Russell O. Pieper PhD
Professor and Vice Chair of Neurological Surgery
Suzanne Marie and Robert Vincent Haderle Endowed Chair in Molecular Neuro-Oncology
Principal Investigator and Director of Basic Science, Brain Tumor Research Center
Dr. Pieper's research program is divided into two components. The first component focuses on cell signaling and the influence of cell-cycle regulation on chemotherapeutic response of gliomas to the methylating agent temozolomide (TMZ). Work in Dr. Pieper's laboratory has identified pathways involving the DNA damage sensors Chk1 and p38 that lead to drug resistance to TMZ and that might serve as targets for sensitization of tumors to this important chemotherapeutic agent. The second program in Dr. Pieper's laboratory involves trying to understand the genetic events important in the formation of human brain tumors. It is known that single defined genetic alterations can result in the transformation of rodent cells, likely because these alterations lead to genomic instability and a variety of other genetic changes. Dr. Pieper's laboratory has identified four key pathways critical in controlling glioma development, and is further examining how disregulation of these pathways leads to glioma formation. Of particular note is the recent observation from Dr. Pieper's laboratory that some of the same pathways that contribute to astrocytic transformation also suppress the ability of cells to be eliminated by apoptosis-inducing agents such as TRAIL, and perhaps by the immune system itself. These observations are expected to lead to new ways to suppress both drug resistance and tumorigenicity in human gliomas. Read about Dr. Pieper's current research ►
Education, Training, and Previous Positions
- 1982: BS, University of Wisconsin
1987: PhD, The George Washington University
1987-1990: Postdoctoral Fellow, Section of Hematology/Oncology, Loyola University Medical Center
1990-1991: Research Assistant Professor, Section of Hematology/Oncology, Loyola University Medical Center
1991-1996: Assistant Professor of Medicine and Pharmacology, Loyola University Medical Center
1991-1998: Associate Professor of Medicine and Pharmacology, Loyola University Medical Center
Selected Professional Memberships and Appointments
- Editorial Advisory Board: The Journal of Pharmacology and Experimental Therapeutics
Editorial Advisory Board: Apoptosis
Editorial Advisory Board: Neuro-Oncology
Editorial Advisory Board: Cancer Research
Member, NIH/NCI Initial Review Group Subcommittee I, Career Development (NCI-I)
Selected Honors and Awards
- 1989-1991: National Research Service Award Fellowship, National Institutes of Health, National Cancer Institute
2001 - present: Suzanne Marie Haderle and Robert Vincent Haderle Endowed Chair in Molecular Neuro-Oncology
Selected Recent Publications
Nakamura JL, Phong C, Pinarbasi E, Kogan SC, Vandenberg S, Horvai AE, Faddegon BA, Fiedler D, Shokat K, Houseman BT, Chao R, Pieper RO, Shannon K. Dose-dependent effects of focal fractionated irradiation on secondary malignant neoplasms in Nf1 mutant mice. Cancer Res 2011;71(1):106-15.
Waldron JS, Yang I, Han S, Tihan T, Sughrue ME, Mills SA, Pieper RO, Parsa AT. Implications for immunotherapy of tumor-mediated T-cell apoptosis associated with loss of the tumor suppressor PTEN in glioblastoma. J Clin Neurosci 2010;17(12):1543-7.
Panner A, Crane CA, Weng C, Feletti A, Fang S, Parsa AT, Pieper RO. Ubiquitin-specific protease 8 links the PTEN-Akt-AIP4 pathway to the control of FLIPS stability and TRAIL sensitivity in glioblastoma multiforme. Cancer Res 2010;70(12):5046-53.
Dai B, Pieper RO, Li D, Wei P, Liu M, Woo SY, Aldape KD, Sawaya R, Xie K, Huang S. FoxM1B regulates NEDD4-1 expression, leading to cellular transformation and full malignant phenotype in immortalized human astrocytes. Cancer Res 2010;70(7):2951-61.
Han SJ, Ahn BJ, Waldron JS, Yang I, Fang S, Crane CA, Pieper RO, Parsa AT. Gamma interferon-mediated superinduction of B7-H1 in PTEN-deficient glioblastoma: a paradoxical mechanism of immune evasion. Neuroreport 2009;20(18):1597-602.
Panner A, Crane CA, Weng C, Feletti A, Parsa AT, Pieper RO. A novel PTEN-dependent link to ubiquitination controls FLIPS stability and TRAIL sensitivity in glioblastoma multiforme. Cancer Res 2009;69(20):7911-6.
Crane C, Panner A, Pieper RO, Arbiser J, Parsa AT. Honokiol-mediated inhibition of PI3K/mTOR pathway: a potential strategy to overcome immunoresistance in glioma, breast, and prostate carcinoma without impacting T cell function. J Immunother 2009;32(6):585-92.
Park S, Hatanpaa KJ, Xie Y, Mickey BE, Madden CJ, Raisanen JM, Ramnarain DB, Xiao G, Saha D, Boothman DA, Zhao D, Bachoo RM, Pieper RO, Habib AA. The receptor interacting protein 1 inhibits p53 induction through NF-kappaB activation and confers a worse prognosis in glioblastoma. Cancer Res 2009;69(7):2809-16.
Nakamura JL, Garcia E, Pieper RO. S6K1 plays a key role in glial transformation. Cancer Res. 2008;68(16):6516-23.
Parsa AT, Waldron JS, Panner A, Crane CA, Parney IF, Barry JJ, Cachola KE, Murray JC, Tihan T, Jensen MC, Mischel PS, Stokoe D, Pieper RO. Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma. Nat Med 2007;13(1):84-8.
Panner A, Murray JC, Berger MS, Pieper RO. Heat shock protein 90alpha recruits FLIPS to the death-inducing signaling complex and contributes to TRAIL resistance in human glioma. Cancer Res 2007;67(19):9482-9.
Nakamura JL, Haas-Kogan DA, Pieper RO. Glioma invasiveness responds variably to irradiation in a co-culture model. Int J Radiat Oncol Biol Phys 2007;69(3):880-6.
Kanamori M, Kawaguchi T, Nigro JM, Feuerstein BG, Berger MS, Miele L, Pieper RO. Contribution of Notch signaling activation to human glioblastoma multiforme. J Neurosurg 2007;106(3):417-27.
Kawaguchi T, Yamashita Y, Kanamori M, Endersby R, Bankiewicz KS, Baker SJ, Bergers G, Pieper RO. The PTEN/Akt pathway dictates the direct alphaVbeta3-dependent growth-inhibitory action of an active fragment of tumstatin in glioma cells in vitro and in vivo. Cancer Res 2006;66(23):11331-40.
Mirzoeva OK, Kawaguchi T, Pieper RO. The Mre11/Rad50/Nbs1 complex interacts with the mismatch repair system and contributes to temozolomide-induced G2 arrest and cytotoxicity. Mol Cancer Ther 2006;5(11):2757-66.
Kanamori M, Kawaguchi T, Berger MS, Pieper RO. Intracranial microenvironment reveals independent opposing functions of host alphaVbeta3 expression on glioma growth and angiogenesis. J Biol Chem 2006;281(48):37256-64.
Panner A, Parsa AT, Pieper RO. Use of APO2L/TRAIL with mTOR inhibitors in the treatment of glioblastoma multiforme [Review]. Expert Rev Anticancer Ther 2006;6(9):1313-22.
Katayama M, Kawaguchi T, Berger MS, Pieper RO. DNA damaging agent-induced autophagy produces a cytoprotective adenosine triphosphate surge in malignant glioma cells. Cell Death Differ 2007;14(3):548-58.
Lee JC, Vivanco I, Beroukhim R, et al. Epidermal growth factor receptor activation in glioblastoma through novel missense mutations in the extracellular domain. PLoS Med 2006;3(12):e485.
Panner A, Nakamura JL, Parsa AT, Rodriguez-Viciana P, Berger MS, Stokoe D, Pieper RO. mTOR-independent translational control of the extrinsic cell death pathway by RalA. Mol Cell Biol 2006;26(20):7345-57.
Panner A, Parsa AT, Pieper RO. Translational regulation of TRAIL sensitivity. Cell Cycle 2006;5(2):147-50.
Panner A, James CD, Berger MS, Pieper RO. mTOR controls FLIPS translation and TRAIL sensitivity in glioblastoma multiforme cells. Mol Cell Biol 2005;25(20):8809-23.