Formally trained in biomedical pharmacology, I have extensive training and expertise in cancer biology with an emphasis on cancer metabolism. A focus of my research is to understand the role of fatty acid synthases (FASN), a key enzyme for de novo lipogenesis, in colorectal cancer. My published and ongoing work has revealed the critical importance of FASN in the regulation of signaling pathways that contribute to the metastatic phenotype in colorectal cancer. My current studies investigate how FASN regulates colorectal cancer cell survival and metastasis. I use the combination of metabolomics, proteopmics, and molecular biology techniques and a novel FASN inhibitor, which is currently in Phase I clinical trial (3V-Bioscience), to elucide the effect of FASN inhibition of growth, survival and metastasis in primary CRC cells and patient-derived xenografts (PDX) models.

Positions and Honors

Positions and Employment

1993-2003       Laboratory technologist, Aksay Central Hospital, Aksay, Rostov Region, Russia

2004-2005       Laboratory technician, University of Kentucky, Department of Biology, Lexington, KY

2015-present   Research Assistant Professor, University of Kentucky, Department of Toxicology and Cancer Biology, Lexington, KY

Other Experience and Professional Memberships

2008-present   Associate Member, American Association for Cancer Research

2008-present   Woman in Cancer Research

2011-present   American Gastroenterological Association

2011-2014       Postdoctoral Advisory Committee, College of Medicine, University of Kentucky

Honors

2007                26th Annual UK symposium in Reproductive Sciences, Poster Competition, 3rd place

2008                27th Annual UK Symposium in Reproductive Sciences, Poster Competition, 1st place

2008                Commonwealth Research Award

2008                Graduate School Travel Award

2009                28th Annual UK Symposium in Reproductive Sciences, Poster Competition, 1st place

2011                Markey Cancer Center Research Day, Poster Competition, 2nd place

2012               Oral Presentation, Markey Cancer Center Research Day

2012               Oral Presentation, Digestive Disease Week, San Diego, CA

2013                6th Annual Postdoctoral Poster Session, the UK College of Medicine, 2nd place

2014                Seahorse Bioscience Travel Award

2015                Markey Cancer Center Research Day, Poster Competition, 1st place

2013-2015      T32 Interdisciplinary Research Training in Cancer Biology grant

Contributions to science

1.   My current research interest is to elucidate the role of de novo lipogenesis in colorectal cancer (CRC) progression. Fatty Acid Synthase (FASN), a key enzyme of de novo lipogenesis, has been investigated as a potential target for cancer therapy. Using tissue microarray analysis, we demonstrated that an increased expression of FASN is associated with increased CRC stage. Our studies are the first to demonstrate the importance of FASN upregulation in the development of CRC metastasis. We showed that shRNA-mediated inhibition of FASN significantly reduced lung and hepatic metastases in nude mice and inhibited angiogenesis in an orthotopic CRC mouse model. Furthermore, our recent work suggests that overexpression of FASN promotes a metabolic switch that fuels bioenergetics pathways to enhance cancer cell survival and support metastasis, particularly, under energy stress conditions. More importantly, I showed that, even in the presence of exogenous fatty acids, CRC cells preferentially oxidize endogenous fatty acids synthesized by FASN, thus providing further evidence of the crucial role of de novo lipid synthesis in CRC progression. My studies on FASN significantly contributed to the understanding of the role of de novo lipid synthesis in CRC progression and have been cited in multiple publications.

1. Zaytseva YY, Rychahou PG, Gulhati P, Elliott VA, Mustain WC, O'Connor K, Morris AJ, Sunkara M, Weiss HL, Lee EY, Evers BM. Inhibition of fatty acid synthase attenuates CD44-associated signaling and reduces metastasis in colorectal cancer. Cancer Res 2012, 72:1504-1517. PMCID: PMC3596828
2. Zaytseva YY, Elliott VA, Rychahou PG, Mustain WC, Kim JT, Valentino J, Gao T, O’Connor KL, Neltner JM, Weiss HL, and Evers BM. Tumor-specific expression of fatty acid synthase regulates activity of endothelial cells and promotes angiogenesis in colorectal cancer. Carcinogenesis 2014, 35:1341-1351. PMCID: PMC4043242
3. Zaytseva YY, Harris JW, Mitov MI, Kim JT, Butterfield DA, Lee EY, Weiss HL, Gao T, Evers BM. Increased expression of fatty acid synthase provides a survival advantage to colorectal cancer cells via upregulation of cellular respiration. Oncotarget 6:18891-18904, 2015.

2.   As a graduate student, I studied the functional significance of endogenous activation of Peroxisome Proliferator Activated Receptor gamma (PPARγ) in breast cancer. I showed that PPARγ is overexpressed in breast cancer cell lines and that shRNA-mediated knockdown of this receptor leads to a decrease in proliferation and an increase in apoptosis, suggesting that PPARγ plays an important role in malignant transformation. Additional studies demonstrated that pharmacologic inhibition of PPARγ with T007907, a selective PPARγ antagonist, significantly reduced cellular proliferation, migration and invasion via PPARγ-dependent and independent mechanisms. We also showed that PPARγ1 ligands, such as rosiglitazone, can transactivate estrogen receptor alpha and induce proliferation in breast cancer cells. All together our findings warranted further investigations regarding the role of PPARγ1 in breast cancer and the use of PPARγ1 ligands, such as thiazolidinediones, in patients who are predisposed or already diagnosed with breast cancer.

1. Talbert DR, Allred CD, Zaytseva YY, Kilgore MW. Transactivation of ERalpha by Rosiglitazone induces proliferation in breast cancer cells. Breast Cancer Res Treat 108:23-33, 2008.
2. Zaytseva YY, Wang X, Southard RC, Wallis NK, Kilgore MW. Down-regulation of PPARgamma1 suppresses cell growth and induces apoptosis in MCF-7 breast cancer cells. Mol Cancer 7:90, 2008. PMCID: PMC2614423
3. Zaytseva YY, Wallis NK, Southard RC, Kilgore MW. The PPARgamma antagonist T0070907 suppresses breast cancer cell proliferation and motility via both PPARgamma-dependent and -independent mechanisms. Anticancer Res 31:813-823, 2011.

3.   In additional to research described above, my work significantly contributed to a better understanding the role of the PI3K/Akt/mTOR pathway in progression of CRC and in neuroendocrine tumors. I am a first author of the review on mTOR inhibitors cited in more that 80 publications and a co-author on several publications elucidating the consequences of pharmacologic inhibition of PI3K/Akt/mTOR and RAS/MAPK pathways. Our studies have demonstrated that CRCs harboring coexistent KRAS and PIK3CA mutations are partially sensitive to either rapamycin or sorafenib monotherapy, but highly sensitive to the drugs in combination. Furthermore, we showed that treatments with small interfering RNA to both PIK3CA and KRAS offer an effective therapy against CRC cells with coexisting mutations in both pathways. Additional studies showed that dual inhibition of the PI3K and RAS/MEK pathways results in an enhanced therapeutic benefit compared with either agent alone in neuroendocrine tumors. Collectively, our data strongly support combination strategies as an effective treatment for CRCs and NETs.