Dr. Marianne Manchester: Drug Discovery

Research Summary: Targeted Nanotherapeutics

Dr. Manchester's laboratory is interested in contemporary therapeutic strategies for generating new and more efficient nanotechnology-based imaging agents, cancer therapeutics and antimicrobials. Viruses are increasingly being used in nanotechnology, for the design of molecular therapeutics. Viral nanoparticles (VNPs) are natural nanomaterials, and each type of VNP displays unique properties of cell adhesion and pharmacodynamics in vivo. Understanding the molecular basis of these properties for each VNP ensures that natural features may be paired with the most appropriate physiologic goal such as tumor targeting or molecular imaging.

Chemotherapeutics may be packaged inside VNPs and specifically delivered to tumors. These principles of targeted delivery may enhance the differential between specific targeting and reticuloendothelial clearance in vivo. The lab is currently applying these targeting principles to models of atherosclerosis and central nervous system inflammation, and infectious disease. Additional research in the lab is involved in combining these principles with the new field of mass spectrometry-based metabolomics, to develop a deep understanding of physiologic disease states in vivo, with a view toward identifying novel targets for diagnostic and therapeutic approaches.

Academic Achievements

Education: B.A. in Molecular, Cellular and Developmental Biology (1988) University of Colorado; Ph.D. in genetics (1992) University of North Carolina at Chapel Hill; NIH Postdoctoral Fellowship (1993) Scripps Research Institute; World-Health Organization Postdoctoral Fellow (1996) Scripps Research Institute.

Awards and Honors: Lineberger Fellow of the UNC Lineberger Comprehensive Cancer Center (1992); Fellow American Association of Nanomedicine (2007).

Leadership Experience:Program Director for NIH-sponsored program on novel therapeutics for anthrax (2002-2009); Director of multidisciplinary National Cancer Institute-sponsored program on nanotechnology-based therapeutics (2001-present). Scientific Advisory Board, Alliance for NanoHealth (2007).

Teaching

• Clinical Pharmacokinetics and Pharmacodynamics (SPPS 226)

Key Contributions to Pharmaceutical Sciences

• Developed novel nanoparticle-based therapeutics and vaccines for anthrax.
• Developed tumor-specific targeted viral nanoparticles.
• Developed strategies to probe the blood-brain barrier endothelium using VNPs.
• Developed novel strategies to identify metabolic pathways associated with disease.

Selected Recent Publications (from >75 peer-reviewed articles)

Brunel et al. (2010) Hydrazone ligation strategy to assemble multifunctional viral nanoparticles for cell imaging and tumor targeting. Nano Letters 10:1093-7.

Leong et al. (2010) Intravital imaging of embryonic and tumor neovasculature using viral nanoparticles. Nature Protocols 5:1406-17.

Steinmetz et al. (2011) Cowpea mosaic virus nanoparticles target surface vimentin on cancer cells. Nanomedicine 6:351-64.

Patti et al. (2012) Metabolomics implicates altered sphingolipids in chronic pain of neuropathic origin. Nature Chem. Biol. 8:232-234.

Plummer et al. (2012) Interaction of cowpea mosaic virus nanoparticles with surface vimentin and inflammatory cells in atherosclerotic lesions. Nanomedicine 7:877-88

Potential Collaborative Programs with the Pharmaceutical Industry

• 18 year’s experience developing in vivo models for infectious and inflammatory diseases and tumor therapeutics.
• Broad array of structural, molecular, chemical, and mass spectrometry-based approaches to define targeting strategies and disease signatures.