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Nancy Ratner, PhD

Title

Professor

Appointment

Professor

Email

nancy.ratner@cchmc.org

Phone

513-636-9469

Fax

513-636-3549

Office Location

Location R, 2325

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 with Dr. David Williams laboratory as well as Dr. Yi Zheng's laboratory at TCHRF to investigate Rac signaling in Schwann cells.

Research Grants and Contracts

U.S. Army NF Program (Ratner) 9/2005 – 8/2008
Modelling Brain Defects in NF1

NIH-R01 NS 28840-17 (Ratner) 2/2001/2011
Mitogenic Activities in Neurofibromatosis

U.S. Army NF Program, USA (Ratner) 11/2004 – 10/2008
Med Res W81XWH-04-1-0273; "Therapeutic Targets for Neurofibromas: Identification by Cross-Species Gene Expression Analysis"

Publications, Most Recent

Connect to Nancy Ratner's publication on PubMed

Wu J, Crimmins JT, Monk KR, Williams JP, Fitzgerald ME, Tedesco S, Ratner N. Perinatal epidermal growth factor receptor blockade prevents peripheral nerve disruption in a mouse model reminiscent of benign world health organization grade I neurofibroma.Am J Pathol. 2006 May;168(5):1686-96.

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, Ratner N. Large-scale molecular comparison of human Schwann cells to malignant peripheral nerve sheath tumor cell lines and tissues. Cancer Research. 2006;66(5):2584-91.

Mahller YY, Rangwala F, Ratner N, Cripe TP. Malignant peripheral nerve sheath tumors with high and low Ras-GTP are permissive for oncoloytic herpes simplex virus mutants.Pediatr Blood Cancer. 2006 Jun;46(7):745-754.

Wu J, Crimmins J, Monk K, Williams J, Fitzgerald M, Tedesco S, Ratner N. Perinatal EGFR blaockade prevents peripheral nerve disruption in a model reminiscent of WHO Grade 1 neurofibroma. Am. J. Pathol. 2006;168(5):1686-1696.

Nakai Y, Zheng Y, McCollin M, Ratner N. Temporal control of Rac-GTP in Schwann cell-axon interaction is disrupted in NF2-mutant schwannoma cells. J. Neurosci. 2006;26(13):3390-5.

Ratner N, Miller SJ. Model systems for neurofibroma and malignant peripheral nerve sheath tumor. Drug Discovery Today. 2006;3(2): 175-182.

Ratner N, Williams JP, Kordich JP, Kim HA. Schwann cell preparation from single mouse embryos: Analyses of neurofibromin function in Schwann cells. Meth. Enzymol. 2005; 407:22-33 in Regulators and Effoctors of Small GTPases, Part D: Ras Family. Ed. Balch, Cer CJ, Hall A.

Aguirre A, Rizvi TA, Ratner N, Gallo V. Overexpression of the epidermal growth factor receptor confers migratory properties to nonmigratory postnatal neural progenitors.J Neurosci. 2005 Nov 30;25(48):11092-106.

Ling BC, Wu J, Miller SJ, Monk KR, Shamekh R, Rizvi TA, Decourten-Myers G, Vogel KS, DeClue JE, Ratner N. Role for the epidermal growth factor receptor in neurofibromatosis-related peripheral nerve tumorigenesis.Cancer Cell. 2005 Jan;7(1):65-75.

Tang Y, Lu A, Ran R, Aronow BJ, Schorry EK, Hopkin RJ, Gilbert DL, Glauser TA, Hershey AD, Richtand NW, Privitera M, Dalvi A, Sahay A, Szaflarski JP, Ficker DM, Ratner N, Sharp FR. Human blood genomics: distinct profiles for gender, age and neurofibromatosis type 1. Brain Res Mol Brain Res. 2004 Dec 20;132(2):155-67.

Stickney JT, Bacon WC, Rojas M, Ratner N, Ip W. Activation of the tumor suppressor merlin modulates its interaction with lipid rafts.Cancer Res. 2004 Apr 15;64(8):2717-24.

Huang Y, Rangwala F, Fulkerson PC, Ling B, Reed E, Cox AD, Kamholz J, Ratner N. Role of TC21/R-Ras2 in enhanced migration of neurofibromin-deficient Schwann cells.Oncogene. 2004 Jan 15;23(2):368-78.