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- Eugenia Broude
Faculty and Staff
Eugenia Broude, Ph.D.
|Department:||Drug Discovery & Biomedical Sciences (DDBS)
College of Pharmacy
|Office:||College of Pharmacy
715 Sumter Street - CLS 713C
Columbia, SC 29208
Ph.D. Biochemistry / Molecular Biology, Ukrainian Academy of Sciences, 1990
M.S. Kiev State University, Ukraine, 1983
Postdoctoral Fellowship, Molecular Biology, Neuroscience (1991-1994)
National Institute of Child Health & Human Development, Bethesda, MD
Eugenia Broude, Ph.D., is an Associate Professor in the Department of Drug Discovery & Biomedical Sciences (DDBS) at the University of South Carolina College of Pharmacy. She received her Ph.D. in Biochemistry/Molecular Biology in 1990 from the Ukrainian Academy of Sciences. Following her doctoral studies, she completed a postdoctoral fellowship in Molecular Biology and Neuroscience at the National Institute of Child Health & Human Development. Dr. Broude's research focuses on the effects of anticancer drugs on the mammalian cell cycle in order to aid in discovery of new drug targets and improve the efficacy of current cancer treatments.
- Role of transcription-regulating kinases in cancer
- Breast cancer targeted therapy
- Effects of anticancer drugs
- Tumor microenvironment and metastasis
Our laboratory investigates cancer therapeutics using a combination of techniques from cell biology, pharmacology, experimental oncology in animal models, and molecular genetics, along with advanced fluorescence and live video microscopy and flow cytometry. Our discovery that chemotherapeutic drugs induce senescence in tumor cells started a line of work that eventually led to the identification of transcription-regulating Mediator kinase (CDK8/19) as a druggable mediator of tumor-promoting activities of damaged and senescent cells and the development of the first selective Mediator kinase inhibitors to reach clinical trials.
Currently, our lab's research focuses on understanding the role of Mediator kinase in female cancers, primarily breast and ovarian cancer, as well as some other cancers, including pediatric osteosarcoma. We are investigating the effects of CDK8/19 inhibitors on cancer growth, drug resistance, and metastasis. Our studies have identified CDK8/19 as a key player in the HER2 pathway and a novel druggable mediator of the mitogenic effects of estrogen in ER-positive breast cancers. This finding has provided the basis for the first-in-class clinical trial of a Mediator kinase inhibitor. We also found that CDK8/19 inhibitors suppress or delay the development of resistance to different therapeutic modalities in triple-negative breast cancer, a major unmet medical need. We have also discovered that CDK8/19 inhibition suppresses in-vivo invasion and the growth of metastatic tumors in various cancers. Through its broad role in transcriptional reprogramming, the Mediator kinase is involved but in many pathological processes aside from cancer, and we are now investigating the effects of CDK8/19 inhibitors on inflammation and on some of the key aspects of Alzheimer’s disease.
Sharko AC, Lim CU, McDermott MSJ, Hennes C, Philavong KP, Aiken T, et al. The Inhibition of CDK8/19 Mediator Kinases Prevents the Development of Resistance to EGFR-Targeting Drugs. Cells. 2021;10(1).1.
Alam A, Kowal J, Broude E, Roninson I, Locher KP. Structural insight into substrate and inhibitor discrimination by human P-glycoprotein. Science. 2019;363(6428):753-6.
McDermott MSJ, Sharko AC, Munie J, Kassler S, Melendez T, Lim CU, et al. CDK7 Inhibition is Effective in all the Subtypes of Breast Cancer: Determinants of Response and Synergy with EGFR Inhibition. Cells. 2020;9(3).
Alam A, Küng R, Kowal J, McLeod RA, Tremp N, Broude EV, et al. Structure of a zosuquidar and UIC2-bound human-mouse chimeric ABCB1. Proc Natl Acad Sci U S A. 2018;115(9):E1973-e82.
McDermott MS, Chumanevich AA, Lim CU, Liang J, Chen M, Altilia S, et al. Inhibition of CDK8 mediator kinase suppresses estrogen dependent transcription and the growth of estrogen receptor positive breast cancer. Oncotarget. 2017;8(8):12558-75.
Liang J, Chen M, Hughes D, Chumanevich AA, Altilia S, Kaza V, et al. CDK8 Selectively Promotes the Growth of Colon Cancer Metastases in the Liver by Regulating Gene Expression of TIMP3 and Matrix Metalloproteinases. Cancer Res. 2018;78(23):6594-606.
Gonzalez RE, Lim CU, Cole K, Bianchini CH, Schools GP, Davis BE, et al. Effects of conditional depletion of topoisomerase II on cell cycle progression in mammalian cells. Cell Cycle. 2011;10(20):3505-14.
Porter DC, Farmaki E, Altilia S, Schools GP, West DK, Chen M, et al. Cyclin-dependent kinase 8 mediates chemotherapy-induced tumor-promoting paracrine activities. Proc Natl Acad Sci U S A. 2012;109(34):13799-804.
Broude EV, Demidenko ZN, Vivo C, Swift ME, Davis BM, Blagosklonny MV, et al. p21 (CDKN1A) is a negative regulator of p53 stability. Cell Cycle. 2007;6(12):1468-71.
Broude EV, Swift ME, Vivo C, Chang BD, Davis BM, Kalurupalle S, et al. p21(Waf1/Cip1/Sdi1) mediates retinoblastoma protein degradation. Oncogene. 2007;26(48):6954-8.