Gender	Male
E-mail	marius.sudol@mssm.edu
Education and Training	PhD, The Rockefeller University
	Postdoctoral Training, The Rockefeller University

Education and Training	PhD, The Rockefeller University
	Postdoctoral Training, The Rockefeller University

Analysis of modular protein domains in signal transduction

The tools of molecular biology, biochemistry, structural biology and bio-informatics are used to understand signal transduction steps that use modular protein domains. Special focus is on the WW domain, a small protein module composed of 40 amino acids that interacts specifically with protein ligands containing proline-rich motifs. The domain is implicated in several genetic diseases. The best example is the Liddle syndrome of hypertension in which mutations of amiloride?"sensitive sodium channel, ENaC, abrogate binding to WW domain proteins involved in regulation of the channel turnover. In collaboration with several labs and AxCell Biosciences Company we are characterizing contribution of the WW domain to the function of the human proteome using several proteomic platforms. Our final aim is to design strategies for rational therapeutic interventions based on the detailed knowledge of the structure and function of WW domain. Ultimately, such therapeutics could be used to control hypertension and other human diseases.

Current projects focused on the basic biology of the kidney include (1) the role of beta-dystroglycan and its multi-component protein complexes in podocyte function and (2) the analysis of putative WW and SH3 sites in the C-terminal domain of the PKD1-encoded protein, polycystin-1.

Huang X, Poy F, Zhang R, Sudol M, Joachimiak A, Eck MJ. Structure of a WW domain containing fragment of dystrophin in complex with beta-dystroglycan. Nat Struct Biol. 2000 Aug ; 7(8): 634-8.

Chang A, Cheang S, Espanel X, Sudol M. Rsp5 WW domains interact directly with the carboxyl-terminal domain of RNA polymerase II. J Biol Chem. 2000 Jul 7; 275(27): 20562-71.

Sudol M, Hunter T. New wrinkles for an old domain. Cell 2000 Dec 22; 103(7): 1001-4.

Sudol M, Sliwa K , Russo T . Functions of WW domains in the nucleus. FEBS Lett. 2001 Feb 16; 490(3): 190-5.

Wu X, Chang A, Sudol M, Hanes SD. Genetic interactions between the ESS1 prolyl-isomerase and the RSP5 ubiquitin ligase reveal opposing effects on RNA polymerase II function. Curr Genet. 2001 Dec; 40(4): 234-42.

Sotgia F, Lee H, Bedford MT, Petrucci T, Sudol M, Lisanti MP. Tyrosine phosphorylation of beta-dystroglycan at its WW domain binding motif, PPxY, recruits SH2 domain containing proteins. Biochemistry 2001 Dec 4; 40(48): 14585-92.

Sudol M, Espanel X . Yes-associated protein and p53-binding protein-2 interact through their WW and SH3 domains. J Biol Chem. 2001 Apr 27; 276(17): 14514-23.

Macias MJ, Wiesner S, Sudol M. WW and SH3 domains, two different scaffolds to recognize proline-rich ligands. FEBS Lett. 2002 Feb 20; 513(1): 30-7.

Basu S, Totty NF, Irwin MS, Sudol M, Downward J. Akt phosphorylates the Yes-associated protein, YAP, to induce interaction with 14-3-3 and attenuation of p73-mediated apoptosis. Mol Cell. 2003 Jan ; 11(1): 11-23.

Komuro A, Nagai M, Navin NE, Sudol M. WW domain-containing protein YAP associates with ErbB-4 and acts as a co-transcriptional activator for the carboxyl-terminal fragment of ErbB-4 that translocates to the nucleus. J Biol Chem. 2003 Aug 29; 278(35): 33334-41.