Profile

In the laboratory we study molecular signaling pathways in the developing nervous system. We are interested in learning how inductive signals are generated, received and implemented to coordinate cellular growth and differentiation during brain and spinal cord development. Hedgehog proteins are one of several secreted signaling molecules that are essential for normal embryonic development. Sonic hedgehog is the best characterized of three vertebrate Hedgehog signaling proteins and is of considerable interest because of its role in directing the fate of neuronal progenitor cells and in the initiation and growth of medulloblastomas, a pediatric brain tumor. Past efforts have been directed at the identification and characterization of teratogenic, plant-derived compounds as modulators of the Hedgehog pathway. These studies have served to further our understanding of how the Hedgehog signal transduction apparatus functions, to provide tools for dissecting the roles of Hedgehog signaling in both neurogenesis and organ function, and to identify a potential mechanism-based cancer therapy. Current research efforts are directed at understanding the molecular events through which Hedgehog signaling influences progenitor cell proliferation and neuronal specification. To gain a molecular understanding of these cellular responses we have recently embarked on a systematic effort to identify and characterize Sonic hedgehog gene targets. In addition to learning more about how cells respond to Hedgehog signaling in the developing brain, we are using this information to explore later roles for Hedgehog signaling in neurogenesis within the adult brain. Our hope is that molecular insight into normal pathways of neurogenesis can contribute to the understanding of a host of nervous system diseases and to better strategies for the treatment of those disorders.

Publications

The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

1. Cancer stem cells in glioma: challenges and opportunities. Wang J, Ma Y, Cooper MK (2013) Transl Cancer Res 2(5): 429-441
   › Primary publication · 24634854 (PubMed) · PMC3952560 (PubMed Central)
2. p75 neurotrophin receptor cleavage by α- and γ-secretases is required for neurotrophin-mediated proliferation of brain tumor-initiating cells. Forsyth PA, Krishna N, Lawn S, Valadez JG, Qu X, Fenstermacher DA, Fournier M, Potthast L, Chinnaiyan P, Gibney GT, Zeinieh M, Barker PA, Carter BD, Cooper MK, Kenchappa RS (2014) J Biol Chem 289(12): 8067-85
   › Primary publication · 24519935 (PubMed) · PMC3961639 (PubMed Central)
3. Cytogenetic prognostication within medulloblastoma subgroups. Shih DJ, Northcott PA, Remke M, Korshunov A, Ramaswamy V, Kool M, Luu B, Yao Y, Wang X, Dubuc AM, Garzia L, Peacock J, Mack SC, Wu X, Rolider A, Morrissy AS, Cavalli FM, Jones DT, Zitterbart K, Faria CC, Schüller U, Kren L, Kumabe T, Tominaga T, Shin Ra Y, Garami M, Hauser P, Chan JA, Robinson S, Bognár L, Klekner A, Saad AG, Liau LM, Albrecht S, Fontebasso A, Cinalli G, De Antonellis P, Zollo M, Cooper MK, Thompson RC, Bailey S, Lindsey JC, Di Rocco C, Massimi L, Michiels EM, Scherer SW, Phillips JJ, Gupta N, Fan X, Muraszko KM, Vibhakar R, Eberhart CG, Fouladi M, Lach B, Jung S, Wechsler-Reya RJ, Fèvre-Montange M, Jouvet A, Jabado N, Pollack IF, Weiss WA, Lee JY, Cho BK, Kim SK, Wang KC, Leonard JR, Rubin JB, de Torres C, Lavarino C, Mora J, Cho YJ, Tabori U, Olson JM, Gajjar A, Packer RJ, Rutkowski S, Pomeroy SL, French PJ, Kloosterhof NK, Kros JM, Van Meir EG, Clifford SC, Bourdeaut F, Delattre O, Doz FF, Hawkins CE, Malkin D, Grajkowska WA, Perek-Polnik M, Bouffet E, Rutka JT, Pfister SM, Taylor MD (2014) J Clin Oncol 32(9): 886-96
   › Primary publication · 24493713 (PubMed) · PMC3948094 (PubMed Central)
4. Primary orthotopic glioma xenografts recapitulate infiltrative growth and isocitrate dehydrogenase I mutation. Valadez JG, Sarangi A, Lundberg CJ, Cooper MK (2014) J Vis Exp (83): e50865
   › Primary publication · 24458098 (PubMed) · PMC4396882 (PubMed Central)
5. Voltage-gated potassium channel EAG2 controls mitotic entry and tumor growth in medulloblastoma via regulating cell volume dynamics. Huang X, Dubuc AM, Hashizume R, Berg J, He Y, Wang J, Chiang C, Cooper MK, Northcott PA, Taylor MD, Barnes MJ, Tihan T, Chen J, Hackett CS, Weiss WA, James CD, Rowitch DH, Shuman MA, Jan YN, Jan LY (2012) Genes Dev 26(16): 1780-96
   › Primary publication · 22855790 (PubMed) · PMC3426758 (PubMed Central)
6. Subgroup-specific structural variation across 1,000 medulloblastoma genomes. Northcott PA, Shih DJ, Peacock J, Garzia L, Morrissy AS, Zichner T, Stütz AM, Korshunov A, Reimand J, Schumacher SE, Beroukhim R, Ellison DW, Marshall CR, Lionel AC, Mack S, Dubuc A, Yao Y, Ramaswamy V, Luu B, Rolider A, Cavalli FM, Wang X, Remke M, Wu X, Chiu RY, Chu A, Chuah E, Corbett RD, Hoad GR, Jackman SD, Li Y, Lo A, Mungall KL, Nip KM, Qian JQ, Raymond AG, Thiessen NT, Varhol RJ, Birol I, Moore RA, Mungall AJ, Holt R, Kawauchi D, Roussel MF, Kool M, Jones DT, Witt H, Fernandez-L A, Kenney AM, Wechsler-Reya RJ, Dirks P, Aviv T, Grajkowska WA, Perek-Polnik M, Haberler CC, Delattre O, Reynaud SS, Doz FF, Pernet-Fattet SS, Cho BK, Kim SK, Wang KC, Scheurlen W, Eberhart CG, Fèvre-Montange M, Jouvet A, Pollack IF, Fan X, Muraszko KM, Gillespie GY, Di Rocco C, Massimi L, Michiels EM, Kloosterhof NK, French PJ, Kros JM, Olson JM, Ellenbogen RG, Zitterbart K, Kren L, Thompson RC, Cooper MK, Lach B, McLendon RE, Bigner DD, Fontebasso A, Albrecht S, Jabado N, Lindsey JC, Bailey S, Gupta N, Weiss WA, Bognár L, Klekner A, Van Meter TE, Kumabe T, Tominaga T, Elbabaa SK, Leonard JR, Rubin JB, Liau LM, Van Meir EG, Fouladi M, Nakamura H, Cinalli G, Garami M, Hauser P, Saad AG, Iolascon A, Jung S, Carlotti CG, Vibhakar R, Ra YS, Robinson S, Zollo M, Faria CC, Chan JA, Levy ML, Sorensen PH, Meyerson M, Pomeroy SL, Cho YJ, Bader GD, Tabori U, Hawkins CE, Bouffet E, Scherer SW, Rutka JT, Malkin D, Clifford SC, Jones SJ, Korbel JO, Pfister SM, Marra MA, Taylor MD (2012) Nature 488(7409): 49-56
   › Primary publication · 22832581 (PubMed) · PMC3683624 (PubMed Central)
7. Widespread contribution of Gdf7 lineage to cerebellar cell types and implications for hedgehog-driven medulloblastoma formation. Cheng FY, Huang X, Sarangi A, Ketova T, Cooper MK, Litingtung Y, Chiang C (2012) PLoS One 7(4): e35541
   › Primary publication · 22539980 (PubMed) · PMC3335071 (PubMed Central)
8. Identification of blood protein biomarkers that aid in the clinical assessment of patients with malignant glioma. Xu BJ, An QA, Srinivasa Gowda S, Yan W, Pierce LA, Abel TW, Rush SZ, Cooper MK, Ye F, Shyr Y, Weaver KD, Thompson RC (2012) Int J Oncol 40(6): 1995-2003
   › Primary publication · 22307528 (PubMed)
9. Lipid modifications of Sonic hedgehog ligand dictate cellular reception and signal response. Grover VK, Valadez JG, Bowman AB, Cooper MK (2011) PLoS One 6(7): e21353
   › Primary publication · 21747935 (PubMed) · PMC3128587 (PubMed Central)
10. Transventricular delivery of Sonic hedgehog is essential to cerebellar ventricular zone development. Huang X, Liu J, Ketova T, Fleming JT, Grover VK, Cooper MK, Litingtung Y, Chiang C (2010) Proc Natl Acad Sci U S A 107(18): 8422-7
    › Primary publication · 20400693 (PubMed) · PMC2889567 (PubMed Central)
11. Activation of the Hedgehog pathway in pilocytic astrocytomas. Rush SZ, Abel TW, Valadez JG, Pearson M, Cooper MK (2010) Neuro Oncol 12(8): 790-8
    › Primary publication · 20223881 (PubMed) · PMC2940682 (PubMed Central)

Keywords & MeSH Terms

MeSH terms are retrieved from PubMed records. Learn more.

Key: MeSH Term Keyword

AC133 Antigen Adult Anticholesteremic Agents Antineoplastic Agents Biomarkers, Tumor Brain CD2 Antigens Cerebellar Neoplasms Drosophila Ether-A-Go-Go Potassium Channels Gene Expression Profiling Genotype Herpesvirus 4, Human In Situ Hybridization, Fluorescence Intracellular Signaling Peptides and Proteins Mice, Nude Mutation, Missense Neurogenesis Nursing Diagnosis Ohio Organ Culture Techniques Patient Readmission Patient Satisfaction Precipitin Tests Receptors, G-Protein-Coupled Risk Management ROC Curve Time Factors Trans-Activators Tumor Cells, Cultured Zebrafish