Dr. Tautz is a chemical biologist—integrating the fields of organic and medicinal chemistry, biochemistry, and molecular and cell biology.
Dr. Tautz earned his Ph.D. in Organic Chemistry and Biochemistry from the University of Karlsruhe in Germany.
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LYP inhibits T-cell activation when dissociated from CSK.
Vang T, Liu WH, Delacroix L, Wu S, Vasile S, Dahl R, Yang L, Musumeci L, Francis D, Landskron J, Tasken K, Tremblay ML, Lie BA, Page R, Mustelin T, Rahmouni S, Rickert RC, Tautz L
Nat Chem Biol. 2012 May;8(5):437-46
Inhibition of hematopoietic protein tyrosine phosphatase augments and prolongs ERK1/2 and p38 activation.
Sergienko E, Xu J, Liu WH, Dahl R, Critton DA, Su Y, Brown BT, Chan X, Yang L, Bobkova EV, Vasile S, Yuan H, Rascon J, Colayco S, Sidique S, Cosford ND, Chung TD, Mustelin T, Page R, Lombroso PJ, Tautz L
ACS Chem Biol. 2012 Feb 17;7(2):367-77
Distinct functional and conformational states of the human lymphoid tyrosine phosphatase catalytic domain can be targeted by choice of the inhibitor chemotype.
Vidović D, Xie Y, Rinderspacher A, Deng SX, Landry DW, Chung C, Smith DH, Tautz L, Schürer SC
J Comput Aided Mol Des. 2011 Sep;25(9):873-83
Inhibition of the Hematopoietic Protein Tyrosine Phosphatase by Phenoxyacetic Acids.
Bobkova EV, Liu WH, Colayco S, Rascon J, Vasile S, Gasior C, Critton DA, Chan X, Dahl R, Su Y, Sergienko E, Chung TD, Mustelin T, Page R, Tautz L
ACS Med Chem Lett. 2011 Feb;2(2):113-118
Inhibition of lymphoid tyrosine phosphatase by benzofuran salicylic acids.
Vang T, Xie Y, Liu WH, Vidović D, Liu Y, Wu S, Smith DH, Rinderspacher A, Chung C, Gong G, Mustelin T, Landry DW, Rickert RC, Schürer SC, Deng SX, Tautz L
J Med Chem. 2011 Jan 27;54(2):562-71
Visualizing active-site dynamics in single crystals of HePTP: opening of the WPD loop involves coordinated movement of the E loop.
Critton DA, Tautz L, Page R
J Mol Biol. 2011 Jan 21;405(3):619-29
Multidentate small-molecule inhibitors of vaccinia H1-related (VHR) phosphatase decrease proliferation of cervix cancer cells.
Wu S, Vossius S, Rahmouni S, Miletic AV, Vang T, Vazquez-Rodriguez J, Cerignoli F, Arimura Y, Williams S, Hayes T, Moutschen M, Vasile S, Pellecchia M, Mustelin T, Tautz L
J Med Chem. 2009 Nov 12;52(21):6716-23
In silico screening for PTPN22 inhibitors: active hits from an inactive phosphatase conformation.
Wu S, Bottini M, Rickert RC, Mustelin T, Tautz L
ChemMedChem. 2009 Mar;4(3):440-4
Protein tyrosine phosphatases in autoimmunity.
Vang T, Miletic AV, Arimura Y, Tautz L, Rickert RC, Mustelin T
Annu Rev Immunol. 2008;26:29-55
Strategies for developing protein tyrosine phosphatase inhibitors.
Tautz L, Mustelin T
Methods. 2007 Jul;42(3):250-60
Targeting the PTPome in human disease.
Tautz L, Pellecchia M, Mustelin T
Expert Opin Ther Targets. 2006 Feb;10(1):157-77
Inhibition of Yersinia tyrosine phosphatase by furanyl salicylate compounds.
Tautz L, Bruckner S, Sareth S, Alonso A, Bogetz J, Bottini N, Pellecchia M, Mustelin T
J Biol Chem. 2005 Mar 11;280(10):9400-8
Lutz Tautz's Research Focus
Alzheimer's Disease, Cancer, Cardiovascular Diseases, Inflammatory/Autoimmune Disease, Leukemia/Lymphoma, Neurodegenerative and Neuromuscular Diseases
Dr. Tautz is a chemical biologist—integrating the fields of organic and medicinal chemistry, biochemistry, and molecular and cell biology—to develop small-molecule compounds that perturb and probe intracellular signaling cascades, with a focus on those that rely on the phosphorylation and dephosphorylation of signaling molecules. About one third of all proteins are transiently phosphorylated in response to distinct signaling events, and many inherited or acquired human diseases stem from abnormalities in the activities of protein kinases and protein phosphatases, the effectors of protein phosphorylation and dephosphorylation, respectively. While efficacious therapeutics targeting protein kinases have been successfully used to treat human diseases (e.g. Gleevec, Iressa, Nexavar, Tarceva), effective strategies to target specific protein phosphatases are still elusive. Dr. Tautz’ laboratory is focused on the development of protein tyrosine phosphatase (PTP) inhibitors. These targets are challenging because they have highly conserved active sites and thus inhibitors that target the PTP catalytic site are often potent, but poorly selective. Dr. Tautz has significantly transformed conventional drug discovery strategies to substantially improve upon both the selectivity and bioavailability of potent PTP inhibitors. Novel, innovative strategies include the targeting of ‘open-state’ PTP conformations, which allows for the generation of more selective compounds, and the identification and targeting of novel allosteric sites that are distal from the PTP catalytic center. The resulting compounds are then used to study complex biological processes in cells or animal models with a resolution that is not offered by genetic approaches. Besides being invaluable tools for basic research, the chemical probes he generates also provide starting points for the development of novel therapeutics. Research projects:
• Regulation of MAP kinase signaling in acute leukemias through inhibition of the hematopoietic protein tyrosine phosphatase (HePTP).
• T cell activation in individuals carrying a gain-of-function mutant of the lymphoid tyrosine phosphatase (LYP), which confers increased risk for autoimmunity, including diseases like type 1 diabetes, rheumatoid arthritis, and systemic lupus erythematosus.
• Inhibition of the striatal-enriched protein tyrosine phosphatase (STEP), a novel drug target in Alzheimer’s disease and schizophrenia.
• Targeting of the dual-specificity phosphatase VHR, a critical regulator in cell cycle progression in cervix cancer cells.
• Inhibitors of the SHP2 (PTPN11) phosphatase as novel therapeutics in various leukemias and other cancers.
• Inhibitors of PTP1B as potential therapeutics in breast cancers.
About Lutz Tautz
Dr. Tautz earned his Ph.D. in Organic Chemistry and Biochemistry from the University of Karlsruhe (Germany) with Dr. Janos Retey in 2002. He continued his research at the Burnham Institute with Dr. Tomas Mustelin, first as a postdoc and later as a staff scientist. In 2009 Dr. Tautz joined the faculty of the Sanford-Burnham Medical Research Institute.
Ph.D., University of Karlsruhe, Germany, Chemistry, Biochemistry, 2002 M.S., University of Karlsruhe, Germany, Chemistry, 1997
Funding Awards and Collaborative Grants
American Heart Association Innovative Research Grant
Honors and Recognition
Semifinalist, Stadtman Investigator Search, National Institutes of Health, 2014
Society for Biomolecular Sciences Travel Awards, 2008/2006
American Chemical Society Travel Award, 2006
William and Lillian Fishman Award for Exceptional Postdoctoral Research, 2006
Ph.D. in Chemistry magna cum laude, University of Karlsruhe, Germany, 2002