To contact Dr. Yoon:
1670 University Blvd.
Phone: Office (205) 934-6761; Lab (205) 934-6768; Tumorgraft Facility (205) 934-6760
Fax: (205) 934-8240
- Molecular and cellular mechanisms of cancer metastasis
- The role of cell adhesion molecules in tumor progression and metastasis
- Novel therapeutic interventions to prevent metastatic progression
- Pancreatic cancer
- Primary human tumor xenograft models of solid tumors
The primary cause of death for patients with solid tumors is the development of metastatic disease. For many tumor types once metastasis has occurred few, if any, treatments are effective. Our primary research focus is to understand mechanisms underlying the metastasis of neuroblastoma, a major cause of mortality in high-risk neuroblastoma patients. We propose that studies with neuroblastoma will serve as model systems for mechanisms of metastasis of other types of solid tumors. Our data indicate that one of the cell adhesion molecules, Intercellular Adhesion Molecule-2 (ICAM-2), functions as a key regulator of metastatic progression in neuroblastoma. Importantly, immunostaining of a primary neuroblastoma tissue microarray corroborated this observation in that ICAM-2 expression in primary tumor cells was associated with stage of disease or tumor cell morphology of primary neuroblastoma cells recognized to have limited metastatic potential and favorable clinical features. Our immediate goal is to define the molecular mechanisms by which ICAM-2 suppresses the metastatic progression of neuroblastoma cells. Ultimately, the long-term goal of our lab is to identify novel pathways involved in metastatic solid tumor progression that might be exploited therapeutically.
We also are developing a panel of mouse models of pancreatic cancer using primary human tumor specimens implanted subcutaneously into immune compromised mice. Primary human tumor xenograft models established directly from human tumors most accurately reflect the genetic and molecular characteristics of specific human tumors. These molecularly characterized models will serve as valuable tools for cancer-type specific drug testing and biomarker discovery.
The central principle of our research is a multidisciplinary and integrative approach to the analysis of molecular, mechanistic characteristics of cancer metastasis, using a combination of molecular biology, animal models and in vitro / in vivo imaging techniques. We use a wide range of techniques to achieve our research goals. These techniques include but are not limited to the following: RT-PCR, RT Q-PCR, immunoblots, co-immunoprecipitations, flow cytometry, immunohistochemistry, animal imaging, drug studies, molecular cloning, and small animal surgery.
Yoon KJ, Danks MK. Cell adhesion molecules as targets for therapy of neuroblastoma. Cancer Biol Ther 8(4):306-311, 2009. PMID: 19197150.
Yoon KJ, Phelps DA, Bush RA, Remack JS, Billups CA, Khoury JD. ICAM-2 expression mediates a membrane-actin link, confers a nonmetastatic phenotype and reflects favorable tumor stage or histology in neuroblastoma. PLoS One 3(11):e3629, 2008. PMID: 18978946.
Wagner LM, McLendon RE, Yoon KJ, Weiss BD, Billups CA, Danks MK. Targeting methylguanine-DNA methyltransferase in the treatment of neuroblastoma. Clin Cancer Res 15;13(18 Pt 1): 5418-5425, 2007. PMID: 17875772.
Danks MK, Yoon KJ, Bush RA, Remack JS, Wierdl M, Tsurkan L, Kim SU, Garcia E, Metz MZ, Najbauer J, Potter PM, Aboody KS. Tumor-targeted enzyme/prodrug therapy mediates long-term disease-free survival of mice bearing disseminated neuroblastoma. Cancer Res 67(1): 22-25, 2007. PMID: 17210679.
Yoon KJ, Qi J, Remack JS, Virga KG, Hatfield MJ, Potter PM, Lee RE, Danks MK. Development of an etoposide prodrug for dual prodrug-enzyme antitumor therapy. Mol Cancer Ther 5(6): 1577-1584, 2006. PMID: 16818517.
Yoon KJ, Danks MK, Ragsdale ST, Valentine MB, Valentine VA. Translocations of 17q21 approximately qter in neuroblastoma cell lines infrequently include the topoisomerase IIalpha gene. Cancer Genet Cytogenet 167(1):92-94, 2006. PMID: 16682295.
Yoon KJ, Potter PM, Danks MK. Development of prodrugs for enzyme-mediated, tumor-selective therapy. Curr Med Chem Anticancer Agents 5(2):107-113, 2005. PMID: 15777218.
Yoon KJ, Hyatt JL, Morton CL, Lee RE, Potter PM, Danks MK. Characterization of inhibitors of specific carboxylesterases: development of carboxylesterase inhibitors for translational application. Mol Cancer Ther 3(8):903-909, 2004. PMID: 15299073.
Yoon KJ, Krull EJ, Morton CL, Bornmann WG, Lee RE, Potter PM, Danks MK. Activation of a camptothecin prodrug by specific carboxylesterases as predicted by quantitative structure-activity relationship and molecular docking studies. Mol Cancer Ther 2(11):1171-1181, 2003. PMID: 14617791.