Molly Duman Scheel
Assistant Professor, Medical and Molecular Genetics
Indiana University School of Medicine-South Bend

Adjunct Assistant Professor, Dept. of Biological Sciences
Eck Institute for Global Health, Walther Cancer Institute, University of Notre Dame

Email: mscheel@nd.edu
Phone: Office: (574) 631-7194
Lab: (574) 631-7192
Location: Raclin-Carmichael Hall, Rm. 127

Ph.D., University of Chicago
Postdoctoral Training, University of Chicago
B.S., University of Notre Dame

Current Research Projects:
Current research interests in our laboratory include genetic and comparative analysis of invasive cellular growth, with emphasis on understanding axon growth and guidance. This work has implications for cancer biology, regenerative medicine, and vector biology.

1. Genetic Analysis of Invasive Growth:
In recent years, a number of nervous system development genes, such as the Netrin, DCC, Semaphorin, and Plexin axon guidance regulators, have been linked to many different types of human cancer. However, the cellular processes by which these genes regulate nervous system development and cancer are still being elucidated. A more detailed understanding of how guidance molecules function to regulate development will provide insight into their roles in oncogenesis. In particular, although the majority of cancer fatalities are due to the ability of late stage tumors to metastasize, relatively little is known about the genetic alterations that cause noninvasive tumors to become metastatic. Since both nervous system development and metastasis involve changes in cell polarity which accompany invasive growth, analysis of the functions of axon guidance molecules may lead to a better understanding of tumor metastasis. Both CNS development and the transformation of a cell and its clonal progeny into a metastatic tumor occur in the context of surrounding cells. It is therefore important to study the process of tumorigenesis in genetically tractable animal models in which interactions between cells can be investigated. Recent studies in Drosophila have provided insight as to how tumor suppressor genes impact cellular growth and metastasis. A particular advantage of the Drosophila system is the ability to mimic human cancers by creating somatic clones of cells bearing multiple genetic mutations. We exploit the advantages of the Drosophila system in our ongoing research studies, which include: (1) Characterization of the impacts and targets of axon guidance protein signaling on cellular growth during development, (2) Characterization of invasive phenotypes resulting from genetic alterations in axon guidance molecules, and (3) Discovery of genetic suppressors of growth and metastasis resulting from genetic lesions in axon guidance genes.

2. Analysis of Axon Guidance Gene Function in Vector Mosquitoes:
Our laboratory has broad interests in comparative analysis of arthropod development, with current focuses on comparative analysis of nervous system development and developmental growth regulation. In collaboration with David Severson's laboratory, we recently extended our comparative studies in arthropods to include mosquitoes, arthropod vectors of human pathogens. Our studies involve applying knowledge of developmental genetics in the fruit fly Drosophila melanogaster, a well-characterized genetically tractable developmental model organism, to better understand development of other arthropods, such as the dengue and yellow fever virus vector Aedes aegypti (pictured above) and the malaria vector mosquito Anopheles gambiae. Our ongoing studies have led to characterization of molecular markers in the mosquito CNS, including netrin, a regulator of CNS development. Conserved netrin accumulation patterns in insects and crustaceans indicate that arthropod midline glia are homologous, and that netrin proteins play conserved roles in arthropod CNS development. We are now investigating the function of additional axon guidance molecules and are pursuing functional analyses of these genes during mosquito development, with an ultimate goal of developing new methods of vector mosquito control.

Laboratory Personnel:
Ellen Flannery, Graduate Student, Univ. of Notre Dame Dept. of Biological Sciences
Anthony Clemons, Graduate Student, Univ. of Notre Dame Dept. of Biological Sciences
Morgan Haugen, Laboratory Technician, Indiana Univ. School of Medicine-South Bend
Michael Tomchaney, Undergraduate, Univ. of Notre Dame Dept. of Biological Sciences
Kristopher Kast, Undergraduate, Univ. of Notre Dame Dept. of Biological Sciences

Publications:

• Duman-Scheel, M. Netrin and DCC: Axon Guidance Regulators at the Intersection of Nervous System Development and Cancer. 2009. Current Drug Targets 10(7): 602-610.
• Flannery, E. and Duman-Scheel., M. 2009. Semaphorins at the interface of development and cancer. Current Drug Targets 10(7): 611-619.
• Duman-Scheel, M. Developmental genes and cancer (editorial). Current Drug Targets 10(7): 579-80.
• Simanton, W., Clark, S., Clemons, A., Jacowski, C., VanZomeren-Dohm, A., Beach, P., Browne, W., and Duman-Scheel, M. 2009. Conservation of arthropod midline netrin accumulation revealed with a cross-reactive antibody provides evidence for midline cell homology. Evol Dev., 11(3): 260-268.
• VanZomeren-Dohm, A., Flannery, E., and Duman-Scheel, M. 2008. A method for in situ hybridization detection of RNA levels in conjunction with GFP-marked somatic clones in Drosophila imaginal discs. Fly 2(6): 323-25
• Duman-Scheel, M., Clark, S., Grunow, E., Hasley, A., Hill, B., and Simanton, W. 2007. Delayed onset of midline netrin expression in Artemia franciscana coincides with commissural axon growth and provides evidence for homology of midline cells in distantly related arthropods. Evol Dev. 9(2): 131-140
• Duman-Scheel, M., Johnston, L., and Du W. 2004. Repression of dMyc expression by wingless promotes RBF-induced G1 arrest in the presumptive Drosophila wing margin. PNAS, USA, 101(11): 3857-3862.
• Duman-Scheel, M., Weng, L., Xin, S., and Du, W. 2002. Hedgehog regulates cell growth and proliferation by inducing Cyclin D and Cyclin E. Nature 417: 299-304.
• Duman-Scheel, M., Pirkl, N., and Patel, N.H. 2002. Analysis of the expression pattern of Mysidium columbiae wingless provides evidence for conserved mesodermal and retinal patterning processes among insects and crustaceans. Dev., Genes, Evol. 212: 114-123.
• Duman-Scheel, M. and Patel N.H. 1999. Analysis of molecular marker expression reveals neuronal homology in distantly related arthropods. Development 126 (11): 2327-2334.
• Duman-Scheel, M., Li, X., Orlov, I., Noll, M. and Patel, N.H. 1997. Genetic separation of neural and cuticular patterning functions of gooseberry. Development 124 (15): 2855-2865.
• Eldon, E., Kooyer, S., D'Evelyn, D., Duman, M., Lawinger, P., Botas, J. and Bellen, H. 1994. The Drosophila 18 wheeler gene is required for morphogenesis and has striking similarities to Toll. Development 120(4): 885-899.

Research Support:

Current
• 1 R01 AI081795-01, NIH/NIAID, 8/09-7/13, Analysis of the functions of axon guidance genes during vector mosquito development, Role: P.I.
• IUSM Research Support Funds Grant Award, 1/09-12/09, Functional Analysis of DCC during Anopheles gambiae development, Role: P.I.

Completed
• 1 R15 NS 048904-01, NIH/NINDS, 7/1/04-12/30/07, Netrins: Creating Divergent Axon Morphologies, Role: P.I.
• IUSM Research Enhancement Grant Award, 8/08-7/09, Analysis of the regulation of cellular growth by axon guidance molecules, Role: P.I.