My research group focuses on utilizing novel technologies to develop new therapeutics and diagnostics for autoimmune and inflammatory diseases. The development of mutli-functional drugs, i.e. theranostics, allows simultaneous imaging of tissue pathology coupled with treatment, increasing efficacy and reducing toxicity. To this end, my group uses mass spectrometry-based metabolomics, molecular imaging, and viral nanoparticles to identify and target cellular pathways that are involved in disease pathogenesis.
Metabolomics and In Situ Metabolite Imaging
Technological advances in liquid chromatography/mass spectrometry have enabled systems-level analysis of metabolites and metabolic pathways. This approach, called metabolomics, allows the global quantification of metabolite alterations in biological systems during health and disease. To complement the liquid chromatography/mass spectrometry-based metabolomic approach, we also utilize a novel mass spectrometry-based imaging technology, nanostructure initiator mass spectrometry (NIMS), to localize metabolites of interest within tissue and connect them to disease pathogenesis. We are interested in applying these technologies to understand metabolic perturbations that occur during central nervous system autoimmunity and identify biochemical pathways involved in demyelination and/or remyelination that may function as therapeutic targets. We are also working toward developing new metabolomic technologies that aid in the analysis of biological samples, including software that can combine global profiling and molecular imaging data as well as expanding the database of CNS-specific metabolites.
Viral Nanoparticles as Platforms for Targeted Drug Delivery
Cowpea mosaic virus (CPMV) is a novel nanoparticle platform for the targeted delivery of drugs and imaging agents to sites of disease. CPMV has several advantages as a drug delivery vehicle including biocompatibility, the ability to withstand a wide range of temperatures and pHs, and its chemical addressability which allows modification of the capsid surface to display targeting ligands. Using this viral nanoparticle, we are interested in developing imaging agents for the detection of central nervous system demyelination by MRI as well as encapsulating anti-inflammatory and regenerative agents for the targeted treatment of neurodegeneration.
Plummer EM, Thomas D, Destito G, Shriver LP, Manchester M. (2012) Interaction of cowpea mosaic virus nanoparticles with surface vimentin and inflammatory cells in atherosclerotic lesions. Nanomedicine (Lond). 7(6):877-88
Patti GJ, Yanes O, Shriver LP, Courade JP, Tautenhahn R, Manchester M, Siuzdak G. (2012) Metabolomics implicates altered sphingolipids in chronic pain of neuropathic origin. Nat Chem Biol. 22;8(3):232-4.
Shriver LP, Manchester M. (2011) Inhibition of fatty acid metabolism ameliorates disease activity in an animal model of multiple sclerosis. Sci Rep. 1:79.
Patti GJ, Shriver LP, Wassif CA, Woo HK, Uritboonthai W, Apon J, Manchester M, Porter FD, Siuzdak G. (2010) Nanostructure-initiator mass spectrometry (NIMS) imaging of brain cholesterol metabolites in Smith-Lemli-Opitz syndrome. Neuroscience. 170(3):858-64.
Patti GJ, Woo HK, Yanes O, Shriver L, Thomas D, Uritboonthai W, Apon JV, Steenwyk R, Manchester M, Siuzdak G. (2010) Detection of carbohydrates and steroids by cation-enhanced nanostructure-initiator mass spectrometry (NIMS) for biofluid analysis and tissue imaging. Anal Chem. 2010 Jan 1;82(1):121-8.
Shriver LP, Koudelka KJ, Manchester M. (2009) Viral nanoparticles associate with regions of inflammation and blood brain barrier disruption during CNS infection. J Neuroimmunol. 211(1-2):66-72.
Yanes O, Woo HK, Northen TR, Oppenheimer SR, Shriver L, Apon J, Estrada MN, Potchoiba MJ, Steenwyk R, Manchester M, Siuzdak G. (2009) Nanostructure initiator mass spectrometry: tissue imaging and direct biofluid analysis. Anal Chem. 81(8):2969-75.