P U B L I C A T I O N Shttp://msb.embopress.org/content/10/8/746.long


Swamy M, Beck-Garcia K, Beck-Garcia E, Hartl FA, Morath A, Yousefi OS, Dopfer EP, Molnar E, Schulze AK, Blanco R, Borroto A, Martin-Blanco N, Alarcon B, Hoefer T, Minguet S, Schamel WW: A Cholesterol-Based Allostery Model of T Cell Receptor Phosphorylation. (2016) Immunity 44 (5), 1091-1101.

Hoefer T, Busch K, Klapproth K, Rodewald HR: Fate Mapping and Quantitation of Hematopoiesis In Vivo. (2016) Annual Review of Immunology 34, 449-478.

Hoefer T, Barile M, Flossdorf M: Stem-cell dynamics and lineage topology from in vivo fate mapping in the hematopoietic system. (2016) Current Opinion in Biotechnology 39, 150-156.

Talemi SR, Tiger CF, Andersson M, Babazadeh R, Welkenhuysen N, Klipp E, Hohmann S, Schaber J: Systems Level Analysis of the Yeast Osmo-Stat. (2016) Scientific Reports 6, 30950.

Hoefer T, Rodewald HR: Output without input: the lifelong productivity of hematopoietic stem cells. (2016) Current Opinion in Cell Biology 43, 69-77.

Ochoa R, Watowich SJ, Florez A, Mesa CV, Robledo SM, Muskus C: Drug search for leishmaniasis: a virtual screening approach by grid computing. (2016) Journal of Computer-Aided Molecular Design 30 (7), 541-552.

Henrich KO, Bender S, Saadati M, Dreidax D, Gartlgruber M, Shao C, Herrmann C, Wiesenfarth M, Parzonka M, Wehrmann L, Fischer M, Duffy DJ, Bell E, Torkov A, Schmezer P, Plass C, Hoefer T, Benner A, Pfister SM, Westermann F: Integrative Genome-Scale Analysis Identifies Epigenetic Mechanisms of Transcriptional Deregulation in Unfavorable Neuroblastomas. (2016) Cancer Research 76 (18), 5523-5537.

Cvijovic M, Hoefer T, Acimovic J, Alberghina L, Almaas E, Besozzi D, Blomberg A, Bretschneider T, Cascante M, Collin O, de Atauri P, Depner C, Dickinson R, Dobrzynski M, Fleck C, Garcia-Ojalvo J, Gonze D, Hahn J, Hess H M, Hollmann S, Krantz M, Kummer U, Lundh T, Martial G, Martins dos Santos V, Mauer-Oberthür A, Regierer B, Skene B, Stalidzans E, Stelling J, Teusink B, Workman C T, Hohmann S: Strategies for structuring interdisciplinary education in Systems Biology: an European perspective. (2016) NPJ Systems Biology and Applications 2 (16011).

Lodrini M, Poschmann G, Schmidt V, Dreidax D, Witt O, Hoefer T, Meyer H E, Stühler K, Eggert A, Deubzer H E: The MCM complex is a critical node in the miR-183 signaling network of MYCN-amplified neuroblastoma cells. (2016) Journal of Proteome Research 15 (7), 2178-2186.

Poschke I, Faryna M, Bergmann F, Flossdorf M, Lauenstein C, Hermes J, Hinz U, Hank T, Ehrenberg R, Volkmar M, Loewer M, Glimm H, Hackert T, Sprick M R, Hoefer T, Trumpp A, Halama N, Hassel J C, Strobel O, Buechler M, Sahin U, Offringa R: Identification of a tumor-reactive T-cell repertoire in the immune infiltrate of patients with resectable pancreatic ductal adenocarcinoma. (2016) OncoImmunology e1240859.

Shao C, Hoefer T: Robust classification of single-cell transcriptome data by nonnegative matrix factorization. (2016) Bioinformatics btw607.

Shao C, Westermann F, Hoefer T. Synlet: an R package for systemically analyzing synethetic lethal RNA interference screen data. (2016) bioRxiv 043570.


Peifer M, Hertwig F, Roels F, Dreidax D, Gartlgruber M, Menon R, Krämer A, Roncaioli JL, Sand F, Heuckmann J, Ikram F, Schmidt R, Ackermann S, Engesser A, Kahlert Y, Vogel W, Altmüller J, Nürnberg P, Thierry-Mieg J, Thierry-Mieg D, Mariappan A, Heynck S, Mariotti E, Henrich KO, Glöckner C, Bosco G, Leuschner I, Schweiger MR, Savelyeva L, Watkins SC, Shao C, Bell E, Höfer T, Achter V, Lang U, Theissen J, Volland R, Saadati M, Eggert A,  de Wilde B, Berthold F, Peng Z, Zhao C, Shi L, Ortmann M, Büttner R, Perner S, Hero B, Schramm A, Schulte J, Herrmann C, O’Sullivan RJ, Westermann F, Thomas RK, Fischer M (2015) Telomerase activation by genomic rearrangements in high-risk neuroblastoma. (2015) Nature 526(7575):700-4. doi: 10.1038/nature14980.

Flossdorf M, Roessler J, Buchholz V, Busch D* and Höfer T* (2015) CD8+ T cell diversification by asymmetric cell division. Nature Immunology 16, 891-893. (*joint corresponding authors)

Raue A, Steiert B, Schelker M, Kreutz C, Maiwald T, Hass H, Vanlier J, Tönsing C, Adlung L, Engesser R, Mader W, Heinemann T, Hasenauer J, Schilling M, Höfer T, Klipp E, Theis F, Klingmüller U, Schöberl B, Timmer J (2015) Data2Dynamics: a modeling environment tailored to parameter estimation in dynamical systems. Bioinformatics Jul 3. pii: btv405  [Epub ahead of print].

Mende N, Kuchen EE, Grinenko T, Lesche M, Hanenberg H, Lindemann D, Dahl A, Platz A, Höfer T, Calegari F, and Waskow C (2015) CCND1/CDK4-mediated cell cycle progression provides a competitive advantage for human hematopoietic stem cells in vivo. Journal of Experimental Medicine 212, 1171-1183.

Thurley K, Gerecht D, Friedmann E, and Höfer T (2015) Three-dimensional gradients of cytokine signaling between T cells. PLoS Computational Biology, 11, e1004206.

Busch K, Klapproth K#, Barile M#, Flossdorf M#, Holland-Letz M, Schlenner SM, Reth M, Höfer T* and Rodewald HR* (2015) Fundamental properties of unperturbed hematopoiesis from stem cells in vivo. Nature 518, 542-546. (# equal contribution, *corresponding authors)

Helmstetter C#, Flossdorf M#, Peine M#, Kupz A, Zhu J, Hegazy AN, Duque-Correa MA, Zhang Q, Vainshtein Y, Radbruch A, Kaufmann SH, Paul WE, Höfer T* and Löhning M* (2015) Individual T helper cells have a quantitative cytokine memory. Immunity 42, 108-122. (#equal contribution, *corresponding authors)


Gaspers LD#, Bartlett PJ#, Politi A#, Burnett P, Metzger W, Johnston J, Joseph SK, Höfer T, Thomas AP (2014) Hormone-induced calcium oscillations depend on cross-coupling with inositol 1,4,5-trisphosphate oscillations. Cell Reports 9(4), 1209-1018, 2014. (#equal contribution)

Müller-Ott K, Erdel F, Matveeva A, Mallm JP, Rademacher A, Hahn M, Marth C, Zhang Q, Kaltofen S, Schotta G, Höfer T and Rippe K (2014) Specificity, propagation and epigenetic memory of pericentric heterochromatin in mouse fibroblasts. Molecular Systems Biology 10:746.

Graef P, Buchholz VR, Stemberger C, Flossdorf M, Henkel L, Schiemann M, Drexler I, Höfer T, Riddell SM and Busch DH (2014) Serial transfer of single cell-derived immunocompetence reveals stemness of CD8+ central memory T cells. Immunity 41, 116-126.

Teif VB, Beshnova DA, Vainshtein Y, Marth C, Mallm JP, Höfer T and Rippe K (2014) Nucleosome repositioning links DNA (de)methylation and differential CTCF binding during stem cell development. Genome Research 24, 1285-1295.

Verbruggen, P.*, Heinemann, T.*, Manders, E., von Bornstaedt, G., van Driel, R., Höfer, T. (2014) Robustness of DNA repair through collective rate control. PLoS Computational Biology, 10(1):e1003438 (* equal contribution)

Litzenburger U, Opitz CA, Sahm F, Rauschenbach KJ, Ott M, Lutz C, Liu X,  Anastasov N, Höfer T, von Deimling A, Wick W, Platten M (2014) Constitutive IDO expression in human cancer is sustained by an autocrine signaling loop involving IL-6, STAT3 and the AHR. Oncotarget 5, 1038-1051.


Teif, VB., Erdel, F., Beshnova, DA., Vainshtein, Y., Mallm, JP., Rippe, K. (2013) Taking into account nucleosomes for predicting gene expression. Methods 62 (1), 26-38.

Karlebach G. (2013) Inferring Boolean network states from partial information. EURASIP Journal on Bioinformatics and Systems Biology 2013 (1), Art. Nr.: 11.

Peine, M., Rausch, S., Helmstetter, C., Fröhlich, A., Hegazy, A.N., Kühl, A.A., Grevelding, C.G., Höfer, T., Hartmann, S. and Löhning, M. (2013) Stable T-bet+GATA-3+ Th1/Th2 hybrid cells arise in vivo, can develop directly from naive precursors, and limit immunopathologic inflammation. PLoS Biology 11 (8)e1001633, 2013.

Gin, E., Diernfellner, A.C., Brunner, M., Höfer, T. (2013) The Neurospora photoreceptor VIVID exerts negative and positive control on light sensing to achieve adaptation. Mol. Syst. Biol. 9:66.

Buchholz, V.R.,# Flossdorf, M.,# Hensel, I., Kretschmer, L., Weissbrich, B., Gräf, P., Verschoor, A., Schiemann, M., Höfer, T.* and Busch, D.H.* (2013) Disparate individual fates compose robust CD8+ T cell immunity. Science. March 14. [Epub ahead of print] (#first authors, *corresponding authors).


Meyer, R.*, D’Alessandro, L.A.*, Kar, S.*, Kramer, B., She, B., Kaschek, D., Hahn, B., Wrangborg, D., Karlsson, J., Kvarnström, M., Jirstrand, M., Lehmann, W.-D., Timmer, J., Höfer, T. and Klingmüller, U. (2012) Heterogeneous kinetics of AKT signaling in individual cells are accounted for by variable protein concentration. Front.Physiol. 3:451. (*equal contribution)

Teif, V., Vainshtein, Y. Mallm, J.P., Marth, C., Caudron-Herger, M., Höfer, T. and Rippe, K. (2012) Genome-wide nucleosome positioning during embryonic stem cell development. Nat. Struct. Mol. Biol. 19, 1185-1192.

Höfer, T. Krichevsky, O. and Altan-Bonnet, G. (2012) Competition for IL-2 between regulatory and effector T cells to chisel immune responses. Front. Immun. 3:268.

Rand U.,# Rinas M.,# Schwerk J., Nöhren G., Linnes M., Kröger A., Flossdorf M., Kály-Kullai K., Hauser H., Höfer T.* and Köster M.* (2012) Multi-layered stochasticity and paracrine signal propagation shape the type-I interferon response. Mol. Syst. Biol. 8:584. (#first authors, *corresponding authors).

Alberghina, L., Höfer, T. and Vanoni, M. (2012) Systems biology for biomedical innovation. Biotechnol. Adv. 30, 1-3.


Sancar, G., Sancar, C., Brügger, B., Ha, N., Sachsenheimer, T., Gin, E., Wdowik S., Lohmann, I., Wieland, F., Hoefer, T., Diernfellner, A., Brunner, M.  (2011) A global circadian repressor controls anti-phasic expression of metabolic genes in Neurospora. Mol Cell 44, 687-697.

Querfurth, C., Diernfellner, A., Gin, E., Höfer, T. and Brunner, M. (2011) Circadian conformational change of the Neurospora clock protein FREQUENCY triggered by clustered hyperphosphorylation of a basic domain. Mol. Cell 43, 712-722.

Deswal, S., Schulze, A., Höfer, T. and Schamel, W.W. (2011) Quantitative analysis of protein phosphorylations and interactions by multi-colour IP-FCM as an input for kinetic modelling of signalling networks. PLoS ONE 6:e22928


Salazar, C., Brümmer, A., Alberghina, L. and Höfer, T. (2010) Timing control in regulatory networks by multisite protein modifications. Trends Cell Biol. 20, 634-41.

Nika, K., Soldani, S., Salek, M., Gray, A., Etzensperger, R., Fugger, L., Polzella, P., Cerundolo, V., Dushek, O., Höfer, T., Viola, A. and Acuto, O. (2010) Constitutive high levels of activated Lck drive T cell antigen receptor signal transduction. Immunity 32, 766-777.

Luijsterburg, M.S., von Bornstaedt, G., Gourdin, A.M., Politi, A.Z., Moné, M.J., Warmerdam, D.O., Goedhart, J., Vermeulen, W., van Driel, R. and Höfer, T. (2010) Stochastic and reversible assembly of a multiprotein DNA repair complex ensures accurate target site recognition and efficient repair. J. Cell Biol. 189, 3445-3463.

Brümmer, A., Salazar, C., Zinzalla, V., Alberghina, L., Höfer, T. (2010) Mathematical modelling of DNA replication reveals a trade-off between coherence of origin activation and robustness against rereplication. PLoS Comp. Biol. 6:e1000783.

Mariani, L., Schulz, E., Lexberg, M., Helmstetter, C., Radbruch, A., Löhning, M., and Höfer, T. (2010) Short-term memory in gene induction reveals the regulatory principle behind stochastic interleukin-4 expression. Mol. Syst. Biol. 6:359.

Busse, D., de la Rosa, M., Hobiger, K., Thurley, K., Floßdorf, M., Scheffold, A. and Höfer, T. (2010) Competing feedback loops shape IL-2 signaling between helper and regulatory T cells in cellular microenvironments. Proc. Natl. Acad. Sci. USA 107, 3058–3063.

Stittrich, A., Haftmann, C., Sgouroudis, E., Kühl, A.A., Hegazy, A.N., Riedel, R., Flossdorf, M., Dong, J., Fuhrmann, F., Heinz, G.A., Li, N., Fang, Z., Bissels, U., Hatam, F., Jahn, A., Hammoud, B., Matz, M., Schulze, F.M., Baumgrass, R., Bosio, A., Mollenkopf, H., Grün, J., Thiel, A., Chen, W., Höfer, T., Loddenkemper, C., Löhning, M., Chang, H., Rajewsky, N., Radbruch, A. and Mashreghi, M.F. (2010) MicroRNA-182 is induced by interleukin-2 and promotes clonal expansion of activated T helper lymphocytes. Nat. Immunol. 11, 1057-62.


Schulz, E., Mariani, L., Radbruch, A., and Höfer, T. (2009) Sequential polarization and imprinting of T-helper type 1 differentiation by interferon-γ and interleukin-12. Immunity, 30, 673-683.

Diernfellner, A., Querfurth, C., Salazar, C., Höfer, T. and Brunner, M. (2009) Phosphorylation modulates rapid nucleo-cytoplasmic shuttling and cytoplasmic accumulation of Neurospora clock protein FRQ on a circadian time scale. Genes Dev. 23, 2192-2200.

Alberghina, L., Höfer, T., and Vanoni, M. (2009) Molecular networks and system-level properties. J. Biotechnol. 144, 224-233.

Dinant, C., Luijsterburg, M.S., Höfer, T., Von Bornstaedt, G., Vermeulen, W., Houtsmuller, A.B. and Van Driel, R. (2009) Assembly of multi-protein complexes that control genome function. J. Cell Biol. 185, 21-26.

Salazar, C. and Höfer, T. (2009) Multisite protein phosphorylation: From molecular mechanisms to kinetic models. FEBS J., 276, 3177-3198.

Figueiredo, S., Höfer, T., Klotz, C., Sers, C., Hartmann, S., Lucius, R., and Hammerstein, P. (2009) Modelling IL-10 regulation by macrophages after stimulation with an immunomodulator of parasitic nematodes. FEBS J., 276, 3454-3469.

Roszol, L., Kaly-Kullai, K., Volford, A. (2009) Chemical waves in inhomogeneous media with circular symmetry. Chemical Physics Letters 478 (1-3), 75-79. Reprint (0.4 MB)


Salazar, C., Politi, A., and Höfer, T. (2008) Decoding of Ca2+ oscillations by phosphorylation cycles: analytic results. Biophys. J. 94:1203-1215.

Löhning, M., Hegazy, A.N., Pinschewer, D.D., Busse, D., Lang, K.S., Höfer, T., Radbruch, A., Zinkernagel, R.M, and Hengartner, H. (2008) Long-lived virus-reactive memory T cells generated from purified cytokine-secreting T helper type 1 and type 2 effectors. J. Exp. Med. 205, 53-61.

Matthäus F., Salazar C. and Ebenhöh O. (2008) Biosynthetic potentials of metabolites and their hierarchical organization. PLoS Comput. Biol. 4, e1000049


Scheffold, A., Murphy, K.M., and Höfer, T. (2007) Competition for cytokines: Treg cells take all. Nat. Immunol. 8, 1285-1287.

Podtschaske, M., Benary, U., Zwinger, S., Höfer, T., Radbruch, A., and Baumgraß, R. (2007) Digital NFATc2 activation per cell transforms graded T cell receptor activation into an all-or-none IL-2 expression. PLoS ONE 2, e935.

Salazar, C. and Höfer, T. (2007) Versatile regulation of multisite protein phosphorylation by the order of phosphate processing and protein-protein interactions. FEBS J. 274, 1046-1061.

Höfer, T. (2007) In remembrance: Reinhart Heinrich 1946-2006. PLoS Comput. Biol. 3, e18.

Selected publications before 2007

Politi, A., Gaspers, L.D., Thomas, A.P., and Höfer, T. (2006) Models of IP3 and Ca2+ oscillations: Frequency encoding and identification of underlying feedbacks. Biophys. J. 90, 3120-3133.

Höfer, T., Mühlinghaus, G., Moser, K., Yoshida, T.E., Mei, H., Hebel, K., Hauser, A., Hoyer, B., Luger E., Dörner, T., Manz, R.A., Hiepe, F., and Radbruch A. (2006) Adaptation of humoral memory. Immunol. Rev. 211, 295-302.

Scheffold, A., Hühn, J., and Höfer, T. (2005) Regulation of CD4+CD25+ regulatory T cell activity: It takes IL-2 to tango. Eur. J. Immunol. 35, 1336-1361.

Mariani, L., Löhning, M., Radbruch, A., and Höfer, T. (2004) Transcriptional control networks of cell differentiation: Insights from T lymphocytes. Progr. Biophys. Mol. Biol. 86,  45-76.

Salazar, C. and Höfer, T. (2003) Allosteric regulation of the transcription factor NFAT1 by multiple phosphorylation sites: a mathematical analysis. J. Mol. Biol. 327, 31-45.

Höfer, T., Nathanson, H., Löhning, M., Radbruch, A., and Heinrich, R. (2002) GATA-3 transcriptional imprinting in Th2 lymphocytes: a mathematical model. Proc. Natl. Acad. Sci. USA 99, 9364-9368.

Höfer, T., Venance, L., and Giaume, C. (2002) Control and plasticity of intercellular calcium waves in astrocytes: a modeling approach. J. Neurosci. 22, 4850-4859.

Schuster, S., Marhl, M., and Höfer, T. (2002) Modelling of simple and complex calcium oscillations: From single-cell responses to intercellular signalling. Eur. J. Biochem. 269, 1333-1355.

Höfer, T., Politi, A., and Heinrich, R. (2001) Intercellular Ca2+ wave propagation through gap-junctional Ca2+ diffusion: A theoretical study. Biophys. J. 80, 75-87.

Höfer, T. (1999) Model of intercellular calcium oscillations in hepatocytes: synchronization of heterogeneous cells. Biophys. J. 77, 1244-1256.

Höfer, T. and Maini, P.K.  (1996) Turing patterns in fish skin. Nature 380, 678.

Höfer, T., Sherratt, J.A., and Maini, P.K. (1995) Dictyostelium discoideum: Cellular self-organization in an excitable biological medium. Proc. Roy. Soc. Lond. B 259, 249-257.