Area of interest
Viruses are remarkably plastic entities. New strains evolve constantly driven by genetic drift and iterative mutagenesis. Acceleration of these evolutionary processes in a laboratory setting will greatly impact our ability to carry out studies focused on understanding molecular mechanisms underlying viral infection. The overarching goal of my lab is to combine the tools and principles of molecular biology and genetics with chemistry to generate a synthetic viral toolkit. The resulting hybrid viral entities are utilized to unravel viral infectious pathways, provide novel vectors for gene therapy and reagents for molecular genetics applications.
The Adeno-Associated Virus (AAV) Capsid
AAV is a non-pathogenic member of the Parvoviridae family that is rapidly gaining popularity as a vector for gene transfer. Among the smallest known viruses at a diameter of 25nm, the icosahedral AAV shell is comprised of 60 protein subunits and encapsidates a single-stranded DNA genome. We are interested in understanding the biology of the AAV capsid at the molecular level. For instance, how does the capsid self-assemble? How do changes in amino acid residues result in capsids with altered tissue tropism? To answer these questions, we utilize an ever-expanding synthetic AAV toolkit generated through a combination of rational and combinatorial mutagenesis as well as new tools at the interface of chemistry and molecular biology.
The Lentiviral Envelope
The Lentivirus (e.g., HIV), a genus of the Retroviridae family, is another popular tool for gene transfer applications. The spherical virions are enveloped with lipids derived from host cell membranes and package an RNA genome. Using metabolic engineering tools, we are interested in manipulating molecular components of the lentiviral envelope to generate a synthetic lentiviral panel for mechanistic studies and gene therapy applications.
The Viral Genome
Manipulation of genomic material packaged within viruses is critical towards vector development for gene therapy applications. Towards this end, we are interested in (a) incorporation of novel regulatory elements in viral vector genomes, (b) identification and mechanistic characterization of small molecules that impact viral gene expression and (c) exploring the possibility whether viruses can package chemically altered genomes.
Our long term goal is to develop new lab-derived viral vector strains ideal for translational studies in areas including genetic disorders, infectious disease and cancer.