Directory Profile
Office: Salk Pavillon Office 305, 335 Sutherland drive, Pittsburgh PA 15261
Email: sib51@pitt.edu
URL: brixiuslab.org
Simone Brixius-Anderko, PhDAssistant Professor, Pharmaceutical Sciences
Dr. Simone Brixius-Anderko earned a diploma in molecular biology and a Ph.D. in biochemistry at Saarland University (Germany) in the laboratory of Prof. Rita Bernhardt. In collaboration with an industrial partner she developed a sustainable biotechnological process to generate pharmaceutical steroids exploiting human cytochrome P450 enzymes (P450s). As postdoctoral fellow in the Bernhardt lab she then studied the impact of prostate cancer drugs on P450-mediated steroid production. Since her interested in P450 structure/function relationship grew she transitioned to the laboratory of Prof. Emily Scott at the University of Michigan (College of Pharmacy) to receive training in X-ray protein crystallography. She was particularly interested in cortisol-producing P450 CYP11B1 and aldosterone-producing CYP11B2, since they are important drug targets for Cushing’s disease and aldosterone-derived hypertension, respectively. Funded by a postdoctoral fellowship of the American Heart Association, she could solve several structures of CYP11B2 in complex with ligands and redox partner proteins to find new treatment approaches for hypertension.
How does fatty acid metabolism contribute to cancer progression? We will solve these questions by elucidating the role of cytochrome P450 enzymes (P450, CYP) in cancer-related fatty acid metabolism and microbiome-mediated biotransformation of compounds in the human body. P450 enzymes are a superfamily of heme-thiolate proteins. In humans, they are indispensable for detoxification in the liver, steroid hormone biosynthesis, and fatty acid metabolism. In bacteria and fungi, they synthesize secondary metabolites, such as antibiotics, and are involved in energy metabolism. Although of significance, P450s involved in human fatty acid metabolism are heavily understudied. These enzymes are highly upregulated in several cancer types generating lipid mediators which promote tumor growth and metastasis and, thus, are new potential drug targets for cancer treatment.
The Brixius-Anderko lab will use biochemical and biophysical techniques, structural biology, and cell biology to elucidate how P450 enzymes contribute to cancer progression.
1. Loomis C.L., Brixius-Anderko, S., Scott, E.E. (2022) Redox Partner Adrenodoxin Alters Cytochrome P450 11B1 Ligand Binding and Inhibition. Journal of Inorganic Biochemistry ICCP450 Special Issue, in press
2. Brixius-Anderko, S., Scott, E.E. (2021) Aldosterone synthase structure with the Cushing’s disease drug LCI699. Hypertension, Sep;78(3):751-759, PMID: 34247511
3. Brixius-Anderko, S., Scott, E.E. (2021) Structural and functional insights into aldosterone synthase interaction with its redox partner protein adrenodoxin. Journal of Biological Chemistry, Jan-Jun 2021;296:100794, PMID: 34015331
4. Wróbel, T.M., Rogova, O., Anderson, K.L., Yadav, R., Brixius-Anderko, S., Scott, E.E., Olsen, L., Jørgensen, F.S., Björkling, F. (2020) Discovery of novel non-steroidal cytochrome P450 17A1 inhibitors as potential prostate cancer agents. International Journal of Molecular Sciences, 21:4868-4879, PMID: 32660148
5. Koenig, L., Szczesny, S., Brixius-Anderko, S., M., Hannemann, F., Bernhardt, R. (2020) Mixed-culture fermentation for enhanced C21 hydroxylation of glucocorticoids. Journal of Biotechnology, 314-315:14-24, PMID: 32246945
6. Koenig, L., Brixius-Anderko, S., Tavouli, D., Milhim, M., Hannemann, F., Bernhardt, R. (2019) Identification and circumvention of bottlenecks in CYP21A2-mediated premedrol production using recombinant Escherichia coli. Biotechnology and Bioengineering, 117(4):901-911, PMID: 31814109
7. Malikova, J., Zingg, T., Fingerhut, R., Sluka, S., Groessl, M., Brixius-Anderko, S., Bernhardt, R., McDougall, J., Pandey, A.V., Flück, C. (2019) HIV drug efavirenz inhibits 21-hydroxylase activity with possible clinical implications. Hormone Research in Pediatrics, 91(4):262-270, PMID: 31256164
8. Brixius-Anderko, S., Scott, E.E. (2018) Structure of human cortisol-producing cytochrome P450 11B1 bound to the breast cancer drug fadrozole provides insights for drug design. Journal of Biological Chemistry, 294, 453-460, PMID: 30425102
9. Malikova, J.*, Brixius-Anderko, S.*, Udhane, S., Parween, S., Dick, B., Bernhardt, R., and Pandey, A. V. (2017) CYP17A1 inhibitor abiraterone, an anti-prostate cancer drug, also inhibits the 21-hydroxylase activity of CYP21A2. The Journal of Steroid Biochemistry and Molecular Biology, 174:192-200. PMID: 28893623 (*shared first authorship)
10. Brixius-Anderko, S., Hannemann, F., Ringle, M., Khatri, Y., and Bernhardt, R. (2016) An indole deficient Escherichia coli strain improves screening of cytochromes P450 for biotechnological applications. Biotechnology and Applied Biochemistry 64(3):315-326. PMID: 26913738.
11. Schiffer, L., Müller, A.-R., Hobler, A., Brixius-Anderko, S., Zapp, J., Hannemann, F., and Bernhardt, R. (2016) Biotransformation of the mineralocorticoid receptor antagonists spironolactone and canrenone by human CYP11B1 and CYP11B2: Characterization of the products and their influence on mineralocorticoid receptor transactivation, Journal of Steroid Biochemistry and Molecular Biology, 163:68-76. PMID: 27125452.
12. Schiffer, L., Brixius-Anderko, S., Hannemann, F., Zapp, J., Neunzig, J., Thevis, M., and Bernhardt, R. (2016) Metabolism of oral-turinabol by human steroid hormone- synthesizing cytochromes P450. Drug Metabolism and Disposition 44(2):227-37. PMID: 26658226.
13. Brixius-Anderko, S., Schiffer, L., Hannemann, F., Janocha, B., and Bernhardt, R. (2015) A CYP21A2 based whole-cell system in Escherichia coli for the biotechnological production of Premedrol. Microbial Cell Factories 14:135. PMCID: PMC4572648
14. Schiffer, L., Anderko, S., Hobler A., Hannemann F., Kagawa N., and Bernhardt, R. (2015) A recombinant CYP11B1 dependent Escherichia coli biocatalyst for selective cortisol production and optimization towards a preparative scale. Microbial Cell Factories 14:25. PMCID: PMC4347555.
15. Schiffer, L., Anderko, S., Hannemann, F., Eiden-Plach, A., and Bernhardt, R. (2014) The CYP11B subfamily. The Journal of Steroid Biochemistry and Molecular Biology, 151:38-51. PMID: 25465475.
Selected:
1. Leading Edge New Faculty Fellow 2021
2. Kristen L. McGlone Award for Excellence in Research (2020), University of Michigan, College of Pharmacy
3. Postdoctoral Fellowship Award, American Heart Association (2019-2020): Understanding Aldosterone Biosynthesis for Enhanced Treatment of Hypertension
4. Christiane Nuesslein-Volhard Fellowship (2013-2015)
5. For Women in Science Award (2013), awarded by L´Oréal, UNESCO and the Christiane Nuesslein-Volhard foundation
6. StudienStiftungSaar (Germany) Scholarship for Biotechnological Research (2011)
Selected:
1. Talk at the 79th Pittsburgh Diffraction Conference at Argonne Lightsource (2022) Targeting Aldosterone Biosynthesis for the Treatment of Resistant Hypertension
2. Talk at the International Conference on Cytochrome P450 in Washington DC (2022) Targeting Aldosterone Biosynthesis for the Treatment of Resistant Hypertension
3. Seminar Talk at ASPET Focus on Pharmacology Meeting: Current Advances in Drug Metabolism Virtual Series Part 3 (2022) Targeting Cytochrome P450 enzymes to Treat Human Disease
4. Experimental Biology (virtual), ASPET Datablitz (2021) Structural and Functional Insights into Aldosterone Biosynthesis
5. Seminar Talk at the Institute of Metabolism and Systems Research (IMSR), University of Birmingham (UK) (2020) Understanding Aldosterone Biosynthesis for Enhanced Treatment of Hypertension
6. Hypertension Scientific Session, American Heart Association (virtual) (2020) Aldosterone synthase structure with Cushing’s disease drug osilodrostat provides clues for treatment of primary aldosteronism
7. Experimental Biology, ASPET Drug Metabolism and Disposition Young Investigators Platform Session, Orlando, FL (2019) Structural Insights into Cytochromes P450 11B1 and 11B2 for Enhanced Treatment of Hypertension and Cushing’s disease
AACP New Investigator Award "Targeting cytochrome P450 mediated fatty acid metabolism in lung cancer" (03/2023 - 02/2024)