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Anna Obenauf

Metastasis is the final stage of cancer progression and responsible for more than 90% of cancer-related deaths. Effective therapeutic strategies are still lacking and resistance to current therapies pose a formidable challenge. Informed by clinical data and using functional in vivo and in vitro models, our group seeks to understand the mechanistic determinants for metastatic competence and resistance to therapies. Both rely on programs that ensure the cancer cells’ survival during periods of enhanced cellular stress, limited survival cues and attacks by the immune system. Our goal is to enhance the efficacy of current therapies using combinatorial treatment regimens and find new therapeutic avenues to fight metastatic cancer.

Publications

2023

Bayerl, F., Meiser, P., Donakonda, S., Hirschberger, A., Lacher, SB., Pedde, AM., Hermann, CD., Elewaut, A., Knolle, M., Ramsauer, L., Rudolph, TJ., Grassmann, S., Öllinger, R., Kirchhammer, N., Trefny, M., Anton, M., Wohlleber, D., Höchst, B., Zaremba, A., Krüger, A., Rad, R., Obenauf, AC., Schadendorf, D., Zippelius, A., Buchholz, VR., Schraml, BU., Böttcher, JP. (2023)

Tumor-derived prostaglandin E2 programs cDC1 dysfunction to impair intratumoral orchestration of anti-cancer T cell responses.

 Immunity. 56(6):1341-1358.e11
Leiendecker, L., Neumann, T., Jung, PS., Cronin, SM., Steinacker, TL., Schleiffer, A., Schutzbier, M., Mechtler, K., Kervarrec, T., Laurent, E., Bachiri, K., Coyaud, E., Murali, R., Busam, KJ., Itzinger-Monshi, B., Kirnbauer, R., Cerroni, L., Calonje, E., Rütten, A., Stubenrauch, F., Griewank, KG., Wiesner, T., Obenauf, AC. (2023)

Human Papillomavirus 42 Drives Digital Papillary Adenocarcinoma and Elicits a Germ Cell-like Program Conserved in HPV-Positive Cancers.

 Cancer Discov. 13(1):70-84

2022

Obenauf, AC. (2022)

Mechanism-based combination therapies for metastatic cancer.

 Sci Transl Med. 14(655):eadd0887

2021

Breitenecker, K., Homolya, M., Luca, AC., Lang, V., Trenk, C., Petroczi, G., Mohrherr, J., Horvath, J., Moritsch, S., Haas, L., Kurnaeva, M., Eferl, R., Stoiber, D., Moriggl, R., Bilban, M., Obenauf, AC., Ferran, C., Dome, B., Laszlo, V., Győrffy, B., Dezso, K., Moldvay, J., Casanova, E., Moll, HP. (2021)

Down-regulation of A20 promotes immune escape of lung adenocarcinomas.

 Sci Transl Med. 13(601)
Haas L, Elewaut A, Gerard CL, Umkehrer C, Pedersen M, Leiendecker L, Krecioch I, Hoffmann D, Novatchkova M, Kuttke M, Neumann T, Pires de Silva I, Witthock H, Cuendet MA, Carotta S, Harrington KJ, Zuber J, Scolyer RA, Long GV, Wilmott JS, Michielin O, Vanharanta S, Wiesner T, Obenauf AC. (2021)

Acquired resistance to anti-MAPK targeted therapy confers an immune-evasive tumor microenvironment and cross-resistance to immunotherapy in melanoma

 Nature Cancer . 2:693–708
Haas, L., Elewaut, A., Gerard, CL., Umkehrer, C., Leiendecker, L., Pedersen, M., Krecioch, I., Hoffmann, D., Novatchkova, M., Kuttke, M., Neumann, T., da Silva, IP., Witthock, H., Cuendet, MA., Carotta, S., Harrington, KJ., Zuber, J., Scolyer, RA., Long, GV., Wilmott, JS., Michielin, O., Vanharanta, S., Wiesner, T., Obenauf, AC. (2021)

Acquired resistance to anti-MAPK targeted therapy confers an immune-evasive tumor microenvironment and cross-resistance to immunotherapy in melanoma.

 Nat Cancer. 2(7):693-708
Leiendecker, L., Jung, PS., Obenauf, AC. (2021)

Targeting CD56 with an antibody-drug conjugate in Merkel cell carcinoma.

 Br J Dermatol.
Umkehrer, C., Holstein, F., Formenti, L., Jude, J., Froussios, K., Neumann, T., Cronin, SM., Haas, L., Lipp, JJ., Burkard, TR., Fellner, M., Wiesner, T., Zuber, J., Obenauf, AC. (2021)

Isolating live cell clones from barcoded populations using CRISPRa-inducible reporters.

 Nat Biotechnol. 39(2):174-178

2020

Leiendecker, L., Jung, PS., Krecioch, I., Neumann, T., Schleiffer, A., Mechtler, K., Wiesner, T., Obenauf, AC. (2020)

LSD1 inhibition induces differentiation and cell death in Merkel cell carcinoma.

 EMBO Mol Med. 12(11):e12525

2019

Haas, L., Obenauf, AC. (2019)

Allies or Enemies-The Multifaceted Role of Myeloid Cells in the Tumor Microenvironment.

 Front Immunol. 10:2746

2018

Benke, S., Agerer, B., Haas, L., Stöger, M., Lercher, A., Gabler, L., Kiss, I., Scinicariello, S., Berger, W., Bergthaler, A., Obenauf, AC., Versteeg, GA. (2018)

Human tripartite motif protein 52 is required for cell context-dependent proliferation.

 Oncotarget. 9(17):13565-13581
Haas, L., Wiesner, T., Obenauf, AC. (2018)

A new era of proactive melanoma therapy: hit hard, hit early.

 Br J Dermatol. 178(4):817-820
Muhar, M., Ebert, A., Neumann, T., Umkehrer, C., Jude, J., Wieshofer, C., Rescheneder, P., Lipp, JJ., Herzog, VA., Reichholf, B., Cisneros, DA., Hoffmann, T., Schlapansky, MF., Bhat, P., von Haeseler, A., Köcher, T., Obenauf, AC., Popow, J., Ameres, SL., Zuber, J. (2018)

SLAM-seq defines direct gene-regulatory functions of the BRD4-MYC axis.

 Science. 360(6390):800-805

2016

Massagué, J., Obenauf, AC. (2016)

Metastatic colonization by circulating tumour cells.

 Nature. 529(7586):298-306
Mlecnik, B., Bindea, G., Angell, HK., Maby, P., Angelova, M., Tougeron, D., Church, SE., Lafontaine, L., Fischer, M., Fredriksen, T., Sasso, M., Bilocq, AM., Kirilovsky, A., Obenauf, AC., Hamieh, M., Berger, A., Bruneval, P., Tuech, JJ., Sabourin, JC., Le Pessot, F., Mauillon, J., Rafii, A., Laurent-Puig, P., Speicher, MR., Trajanoski, Z., Michel, P., Sesboüe, R., Frebourg, T., Pagès, F., Valge-Archer, V., Latouche, JB., Galon, J. (2016)

Integrative Analyses of Colorectal Cancer Show Immunoscore Is a Stronger Predictor of Patient Survival Than Microsatellite Instability.

 Immunity. 44(3):698-711
Mlecnik, B., Bindea, G., Kirilovsky, A., Angell, HK., Obenauf, AC., Tosolini, M., Church, SE., Maby, P., Vasaturo, A., Angelova, M., Fredriksen, T., Mauger, S., Waldner, M., Berger, A., Speicher, MR., Pagès, F., Valge-Archer, V., Galon, J. (2016)

The tumor microenvironment and Immunoscore are critical determinants of dissemination to distant metastasis.

 Sci Transl Med. 8(327):327ra26

2015

Jacob, LS., Vanharanta, S., Obenauf, AC., Pirun, M., Viale, A., Socci, ND., Massagué, J. (2015)

Metastatic Competence Can Emerge with Selection of Preexisting Oncogenic Alleles without a Need of New Mutations.

 Cancer Res. 75(18):3713-9
Obenauf, AC., Massagué, J. (2015)

Surviving at a distance: organ specific metastasis.

 Trends Cancer. 1(1):76-91
Obenauf, AC., Zou, Y., Ji, AL., Vanharanta, S., Shu, W., Shi, H., Kong, X., Bosenberg, MC., Wiesner, T., Rosen, N., Lo, RS., Massagué, J. (2015)

Therapy-induced tumour secretomes promote resistance and tumour progression.

 Nature. 520(7547):368-72
Wiesner, T., Lee, W., Obenauf, AC., Ran, L., Murali, R., Zhang, QF., Wong, EW., Hu, W., Scott, SN., Shah, RH., Landa, I., Button, J., Lailler, N., Sboner, A., Gao, D., Murphy, DA., Cao, Z., Shukla, S., Hollmann, TJ., Wang, L., Borsu, L., Merghoub, T., Schwartz, GK., Postow, MA., Ariyan, CE., Fagin, JA., Zheng, D., Ladanyi, M., Busam, KJ., Berger, MF., Chen, Y., Chi, P. (2015)

Alternative transcription initiation leads to expression of a novel ALK isoform in cancer.

 Nature. 526(7573):453-7

2014

Mlecnik, B., Bindea, G., Angell, HK., Sasso, MS., Obenauf, AC., Fredriksen, T., Lafontaine, L., Bilocq, AM., Kirilovsky, A., Tosolini, M., Waldner, M., Berger, A., Fridman, WH., Rafii, A., Valge-Archer, V., Pagès, F., Speicher, MR., Galon, J. (2014)

Functional network pipeline reveals genetic determinants associated with in situ lymphocyte proliferation and survival of cancer patients.

 Sci Transl Med. 6(228):228ra37
Valiente, M., Obenauf, AC., Jin, X., Chen, Q., Zhang, XH., Lee, DJ., Chaft, JE., Kris, MG., Huse, JT., Brogi, E., Massagué, J. (2014)

Serpins promote cancer cell survival and vascular co-option in brain metastasis.

 Cell. 156(5):1002-16

2013

Bindea, G., Mlecnik, B., Tosolini, M., Kirilovsky, A., Waldner, M., Obenauf, AC., Angell, H., Fredriksen, T., Lafontaine, L., Berger, A., Bruneval, P., Fridman, WH., Becker, C., Pagès, F., Speicher, MR., Trajanoski, Z., Galon, J. (2013)

Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer.

 Immunity. 39(4):782-95

2012

Katz, SF., Lechel, A., Obenauf, AC., Begus-Nahrmann, Y., Kraus, JM., Hoffmann, EM., Duda, J., Eshraghi, P., Hartmann, D., Liss, B., Schirmacher, P., Kestler, HA., Speicher, MR., Rudolph, KL. (2012)

Disruption of Trp53 in livers of mice induces formation of carcinomas with bilineal differentiation.

 Gastroenterology. 142(5):1229-1239.e3
Mathiesen, RR., Fjelldal, R., Liestøl, K., Due, EU., Geigl, JB., Riethdorf, S., Borgen, E., Rye, IH., Schneider, IJ., Obenauf, AC., Mauermann, O., Nilsen, G., Christian Lingjaerde, O., Børresen-Dale, AL., Pantel, K., Speicher, MR., Naume, B., Baumbusch, LO. (2012)

High-resolution analyses of copy number changes in disseminated tumor cells of patients with breast cancer.

 Int J Cancer. 131(4):E405-15

2011

Wiesner, T., Obenauf, AC., Murali, R., Fried, I., Griewank, KG., Ulz, P., Windpassinger, C., Wackernagel, W., Loy, S., Wolf, I., Viale, A., Lash, AE., Pirun, M., Socci, ND., Rütten, A., Palmedo, G., Abramson, D., Offit, K., Ott, A., Becker, JC., Cerroni, L., Kutzner, H., Bastian, BC., Speicher, MR. (2011)

Germline mutations in BAP1 predispose to melanocytic tumors.

 Nat Genet. 43(10):1018-21

2010

Obenauf, AC., Schwarzbraun, T., Auer, M., Hoffmann, EM., Waldispuehl-Geigl, J., Ulz, P., Günther, B., Duba, HC., Speicher, MR., Geigl, JB. (2010)

Mapping of balanced chromosome translocation breakpoints to the basepair level from microdissected chromosomes.

 J Cell Mol Med. 14(8):2078-84
Roetzer, KM., Schwarzbraun, T., Obenauf, AC., Hauser, E., Speicher, MR. (2010)

Further evidence for the pathogenicity of 15q24 microduplications distal to the minimal critical regions.

 Am J Med Genet A. 152A(12):3173-8
Schallmoser, K., Bartmann, C., Rohde, E., Bork, S., Guelly, C., Obenauf, AC., Reinisch, A., Horn, P., Ho, AD., Strunk, D., Wagner, W. (2010)

Replicative senescence-associated gene expression changes in mesenchymal stromal cells are similar under different culture conditions.

 Haematologica. 95(6):867-74
Van Raamsdonk, CD., Griewank, KG., Crosby, MB., Garrido, MC., Vemula, S., Wiesner, T., Obenauf, AC., Wackernagel, W., Green, G., Bouvier, N., Sozen, MM., Baimukanova, G., Roy, R., Heguy, A., Dolgalev, I., Khanin, R., Busam, K., Speicher, MR., O'Brien, J., Bastian, BC. (2010)

Mutations in GNA11 in uveal melanoma.

 N Engl J Med. 363(23):2191-9
Wiesner, T., Obenauf, AC., Cota, C., Fried, I., Speicher, MR., Cerroni, L. (2010)

Alterations of the cell-cycle inhibitors p27(KIP1) and p16(INK4a) are frequent in blastic plasmacytoid dendritic cell neoplasms.

 J Invest Dermatol. 130(4):1152-7

2009

Begus-Nahrmann, Y., Lechel, A., Obenauf, AC., Nalapareddy, K., Peit, E., Hoffmann, E., Schlaudraff, F., Liss, B., Schirmacher, P., Kestler, H., Danenberg, E., Barker, N., Clevers, H., Speicher, MR., Rudolph, KL. (2009)

p53 deletion impairs clearance of chromosomal-instable stem cells in aging telomere-dysfunctional mice.

 Nat Genet. 41(10):1138-43
Geigl, JB., Obenauf, AC., Waldispuehl-Geigl, J., Hoffmann, EM., Auer, M., Hörmann, M., Fischer, M., Trajanoski, Z., Schenk, MA., Baumbusch, LO., Speicher, MR. (2009)

Identification of small gains and losses in single cells after whole genome amplification on tiling oligo arrays.

 Nucleic Acids Res. 37(15):e105
Reinisch, A., Hofmann, NA., Obenauf, AC., Kashofer, K., Rohde, E., Schallmoser, K., Flicker, K., Lanzer, G., Linkesch, W., Speicher, MR., Strunk, D. (2009)

Humanized large-scale expanded endothelial colony-forming cells function in vitro and in vivo.

 Blood. 113(26):6716-25
Schallmoser, K., Rohde, E., Bartmann, C., Obenauf, AC., Reinisch, A., Strunk, D. (2009)

Platelet-derived growth factors for GMP-compliant propagation of mesenchymal stromal cells.

 Biomed Mater Eng. 19(4-5):271-6
Schwarzbraun, T., Obenauf, AC., Langmann, A., Gruber-Sedlmayr, U., Wagner, K., Speicher, MR., Kroisel, PM. (2009)

Predictive diagnosis of the cancer prone Li-Fraumeni syndrome by accident: new challenges through whole genome array testing.

 J Med Genet. 46(5):341-4
Wiesner, T., Obenauf, AC., Geigl, JB., Vallant, EM., Speicher, MR., Fink-Puches, R., Kerl, H., Cerroni, L. (2009)

9p21 deletion in primary cutaneous large B-cell lymphoma, leg type, may escape detection by standard FISH assays.

 J Invest Dermatol. 129(1):238-40

2008

Geigl, JB., Obenauf, AC., Schwarzbraun, T., Speicher, MR. (2008)

Defining 'chromosomal instability'.

 Trends Genet. 24(2):64-9
Schallmoser, K., Rohde, E., Reinisch, A., Bartmann, C., Thaler, D., Drexler, C., Obenauf, AC., Lanzer, G., Linkesch, W., Strunk, D. (2008)

Rapid large-scale expansion of functional mesenchymal stem cells from unmanipulated bone marrow without animal serum.

 Tissue Eng Part C Methods. 14(3):185-96