Fredric P. Manfredsson, PhD
- Faculty, Training Faculty, Cellular & Molecular
Assistant Professor, Translational Science & Molecular Medicine
Ph.D., 2006, University of Florida
My research has a two-pronged approach. On one hand my work focuses on the development and characterization of viral vectors (primarily recombinant adeno-associated virus) for the delivery of genes or other genetic elements to the central nervous system. The ultimate goal of this work is to create a library of viral vectors that exhibit distinct properties in their ability to infect certain cell-types and anatomically distinct circuits of the brain. Another important component of these vectors that is being investigated is the manipulation of gene-expression. By modifying promoter elements in the recombinant viral genome we aim to guide expression of our genetic payload to a certain cell-type, a certain cellular condition such as oxidative stress, or to a specific cellular process such as axonal transport.
On the other hand, I utilize these vectors to study the molecular pathology of neurodegenerative disease (especially Parkinson’s Disease (PD)) as well as to deliver therapeutic agents aimed at treating disease. For instance, a current focus of my research involves virally mediated modulation of alpha-synuclein in the neuronal circuit afflicted in PD. Alpha-synuclein is a protein that has been linked to a certain heritable form of PD. Although transgenic mice lacking alpha-synuclein display a minimal phenotype, we have shown that virally mediated reduction of the protein in adult animals result in severe toxicity and parkinsonian-like motor behavior. Using a combination of viral vectors I am now working to establish a connection between alpha-synuclein, the function of neurotransmitter vesicles, and the generation of oxidative stress as a component of alpha-synuclein dependent PD.