Zhaozhong Han, Ph.D.
Vanderbilt-Ingram Cancer Center Radiation Oncology
22nd at Pierce Avenue, B1034
Nashville, TN 37232-5671
Vanderbilt Department of Radiation Oncology
Medical Center North, E1220
Nashville, TN 37232-5671
molecular cancer pathology, metastasis, cell migration and invasion, tumor microenvironment, angiogenesis, DNA damage repair, Biomarker discovery and development, Phage display, Protein engineering, Cellular and molecular imaging of cancer, Targeting drug delivery, Therapeutic peptide or protein
The past decades have witnessed the dramatic development in molecular targeted therapy for cancers. Treatments approved for targeting molecular events within cancers include those modulating cell survival, proliferation, invasion, metastasis and angiogenesis. However, patients respond to the molecular targeted therapy with a broad spectrum of efficacy because of the biological heterogeneity of cancers. It is increasingly important to understand systematically how cancer cells respond to the treatment so that the tumor responsiveness can be monitored and the personalized treatment can be justified in time. This lab is devoted to investigate and develop such treatment-inducible molecular signatures within tumors for cancer imaging, drug delivery and drug discovery. Currently, we are interested in how cancers respond to tyrosine kinase inhibitors (TKIs) and ionizing radiation (IR). Ongoing projects in this lab include: 1) biomarker discovery. We are using phage-displayed peptides, engineered protein scaffolds and antibody fragments to profile the TKIs/IR-induced changes in the plasma membrane proteome of cancer cells; 2) molecular and cellular imaging to assess tumor response to TKIs/IR treatment; 3) tumor-targeted drug delivery; 4) biological function of tax-interacting protein 1 (TIP-1) within cancer cells, especially its roles in cancer cell response to chemotherapy and radiotherapy, local invasion and long distance metastasis, and angiogenesis. The long term goal is to develop tools and rationales to personalize molecular targeted therapy for cancer patients.
- Han, M, Wang, H, Zhang, HT, Han, Z Expression of Tax-interacting protein 1 (TIP-1) facilitates angiogenesis and tumor formation of human glioblastoma cells in nude mice. Cancer Lett, 328(1), 55-64, 2013.
- Wang H, Han M, Whetsell W, Wang J, Rich J, Hallahan DE, Han Z "Tax-interacting protein 1 coordinates the spatiotemporal activation of Rho GTPases and regulates the infiltrative growth of human glioblastoma." Oncogene, (in press), 2013.
- Han, M, Wang, H, Zhang, HT, Han, Z Expression of TIP-1 confers radioresistance of malignant glioma cells. PLoS One, 7(9), e45402, 2012.
- Wang H, Han M, Han Z "Recombinant peptides for non-invasive imaging assessment of tumor response to ionizing radiation and tyrosine kinase inhibitors." Ionizing Radiation, p495-510, 2012.
- Han, M, Wang, H, Zhang, HT, Han, Z The PDZ protein TIP-1 facilitates cell migration and pulmonary metastasis of human invasive breast cancer cells in athymic mice. Biochem Biophys Res Commun, 422(1), 139-45, 2012.
- Lowery, A, Han, Z Assessment of tumor response to tyrosine kinase inhibitors. Front Biosci, 171996-2007, 2011.
- Lowery, A, Onishko, H, Hallahan, DE, Han, Z Tumor-targeted delivery of liposome-encapsulated doxorubicin by use of a peptide that selectively binds to irradiated tumors. J Control Release, 150(1), 117-24, 2011.
- Hariri, G, Yan, H, Wang, H, Han, Z, Hallahan, DE Radiation-guided drug delivery to mouse models of lung cancer. Clin Cancer Res, 16(20), 4968-77, 2010.
- Wang, H, Yan, H, Fu, A, Han, M, Hallahan, D, Han, Z TIP-1 Translocation onto the Cell Plasma Membrane Is a Molecular Biomarker of Tumor Response to Ionizing Radiation. PLoS One, 5(8), 2010.
- Jaboin, JJ, Han, Z, Hallahan, DE Using in vivo biopanning for the development of radiation-guided drug delivery systems. Methods Mol Biol, 542285-300, 2009.
- Han, Z, Fu, A, Wang, H, Diaz, R, Geng, L, Onishko, H, Hallahan, DE Noninvasive assessment of cancer response to therapy. Nat Med, 14(3), 343-9, 2008.
- Hariri, G, Zhang, Y, Fu, A, Han, Z, Brechbiel, M, Tantawy, MN, Peterson, TE, Mernaugh, R, Hallahan, D Radiation-guided P-selectin antibody targeted to lung cancer. Ann Biomed Eng, 36(5), 821-30, 2008.
- Han, Z, Wang, H, Hallahan, DE Radiation-guided gene therapy of cancer. Technol Cancer Res Treat, 5(4), 437-44, 2006.
- Han ZZ, Hariri G, Hallahan DE "Radiotherapy and tumor-targeted drug delivery." “Multimodal Concepts for Integration of Cytotoxic Drugs and Radiation Therapy”. Edited by Brown JM, Mehta MP and Nieder C. , Springer Press. 151-162, 2006.
- Karatan E, Han ZZ, Kay BK "Molecular Display Technologies." In “Encyclopedia of Molecular Cell Biology and Molecular Medicine”, Wiley(8), 8:409-420, 2005.
- Han ZZ, Karatan E, and Kay BK "Protein Interaction Networks." in “Phage Display in Biotechnology and Drug Discovery”. Edited by Sidhu SS, CRC Press, Baton Rouge, FL. 321-346, 2005.
- Han, Z, Karatan, E, Scholle, MD, McCafferty, J, Kay, BK Accelerated screening of phage-display output with alkaline phosphatase fusions. Comb Chem High Throughput Screen, 7(1), 55-62, 2004.
- Kwon, Y, Han, Z, Karatan, E, Mrksich, M, Kay, BK Antibody arrays prepared by cutinase-mediated immobilization on self-assembled monolayers. Anal Chem, 76(19), 5713-20, 2004.
- Han, Z, Simpson, JT, Fivash, MJ, Fisher, R, Mori, T Identification and characterization of peptides that bind to cyanovirin-N, a potent human immunodeficiency virus-inactivating protein. Peptides, 25(4), 551-61, 2004.
- Karatan, E, Merguerian, M, Han, Z, Scholle, MD, Koide, S, Kay, BK Molecular recognition properties of FN3 monobodies that bind the Src SH3 domain. Chem Biol, 11(6), 835-44, 2004.
- Wasiak, S, Denisov, AY, Han, Z, Leventis, PA, de Heuvel, E, Boulianne, GL, Kay, BK, Gehring, K, McPherson, PS Characterization of a gamma-adaptin ear-binding motif in enthoprotin. FEBS Lett, 555(3), 437-42, 2003.
- Han, Z, Xiong, C, Mori, T, Boyd, MR Discovery of a stable dimeric mutant of cyanovirin-N (CV-N) from a T7 phage-displayed CV-N mutant library. Biochem Biophys Res Commun, 292(4), 1036-43, 2002.
- Mori, T, Barrientos, LG, Han, Z, Gronenborn, AM, Turpin, JA, Boyd, MR Functional homologs of cyanovirin-N amenable to mass production in prokaryotic and eukaryotic hosts. Protein Expr Purif, 26(1), 42-9, 2002.
- Barrientos, LG, Louis, JM, Botos, I, Mori, T, Han, Z, O''Keefe, BR, Boyd, MR, Wlodawer, A, Gronenborn, AM The domain-swapped dimer of cyanovirin-N is in a metastable folded state: reconciliation of X-ray and NMR structures. Structure, 10(5), 673-86, 2002.