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

Our laboratory studies the effects of anticancer drugs and ionizing radiation on the mammalian cell cycle, including the role of cell cycle checkpoints in tumor cell susceptibility to treatment and damage-induced perturbations of the cell cycle, especially mitosis; and cellular and molecular mechanisms of mitotic catastrophe (abnormal mitosis that leads to eventual cell death or senescence), which is induced by DNA-damaging agents and by damage-inducible cyclin-dependent kinase inhibitor proteins in normal and tumor cells. In recent years, the main focus of our studies was on the role of cell cycle regulating kinase CDK4/6 and transcription-regulating kinases CDK7 and CDK8/19 and their interactive proteins in breast and ovarian cancers and age-related diseases (such as Alzheimer’s disease and neuroinflammation).

These studies combine methods of cell biology, pharmacology, experimental oncology in animal models and molecular genetics with advanced fluorescence and live video microscopy and flow cytometry techniques. Elucidation of the mechanisms of cell cycle perturbation, stress-induced transcription, treatment-induced adaptation and especially drug resistance should help in discovery of new drug targets, improving the efficacy of existing anticancer agents, understanding the basic mechanisms of cancer control and ultimately developing new agents against cancer and age-related diseases.

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Publications

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.

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