My lab studies the molecular biology of cancer stem cells (CSC) with the goals of advancing understanding of their biology and developing better diagnostic and therapeutic strategies. CSCs are the hypothesized drivers of rapid brain cancer recurrence in patients, exhibit stem cell-like properties of self-renewal and multipotent differentiation, and initiate tumors with high efficiency in a xenograft model. Using human glioblastoma cancer stem cell (GSC) lines and animal xenograft models, we are studying tumorigenic signaling/developmental pathways, oncogenic/tumor suppressor microRNAs, de novo screens for GSC-specific markers, and differential mechanisms of GSC invasiveness to identify new GBM clinical biomarkers. We also test novel therapies in vitro and in vivo, including novel cancer-targeting analogs and immune-specific agents for translation to clinical trials in GBM and metastatic cancers to brain.
John S. Kuo, MD, PhD
Box 8660, K3/803 Clinical Science Center
600 Highland Avenue
Madison, WI 53792
608.261.1877 (L); 608.262.7303 (Mary Benkaddour – admin assistant)
MD, Harvard Medical School
PhD, Massachusetts Institute of Technology
Molecular biology of cancer stem cells
Zhang RR, Schroeder AB, Grudzinski JJ, Rosenthal EL, Warram JM, Pinchuk AN, Eliceiri KW*, Kuo JS*, Weichert JP* “Beyond the margins: Real time detection of cancer using targeted fluorophores.” (*Co-senior authors), Nature Reviews Clinical Oncology (published online January 17, 2017).
Pointer KB, Clark PA, Eliceiri KW, Robertson G, Kuo JS “Administration of non-torsadogenic human Ether-à-go-go Related Gene (hERG) inhibitors is associated with better survival for high hERG-expressing glioblastoma patients.” Clinical Cancer Research 23 (1): 73-80 (published online September 15, 2016) *highlighted article, also paired with CCR Translations commentary.
Clark PA, Bhattacharya S, Elmayan A, Soesiawati RD, Thuro BA, Yan M, van Ginkel PR, Polans AS, Kuo JS “Resveratrol targets glioblastoma and glioblastoma stem-like cells via widespread anti-tumorigenic mechanisms involving AKT and p53 activation.” Journal of Neurosurgery (published online July 15, 2016).
Clark PA, Al-Ahmad AJ, Qian T, Zhang RR, Wilson HK, Weichert JP, Palecek SP, Kuo JS*, Shusta EV* “Analysis of cancer-targeting alkylphosphocholine analogs permeability characteristics using a human induced pluripotent stem cell blood brain barrier model.” (*Co-senior authors) Molecular Pharmaceutics 13 (9): 3341-9 (published online July 15, 2016).
Swanson KI, Clark PA, Zhang RR, Kandela IK, Farhoud M, Weichert JP, Kuo JS “Fluorescent cancer-selective alkylphosphocholine analogs for intraoperative glioma detection.” Neurosurgery 76 (2): 115-24 (*featured as High Impact Manuscript, chosen for the cover and a video abstract).
Weichert JP*, Clark PA, Kandela IK, Vaccaro AM, Clark W, Longino MA, Pinchuk AN, Farhoud M, Swanson KI, Floberg JM, Grudzinksi J, Titz B, Traynor AM, Chen HE, Hall LT, Pazoles CJ, Pickhardt PJ, Kuo JS* “Alkylphosphocholine analogs for broad spectrum cancer imaging and therapy.” (*Co-senior authors) Science Translational Medicine 6, 240ra75 (June 11, 2014). *Chosen for cover illustration, featured with podcast.
Pointer KB, Zorniak M, Clark PA, Alrfaei BM, Kuo JS “Glioblastoma cancer stem cells: Biomarker and therapeutic advances.” Neurochemistry International 71: 1-7 (published online March 19, 2014). *2nd most downloaded paper of January-June 2014.
Alrfaei BM, Vemuganti R, Kuo JS “MicroRNA100 targets SMRT, reduces proliferation and improves survival in glioblastoma.” PLoS One 8 (11): e80865 (published online November 14, 2013).
Zorniak M, Clark PA, Leeper HE, Tipping M, Francis D, Kozak KR, Salamat MS, Kuo JS “Differential expression of 2’,3’-cyclic nucleotide 3’-phosphodiesterase and neural lineage markers correlate with glioblastoma xenograft infiltration and patient survival.” Clinical Cancer Research 18 (13): 3628-36 (published online May 15, 2012).
Clark PA, Treisman D, Iida M, Kalluri H, Ezhilan S, Zorniak M, Salamat S, Wheeler D, Kuo JS “Activation of multiple ERRB family receptors mediates glioblastoma cancer stem cell resistance to EGFR-targeted inhibition.” Neoplasia 14 (5): 420-8 (2012).