Stem Cell Biology and Regenerative Medicine
Jennifer Yu, M.D., Ph.D.
Lerner Research Institute
9500 Euclid Avenue
Cleveland, Ohio 44195
Phone: (216) 444-0852
Fax: (216) 636-5454
Glioblastoma is the most common primary brain tumor and is fatal despite maximal therapy. Glioma stem cells (GSCs) are a subpopulation of cells that contribute to tumor progression. Glioma stem cells have a high capacity for self-renewal, survival under hypoxic conditions, resistance to radiation, and high invasive potential. Our lab is focused on understanding mechanisms underlying these key GSC tumorigenic properties with a long-term goal of uncovering potential therapeutic targets. We have 3 major areas of focus:
1. GSC co-option of core developmental pathways. We have identified that GSCs preferentially re-activate the Semaphorin-Neuropilin-Plexin axonal guidance program. GSCs secrete Sema3C and engage PlexinA2/PlexinD1 receptors to regulate GSC survival and invasion. We are focused on understanding the mechanisms by which Sema3C contributes to tumor progression.
2. GSC survival under hypoxic conditions through HIF-mediated pathways. We aim to understand the repertoire of HIF1-target genes that contribute to GSC survival and expansion.
3. GSC resistance to radiation due to upregulation of pro-survival signaling and enhanced DNA damage repair capacity. We are interested in improving the radiosensitivity of GSCs with thermal therapy, modifications in radiation delivery and radiosensitizing drugs. Our goal is to expedite the translation of experimental therapeutics to clinical trials.
Man J, Shoemake S, Zhou W, Fang X, Wu Q, Rizzo A, Prayson R, Bao S, Rich JN, Yu JS*, Sema3C Promotes The Survival and Tumorigenicity of Glioma Stem Cells Through Rac1 Activation. Cell Reports 2014, 9(5):1812-26.
Man J, Shoemake S, Ma R. Rizzo A, Godley AR, Wu Q, Mohammadi A, Bao S, Rich JN, Yu JS*, Hyperthermia sensitizes glioma stem-like cells to radiation by inhibiting AKT signaling. Cancer Research 2015, 75(8):1960-9. PMID:25712125, PMCID: PMC4401644.
Fang X, Huang Z, zhou W, Wu Q, Sloan AE, Ouyang G, McLendon R, Yu JS, Rich JN, Bao S. The Transcription Factor ZFX Is Required for Maintaining the Tumorigenic Potential of Glioblastoma Stem Cells. Stem Cells 2014, 32(8): 2033-47.
Liu J, Lubelski D, Schonberg D, Wu Q, Hale J, Flavahan W, Man J, Hjelmeland A, Yu JS, Lathia J, Mulkearns-Hubert E, Rich JN, Phage Display Discovery of Novel Molecular Targets in Glioblastoma Initiating Cells. Cell Death and Differentiation 2014, 21(8):1325-39.
Hopkins BD, Fine B, Steinbach N, Dendy M, Rapp Z, Shaw J, Pappas K, Yu JS, Hodakoski C, Mense S, Klein J, Pegno S, Sulis M, Goldstein H, Amendolara B, Lei L, Maurer M, Bruce J, Canoll P, Hibshoosh H, Parsons RE, PTEN-Long, a secreted from of PTEN that enters cells to alter signaling and survival. Science 2013, 341(6144):399-402.
Rivera M, Sukhdeo K, Yu JS*, Ionizing radiation in glioblastoma initiating cells. Frontiers in Oncology 2013, 3:74.
Wong CE, Yu JS, Quigley DA, To MD, Jen KY, Del Rosario R, Balmain A, Inflammation and H-ras Signaling control epithelial-mesenchymal transition during skin tumor progression. Genes and Development 2013, 27:670-682.