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.
- Miller N., Shriver L.P., Bodiga V.L., Ray A., Basu S., Ahuja R., Jana A., Pahan K., Dittel B.N. Lymphocytes with cytotoxic activity induce rapid microtubule axonal destabilization independently and before signs of neuronal death (2013) ASN Neuro. Jan 4.
- Patti G.J., Tautenhahn R., Shriver L.P., Manchester M., Cho K., and Siuzdak G.,(2013) Mirror Plot, Visualizing Global Metabolomics Data for Biological Insight, Anal Chem. 2013 Jan 15;85(2):798-804.
- Shriver L.P., Plummer E.M., Thomas D., Ho S., and Manchester M. (2013) Localization of gadolinium-loaded CPMV to sites of inflammation during central nervous system autoimmunity, J Mater Chem B. 5256-5263.
- Koudelka K.J., Ippoliti S., Medina E., Shriver L.P., Trauger S.A., Catalano C.E., Manchester M. (2013) Lysine Addressability and Mammalian Cell Interactions of Bacteriophage λ Procapsids. Biomacromolecules Dec 9;14(12):4169-76.
- Chen Y.J., Hill S., Huang H., Taraboletti A., Cho K., Gallo R. Manchester M., Shriver, L.P., and Patti G. J. (2014) Inflammation triggers production of dimethylsphingosine from oligodendrocytes., Neuroscience, Oct 24;279:113-21.
- Johnson C.H., Patti G.J., Courade J.P., Shriver L.P., Hoang L.T., Manchester M., Siuzdak G. (2015) Alterations in Spinal Cord Metabolism during Treatment of Neuropathic Pain. J Neuroimmune Pharmacol. Sep;10(3):396-401.
- Huang H., Taraboletti A., and Shriver, L.P. (2015) Dimethyl fumarate modulates antioxidant and lipid metabolism in oligodendrocytes. Redox Biol. Apr; 29;5:169-175.
- Yang J., Shanahan K. J. , Shriver L.P. , Luciano M.G. (2016) Exercise-induced respondent changes of CSF vascular endothelial growth factor in adult chronic hydrocephalus patients. J Clin Neuroscience, Feb; 24:52-6.
- Patil P.S., Fountas-Davis N., Huang H., Chapman M., Fulton J., Shriver, L.P. Leipzig N.D. (2016) Fluorinated methacrylamide chitosan hydrogels enhances collagen synthesis in wound healing by enhanced oxygenation. ACTBIO, May;36:164-74.
- Huang H., Yang J., Luciano M., and Shriver L.P. (2016) Longitudinal metabolite profiling of cerebrospinal fluid in normal pressure hydrocephalus links brain metabolism with exercise-induced VEGF production, Neurochem Res, Jul;41(7):1713-22.