Since October 2002 I've been working as a postdoctoral fellow in Dr. Tomas Mustelin's group at the Burnham Institute for Medical Research in La Jolla, CA. I am investigating a family of enzymes called protein tyrosine phosphatases (PTPs).

PTPs are involved in numerous cellular processes, like growth, survival, and death. Therefore it isn't surprising that they are implicated in a growing number of human disease, ranging from cancer to cardiovascular, immunological, infectious, neurological, and metabolic disease. Studying and understanding the exact function of each of these enzymes is becoming of great importance. Moreover, PTPs are now seen as possible drug targets, and the development of specific small molecules which can regulate their activity, is of increasing interest.

My research focuses on the development of specific small-molecule inhibitors for PTPs, involved in T-cell signaling. Two of them, CD45 and Lyp, are considered as drug targets for treatment of transplant rejection and autoimmune diseases like typ I diabetes (T1D), rheumatoide arthritis, systemic lupuserythematosus (SLE), and Graves disease.

Starting with chemical library screening, followed by enzyme kinetic-, structure-activity-relationship- and in silico docking studies, up to cell based and in vivo assays, our efforts already resulted in the finding of a new class of inhibitors for the tyrosine phosphatase YopH, a Yersinia pestis effector protein which is essential for virulence of the bacterium that causes plague.

Publications in peer reviewed journals:

Tautz L, Pellecchia M, Mustelin T. Targeting the PTPome in human disease. Expert Opin Ther Targets. 2005 Review. (in press)

Vang T, Congia M, Macis MD, Musumeci L, Orru V, Zavattari P, Nika K, Tautz L, Tasken K, Cucca F, Mustelin T, Bottini N. Autoimmune-associated lymphoid tyrosine phosphatase is a gain-of-function variant. Nat Genet. 2005 (Published online: 6 November 2005)

Mustelin T, Tautz L, Page R. Structure of the Hematopoietic Tyrosine Phosphatase (HePTP) Catalytic Domain: Structure of a KIM Phosphatase with Phosphate Bound at the Active Site. J Mol Biol. 2005 Nov 18;354(1):150-63.

Musumeci L, Bongiorni C, Tautz L, Edwards RA, Osterman A, Perego M, Mustelin T, Bottini N. Low molecular weight protein tyrosine phosphatases of Bacillus subtilis. J Bacteriol. 2005 Jul;187(14):4945-56.

Mijakovic I, Musumeci L*, Tautz L*, Petranovic D, Edwards RA, Jensen PR, Mustelin T, Deutscher J, Bottini N. In Vitro Characterization of the Bacillus subtilis Protein Tyrosine Phosphatase YwqE. J Bacteriol. 2005 May;187(10):3384-90. (*shared authorship)

Bruckner S, Rahmouni S, Tautz L, Denault JB, Alonso A, Salvesen GS, Mustelin T. Yersinia phosphatase induces mitochondrially dependent apoptosis of T cells. J Biol Chem. 2005 Mar 18;280(11):10388-94.

Massimo Bottini, Lutz Tautz, Huong Huynh, Edvard Monosov, Nunzio Bottini, Marcia I. Dawson, Stefano Bellucci and Tomas Mustelin. Covalent decoration of multi-walled carbon nanotubes with silica nanoparticles. Chem. Commun., 2005 Feb 14;(6):758-60. Epub 2004 Dec 15.

Tautz L, Bruckner S, Sareth S, Alonso A, Bogetz J, Bottini N, Pellecchia M, Mustelin T. Inhibition of Yersinia tyrosine phosphatase by furanyl salicylate compounds. J Biol Chem. 2005 Mar 11;280(10):9400-8.

Pellecchia, M., Becattini, B., Crowell, K.J., Fattorusso, R., Forino, M., Fragai, M., Jung, D., Mustelin, T. & Tautz, L. NMR-based techniques in the hit identification and optimization process. Expert Opin Ther Targets. 2004 Dec;8(6):597-611.

Massimo Bottini, Almerinda Di Venere, Lutz Tautz, Alessandro Desideri, Paolo Lugli, Luciana Avigliano, Nicola Rosato. Structural Stability of Azurin Encapsulated in Sol-Gel Glasses: A Fluorometric Study. Journal of Sol-Gel Science and Technology, Volume 30, Issue 3, June  2004, Pages 205 – 214.

Mustelin T, Alonso A, Bottini N, Huynh H, Rahmouni S, Nika K, Louis-dit-Sully C, Tautz L, Togo SH, Bruckner S, Mena-Duran AV, al-Khouri AM. Protein tyrosine phosphatases in T cell physiology. Mol Immunol. 2004 Jul;41(6-7):687-700. Review.

Alonso A, Burkhalter S, Sasin J, Tautz L, Bogetz J, Huynh H, Bremer MC, Holsinger LJ, Godzik A, Mustelin T. The minimal essential core of a cysteine-based protein-tyrosine phosphatase revealed by a novel 16-kDa VH1-like phosphatase, VHZ. J Biol Chem. 2004 Aug 20;279(34):35768-74.

Alonso A, Narisawa S, Bogetz J, Tautz L, Hadzic R, Huynh H, Williams S, Gjorloff-Wingren A, Bremer MC, Holsinger LJ, Millan JL, Mustelin T. VHY, a novel myristoylated testis-restricted dual specificity protein phosphatase related to VHX. J Biol Chem. 2004 Jul 30;279(31):32586-91.