Gender	Male
E-mail	thomas.weber@mssm.edu
Education and Training	Ph.D., Swiss Federal Institute of Technology
	Masters, Federal Institute of Technology
	B.S., College Schaffhausen
	Postdoctorate, Memorial Sloan Kettering Cancer Center

Weber Laboratory

Education and Training	Ph.D., Swiss Federal Institute of Technology
	Masters, Federal Institute of Technology
	B.S., College Schaffhausen
	Postdoctorate, Memorial Sloan Kettering Cancer Center

Specific Clinical/Research Interests: Adeno-associated virus biology and Gene Therapy

Postdoctoral Fellows: Vedell Louis-Jeune, Mathieu Nonnenmacher

Summary of Research Studies:
Adeno-Associated Virus Biology and AAV Retargeting Due to its relative safety, enthusiasm for gene therapy vectors based on adeno-associated virus (AAV) has steadily increased among researchers over the last few years. As a result, AAV vectors are being used for a widening variety of therapeutic applications. AAV is particularly attractive because the wild-type virus can integrate its genome into a specific location on chromosome 19. Although recombinant AAV vectors, at present, do not have this property, active research aimed at developing such vectors is ongoing. Such vectors would have the advantage that they would not result in oncogenic transformation caused by random integration of vector DNA. Our lab is focusing on the cellular mechanisms that underlie the cell and tissue specificity of AAV. AAV can transduce a variety of cell types and tissues but with varying efficiencies depending on cell type. Muscle, for instance, is transduced very efficiently, while other tissues and cell types are transduced more poorly. These differences can only be partially explained by variations in receptor densities in various tissues and cell types. It is likely that other cellular barriers also are playing a role in these differences. Our research aims to gain a better understanding of the cellular roadblocks that prevent the efficient transduction of certain cell types and develop methods to improve transduction efficiencies for these cell types and tissues. Specifically, we are developing new methods to target AAV to specific cell types.

Weber Laboratory

Hirosue S, Senn K, Clement N, Nonenmacher M, Gigout L, Linden RM, Weber T. Effect of inhibition of dynein function and microtubule-altering drugs on AAV2 transduction. Virology 2007; 367: 10-18.

Hirosue S, Weber T. pH-Dependent Lytic Peptides Discovered by Phage Display. Biochemistry 2006 May 23; 45(20): 6476-87.

Gigout L, Rebollo P, Clement N, Warrington KH, Muzyczka N, Linden RM, Weber T. Altering AAV tropism with mosaic viral capsids. Mol Ther 2005 Jun; 11(6): 856-865.

Murrell M, Porotto M, Weber T, Greengard O, Moscona A. Mutations in human parainfluenza virus type 3 hemagglutinin-neuraminidase causing increased receptor binding activity and resistance to the transition state sialic acid analog 4-GU-DANA (Zanamivir). J Virol 2003 Jan; 77(1): 309-317.

Weber T, Zemelman BV, Mcnew JA, Westermann B, Gmachl M, Parlati F, Sollner TH, Rothman JE. SNAREpins: minimal machinery for membrane fusion. Cell 1998 Mar 20; 92(6): 759-72.