Signalling pathways as targets for personalized cancer therapies
Signalling pathways control cell and tissue growth during development and regeneration. One of these critical pathways is Wnt signalling, which is particularly involved in bone remodelling and skeletal homeostasis. Mutations and hyperactivation of Wnt signalling proteins and regulators are implicated in tumorigenesis. Dickkopf-1 (DKK-1) is a secreted, negative regulator of WNT signalling and blocks the differentiation of bone-building osteoblasts. High levels of DKK-1 are associated with osteolytic bone metastasis in multiple myeloma and breast cancer. However, additional effects of DKK-1 in cancer, apart from its role in bone biology, have been identified. These include the mediation of stress resistance mechanisms and the recruitment of tumor-promoting myeloid-derived suppressor cells into the tumor microenvironment.
Current research of the Göbel/Rachner team explores the potential of DKK-1 as a target in personalized and precision therapy of human cancers. Preliminary experiments in human cancer cell lines demonstrated that DKK-1 regulates the androgen receptor (AR) in prostate cancer cells. Moreover, breast cancer cells lacking DKK-1 show an increased dependence on glutamine. As DKK-1 can be blocked genetically by CRISPR/Cas9 technology and small-interfering RNAs or pharmacologically by neutralizing antibodies, its potential as a target for personalized cancer therapy will be explored.
- Identify breast cancer patient subpopulations that would mostly benefit from an anti-DKK-1 and glutamine metabolism-targeted therapy
- Elucidate the potential of DKK-1 as a valid predictor of endocrine resistance for individualized risk stratification in patients with prostate cancer
- Assess the potential of the mevalonate pathway as a therapeutic target in human malignancies
- Identification of novel biomarkers in osteotropic malignancies
LAB MEMBERS
© Andy Goebel
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POSITIONS |
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|---|---|
| since 05/2020 | Mildred-Scheel-Nachwuchszentrum (MSNZ) research group leader affiliated with Department of Medicine III, Division for endocrinology, diabetes and bone disorders, University hospital “Carl Gustav Carus” Dresden |
| 2016-2020 | Postdoc at the Department of Medicine III, Division for endocrinology, diabetes and bone disorders, University hospital “Carl Gustav Carus”, Dresden |
| 2017 | Coordination of the DFG Priority Program "µBone" |
| 2012-2016 | Research associate and PhD student at the Department of Medicine III, Division for endocrinology, diabetes and bone disorders, University hospital “Carl Gustav Carus”, Dresden |
| 2011-2012 |
Research associate, Department of immunology, University hospital “Carl Gustav Carus”, Dresden/Germany |
| EDUCATION | |
|---|---|
| 2012-2016 | Doctorate (PhD) (Group Lorenz C. Hofbauer), Department of Medicine III, University hospital “Carl Gustav Carus”, Dresden |
| 2012-2013 |
Graduate school program “Research management for natural scientist”; European project center; Dresden |
| 2005-2011 |
Study of Biology, Technische Universität Dresden, Dresden |
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HONORS |
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| 2020 | Von-Recklinghausen Award, Deutsche Gesellschaft für Endokrinologie |
| 2016 |
Carl-Gustav-Carus award for an outstanding doctoral thesis |
| 2016 |
Postdoc stipend, Graduate Academy Dresden |
MEMBERSHIPS
2019 European Association for Cancer Research
2018 Deutsche Gesellschaft für Endokrinologie
Deutsche Gesellschaft für Senologie
| FUNDINGS | |
|---|---|
| 2019-2022 | Research grant from the Deutsche Krebshilfe: “Die Untersuchung von Mechanismen der durch die 3-Hydroxy-3-Methylglutaryl-Coenzym-A-Reduktase vermittelten Statin-Resistenz in Brustkrebszellen“ (Nr: 70113573) |
| 2018-2021 | Research grant from the Deutsche Forschungsgemeinschaft: “Dissecting the pleiotropic effects of Dickkopf-1 in homing and colonization of breast cancer cells to and within bone” (DFG GO 3055/1-1) |
SELECTED PUBLICATIONS
Göbel A, Rauner M, Hofbauer LC, Rachner TD. Cholesterol and beyond - The role of the mevalonate pathway in cancer biology. Biochim. Biophys. Acta - Rev. Cancer. 2020;1873:188351.
Rachner TD, Göbel A, Hoffmann O, Erdmann K, Kasimir-Bauer S, Breining D, Kimmig R, Hofbauer LC, Bittner A-K. High serum levels of periostin are associated with a poor survival in breast cancer. Breast Cancer Res. Treat. 2020;180:515–24.
Göbel A, Kuhlmann JD, Link T, Wimberger P, Link-Rachner C, Thiele S, Dell’Endice S, Furesi G, Breining D, Rauner M, Hofbauer LC, Rachner TD. Plasma levels of Semaphorin 4D are decreased by adjuvant tamoxifen but not aromatase inhibitor therapy in breast cancer patients. J. Bone Oncol. 2019;16:100237
Göbel A, Breining D, Rauner M, Hofbauer LC, Rachner TD. Induction of 3-hydroxy-3-methylglutaryl-CoA reductase mediates statin resistance in breast cancer cells. Cell Death Dis. 2019;10:91.
for complete publication record see ORCID
© Andy Goebel
PD Dr. med. habil. Tilman Rachner
Send encrypted mail via the SecureMail portal (for TUD external users only).
| POSITIONS | |
|---|---|
| since 05/2020 | Mildred-Scheel-Nachwuchszentrum (MSNZ) research group leader affiliated with the Department of Endocrinology, Diabetes and Metabolic Bone Disorders, Medical Department III, University Hospital Dresden (UKD) |
| since 2020 | Senior Consultant for Internal Medicine, UKD |
| since 2018 | Associate Consultant for Internal Medicine, UKD |
| since 2014 | Junior Group leader at the Department of Endocrinology, Diabetes and Metabolic Bone Disorders, Medical Department III, UKD |
| 2010-2018 | Resident in the Department of Endocrinology, Diabetes and Metabolic Bone Disorders, Medical Department III, UKD |
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EDUCATION/CLINICAL TRAINING |
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|---|---|
| 2019 |
Board certification Endocrinology |
| 2018 | Habilitation Internal Medicine |
| 2018 | Board certification Internal Medicine |
| 2006-2009 | Medical doctorate in the laboratory of Prof. Hofbauer, Department of Endocrinology, Philipps-Universität, Marburg |
| 2003-2009 | Medical Studies, Philipps-Universität, Marburg |
| HONORS | |
|---|---|
| 2020 | Von-Recklinghausen Preis, Deutsche Gesellschaft für Endokrinologie |
| 2017 |
Friedrich-Heuck Osteologie Preis, Deutsche Akademie der osteologischen und rheumatologischen Wissenschaften e.V. (DAdorW) |
| 2017 |
Recklinghausen Preis, Deutsche Gesellschaft für Endokrinologie |
| 2014 |
Novartis Award „Junge Endokrinologie“ 2014, Deutsche Gesellschaft für Endokrinologie |
| 2010 |
Medical Student Achievement Award der Endocrine Society, Washington, DC, USA |
| 2010 |
Research Award (Copp-Preis) of the “Deutsche Gesellschaft für Osteologie”, Berlin |
| MEMBERSHIPS | |
|---|---|
| since 2014 | Deutsche Gesellschaft für Hämatologie und Onkologie |
| since 2014 | Deutsche Gesellschaft für Endokrinologie |
| since 2010 | Deutsche Gesellschaft für Osteologie (seit 2014 Vorstandsmitglied) |
| FUNDINGS | |
|---|---|
| 2020-2023 |
Research grant from the Deutsche Forschungsgemeinschaft: Neue Biomarker für Knochenmetastasen – von Mechanismen zur Analytik und zurück“ (DFG RA 2151/5-1) |
| 2019-2022 | Research grant from the Deutsche Krebshilfe: “Die Untersuchung von Mechanismen der durch die 3-Hydroxy-3-Methylglutaryl-Coenzym-A-Reduktase vermittelten Statin-Resistenz in Brustkrebszellen“ (Nr: 70113573) |
| 2018-2021 | Research grant from the Deutsche Forschungsgemeinschaft: “Dissecting the pleiotropic effects of Dickkopf-1 in homing and colonization of breast cancer cells to and within bone” (DFG RA 2151/4-1) |
SELECTED PUBLICATIONS
Rachner TD, Göbel A, Hoffmann O, Erdmann K, Kasimir-Bauer S, Breining D, Kimmig R, Hofbauer LC, Bittner A-K. High serum levels of periostin are associated with a poor survival in breast cancer Breast Cancer Res. Treat. 2020; 180:515–24.
Rachner TD, Coleman R, Hadji P, Hofbauer LC. Bone health during endocrine therapy for cancer. Lancet Diabetes Endocrinol. 2018; 6:901-910.
Rachner TD, Kasimir-Bauer S, Göbel A, Erdmann K, Hoffmann O, Browne AJ, Wimberger P, Rauner M, Hofbauer LC, Kimmig R, Bittner AK. Prognostic value of RANKL/OPG serum levels and disseminated tumor cells in non-metastatic breast cancer. Clin Cancer Res 2019; 25:1369-1378.
for complete publication record see ORCID
© Andy Goebel
technician
NameDorit Breining M.Sc.
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© Andy Goebel
Dr.med.univ. Nikolai Jaschke
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© Andy Goebel
Postdoc
NamePhD Stefania Dell’Endice
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© Andy Göbel
Sophie Pählig M.Sc.
Phd-student
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© Andy Göbel
Postdoc
NamePhD, Amna Shahid
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SELECTED PUBLICATIONS
Andy Göbel, Stefania Dell’Endice, Nikolai Jaschke, Sophie Pählig , Amna Shahid , Lorenz C. Hofbauer and Tilman D. Rachner The Role of Inflammation in Breast and Prostate Cancer Metastasis to Bone International Journal of Molecular Science. 2021, 22(10), 5078
Göbel A, Rauner M, Hofbauer LC, Rachner TD. C Cholesterol and beyond - The role of the mevalonate pathway in cancer biology. Biochim. Biophys. Acta - Rev. Cancer. 2020; 1873:188351.
Rachner TD, Göbel A, Hoffmann O, Erdmann K, Kasimir-Bauer S, Breining D, Kimmig R, Hofbauer LC, Bittner A-K. . High serum levels of periostin are associated with a poor survival in breast cancer. Breast Cancer Res. Treat. 2020; 180:515–24.
Rachner TD, Kasimir-Bauer S, Göbel A, Erdmann K, Hoffmann O, Browne AJ, Wimberger P, Rauner M, Hofbauer LC, Kimmig R, Bittner AK. Prognostic value of RANKL/OPG serum levels and disseminated tumor cells in non-metastatic breast cancer. Clin Cancer Res 2019; 25:1369-1378.
Rachner TD, Göbel A, Thiele S, Rauner M, Benad-Mehner P, Hadji P, Bauer T, Muders MH, Baretton GB, Jakob F, Ebert R, Bornhäuser M, Schem C, Hofbauer LC. Dickkopf-1 is regulated by the mevalonate pathway in breast cancer. Breast Cancer Res. 2014 16:R20.
LINKS
OPEN POSITIONS
We are looking for a motivated technician (MTA, BTA, CTA) to complement our team as soon as possible. Check out the job offer, we are happy to receive your application!
CONTACT
© Marc Eisele
Tandemlab Goebel/Rachner
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Visiting address:
Division of Endocrinology, Diabetes, and Bone Diseases Dresden
Haus19/5th floor, 5.128
Fetscherstraße 74
01307 Dresden
Postal address:
TUD Dresden University of Technology Division of Endocrinology, Diabetes, and Bone Diseases Dresden Fetscherstrasse 74
01307 Dresden