Nancy Ratner, PhD
Title
Beatrice C. Lampkin Chair in Cancer Biology
Appointment
Professor, Division of Experimental Hematology and Cancer Biology
Email
nancy.ratner@cchmc.org
Phone
513-636-9469
Fax
513-636-3549
Bio
Nancy Ratner is a Professor in the Division of Experimental Hematology. She graduated from Brown University in 1975 and received her Ph.D. from Indiana University in 1982. From 1982-1987 she was a postdoctoral fellow at Washington University at St. Louis. From 1987 - 2004 she was on the faculty of the Department of Cell Biology, Neurobiology & Anatomy, University of Cincinnati College of Medicine. She is a member of the International Consortium for the Molecular Biology of NF1 and NF2.
Credentials
Postdoctoral Fellow Washington University St. Louis, 1982-1987
PhD Indiana University, 1982
BA Brown University, 1975
Position History
1997-2004 Professor, Department of Cell Biology, Neurobiology and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio
1992-1997 Associate Professor, Department of Cell Biology, Neurobiology and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio
1987-1992 Assistant Professor, Department of Anatomy and Cell Biology, University of Cincinnati College of Medicine, Cincinnati, Ohio
1993- Member, Developmental Biology Training Program, University of Cincinnati College of Medicine, Cincinnati, Ohio
1995 Sabbatical leave, Dept. of Molecular Genetics, University of Cincinnati (mentor: Dr. Joanna Groden)
1994- Member, Neuroscience Training Program, University of Cincinnati College of Medicine, Cincinnati, OH
1986-1987 Instructor in Biological Chemistry, Washington University School of Medicine, St. Louis, Missouri
1977-1982 Graduate Student, Department of Chemistry, Indiana University, Bloomington, Indiana (mentor: Dr. Henry Mahler)
Fall 1981 Visiting student, laboratory of Dr. Thomas Reese, Marine Biological Laboratory, Woods Hole, Massachusetts
1975-1977 Research Assistant, Department of Biology, Indiana University, Bloomington, Indiana
Awards and Honors
- Co-chair 1990-2001, International Consortium on the Molecular Biology of Neurofibromatosis Type 1 and Neurofibromatosis type 2
- Frank R. Lillie and Herbert W Rand Fellowships, Marine Biological Laboratory, Woods Hole, MA, 2002
- Harry Weaver Junior Scholar Award, National Multiple Sclerosis Society, 1987 – 1992
- National Neurofibromatosis Foundation Young Investigator Award, 1986 – 1989
- Burroughs Wellcome Fellow of the Life Sciences Research Foundation,1983 – 1986
- Student, Neurobiology Course, Marine Biological Laboratory, Woods Hole, MA, 1980
Research
Connect to Nancy Ratner's laboratory pages
My laboratory is interested in peripheral nerve glia known as Schwann cells. We study Schwann cells during normal development, and during abnormal development associated with tumor formation. The current focus of our research is genetic mutations in tumor suppressor genes and the effect of these mutations on Schwan cell development. These genes are thought to contribute to carcinogenesis when mutant or lost. Schwann cell tumors develop in humans who inherit mutations in two of these tumor supressor genes, neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2). Mechanistic analysis of Ras (a modulatoryNF1 activity) pathways and cytoskeleton- Rac (a member of the RhoGTPase family involved in NF2 signaling) intracellular signaling pathways in Schwann cells disrupted by mutations in these genes are being actively investigated. We are using transgenic mouse models, and cells from primary human tumors to define cellular changes that lead to Schwann cell tumor formation, secondary to mutations in the NF1 and NF2 genes.
NF1
The peripheral nerve tumors, neurofibromas, found in NF1 patients contain not only Schwann cells, but also fibroblasts, mast cells and axons. One of our aims is to test how each of these cell types contributes to neurofibroma formation. A current project is aimed at defining the role of mast cells in a mouse transgenic model of neurofibroma formation developed in our laboratory. Schwann cells lacking NF1 show multiple phenotypic changes in culture. Some depend on the Ras modulator function of NF1; others may depend on aberrant activation of non-canonical Ras relatives. Over the next few years, we aim to define the precise function of specific Ras proteins in mediating the Schwann cell phenotypes identified. Understanding how NF1 functions should lead to treatment strategies for human patients. A third major focus in the laboratory is to use microarray expression analysis to define differences between normal Schwann cells and NF1 mutant Schwann cells. We are leading an international effort to define these differences, to identify molecules that drive neurofibroma formation, and provide novel therapeutic targets.
NF2
NF2 patients develop schwannomas, benign tumors made up entirely of Schwann cells. We have shown dramatic cytoskeletal abnormalities in schwannoma cells. Changes in the actin cytoskeleton are consistent with what is known about the NF2 protein, merlin: merlin is a membrane-cytoskeletal linking protein believed to regulate the actin cytoskeleton via small G-protein signaling cascades. We aim to define how merlin functions in Schwann cells, using this model. We are working closely Dr. Yi Zheng's laboratory at TCHRF to investigate Rac signaling in Schwann cells.
Research Grants and Contracts
NIH-R01 NS 28840-18, "Mitogenic Activities in Neurofibromatosis", 3/2006 – 2/2011(20% effort, Ratner, PI); $325K per year direct costs.
NIH-R01 CA118032, "Schwann cells in Neurofibromatosis type 2", 7/2007 – 6/2012 (20% effort, Ratner, PI); $190K per year direct costs.
NIH-P50-NS057531 “Cincinnati Center for Neurofibromatosis Research” 7/2008 – 6/2013: Ratner, PI: Admin Core $48K\year; Project 2 $192K\year
Children’s Tumor Foundation, “Preclinical Testing of Neurofibroma and MPNST”
Cripe, PI, Ratner, Co-PI; Total to Ratner $130K\year. 8/2008 – 7/2011
U.S. Army NF Program, “Comparison of NF1, NF2 and Schwannomatosis Tumors”, Ratner, PI $200K\year. 2/2009 – 1/2011
NIH R21 “Identification of Drug Targets for NF1”
$12,148\year, 04/09-03//11 Dartmouth Sanchez, PI; Ratner Co-I
Publications, Most Recent
Connect to Nancy Ratner's publication on PubMed
Miller, S.J., Lan, Z., Hardiman, A., Wu, J., Kordich, J.J., Patmore, D., Hegde, R., Cripe, T.P., Cancelas, J., Collins M. and Ratner, N. (2009) Inhibition of Eyes Absent Homolog 4 expression induces malignant peripheral nerve sheath tumor necrosis, Oncogene, in press.
Miller, S.J., Jessen, W.J., Mehta, T., Hardiman, A., Sites, E., Kaiser, S., Jegga, A., Li, H., Upadhyaya, M.., Giovannini, M., Muir, D., Wallace, M.R., Lopez, E., Serra, E., Lazaro, C., Stemmer-Rachamimov, A., Page, G., Aronow, B.J. and Ratner, N. Integrative genomic analyses of neurofibromatosis tumors identify SOX9 as biomarker and survival gene (2009) EMBO Mol. Medicine, 1(4): 236-248.
Mahller, Y., Williams, J., Baird, W., Mitton, B., Grossheim, J., Saeki, Y., Cancelas, J., Ratner, N., and Cripe, T. (2009) Neuroblastoma cell lines contain pluripotent tumor initiating cells that are susceptible to a targeted oncolytic virus, PLoS ONE, 4(1):e4235, 1 – 10.
Williams, J.P., Wu, J., Mukouyama, Y., Miller, S.C., Geiger, H., Colbert, M.C., Cancelas, J.A. and Ratner, N. (2008) NFI mutation expands an EGFR -dependent peripheral nerve progenitor population that confers tumorigenic potential. Cell Stem Cell, 3(6):658-69.
Johansson, G., Mahller, Y., Collins, M.H., Kim, M-O., Nobukuni, T., Perentesis, J.P., Cripe, T.P., Lane, H.A., Kozma, S., Thomas, G., Ratner, N. (2008) Effective In Vivo Targeting of the mTOR Pathway in Malignant Peripheral Nerve Sheath Tumor, Mol. Cancer Therapeutics, 7(5):1237-45.
Wu, J., Williams, J.P., Rizvi, T.A., Kordich, J.J., Witte, D., Meijer, D., Stemmer-Rachamimov, A.O., Cancelas, J.A. and Ratner, N. (2008) Plexiform and dermal neurofibromas and pigmentation are caused by Nf1 loss in desert hedgehog expressing cells, Cancer Cell, 13(2), 105–116.
Monk, KR, Wu, J, Williams, JP, Meinhardt, BA, Fitzgerald, ME, Filippi, M, and Ratner, N. (2007) Mast cells can contribute to axon-glial dissociation and fibrosis in peripheral nerve, Neuron Glial Biology 3(3):233-44.
Mahller YY, Vaikunth SS, Currier MA, Miller SJ, Ripberger MC, Hsu Y, Mehrian-Shai R, Collins MH, Crombleholme TM, Ratner N, Cripe TP. (2007) Oncolytic HSV and Erlotinib Inhibit Tumor Growth and Angiogenesis in a novel Malignant Peripheral Nerve Sheath Tumor Xenograft Model. Molec. Therapy 15(2):279-286.
Nakai, Y., Zheng Y., McCollin, M., and Ratner, N. (2006) Temporal control of Rac-GTP in Schwann cell - axon interaction is disrupted in NF2-mutant schwannoma cells, J. Neurosci., 26(13):3390-5.
Wu, J., Crimmins, J., Monk, K., Williams, J., Fitzgerald, M., Tedesco, S. and Ratner, N. (2006) Perinatal EGFR blockade prevents peripheral nerve disruption in a model reminiscent of WHO Grade 1 neurofibroma, Am. J. Pathol., 168(5), 1686-1696.
Miller, SJ, Rangwala, F, Williams, J Kong, S, Jegga, A, Aronow, B, Frahm, S, Kluwe, L, Mautner, V, Upadhyaya, M, Muir, D, Wallace, M, Hagen, J, Quelle, DE, Watson, M, Perry, A, Gutmann, DH, and Ratner, N. (2006) Large-scale molecular comparison of human Schwann cells to malignant peripheral nerve sheath tumor cell lines and tissues, Cancer Research, 66(5):2584-91.
Mahller, Y.Y., Rangwala, F. Ratner, N. and Cripe, T.P. (2006) Malignant Peripheral Nerve Sheath Tumors with High and Low Ras are Permissive for Oncolytic Herpes Simplex Virus Mutants, Pediatric Blood and Cancer, 46(7):745-54.
Professional Organization Memberships
- AAAS
- American Society for Cell Biology
- American Society for Neurochemistry
- Society for Neuroscience
- American Association for Cancer Research (AACR)
Special Interests
Development of the nervous system; peripheral nerve tumor formation
Related Areas
This person works in these other areas at Cincinnati Children's Hospital Medical
Center:
