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Timothy Eubank, Ph.D.

   Dr. Eubank’s research focus is the role of myeloid cells/mononuclear phagocytes in tumor growth, angiogenesis, and metastases as well as monocyte and macrophage HIF (hypoxia inducible factor) biology. His group reported that monocytes and macrophages can be “re-educated” in solid tumors to become anti-angiogenic and were the first to report that GM-CSF stimulates tumor macrophages to overexpress the soluble form of VEGFR-1, which sequesters tumor-produced VEGF from bioactivity, and become more “M1”-like depending on local tumor microenvironment. Further, they were the first to report the disparate functions of HIF-1α and HIF-2α in tumor-associated macrophages and that a hypoxia inducible factor (HIF-2α) can be anti-angiogenic. In more recent and current work, they have discovered different regulatory roles of epigenetic machinery for HIF-1α and HIF-2α and how manipulating the prolyl hydroxylases can augment previously hypermethylated tumor suppressor genes. Dr. Eubank has publications in Immunity, Blood, Cancer Research, and J of Immunology pertaining to our work in breast cancer. Further, he received the K99/R00 Pathway to Independence Award from the NCI for his work with macrophage regulation of breast cancer growth and angiogenesis. His expertise in HIF biology has led to two patent applications submitted by OSU and licensed by Akebia Therapeutics using a novel small molecule compound to stabilize HIF-2α in treatment of solid tumors.

The sphere of interest:

   Dr. Eubank’s current interests include the continuous investigation into the role of novel macrophage subtypes which augment tumor progression, angiogenesis and metastases. One such mechanism of interaction between tumor cells and the microenvironment is extracellular vesicles (EVs) released by macrophages and taken-up by the tumor cells. These EVs regulate tumor cell gene profiles and function leading to different outcomes. I am also interested in how the different macrophage HIFs regulate degree of success of chemotherapy compounds in mouse models of breast cancer. Finally, we are initiating new studies investigating the role of ion channel disruption on cells and tumor initiation and progression.

Selected publications:

- Driesschaert B, Bobko AA, Eubank TD, Samouilov A, Khramtsov VV, Zweier JL. Poly-arginine conjugated triarylmethyl radical as intracellular spin label. Bioorg Med Chem Lett. 2016 Apr 1;26(7):1742-4. doi: 10.1016/j.bmcl.2016.02.048.

- Dhimitruka I, Eubank TD, Gross AC, Khramtsov VV. New class of 8-aryl-7-deazaguanine cell permeable fluorescent probes. Bioorg Med Chem Lett. 2015 Oct 15;25(20):4593-6. doi: 10.1016/j.bmcl.2015.08.054.

- Nelson MT, Short A, Cole SL, Gross AC, Winter J, Eubank TD, Lannutti JJ. Preferential, enhanced breast cancer cell migration on biomimetic electrospun nanofiber 'cell highways'. BMC Cancer. 2014 Nov 10;14:825. doi: 10.1186/1471-2407-14-825.

- Samouilov A, Efimova OV, Bobko AA, Sun Z, Petryakov S, Eubank TD, Trofimov DG, Kirilyuk IA, Grigor'ev IA, Takahashi W, Zweier JL, Khramtsov VV. In vivo proton-electron double-resonance imaging of extracellular tumor pH using an advanced nitroxide probe. Anal Chem. 2014;86(2):1045-52.

- Chen D, Bobko AA, Gross AC, Evans R, Marsh CB, Khramtsov VV, Eubank TD*, Friedman A*. Involvement of tumor macrophage HIFs in chemotherapy effectiveness: mathematical modeling of oxygen, pH, and glutathione. PLoS One. 2014;9(10):e107511.

- Forget MA, Voorhees JL, Cole SL, Dakhlallah D, Patterson IL, Gross AC, Moldovan L, Mo X, Evans R, Marsh CB, Eubank TD. Macrophage colony-stimulating factor augments Tie2-expressing monocyte differentiation, angiogenic function, and recruitment in a mouse model of breast cancer. PLoS One. 2014;9(6):e98623.

- Dhimitruka I, Bobko AA, Eubank TD, Komarov DA, Khramtsov VV. Phosphonated trityl probes for concurrent in vivo tissue oxygen and pH monitoring using electron paramagnetic resonance-based techniques. J Am Chem Soc. 2013;135(15):5904-10.

- Roda JM, Wang Y, Sumner LA, Phillips GS, Marsh CB, Eubank TD. Stabilization of HIF-2alpha induces sVEGFR-1 production from tumor-associated macrophages and decreases tumor growth in a murine melanoma model. J Immunol. 2012;189(6):3168-77.

- Bobko AA#, Eubank TD#, Voorhees JL, Efimova OV, Kirilyuk IA, Petryakov S, Trofimiov DG, Marsh CB, Zweier JL, Grigor'ev IA, Samouilov A, Khramtsov VV. In vivo monitoring of pH, redox status, and glutathione using L-band EPR for assessment of therapeutic effectiveness in solid tumors. Magn Reson Med. 2012;67(6):1827-36.

- Eubank TD, Roda JM, Liu H, O'Neil T, Marsh CB. Opposing roles for HIF-1alpha and HIF-2alpha in the regulation of angiogenesis by mononuclear phagocytes. Blood. 2011;117(1):323-32.

- Eubank TD, Roberts RD, Khan M, Curry JM, Nuovo GJ, Kuppusamy P, Marsh CB. Granulocyte macrophage colony-stimulating factor inhibits breast cancer growth and metastasis by invoking an anti-angiogenic program in tumor-educated macrophages. Cancer Res. 2009;69(5):2133-40.

- Curry JM#, Eubank TD#, Roberts RD, Wang Y, Pore N, Maity A, Marsh CB. M-CSF signals through the MAPK/ERK pathway via Sp1 to induce VEGF production and induces angiogenesis in vivo. PLoS One. 2008;3(10):e3405.

- Eubank TD, Roberts R, Galloway M, Wang Y, Cohn DE, Marsh CB. GM-CSF induces expression of soluble VEGF receptor-1 from human monocytes and inhibits angiogenesis in mice. Immunity. 2004;21(6):831-42.

- Eubank TD, Galloway M, Montague CM, Waldman WJ, Marsh CB. M-CSF induces vascular endothelial growth factor production and angiogenic activity from human monocytes. J Immunol. 2003;171(5):2637-43