Biography
Education
2001: M.S., Genetics, University of Vienna
2005: Ph.D., Molecular Biology (E. Klussmann/W. Rosenthal), Leibniz Institute of Molecular Pharmacology, Berlin and Free University of Berlin
2005 - 2008: Postdoctoral, Dept. of Biochemistry (S.W. Michnick), Université de Montréal
2014: Habilitation, Biochemistry, University of Innsbruck
Professional Experience
2008 - 2014: Sr. Research Associate, Institute of Biochemistry, University of Innsbruck
since 2014: Priv.-Doz., Institute of Biochemistry, University of Innsbruck
03.2017 - 01.2019: Head, Institute of Biochemistry, University of Innsbruck
Publications
55.
Kugler V., Lieb A., Guerin N, Donald BR, Stefan E, Kaserer T. DISRUPTOR: Computational identification of oncogenic mutants disrupting protein interactions.
Communications Biology (in press)
54.
Fleischmann J, Schwaighofer S, De Falco L, Enzler F, Feichtner A, Kugler V, Tschaikner P, Huber RG, Stefan E*. Tracking and blocking interdependencies of cellular BRAF-MEK oncokinase activities. PNAS Nexus (2023)
53.
Moesslacher CS, Auernig E, Woodsmith J, Feichtner A, Jany-Luig E, Jehle S, Worseck JM, Heine CL, Stefan E, Stelzl U. Missense variant interaction scanning reveals a critical role of the FERM domain for tumor suppressor protein NF2 conformation and function. Life Sci Alliance (2023)
52.
Torres-Quesada, O., Doerrier, C., Strich, S., Gnaiger, E., & Stefan, E. Physiological Cell Culture Media Tune Mitochondrial Bioenergetics and Drug Sensitivity in Cancer Cell Models. Cancers, 14(16), 3917. (2022).
51.
Torres-Quesada, O., Strich, S. & Stefan, E. Kinase perturbations redirect mitochondrial function. MitoFit Preprint, (2022).
50.
Guerin N, Feichtner A, Stefan E, Kaserer T, Donald BR. Resistor: An algorithm for predicting resistance mutations via Pareto optimization over multistate protein design and mutational signatures. Cell Syst. 2022 Oct 19;13(10):830-843.e3. doi: 10.1016/j.cels.2022.09.003. PMID: 36265469.
49.
Feichtner A, Kugler V, Schwaighofer S, Nuener T, Fleischmann J, Stefan E. Tracking mutation and drug-driven alterations of oncokinase conformations. Memo. 2022 Jun;15(2):137-142. doi: 10.1007/s12254-021-00790-6. Epub 2022 Jan 21. PMID: 35677701.
48.
Senatore E, Chiuso F, Rinaldi L, Intartaglia D, Delle Donne R, Pedone E, Catalanotti B, Pirone L, Fiorillo B, Moraca F, Giamundo G, Scala G, Raffeiner A, Torres-Quesada O, Stefan E, Kwiatkowski M, van Pijkeren A, Morleo M, Franco B, Garbi C, Conte I, Feliciello A. The TBC1D31/praja2 complex controls primary ciliogenesis through PKA-directed OFD1 ubiquitylation. EMBO J. 2021 May 17;40(10):e106503. doi: 10.15252/embj.2020106503 (2021).
47.
Baffi TR, Lordén G, Wozniak JM, Feichtner A, Yeung W, Kornev AP, King CC, Del Rio JC, Limaye AJ, Bogomolovas J, Gould CM, Chen J, Kennedy EJ, Kannan N, Gonzalez DJ, Stefan E, Taylor SS, Newton AC. mTORC2 controls the activity of PKC and Akt by phosphorylating a conserved TOR interaction motif. Sci Signal. Apr 13;14(678):eabe4509. doi: 10.1126/scisignal.abe4509 (2021).
46.
Fleischmann J, Feichtner A, Falcao L, Schwaighofer S, Kugler V, Huber RG, Stefan E*. Allosteric kinase inhibitors reshape MEK1 kinase activity conformations in cells and in silico. Biomolecules. Mar 30;11(4):518 (2021).
45.
Tschaikner P, Regele D, Röck R, Salvenmoser W, Meyer D, Bouvier M, Geley S, Stefan E*, Aanstad P*. Feedback Control of the Gpr161-G αs-PKA axis contributes to basal Hedgehog repression in zebrafish. Development. Feb 17;148(4):dev192443 (2021).
44.
Prentzell, MT; Rehbein, U; Cadena Sandoval, M; De Meulemeester, A; Baumeister, R; Brohée, L; Berdel, B; Bockwoldt, M; Carroll, B; Chowdhury, SR; von Deimling, A; Demetriades, C; Figlia, G; Eca Guimaraes de Araujo, M; Heberle, AM; Heiland, I; Holzwarth, B; Huber, LA; Jaworski, J; Kedra, M; Kern, K; Kopach, A; Korolchuk, VI; van 't Land-Kuper, I; Macias, M; Nellist, M; Palm, W; Pusch, S; Ramos Pittol, JM; Reil, M; Reintjes, A; Reuter, F; Sampson, JR; Scheldeman, C; Siekierska, A; Stefan, E; Teleman, AA; Thomas, LE; Torres-Quesada, O; Trump, S; West, HD; de Witte, P; Woltering, S; Yordanov, T; Zmorzynska, J; Opitz, CA; Thedieck, K (2021): The G3BP proteins tether the TSC complex 1 to lysosomes and suppress mTORC1 signaling. Cell. Feb 4;184(3):655-674.e27 (2021).
43.
Feurle P, Abentung A, Cera I, Wahl N, Ablinger C, Bucher M, Stefan E, Sprenger S, Teis D, Fischer A, Laighneach A, Whitton L, Morris DW, Apostolova G, Dechant G. SATB2-LEMD2 interaction links nuclear shape plasticity to regulation of cognition-related genes. EMBO J. Feb 1;40(3):e103701. doi: 10.15252/embj.2019103701 (2021).
42.
Mayrhofer JE, Enzler F, Feichtner A, Röck R, Fleischmann J, Raffeiner A, Tschaikner P, Ogris E, Huber RG, Hartl M, Schneider R, Troppmair J, Torres-Quesada O, Stefan E*. Mutation-oriented profiling of autoinhibitory kinase conformations predicts RAF inhibitor efficacies. Proc Natl Acad Sci U S A., Dec 8;117(49):31105-31113. doi: 10.1073/pnas.2012150117 (2020).
41.
Enzler F, Tschaikner P, Schneider R, Stefan E*. KinCon: Cell-based recording of full-length kinase conformations. IUBMB Life, in press (2020).
40.
Tschaikner P, Enzler F, Torres-Quesada O, Aanstad P, Stefan E*. Hedgehog and Gpr161: Regulating cAMP Signaling in the Primary Cilium. Cells, 9, 118 (2020).
39.
Ortner NJ, Pinggera A, Hofer NT, Siller A, Brandt N, Raffeiner A, Vilusic K, Lang I, Blum K, Obermair GJ, Stefan E, Engel J and Striessnig J. RBP2 stabilizes slow Cav1.3 Ca(2+) channel inactivation properties of cochlear inner hair cells. Pflugers Arch. 472(1):3-25 (2020).
38.
Röck R, Mayrhofer JE, Torres-Quesada O, Enzler F, Raffeiner A, Raffeiner P, Feichtner A, Huber RG, Koide S, Taylor SS, Troppmair J, Stefan E*. BRAF inhibitors promote intermediate BRAF(V600E) conformations and binary interactions with activated RAS. Science Advances, in press (2019).
37.
Rinaldi L, Donne R, Catalanotti B, Torres-Quesada O, Moraca F, Nisticò R, Chiuso F, Piccinin S, Enzler F, Bachmann V, Garbi C, Scorziello A, Russo N, Synofzik M, Stelzl U, Annunziato L, Stefan E, Feliciello A. Feedback inhibition of cAMP effector signaling by a chaperone-assisted ubiquitin system. Nat. Commun., 10(1):2572. (2019)
36.
Porpora M, Sauchella S, Rinaldi L, Delle Donne R, Sepe M, Torres-Quesada O, Intartaglia D, Garbi C, Insabato L, Santoriello M, Bachmann V, Synofzik M, Lindner H, Ivan C, Stefan E, Feliciello A. Counterregulation of cAMP-directed kinase activities controls ciliogenesis. Nat. Commun. 9, e1224 (2018).
35.
Stefan E*, Troppmair J, Bister K. Targeting the architecture of deregulated protein complexes in cancer. Adv. Protein Chem. Struct. Biol., 111:101-132 (2018).
34.
Haushalter K, Casteel DE, Raffeiner A, Stefan E, Patel HH, Taylor SS. Phosphorylation of Protein Kinase A (PKA) regulatory subunit RIa by Protein Kinase G (PKG) primes PKA for catalytic activity in cells. J Biol Chem. 293, 4411-4421 (2018).
33.
Torres-Quesada O, Mayrhofer JE, Stefan E*. The many faces of compartmentalized PKA signalosomes. Cell. Signal. 37, 1-11 (2017).
32.
Stefan E, Bister K. MYC and RAF: Key effectors in cellular signaling and major drivers in human cancer. Curr. Top. Microbiol. Immunol. 407, 117-151 (2017).
31.
Raffeiner P, Schraffl A, Schwarz T, Röck R, Ledolter K, Hartl M, Konrat R, Stefan E*, Bister K*. Calcium-dependent binding of Myc to calmodulin. Oncotarget 8, 3327-3343 (2017).
30.
Torres-Quesada O, Röck R, Stefan E*. Systematic quantification of cAMP-controlled PKA interactions. Hormone and Metabolic Research 49, 240-249 (2017).
29.
Bruystens JG, Wu J, Fortezzo A, Del Rio J, Nielsen C, Blumenthal DK, Rock R, Stefan E, Taylor SS. Structure of a PKA RIα Recurrent Acrodysostosis Mutant Explains Defective cAMP-Dependent Activation. J. Mol. Biol. 428, 4890-4904 (2016).
28.
Bachmann VA, Mayrhofer JE, Ilouz R, Tschaikner PM, Raffeiner P, Röck R, Courcelles M, Apelt F, Lu T, Baillie GS, Thibault P, Aanstad P, Stelzl U, Taylor SS, Stefan E*. Gpr161 anchoring of PKA consolidates GPCR and cAMP signaling. Proc. Natl. Acad. Sci. USA 113, 7786-7791 (2016).
27.
Rinaldi L, Delle Donne R, Sepe M, Porpora M, Garbi C, Chiuso F, Gallo A, Parisi S, Russo L, Bachmann V, Huber RG, Stefan E, Russo T, Feliciello A. praja2 regulates KSR1 stability and mitogenic signaling. Cell Death Dis. 7:e2230 (2016).
26.
Röck R, Mayrhofer JE, Bachmann V, Stefan E*. Impact of kinase activating and inactivating patient mutations on binary PKA interactions. Front. Pharmacol. 6:170 (2015).
25.
Stefan E, Hart JR, Bister K. Stopping MYC in its tracks. Aging 7, 463-464 (2015).
24.
Röck R, Bachmann V, Bhang HC, Malleshaiah M, Raffeiner P, Mayrhofer JE, Tschaikner PM, Bister K, Aanstad P, Pomper MG, Michnick SW, Stefan E*. In-vivo detection of binary PKA network interactions upon activation of endogenous GPCRs. Sci. Rep. 5, 5:11133 (2015).
23.
Filteau M, Diss G, Torres-Quiroz F, Dubé AK, Schraffl A, Bachmann VA, Gagnon-Arsenault I, Chrétien AÈ, Steunou AL, Dionne U, Côté J, Bisson N, Stefan E, Landry CR. Systematic identification of signal integration by protein kinase A. Proc. Natl. Acad. Sci. USA. 112, 4501-4506 (2015).
22.
Raffeiner P, Röck R, Schraffl A, Hartl M, Hart JR, Janda KD, Vogt PK, Stefan E*, Bister K*. In vivo quantification and perturbation of Myc-Max interactions and the impact on oncogenic potential. Oncotarget 5, 8869-8878 (2014).
21.
Hart JR, Garner AL, Yu J, Ito Y, Sun M, Ueno L, Rhee J-K, Baksh MM, Stefan E, Hartl M, Bister K, Vogt PK, Janda KD. Inhibitor of MYC identified in a Kröhnke pyridine library. Proc. Natl. Acad. Sci. USA 111, 12556-12561 (2014).
20.
Bachmann VA, Bister K, Stefan E*. Interplay of PKA and Rac: Fine-tuning of Rac localization and signaling. Small GTPases 4, 247-251 (2013).
19.
Lignitto L, Arcella A, Sepe M, Rinaldi L, Delle Donne R, Gallo A, Stefan E, Bachmann VA, Oliva MA, Tiziana Storlazzi C, L'abbate A, Brunetti A, Gargiulo S, Gramanzini M, Insabato L, Garbi C, Gottesman ME, Feliciello A. Proteolysis of MOB1 by the ubiquitin ligase praja2 attenuates Hippo signalling and supports glioblastoma growth. Nat. Commun. 4, 1822 (2013).
18.
Bachmann VA, Riml A, Huber RG, Baillie GS, Liedl KR, Valovka T, Stefan E*. Reciprocal regulation of PKA and Rac signaling. Proc. Natl. Acad. Sci. USA 110, 8531-8536 (2013).
17.
Stückemann T, Wegleiter T, Stefan E, Nägele O, Tarbashevich K, Böck G, Raz E, Aanstad P. Zebrafish Cxcr4a determines the proliferative response to Hedgehog signalling. Development 139, 2711-2720 (2012).
16.
Stefan E*, Malleshaiah MK, Breton B, Ear PH, Bachmann V, Beyermann M, Bouvier M, Michnick SW. PKA regulatory subunits mediate synergy among conserved GPCR cascades. Nat. Commun. 2, 598 (2011).
15.
Lignitto L, Carlucci A, Sepe M, Stefan E, Cuomo O, Nistico R, Scorziello A, Savoia C, Garbi C, Annunziato L, Feliciello A. Control of PKA stability and signalling by RING ligase praja2. Nat. Cell Biol. 13, 412-422 (2011).
14.
Skoumbourdis AP, Leclair CA, Stefan E, Turjanski AG, Maguire W, Titus SA, Huang R, Auld DS, Inglese J, Austin CP, Michnick SW, Xia M, Thomas CJ. Exploration and optimization of substituted triazolothiadiazines and triazolopyridazines as PDE4 inhibitors. Bioorg. Med. Chem. Lett. 19, 3686-3692 (2009).
13.
Nyfeler B, Reiterer V, Wendeler MW, Stefan E, Zhang B, Michnick SW, Hauri HP. Identification of ERGIC-53 as an intracellular transport receptor of alpha1-antitrypsin. J. Cell Biol. 180, 705-712 (2008).
12.
Stefan E, Aquin S, Berger N, Landry CR, Nyfeler B, Bouvier M, Michnick SW. Quantification of dynamic protein complexes using Renilla luciferase fragment complementation applied to protein kinase A activities in vivo. Proc. Natl. Acad. Sci. USA 104, 16916-16921 (2007).
11.
Michnick SW, Ear PH, Manderson EN, Remy I, Stefan E. Universal strategies in research and drug discovery based on protein-fragment complementation assays. Nat. Rev. Drug Discov. 6, 569-582 (2007).
10.
Nedvetsky PI, Stefan E, Frische S, Santamaria K, Wiesner B, Valenti G, Hammer JA 3rd, Nielsen S, Goldenring JR, Rosenthal W, Klussmann E. A role of myosin Vb and Rab11-FIP2 in the aquaporin-2 shuttle. Traffic 8, 110-123 (2007).
9.
Stefan E, Wiesner B, Baillie GS, Mollajew R, Henn V, Lorenz D, Furkert J, Santamaria K, Nedvetsky P, Hundsrucker C, Beyermann M, Krause E, Pohl P, Gall I, MacIntyre AN, Bachmann S, Houslay MD, Rosenthal W, Klussmann E. Compartmentalization of cAMP-dependent signaling by phosphodiesterase-4D is involved in the regulation of vasopressin-mediated water reabsorption in renal principal cells. J. Am. Soc. Nephrol. 18, 199-212 (2007).
8.
McSorley T, Stefan E, Henn V, Wiesner B, Baillie GS, Houslay MD, Rosenthal W, Klussmann E. Spatial organisation of AKAP18 and PDE4 isoforms in renal collecting duct principal cells. Eur. J. Cell Biol. 85, 673-678 (2006).
7.
Hundsrucker C, Krause G, Beyermann M, Prinz A, Zimmermann B, Diekmann O, Lorenz D, Stefan E, Nedvetsky P, Dathe M, Christian F, McSorley T, Krause E, McConnachie G, Herberg FW, Scott JD, Rosenthal W, Klussmann E. High-affinity AKAP7 delta-protein kinase A interaction yields novel protein kinase A-anchoring disruptor peptides. Biochem. J. 396, 297-306 (2006).
6.
Milojevic T, Reiterer V, Stefan E, Korkhov VM, Dorostkar MM, Ducza E, Ogris E, Boehm S, Freissmuth M, Nanoff C. The ubiquitin-specific protease Usp4 regulates the cell surface level of the A2A receptor. Mol. Pharmacol. 69, 1083-1094 (2006).
5.
Henn V, Stefan E, Baillie GS, Houslay MD, Rosenthal W, Klussmann E. Compartmentalized cAMP signalling regulates vasopressin-mediated water reabsorption by controlling aquaporin-2. Biochem. Soc. Trans. 33, 1316-1318 (2005).
4.
Gsandtner I, Charalambous C, Stefan E, Ogris E, Freissmuth M, Zezula J. Heterotrimeric G protein-independent signaling of a G protein-coupled receptor. Direct binding of ARNO/cytohesin-2 to the carboxyl terminus of the A2A adenosine receptor is necessary for sustained activation of the ERK/MAP kinase pathway. J. Biol. Chem. 280, 31898-31905 (2005).
3.
Henn V, Edemir B, Stefan E, Wiesner B, Lorenz D, Theilig F, Schmitt R, Vossebein L, Tamma G, Beyermann M, Krause E, Herberg FW, Valenti G, Bachmann S, Rosenthal W, Klussmann E. Identification of a novel A-kinase anchoring protein 18 isoform and evidence for its role in the vasopressin-induced aquaporin-2 shuttle in renal principal cells. J. Biol. Chem. 279, 26654-26665 (2004).
2.
Klinger M, Kuhn M, Just H, Stefan E, Palmer T, Freissmuth M, Nanoff C. Removal of the carboxy terminus of the A2A-adenosine receptor blunts constitutive activity: Differential effect on cAMP accumulation and MAP kinase stimulation. Naunyn-Schmiedebergs Arch. Pharmacol. 366, 287-298 (2002).
1.
Just H, Stefan E, Czupalla C, Nurnberg B, Nanoff C, Freissmuth M. Beyond G proteins: The role of accessory proteins in G protein-coupled receptor signalling. In Trends in Drug Research III, Pharmacochemistry Library Vol. 32 (van der Goot H, ed), pp. 161-174. Elsevier, Amsterdam (2002).
Patent Applications
Stefan E*, Bachmann V, Huber R. Peptidic inhibitor of signal transmission from Gαs to Gαi-coupled receptor cascades. European Patent Office, PCT/EP2012/074489 (2013); United States Patent Application No.: 14/366874 (2015)
Stefan E*, Huber R, Bachmann V, Liedl KR. Bioactive small molecules modulate GPCR cross talk (07/2012) Submission number K120026 (AWS reference: P1204009); Cast Tirol, University of Innsbruck, Innsbruck, Austria
Stefan E*, Röck R, Raffeiner P, Bachmann V. Intermolecular kinase reporter (submission 05/2016), EU patent application