Jennifer Yu, M.D., Ph.D.
Center for Cancer Stem Cell Research
Lerner Research Institute,
9500 Euclid Avenue, Cleveland, Ohio 44195
Phone: (216) 444-0852
Fax: (216) 636-5454
The mission of our lab is to improve therapy for patients with brain tumors by elucidating the molecular mechanisms driving cancer initiation and progression, and in doing so, promote rigorous science and train the next generation of scientists. We aim to expedite the translation of experimental therapeutics to clinical trials. Brain tumors fall into two categories, primary brain tumors, which originate in the brain, and secondary brain tumors that metastasize to the brain. Our major area of research is in glioblastoma, the most common primary malignant brain tumor. Glioblastoma is fatal despite multimodality therapy. Glioma stem cells (GSCs) are a subpopulation of cells that contribute to tumor progression. GSCs have a high capacity for self-renewal, survival under hypoxic conditions, resistance to radiation and high invasive potential. Our lab is focused on delineating the mechanisms underlying these key GSC tumorigenic properties with a long-term goal of uncovering potential therapeutic targets. 1. GSC co-option of core developmental pathways, including the Semaphorin, Notch and Wnt 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 aim to illuminate mechanisms by which Sema3C contributes to tumor progression. We also aim to understand how the Notch and Wnt core stem cell programs are regulated by GSCs. 2. GSC adaptations to hypoxic conditions. GSCs frequently reside in the hypoxic niche. The hypoxia inducible factors (HIFs) integrate cellular responses to hypoxia. We aim to understand the repertoire of HIF-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. 4. Maintenance of GSCs by non-coding RNAs. Non-coding RNAs are increasingly recognized for their role in oncogenesis. These RNAs include small RNAs and lncRNAs. We aim to understanding how these non-coding RNAs contribute to GSC maintenance. Brain metastases are the most common type of brain tumors, and it is estimated that about 1/3 of cancer patients will develop brain metastases. We aim to understand how brain metastases adapt to their environment and how we can target them better.
Man J, Yu X, Huang H, Zhou W, Xiang C, Miele L, Liu Z, Bebek G, Bao S, Yu JS. Hypoxic Induction of Vasorin Regulates Notch1 Turnover to Maintain Glioma Stem-Like Cells. Cell Stem Cell 2018, 22:104-118.
Zhou W, Chen C, Shi Y, Wu Q, Gimple RC, Fang X, Huang Z, Zhai K, Ke SQ, Ping YF, Feng H, Rich JN, Yu JS, Bao S, Bian XW. Targeting Glioma Stem-Cell Derived Pericytes Disrupts the Blood-Tumor Barrier to Improve Drug Delivery and Chemotherapeutic Efficacy. Cell Stem Cell 2017, 21:591-603.
Huang H, Yu X, Mohammadi AM, Karanthanasis E, Godley A, YuJS. It’s Getting Hot in Here: Targeting Cancer Stem-like Cells with Hyperthermia. Journal of Stem Cell and Transplantation Biology 2017, 2: 1-8.
Sharma M, Jia X, Ahluwalia M, Barnett GH, Vogelbaum MA, Chao ST, Suh JH, Murphy ES, Yu JS, Angelov L, Mohammadi AM. First Follow-up Radiographic Response is One of the Predictors of Local Tumor Progression and Radiation Necrosis After Stereotactic Radiosurgery for Brain Metastases. Cancer Medicine 2017 Sep; 6(9):2076-2086.
Murphy ES, Rogacki K, Godley A, Qi P, Reddy C, Ahluwalia M, Peereboom D, Stevens G, Yu JS, Suh JH, Chao ST. Intensity Modulated Radiation Therapy with Pulsed Reduced Dose Rate as a Re-irradiation Strategy for Recurrent Central Nervous System Tumors: An Institutional Series and Literature Review. Practical Radiation Oncology 2017 Nov-Dec;7(6):e391-e399.
Sharma M, Jia X, Ahluwalia M, Barnett GH, Vogelbaum MA, Chao ST, Suh JH, Murphy ES, Yu JS, Angelov L, Mohammadi AM. Cumulative Intracranial Tumor Volume and Number of Brain Metastases as Predictors of Developing New Lesions After Stereotactic Radiosurgery for Brain Metastasis. World Neurosurgery 2017 Oct; 106:666-675.
Kotecha R, Miller JA, Venur VA, Mohammadi AM, Chao ST, Suh JH, Barnett GH, Murphy ES, Funchain P, Yu JS, Vogelbaum MA, Angelov L, Ahluwalia MS. Melanoma Brain Metastasis: The Impact of Stereotactic Radiosurgery, BRAF Mutational Status, and Targeted/Immune-Based Therapies on Treatment Outcome. Journal of Neurosurgery 2017 Aug 11:1-10.
Bennett EE, Angelov A, Vogelbaum MA, Barnett GH, Chao ST, Murphy ES, Yu JS, Suh JH, Jia XJ, Glen HJ, Ahluwalia MS, Mohammadi, The Prognostic Role of Tumor Volume in the Outcome of Patients with Single Brain Metastasis After Stereotactic Radiosurgery. World Neurosurgery, 2017 Aug;104:229-238.
Mohammadi A, Schroeder J, Angelov L, Chao ST, Murphy E, Yu JS, Neyman G, Jia X, Suh J, Barnett G, Vogelbaum M, Impact of radiosurgery prescription dose on the local control of small (2 cm or less) brain metastases. Journal of Neurosurgery 2017, 126(3):735-743, PMID 27231978.
Miller JA, Bennett EE, Xiao R, Kotecha R, Chao ST, Vogelbaum MA, Barnett GH, Angelov L, Murphy ES, Yu JS, Ahluwalia MS, Suh JH, Mohammadi AM. Association between Radiation Necrosis and Tumor Biology following Stereotactic Radiosurgery for Brain Metastasis. International Journal of Radiation Oncology, Biology, and Physics 2016, 96:1060-1069.
Adams CS#, Yu JS#, Mao JH, Jen KY, Costes S, Wade M, Shoemake J, Aina OH, Del Rosario R, Thuy-Menchavez P, Cardiff R, Wahl GM, Balmain A, The Trp53 Delta Proline Mouse Exhibits Increased Genome Instability and Susceptibility to Radiation-Induced But Not Spontaneous Tumor Development. Molecular Carcinogenesis 2016, 55(9):1387-1396. PMID: 26310697, PMCID PMC4891300. #co-first author
Amoush A, Murray E, Yu JS, Xia P, Impact of Intra-Fraction Motion for the Treatment of Breast Cancer With Supraclavicular Lymph Nodes Using Single-Isocenter 4-Field Hybrid IMRT Plans versus Two-Isocenter Conventional Plans. Journal of Applied Clinical Medical Physics 2015, 16:31-39.
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.
Murphy ES, Xie H, Merchant TE, Yu JS, Chao S, Suh J, Review of Cranial Radiotherapy-Induced Vasculopathy. Journal of Neuro-oncology 2015, May 122(3): 421-429.
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.
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.
Marta GN, Murphy E, Chao S, Yu JS, Suh JH, The incidence of second brain tumors related to cranial irradiation. Expert Review of Anticancer Therapy 2014: 295-304.
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.
Zhuang T, Huang L, Qi P, Yu JS, Radiation therapy: Clinical application of volumetric modulated arc therapy. Applied Radiation Oncology 2013, 6.
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.
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