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Oesterreich Lab

The main interest of Dr. Oesterreich’s laboratory is to further our understanding of hormone action in breast cancer, with the goal to use this knowledge for improved diagnosis and endocrine treatment of breast cancer patients. Specifically, her group studies how the estrogen receptor (ER) functions, how its activity is regulated by co-activator and co-repressor proteins, and if and how these mechanisms are perturbed in cancer cells. The lab is interested in novel concepts of ER action, such as its role in repression of gene transcription, and the involvement of higher order chromatin structure in hormone response. The Oesterreich lab aims to identify genetic markers such as polymorphisms, or epigenetic changes such as DNA methylation, which might be able to predict a patient’s response to endocrine therapy, which can be used to “personalize medicine”. All of these studies include many aspects of translational breast cancer research utilizing basic biochemistry, molecular and cell biology, cell lines, mouse models and clinical samples from retrospective cohort studies, and from clinical trials.

https://mageewomens.org/investigator/steffi-oesterreich-phd/


 

Zheqi Li

I am interested in breast cancer pharmacology, detecting the mechanisms behind estrogen receptor somatic mutations and exploring novel ER-targeted cancer therapies.
 

Steffi Oesterreich, PhD

Molecular mechanism and clinical relevance of endocrine response in breast cancer

The Oesterreich lab includes technicians, graduate students and postdoctoral fellows who are trained in a multi-disciplinary research environment to work in basic, translational, and clinical aspects of breast cancer research. Specifically, our research projects focus on the role of co-regulator proteins in estrogen response in breast cancer. Estrogen mediates its potent mitogenic effects through the estrogen receptor (ER), which has been a successful target for endocrine therapy in breast cancer. Despite the success of such treatment, de novo or acquired resistance remains a major problem. A better understanding of how ER works is critical for the development of more efficient therapies, and better prediction for who should receive which form of endocrine therapy.

Over the last years, many dogmas in hormone response have changed, which has opened many exciting novel research areas. Examples are estrogen-mediated repression of gene transcription, and the role of co-repressors in this process, the close connection between estrogen signaling and epigenetic regulation of gene transcription, and the role of regulatory elements which are located far outside the promoter of the estrogen regulated genes, and which might even be on other chromosomes. We are studying these processes using state-of-the-art molecular and cellular techniques, mouse models, and clinical specimens. The ultimate goal of Dr. Oesterreich's research is to use this knowledge for improved diagnosis and endocrine treatment of breast cancer patients.

https://leeoesterreich.org/

Headshot of Zheqi Li
Zheqi Li
Graduate Student Researcher

Headshot of Steffi Oesterreich, PhD
Steffi Oesterreich, PhD
Professor, The Shear Family Foundation Chair in Breast Cancer Research

Headshot of Sayali Onkar
Sayali Onkar
Graduate Student Researcher

Headshot of Abdalla Wedn
Abdalla Wedn
Graduate Student Researcher

Steffi Oesterreich, PhD

Journal Articles

Pathiraja TN, Nayak S, Xi Y, Jiang S, Garee JP, Edwards DP, Lee AV, Chen J, Shea MJ, Santen RJ, Gannon F, Kangaspeska S Jelinek J, Issa JJ, Richer JK, Elias A, Mcllroy M, Young L, Davidson NE, Schiff R, Li W, and Oesterreich S. Epigenetic reprogramming of HOXC10 in endocrine-resistant breast cancer. Science Transl med 6:229, 2014. PMID: 24670685.
Sikora Mj, Cooper KL, Bahreini A, Luthra S, Wang G, Chandran UR, Davidson NE, Dabbs DJ, Welm AL, Oesterreich S. Invasive lobular carcinoma cell lines are characterized by unique estrogen-mediated gene expression patterns and altered tamoxifen response. Cancer Res 74:1463-1472, 2014.  PMID: 24425047. PMCID: PMC3955299 [Available 2015/3/1]
Oesterreich S, Davidson NE. The search for ESR1 mutations in breast cancer. Nat Genet 45:1415-1416, 2013. PMID: 24270445
Oesterreich S, Brufsky AM, Davidson NE. Using mice to treat (wo)men: Mining genetic changes in patient xenografts to attack breast cancer. Cell Rep 4:1061-1062, 2013. PMID: 24075202
Oesterreich S, R Edwards and A Vlad.  Progestins:  Pro-senescence therapy for ovarian cancer:  Cell Cycle 12:1662-1663, 2013.
Hartmaier RJ, AS Richter, RM Gillihan, JZ Sallit, SE McGuire, J Wang, AV Lee, CK Osborne, BW O'Malley, PH Brown, J Xu, TC Skaar, S Philips, JM Rae, F Azzouz, L Li, J Hayden, NL Henry, AT Nguyen, V Stearns, DF Hayes, DA Flockhart and S Oesterreich.  A SNP in steroid receptor coactivator-1 disrupts a GSK3 beta phosphorylation site and is associated with altered Tamoxifen response in bone.  Mol Endo 26:220-227, 2012.
Watters RJ, PV Benos and S Oesterreich.  To bind or not to bind:  FoxA1 determines estrogen receptor action in breast cancer progression.  Breast Cancer Res 14:312, 2012.
Smith CL, I Migliaccio, V Chaubal, MF Wu, MC Pace, R Hartmaier, S Jiang, DP Edwards, MC Gutierrez, SG Hilsenbeck and S Oesterreich.  Elevated expression of the SMRT corepressor in breast cancer is associated with earlier tumor recurrence.  Breast Cancer Res Treat 136:253-265, 2012.
Steinman RA, AM Brufsky and S Oesterreich.  Zoledronic acid effectiveness against breast cancer metastases:  A role for estrogen in the microenvironment?  Breast Cancer Res 14:213, 2012.
Pathiraja TN, PB Shetty, J Jelinek, R He, R Hartmaier, AL Margossian, SG Hilsenbeck, JP Issa and S Oesterreich.  Progesterone receptor isoform-specific promoter methylation:  Association of PRA methylation with worse outcome in breast cancer patients.  Clin Cancer Res 17:4177-4186, 2011.
Garee JP, R Meyer and S Oesterreich.  Co-repressor activity of scaffold attachment factor B1 requires sumoylation.  Biochem Biophys Res Commun 408:516-522, 2011.
Oesterreich S, AV Lee and NE Davidson.  Is it time to reSET the standard for estrogen receptor testing in breast cancer?  J Clin Oncol 28:4101-4103, 2010.

Nilgun Tasdemir, PhD

Journal Articles

Bossart EA‡, Tasdemir N‡, Sikora MJ, Bahreini A, Levine KM, Chen J, Basudan A, Jacobsen BM, Burns TF, Oesterreich S. (2019). SNAIL is induced by Tamoxifen and leads to growth inhibition in invasive lobular breast carcinoma. Breast Cancer Res Treat. doi: 10.1007/s10549-019-05161-8. [Epub ahead of print]. (‡ equal contributors).
 
Tasdemir N, Bossart EA, Li Z, Zhu L, Levine KM, Jacobsen BM, Tseng GC, Davidson NE, Oesterreich S. (2018). Comprehensive phenotypic characterization of human invasive lobular carcinoma cell lines in 2D and 3D cultures. Cancer Research. 8(21):6209-6222.
 
Banito A, Li X, Laport A, Roe JS, Sánchez-Vega F, Huang CH, Dancsok A, Hatzi A, Chen CC, Tschaharganeh DF, Tasdemir N, et al. (2018). The SS18-SSX oncoprotein hijacks KDM2B-PRC1.1 to drive synovial sarcoma. Cancer Cell. 33(3): 527-541.
 
Sakamaki J, Wilkinson S, Hahn M, Richter B, Tasdemir N, J O’Prey, et al. (2017). Bromodomain protein BRD4 is a transcriptional repressor of autophagy and lysosomal function. Molecular Cell. 66(4): 517-532.
 
Tasdemir N, Banito A, Roe JS, Alonso-Curbelo D, Camiolo M, Tschaharganeh DF, Huang CH, Aksoy O, Bolden JE, Chen CC, Fennell M, Thapar V, Chicas A, Vakoc CR, Lowe SW. (2016). BRD4 connects enhancer remodeling to senescence immune surveillance. Cancer Discovery. 6(6): 612-629.
 
Cheloufi S, Elling U, Hopfgartner B, Jung YL, Murn J, Ninova M, Hubmann M, Badeaux AI, Euong Ang C, Tenen D, Wesche DJ, Abazova N, Hogue M, Tasdemir N, et al. (2015). The histone chaperone CAF-1 safeguards somatic cell identity. Nature. 528: 218-224.
 
Bolden JE‡, Tasdemir N‡, Dow LE‡, van Es JH, Wilkinson JE, Zhao Z, Clevers H, Lowe SW. (2014). Inducible in vivo silencing of Brd4 identifies potential toxicities of sustained BET protein inhibition. Cell Reports. 8(6): 1919-29. (‡equal contributors).
 

Abdalla Wedn

Journal Articles

Wu Y, Li Z, Wedn AM, Casey AN, Brown D, Rao SV, Omarjee S, Hooda J, Carroll JS, Gertz J, Atkinson JM, Lee AV, Oesterreich S. FOXA1 Reprogramming Dictates Retinoid X Receptor Response in ESR1-Mutant Breast Cancer. Mol Cancer Res. 2023 Jun 1;21(6):591-604. doi: 10.1158/1541-7786.MCR-22-0516. PMID: 36930833; PMCID: PMC10239325.