Perelman School of Medicine at the University of Pennsylvania

ROBERTO DOMINGUEZ, Ph.D.
Professor of Physiology

728 Clinical Research Building
415 Curie Boulevard
Philadelphia, PA 19104-6085
droberto@mail.med.upenn.edu

Phone: 215-573-4559
Lab: 215-573-0983
Fax: 215 573-2273
Lab web page:
http://www.med.upenn.edu/dominguez

Other Perelman School of Medicine Affiliations
Biochemistry and Molecular Biophysics Graduate Group

Pennsylvania Muscle Institute

Degrees
Ph.D., Pasteur Institute and Paris-Sud University, France, 1996,
M.S., Odessa State University, formerly-USSR, 1987

Honors
NIH Study Section (MSFC), 2006-present
Co-Chair Motility Subgroup of the Biophysical Society, 2006
American Heart Association, Established Investigator Award, 2002
American Heart Association, Grant-in-Aid Junior Investigator Award, 1999
March of Dimes, Basil O’Connor Scholar, 1998
Fellow of the German Academic Exchange Service (DAAD), 1992
Fellow of the Société Française de Belgique, 1989
Member of the Editorial Board of Biophysical Journal

Professional Affiliations
The American Society for Cell Biology
American Crystallographic Association
Biophysical Society
American Heart Association
American Association for the Advancement of Science

Research Description
The actin cytoskeleton plays an essential role in multiple cellular functions, including cytokinesis, vesicular trafficking and the maintenance of cell shape and polarity. To accomplish these functions, the cytoskeleton undergoes constant remodeling into various forms of structural and functional networks, such as lamellipodia, filopodia, stress fibers and focal adhesions. Remodeling of the cytoskeleton is a tightly regulated process, involving hundreds of actin-binding and signaling proteins. The main focus of the research in our lab is to understand the molecular basis for how protein-protein interaction networks bring together cytoskeleton scaffolding, nucleation, elongation, and signaling proteins to accomplish specific cellular functions.

Our primary research tool is protein X-ray crystallography. The atomic “snapshots” resulting from the X-ray crystal structures of proteins provide a wealth of knowledge, but lack information about the dynamic aspects of protein-protein interactions. To obtain this kind of information we also use a host of other approaches, including mutagenesis, bio-informatics, biophysical and biochemical methods.

Representative Publications

Boczkowska M, Rebowski G, Petoukhov MV, Hayes DB, Svergun DI, Dominguez R. Solution Structure of Activated Arp2/3 Complex by X-ray Scattering. Structure (2008) 16:695-704.

Chereau D, Boczkowska M, Skwarek-Maruszewska, A, Fujiwara I, Rebowski G, Hayes DB, Lappalainen P, Pollard TD, Dominguez R. Leiomodin is an actin filament nucleator in muscle cells. Science (2008) 320:239-243

Ferron F, Rebowski G, Lee SH & Dominguez R (2007). Structural basis for the recruitment of profilin–actin complexes during filament elongation by Ena/VASP. EMBO J. 26:4597-4606.

Lee SH, Hayes DB, Rebowski G, Tardieux I and Dominguez R (2007). Toxofilin from Toxoplasma gondii forms a ternary complex with an antiparallel actin dimer. PNAS 104:16122-16127.

Dominguez R (2007). The b-Thymosin/WH2 Fold: Multifunctionality and Structure. Ann N Y Acad Sci. 1112:86-94.

Lee SH, Kerff F, Chereau D, Ferron F, Klug A, Dominguez R (2007). Structural basis for the actin-binding function of Missing-in-Metastasis. Structure 15:145-55.

Borrego-Diaz E, Kerff F, Lee SH, Ferron F, Li Y, Dominguez R (2006). Crystal structure of the actin-binding domain of alpha-actinin 1: evaluating two competing actin-binding models. J Struct Biol. 155:230-238.

Chereau D, Kerff F, Graceffa P, Grabarek Z, Langsetmo K, Dominguez R (2005). Actin-bound structures of Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 and the implications for filament assembly. PNAS 102:16644-16649.

Dominguez R (2004). Actin-binding proteins - a unifying hypothesis. Trends Biochem Sci. 29:572-578.

Terrak M, Kerff F, Langsetmo K, Tao T, Dominguez R (2004). Structural basis of protein phosphatase 1 regulation. Nature 429:780-784.

Otterbein LR, Graceffa P, Dominguez R (2001). The crystal structure of uncomplexed actin in the ADP state. Science 293:708-711.

Click here for a full list of publications
(searches the National Library of Medicine's PubMed database.)