einsteinmed.edu. Retrieved 2022-04-28.
  23. 23.0 23.1 Stanley, E. R.; Chitu, V. (2014-06-01). "CSF-1 Receptor Signaling in Myeloid Cells". Cold Spring Harbor Perspectives in Biology. 6 (6): a021857. doi:10.1101/cshperspect.a021857. ISSN 1943-0264. PMC 4031967. PMID 24890514.
  24. 24.0 24.1 Stanley, E. Richard; Chitu, Violeta (June 2014). "CSF-1 Receptor Signaling in Myeloid Cells". Cold Spring Harbor Perspectives in Biology. 6 (6): a021857. doi:10.1101/cshperspect.a021857. ISSN 1943-0264. PMC 4031967. PMID 24890514.
  25. 25.0 25.1 Stanley, E. Richard; Chitu, Violeta (2014-06-02). "CSF-1 receptor signaling in myeloid cells". Cold Spring Harbor Perspectives in Biology. 6 (6): a021857. doi:10.1101/cshperspect.a021857. ISSN 1943-0264. PMC 4031967. PMID 24890514.
  26. Biswas, Romi; Stein, David; Stanley, E. Richard (January 2006). "Drosophila Dok is required for embryonic dorsal closure". Development. 133 (2): 217–227. doi:10.1242/dev.02198. ISSN 0950-1991. PMID 16339186. Unknown parameter |s2cid= ignored (help)
  27. Ziegenfuss, Jennifer S.; Biswas, Romi; Avery, Michelle A.; Hong, Kyoungja; Sheehan, Amy E.; Yeung, Yee-Guide; Stanley, E. Richard; Freeman, Marc R. (2008-06-12). "Draper-dependent glial phagocytic activity is mediated by Src and Syk family kinase signalling". Nature. 453 (7197): 935–939. Bibcode:2008Natur.453..935Z. doi:10.1038/nature06901. ISSN 1476-4687. PMC 2493287. PMID 18432193.
  28. Ginhoux, Florent; Greter, Melanie; Leboeuf, Marylene; Nandi, Sayan; See, Peter; Gokhan, Solen; Mehler, Mark F.; Conway, Simon J.; Ng, Lai Guan; Stanley, E. Richard; Samokhvalov, Igor M. (2010-11-05). "Fate mapping analysis reveals that adult microglia derive from primitive macrophages". Science. 330 (6005): 841–845. Bibcode:2010Sci...330..841G. doi:10.1126/science.1194637. ISSN 1095-9203. PMC 3719181. PMID 20966214.
  29. Wei, Suwen; Nandi, Sayan; Chitu, Violeta; Yeung, Yee-Guide; Yu, Wenfeng; Huang, Minmei; Williams, Lewis T.; Lin, Haishan; Stanley, E. Richard (September 2010). "Functional overlap but differential expression of CSF-1 and IL-34 in their CSF-1 receptor-mediated regulation of myeloid cells". Journal of Leukocyte Biology. 88 (3): 495–505. doi:10.1189/jlb.1209822. ISSN 1938-3673. PMC 2924605. PMID 20504948.
  30. Nandi, Sayan; Gokhan, Solen; Dai, Xu-Ming; Wei, Suwen; Enikolopov, Grigori; Lin, Haishan; Mehler, Mark F.; Stanley, E. Richard (2012-07-15). "The CSF-1 receptor ligands IL-34 and CSF-1 exhibit distinct developmental brain expression patterns and regulate neural progenitor cell maintenance and maturation". Developmental Biology. 367 (2): 100–113. doi:10.1016/j.ydbio.2012.03.026. ISSN 1095-564X. PMC 3388946. PMID 22542597.
  31. Chitu, Violeta; Gökhan, Şölen; Stanley, E. Richard (2021-07-05). "Modeling CSF‐1 receptor deficiency diseases – how close are we?". The FEBS Journal: febs.16085. doi:10.1111/febs.16085. ISSN 1742-464X. PMC 8684558 Check |pmc= value (help). PMID 34145972 Check |pmid= value (help). Unknown parameter |pmc-embargo-date= ignored (help)
  32. Coruzzi, P.; Mossini, G. (1996). "L-arginine and salt sensitivity". Nephron. 72 (2): 335. doi:10.1159/000188873. ISSN 1660-8151. PMID 8684558.
  33. Stanley, E. R.; Heard, P. M. (1977-06-25). "Factors regulating macrophage production and growth. Purification and some properties of the colony stimulating factor from medium conditioned by mouse L cells". The Journal of Biological Chemistry. 252 (12): 4305–4312. doi:10.1016/S0021-9258(17)40265-1. ISSN 0021-9258. PMID 301140.
  34. Stanley, E. R.; Chen, D. M.; Lin, H. S. (1978-07-13). "Induction of macrophage production and proliferation by a purified colony stimulating factor". Nature. 274 (5667): 168–170. Bibcode:1978Natur.274..168S. doi:10.1038/274168a0. ISSN 0028-0836. PMID 307187. Unknown parameter |s2cid= ignored (help)
  35. Stanley, E.R.; Guilbert, L.J. (May 1981). "Methods for the purification, assay, characterization and target cell binding of a colony stimulating factor (CSF-1)". Journal of Immunological Methods. 42 (3): 253–284. doi:10.1016/0022-1759(81)90156-3. PMID 6974750.
  36. Stanley, E. R.; Guilbert, L. J. (1981). "Methods for the purification, assay, characterization and target cell binding of a colony stimulating factor (CSF-1)". Journal of Immunological Methods. 42 (3): 253–284. doi:10.1016/0022-1759(81)90156-3. ISSN 0022-1759. PMID 6974750.
  37. Kawasaki, E. S.; Ladner, M. B.; Wang, A. M.; Van Arsdell, J.; Warren, M. K.; Coyne, M. Y.; Schweickart, V. L.; Lee, M. T.; Wilson, K. J.; Boosman, A. (1985-10-18). "Molecular cloning of a complementary DNA encoding human macrophage-specific colony-stimulating factor (CSF-1)". Science. 230 (4723): 291–296. Bibcode:1985Sci...230..291K. doi:10.1126/science.2996129. ISSN 0036-8075. PMID 2996129.
  38. Tushinski, R. J.; Oliver, I. T.; Guilbert, L. J.; Tynan, P. W.; Warner, J. R.; Stanley, E. R. (January 1982). "Survival of mononuclear phagocytes depends on a lineage-specific growth factor that the differentiated cells selectively destroy". Cell. 28 (1): 71–81. doi:10.1016/0092-8674(82)90376-2. ISSN 0092-8674. PMID 6978185. Unknown parameter |s2cid= ignored (help)
  39. Morgan, C.; Pollard, J. W.; Stanley, E. R. (March 1987). "Isolation and characterization of a cloned growth factor dependent macrophage cell line, BAC1.2F5". Journal of Cellular Physiology. 130 (3): 420–427. doi:10.1002/jcp.1041300316. ISSN 0021-9541. PMID 3031090. Unknown parameter |s2cid= ignored (help)
  40. Bartelmez, S. H.; Stanley, E. R. (March 1985). "Synergism between hemopoietic growth factors (HGFs) detected by their effects on cells bearing receptors for a lineage specific HGF: assay of hemopoietin-1". Journal of Cellular Physiology. 122 (3): 370–378. doi:10.1002/jcp.1041220306. ISSN 0021-9541. PMID 2981896.
  41. Guilbert, L. J.; Stanley, E. R. (1986-03-25). "The interaction of 125I-colony-stimulating factor-1 with bone marrow-derived macrophages". The Journal of Biological Chemistry. 261 (9): 4024–4032. doi:10.1016/S0021-9258(17)35616-8. ISSN 0021-9258. PMID 3485098.
  42. Stanley, E. Richard; Bartocci, Anna; Patinkin, Deborah; Rosendaal, Martin; Bradley, T. Ray (1986-06-06). "Regulation of very primitive, multipotent, hemopoietic cells by hemopoietin-1". Cell. 45 (5): 667–674. doi:10.1016/0092-8674(86)90781-6. ISSN 0092-8674. PMID 3085956. Unknown parameter |s2cid= ignored (help)
  43. Guilbert, L. J.; Stanley, E. R. (1986-03-25). "The interaction of 125I-colony-stimulating factor-1 with bone marrow-derived macrophages". The Journal of Biological Chemistry. 261 (9): 4024–4032. doi:10.1016/S0021-9258(17)35616-8. ISSN 0021-9258. PMID 3485098.
  44. Yeung, Y. G.; Jubinsky, P. T.; Sengupta, A.; Yeung, D. C.; Stanley, E. R. (March 1987). "Purification of the colony-stimulating factor 1 receptor and demonstration of its tyrosine kinase activity". Proceedings of the National Academy of Sciences of the United States of America. 84 (5): 1268–1271. Bibcode:1987PNAS...84.1268Y. doi:10.1073/pnas.84.5.1268. ISSN 0027-8424. PMC 304408. PMID 3029775.
  45. Sherr, C. J.; Rettenmier, C. W.; Sacca, R.; Roussel, M. F.; Look, A. T.; Stanley, E. R. (July 1985). "The c-fms proto-oncogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF-1". Cell. 41 (3): 665–676. doi:10.1016/s0092-8674(85)80047-7. ISSN 0092-8674. PMID 2408759. Unknown parameter |s2cid= ignored (help)
  46. Yu, Wenfeng; Chen, Jian; Xiong, Ying; Pixley, Fiona J.; Yeung, Yee-Guide; Stanley, E. Richard (2012-04-20). "Macrophage proliferation is regulated through CSF-1 receptor tyrosines 544, 559, and 807". The Journal of Biological Chemistry. 287 (17): 13694–13704. doi:10.1074/jbc.M112.355610. ISSN 1083-351X. PMC 3340183. PMID 22375015.
  47. Yeung, Yee-Guide; Stanley, E. Richard (November 2003). "Proteomic approaches to the analysis of early events in colony-stimulating factor-1 signal transduction". Molecular & Cellular Proteomics: MCP. 2 (11): 1143–1155. doi:10.1074/mcp.R300009-MCP200. ISSN 1535-9476. PMID 12966146. Unknown parameter |s2cid= ignored (help)
  48. Lee, P. S.; Wang, Y.; Dominguez, M. G.; Yeung, Y. G.; Murphy, M. A.; Bowtell, D. D.; Stanley, E. R. (1999-07-01). "The Cbl protooncoprotein stimulates CSF-1 receptor multiubiquitination and endocytosis, and attenuates macrophage proliferation". The EMBO Journal. 18 (13): 3616–3628. doi:10.1093/emboj/18.13.3616. ISSN 0261-4189. PMC 1171440. PMID 10393178.
  49. Chitu, Violeta; Ferguson, Polly J.; de Bruijn, Rosalie; Schlueter, Annette J.; Ochoa, Luis A.; Waldschmidt, Thomas J.; Yeung, Yee-Guide; Stanley, E. Richard (2009-09-17). "Primed innate immunity leads to autoinflammatory disease in PSTPIP2-deficient cmo mice". Blood. 114 (12): 2497–2505. doi:10.1182/blood-2009-02-204925. ISSN 1528-0020. PMC 2746474. PMID 19608749.
  50. Pixley, F. J.; Lee, P. S.; Dominguez, M. G.; Einstein, D. B.; Stanley, E. R. (1995-11-10). "A heteromorphic protein-tyrosine phosphatase, PTP phi, is regulated by CSF-1 in macrophages". The Journal of Biological Chemistry. 270 (45): 27339–27347. doi:10.1074/jbc.270.45.27339. ISSN 0021-9258. PMID 7592997.
  51. Wiktor-Jedrzejczak, W.; Bartocci, A.; Ferrante, A. W.; Ahmed-Ansari, A.; Sell, K. W.; Pollard, J. W.; Stanley, E. R. (June 1990). "Total absence of colony-stimulating factor 1 in the macrophage-deficient osteopetrotic (op/op) mouse". Proceedings of the National Academy of Sciences of the United States of America. 87 (12): 4828–4832. Bibcode:1990PNAS...87.4828W. doi:10.1073/pnas.87.12.4828. ISSN 0027-8424. PMC 54211. PMID 2191302.
  52. Dai, Xu-Ming; Ryan, Gregory R.; Hapel, Andrew J.; Dominguez, Melissa G.; Russell, Robert G.; Kapp, Sara; Sylvestre, Vonetta; Stanley, E. Richard (2002-01-01). "Targeted disruption of the mouse colony-stimulating factor 1 receptor gene results in osteopetrosis, mononuclear phagocyte deficiency, increased primitive progenitor cell frequencies, and reproductive defects". Blood. 99 (1): 111–120. doi:10.1182/blood.v99.1.111. ISSN 0006-4971. PMID 11756160.
  53. WO2008150383A1, Stanley, Evan Richard & Ying Xiong, "Csf-1r mutants", issued 2008-12-11 
  54. US9671391B2, Stanely, Evan Richard; Sayan NANDI & Yee-Guide YEUNG, "IL-34 receptor assays and uses thereof", issued 2017-06-06 


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