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Benita S. Katzenellenbogen

Swanlund Professor of Molecular & Integrative Physiology
Swanlund Professor of Cell & Developmental Biology

Research Interests

Research Topics

Cell-Cell Interactions, Endocrinology, Genomics, Protein-Nucleic Acid Interactions, Receptor Biochemistry, Regulation of Gene Expression, Reproductive Biology, Signal Transduction

Disease Research Interests

Cancer, Reproductive Diseases, Infertility, and Menopause

Research Description

Regulation of gene expression, signal transduction, and cell proliferation and phenotypic properties by hormones and growth factors; functional analyses of nuclear hormone receptors and their genome-wide activities; mechanisms of hormone and antihormone action in normal and cancer cells and tumors; biomarker discovery and cellular changes underlying resistance to therapeutic agents in breast cancer

We are interested in understanding the biochemistry, physiology, and molecular biology of nuclear hormone (estrogen, progesterone) receptors, intracellular proteins that mediate the biological actions of these hormones in target cells, and the mechanisms by which these proteins regulate gene expression and the growth and functioning of target cells, especially cells of the reproductive system and mammary gland, and of tumors that develop in these tissues. Our studies focus on the characterization of these receptors and their coregulator protein partners; the interaction of receptor agonist versus antagonist ligand complexes with hormone-regulated genes; the interrelationships among hormones, growth factors, and various signal transduction pathways in the regulation of proliferation and phenotypic properties of breast cancer cells and tumors; and the mechanisms by which antihormones (antiestrogens and antiprogestins) antagonize hormone-dependent gene transcription and cell growth. We are doing genome-wide analyses of receptor and other transcription factor cistromes (chromatin binding sites by ChIP-Seq) and transcriptomes (gene expression, miRNAs, other RNAs by RNA-Seq) and are examining the bidirectional cross-talk between nuclear hormone receptors and cell signaling pathways. Our studies involve detailed biochemical and structure-function analyses of the receptors (and of mutant receptor forms) and coregulators and their gene interactions, and examination of their biological activities in normal and cancer, in particular breast cancer, cells and tumors. We have a major interest in hormones and breast cancer and in mechanisms of endocrine sensitivity and resistance to cancer therapies; biomarker discovery and improving cancer treatment effectiveness; and also a strong focus on reproductive biology and the improvement of fertility.

Education

B.A. City University of New York
M.A. Harvard University
PhD. Harvard University
Postdoc. University of Illinois

Awards and Honors

Ernst Oppenheimer Memorial Award of The Endocrine Society for Meritorious Research, 1984
Thomas A. Murphy University Scholar, 1987-1990
MERIT Award from National Institutes of Health, National Cancer Institute, 1991-1999
Faculty Member of the Year Award, University of Illinois College of Medicine, 1994
American Academy of Arts and Sciences, elected Fellow, 1993
Susan G. Komen Breast Cancer Foundation, Scientific Distinction Award, 1996
The Kroc Lectureship, Univ. Texas-Houston Health Science Center and M. D. Anderson Cancer Center, 1998
Jill Rose Award for Breast Cancer Research, The Breast Cancer Research Foundation, 1998
NIEHS Distinguished Lectureship, NIEHS/NIH, 2000, 2005, 2012, 2019
President, The Endocrine Society, 2000-2001
Swanlund Professorship, University of Illinois, 2000-present
Professor in the Center for Advanced Studies, University of Illinois, 2000-present
City University of New York Distinguished Alumni Award, 2002
Roy O. Greep Lecture Award, The Endocrine Society, 2006
Laurea ad Honorem (Honorary Degree) from University of Milan, Italy, 2007
Nobel Conference on Estrogen Signaling: From Molecular Insights to Clinical Understanding, Keynote Address, Stockholm, 2008
Susan G. Komen for the Cure, Brinker Award for Scientific Distinction, 2009
Mentor Award, Women in Endocrinology, 2011
Plenary Lecturer, The Endocrine Society of Australia, Melbourne, 2014
Fred Conrad Koch Lifetime Achievement Award, The Endocrine Society, 2016

Additional Campus Affiliations

Highlighted Publications

Representative Publications

Ziegler Y, Guillen VS, Kim SH, Katzenellenbogen JA, Katzenellenbogen BS. Transcription Regulation and Genome Rewiring Governing Sensitivity and Resistance to FOXM1 Inhibition in Breast Cancer. Cancers. 2021. 13(24), 6282. doi: 10.3390/cancers13246282. PMID: 34944900 [Abstract] [Full Text]

Katzenellenbogen BS. Estrogen receptor gets a grip on RNA. Preview. Cell 2021. https://doi.org/10.1016/j.cell.2021.09.012. PMID: 34559987 [Abstract] [Full Text]

Min J, Nwachukwu JC, Srinivasan S, Rangarajan ES, Nettles CC, Guillen VS, Ziegler Y, Yan S5, Carlson KE, Hou Y, Kim SH, Novick S, Pascal BD, Houtman R, Griffin PR, Izard T, Katzenellenbogen BS, Katzenellenbogen JA, Nettles KW. Dual mechanism estrogen receptor inhibitors. Proc Natl Acad Sci, 2021 118(35): e2101657118, DOI number 10.1073/pnas.2101657118. PMID: 34452998 [Abstract] [Full Text]

Mayne CG, Toy W, Carlson KE, Bhatt T, Fanning SW, Greene GL, Katzenellenbogen BS, Chandarlapaty S, Katzenellenbogen JA, Tajkhorshid E. Defining the Energetic Basis for a Conformational Switch Mediating Ligand-Independent Activation of Mutant Estrogen Receptors in Breast Cancer. Mol. Cancer Res., 2021, May 21;molcanres.1017.2020. doi: 10.1158/1541-7786.MCR-20-1017. PMID: 34021071 PMCID: PMC8419021. [Abstract] [Full Text]

Yan S, Dey P, Ziegler Y, Jiao X, Kim SH, Katzenellenbogen JA, Katzenellenbogen BS. Contrasting activities of estrogen receptor beta isoforms in triple negative breast cancer. Breast Cancer Res Treat. 2021 Jan;185(2):281-292. doi: 10.1007/s10549-020-05948-0. Online ahead of print. PMID: 33001337 PMCID: PMC7867590 [Abstract] [Full Text]

Dey P, Wang A, Ziegler Y, Kim SH, El-Ashry D, Katzenellenbogen JA, Katzenellenbogen BS. Suppression of Tumor Growth, Metastasis, and Signaling Pathways by Reducing FOXM1 Activity in Triple Negative Breast Cancer. Cancers (Basel) 2020, Sep 19;12(9):E2677. doi: 10.3390/cancers12092677. PMID: 32961773 PMCID: PMC7565743 [Abstract] [Full Text]

Laws MJ, Ziegler Y, Shahoei SH, Dey P, Kim SH, Yasuda M, Park BH, Nettles KW, Katzenellenbogen JA, Nelson ER, and Katzenellenbogen BS. Suppression of breast cancer metastasis and extension of survival by a new antiestrogen in a preclinical model driven by mutant estrogen receptors. Breast Cancer Res Treatment 2020. 181(2): 297-307. Apr 10. doi: 10.1007/s10549-020-05629-y. [Epub ahead of print] PMID: 32277377 [Abstract] [Full Text]

Ziegler Y, Laws MJ, Guillen VS, Kim SH, Dey P, Smith BP, Gong P, Bindman N, Zhao Y, Carlson K, Yasuda MA, Singh D, Li Z, El-Ashry D, Madak-Erdogan Z, Katzenellenbogen JA, and Katzenellenbogen BS. Suppression of FOXM1 activities and breast cancer growth in vitro and in vivo by a new class of compounds. npjBreastCancer 2019. 5:45; doi:10.1038/s41523-019-0141-7. eCollection 2019. PMID: 31815181 PMCID: PMC6884575 [Abstract] [Full Text]

Wang L, Guillen V, Sharma N, Flessa K, Min J, Carlson K, Toy W, Braqi S, Katzenellenbogen B, Katzenellenbogen JA, Chandarlapaty S, Sharma A. A New Class of Selective Estrogen Receptor Degraders (SERDs): Expanding the Toolbox of PROTAC Degrons. ACS Medicinal Chemistry Letters, 2018 Jul 5;9(8):803-808. doi: 10.1021/acsmedchemlett.8b00106. eCollection 2018 Aug 9. PMID: 30128071 PMCID: PMC6088359. [Abstract] [Full Text]

Katzenellenbogen JA, Mayne CG, Katzenellenbogen BS, Greene GL, and Chandarlapaty S. Structural underpinnings of oestrogen receptor mutations in endocrine therapy resistance. Nature Reviews Cancer 2018. Apr 16. doi: 10.1038/s41568-018-0001-z. [Epub ahead of print] Review. PMID: 29662238. [Abstract] [Full Text]

Zhao Y, Laws MJ, Guillen VS, Ziegler Y, Min J, Sharma A, Kim SH, Chu D, Park BH, Oesterreich S, Mao C, Shapiro DJ, Nettles KW, Katzenellenbogen JA, and Katzenellenbogen BS. Structurally novel antiestrogens elicit differential responses from constitutively active mutant estrogen receptors in breast cancer cells and tumors. Cancer Research, 2017 Oct 15;77(20):5602-5613. doi: 10.1158/0008-5472. CAN-17-1265. PMID:28904064 PMCID:PMC5645250. [Abstract] [Full Text]

Min J, Guillen VS, Sharma A, Zhao Y, Ziegler Y, Gong P, Mayne CG, Srinivasan S, Kim SH, Carlson KE, Nettles KW4, Katzenellenbogen BS, Katzenellenbogen JA. Adamantyl Antiestrogens with Novel Side Chains Reveal a Spectrum of Activities in Suppressing Estrogen Receptor (ER)-Mediated Activities in Breast Cancer Cells. J Med Chem. 2017 60:6321-36 Jun 14. doi: 10.1021/acs.jmedchem.7b00585. [Epub ahead of print] PMID: 28657320. [Abstract] [Full Text]

Lu W and Katzenellenbogen BS. Estrogen Receptor-β Modulation of the ERα-p53 Loop in Regulating Gene Expression, Proliferation, and Apoptosis in Breast Cancer. Hormones and Cancer, 2017, 8(4), 230-242. DOI: 10.1007/s12672-017-0298-1. PMID:28577282 PMCID:PMC5523813. [Abstract] [Full Text]

Arnal JF, Lenfant F, Metivier R, Flouriot G, Henrion D, Adlanmerini M, Fontaine C, Gourdy P, Chambon P, Katzenellenbogen B, Katzenellenbogen J. Membrane and Nuclear Estrogen Receptor Alpha Actions: From Tissue Specificity to Medical Implications. Physiological Reviews, 2017. Jul 1;97(3):1045-1087. doi: 10.1152/physrev.00024.2016. PMID:28539435. [Abstract] [Full Text]

Srinivasan S, Nwachukwu JC, Bruno NE, Dharmarajan V, Goswami D, Kastrati I, Novick S, Nowak J, Cavett V, Zhou HB, Frasor J, Boonmuen N, Zhao Y, Min J, Frasor J, Katzenellenbogen BS, Griffin PR, Katzenellenbogen JA, Nettles KW. Full Antagonism of the Estrogen Receptor without a Prototypical Ligand Side Chain. Nature Chem Biol. 2017 Jan;13(1):111-118. doi: 10.1038/nchembio.2236. Epub 2016 Nov 21 PMID:27870835 PMCID:PMC5161551. [Abstract] [Full Text]

Gong P, Madak-Erdogan Z, Flaws JA, Shapiro DJ, Katzenellenbogen JA, and Katzenellenbogen BS. Estrogen Receptor-α and Aryl Hydrocarbon Receptor Involvement in the Actions of Botanical Estrogens in Target Cells. Mol Cell Endocrinol. 437:190-200 2016. PMID:27543265. [Abstract] [Full Text]

Madak-Erdogan Z, Kim SH, Gong P, Zhao YC, Zhang H, Chambliss KL, Carlson KE, Mayne CG, Shaul PW, Korach KS, Katzenellenbogen JA, Katzenellenbogen BS. Design of Pathway Preferential Estrogens Affording Beneficial Metabolic and Vascular Actions without Reproductive Tissue Stimulation. Science Signaling 9(429): ra53 2016. PMID:27221711. [Abstract] [Full Text]

Fanning SW, Mayne CG, Dharmarajan V, Carlson KE, Martin TA, Novick SJ, Toy W, Greene B, Panchamukhi S, Katzenellenbogen BS, Tajkhorshid E, Griffin PR, Shen Y, Chandarlapaty S, Katzenellenbogen JA, Greene GL. Estrogen Receptor Alpha Somatic Mutations Y537S and D538G Confer Breast Cancer Endocrine Resistance by Stabilizing the Activating Function-2 Binding Conformation. Elife 2016; Feb 2;5. pii: e12792. doi: 10.7554/eLife.12792 PMID:26836308. [Abstract]

Bhatt S, Stender JD, Joshi S, Wu G and Katzenellenbogen BS. OCT-4: A Novel Estrogen Receptor-α Collaborator That Promotes Tamoxifen Resistance in Breast Cancer Cells. Oncogene 2016, Apr 11. doi: 10.1038/onc.2016.105. [Epub ahead of print]. PMID: 27065334. [Abstract]

Zhao Y, Chen Y, Bagchi MK, Taylor RN, Katzenellenbogen JA, Katzenellenbogen BS. Multiple Beneficial Roles of Repressor of Estrogen Receptor Activity (REA) in Suppressing the Progression of Endometriosis. Endocrinology 157(2):900-12, 2016. Feb. doi: 10.1210/en.2015-1324. Epub 2015 Dec 14. PMID: 26653759. [Abstract]

Boonmuen N, Gong P, Ali Z, Chittiboyina AG, Khan I, Doerge DR, Helferich WG, Carlson KE, Martin T, Piyachaturawat P, Katzenellenbogen JA, and Katzenellenbogen BS. Licorice Root Components in Dietary Supplements are Selective Estrogen Receptor Modulators with a Spectrum of Estrogenic and Anti-Estrogenic Activities. Steroids 105:42-9, 2016 Jan. doi: 10.1002/mnfr.201500445. PMID: 26631549. [Abstract]

Zhao, Y., Gong, P., Chen, Y., Nwachukwu, J.C., Srinivasan, S., Ko, C.M., Bagchi, M.K., Taylor, R.N., Korach, K.S., Nettles, K.W., Katzenellenbogen, J.A., and Katzenellenbogen, B.S. Dual Suppression of Estrogenic and Inflammatory Activities for Targeting of Endometriosis. Sci Transl Med. 7(271):271ra9, 2015.PMID: 25609169. [Abstract]

Gong, P., Madak-Erdoğan, Z., Li, J., Cheng, J., Greenlief, C.M., Helferich, W.G., Katzenellenbogen, J.A., and Katzenellenbogen, B.S. Transcriptomic Analysis identifies gene networks regulated by ERα and ERβ that control distinct effects of different botanical estrogens. Nuclear Receptor Signaling. 2014, 12:e001. doi:10.162/nrs.12001. PMID: 25363786 PMCID: PMC4193135. [Abstract]

Bergamaschi, A., Madak-Erdoğan, Z., Kim, Y.J., Choi, Y.L., Lu, H. and Katzenellenbogen, B.S. The Forkhead Transcription Factor FOXM1 Promotes Endocrine Resistance and Invasiveness in Estrogen Receptor-Positive Breast Cancer by Expansion of Stem-like Cancer Cells. Breast Cancer Research. 16:436, 2014. PMID: 25213081. [Abstract]

Madak-Erdogan, Z., Ventrella, R., Petry, L., and Katzenellenbogen B.S. Novel roles for ERK5 and Cofilin as Critical Mediators Linking Estrogen Receptor α-Driven Transcription, Actin Reorganization and Invasiveness in Breast Cancer. Mol Cancer Res. 12:714-727, 2014. PMID: 24505128. [Abstract]

Holton, S.E., Bergamaschi, A., Katzenellenbogen, B.S. and Bhargava, R. Integration of molecular profiling and chemical imaging to elucidate fibroblast-microenvironment impact on cancer cell phenotype and endocrine resistance in breast cancer. PLoS One. 9(5):e96878, 2014. PMID: 24816718. [Abstract]

Recent Publications

Fébrissy, C., Adlanmerini, M., Péqueux, C., Boudou, F., Buscato, M., Gargaros, A., Gilardi-Bresson, S., Boriak, K., Laurell, H., Fontaine, C., Katzenellenbogen, B. S., Katzenellenbogen, J. A., Guillermet-Guibert, J., Arnal, J. F., Metivier, R., & Lenfant, F. (2024). Reprogramming of endothelial gene expression by tamoxifen inhibits angiogenesis and ERα-negative tumor growth. Theranostics, 14(1), 249-264. https://doi.org/10.7150/thno.87306

Irani, S., Tan, W., Li, Q., Toy, W., Jones, C., Gadiya, M., Marra, A., Katzenellenbogen, J. A., Carlson, K. E., Katzenellenbogen, B. S., Karimi, M., Rajappachetty, R. S., Del Priore, I. S., Reis-Filho, J. S., Shen, Y., & Chandarlapaty, S. (2024). Somatic estrogen receptor α mutations that induce dimerization promote receptor activity and breast cancer proliferation. Journal of Clinical Investigation, 134(1 January), Article e163242. https://doi.org/10.1172/JCI163242

Guillen, V. S., Ziegler, Y., Gopinath, C., Kumar, S., Dey, P., Plotner, B. N., Dawson, N. Z., Kim, S. H., Katzenellenbogen, J. A., & Katzenellenbogen, B. S. (2023). Effective combination treatments for breast cancer inhibition by FOXM1 inhibitors with other targeted cancer drugs. Breast Cancer Research and Treatment, 198(3), 607-621. https://doi.org/10.1007/s10549-023-06878-3

Katzenellenbogen, J. A., Tiwari-Woodruff, S. K., Kim, S. H., & Katzenellenbogen, B. (2023). Estrogen receptor beta ligands for the prevention and treatment of multiple sclerosis (MS) and other demyelinating, inflammatory and neurodegenerative diseases. (U.S. Patent No. 11673866).

Katzenellenbogen, B. S., Guillen, V. S., & Katzenellenbogen, J. A. (2023). Targeting the oncogenic transcription factor FOXM1 to improve outcomes in all subtypes of breast cancer. Breast Cancer Research, 25(1), Article 76. https://doi.org/10.1186/s13058-023-01675-8

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