Scientific Program

Distinguished Lecturers

Professor Russell O. Pieper Professor and Vice Chair of Neurological Surgery,
University of California, San Francisco, U.S.A.

EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable. Add/delete rows as necessary.)

University of Wisconsin-Madison, WI
George Washington University, Washington, DC

A. Personal Statement

Russell O. Pieper, PhD is the Director of Basic Science in the UCSF Brain Tumor Research Center, the Vice-Chairman of the UCSF Department of Neurological Surgery, and a co-PI of the UCSF Brain Tumor SPORE. He is a recognized expert in the areas of cell signaling, temozolomide-based drug resistance, and gliomagenesis. As the Suzanne Marie Haderle and Robert Vincent Haderle Professor of Molecular Neuro-Oncology Dr. Pieper directs a lab that focuses on genetic events that drive brain tumor formation and drug resistance and that in turn may serve as targets for the development of new therapies for brain tumors.

B. Positions and Honors

1987 – 1990
Research Associate, Section of Hematology/Oncology, Dept. of Medicine, Loyola Univ. Med. Center, Maywood, IL
1990 – 1991
Research Assistant Professor, Dept. of Medicine, Loyola University Med. Center
1991 – 1996
Assistant Professor of Medicine and Pharmacology, Loyola University Med. Center
1996 – 1998
Associate Professor of Medicine and Pharmacology, Loyola University Med. Center
1998 – 2004
Associate Professor, Brain Tumor Research Center and the Dept. of Neurological Surgery, University of California, San Francisco, CA
2004 – Present
Professor, Brain Tumor Research Center and the Dept. of Neurological Surgery, University of California, San Francisco, CA
2004 - Present
Editorial Board, Apoptosis
2007 - Present
Editorial Board, Neuro-Oncology
2010 –2014
Board of Directors, Society for Neuro-Oncology
2000 - 2016
Suzanne Marie Haderle and Robert Vincent Haderle Endowed Chair in Molecular Neuro-Oncology
Neill H. and Linda S. Brownstein Chair in Brain Tumor Research

C. Contribution to Science (in chronologic order)

Contribution 1: Identification of DNA methylation as a mechanism for MGMT silencing.
Work in the 19070s demonstrated that chemotherapeutic DNA alkylating agents killed tumor cells by creating DNA double-stand breaks (DSB). The most clinically useful of these agents including BCNU and temozolomide (TMZ) initiated this damage by forming lesions at the O6-postion of guanine in the DNA. Work in the early 1980s showed that a DNA repair protein, O6 methylguanine DNA methyltransferase (MGMT) removed O6 methylguanine lesions before they could go on to cause DNA DSB, and that cells with high levels of MGMT were inherently resistant to the cytotoxic potential of these agents. A subset of tumors were shown to lack MGMT activity and to be inherently sensitive to alkylating agent-induced cytotoxicity, although the basis for the lack of MGMT activity and the potential to use loss of MGMT activity as a biomarker of alkylating agent sensitivity were unknown. I personally was the first to show that the loss of MGMT activity in drug-sensitive tumor cells was the result of loss of MGMT mRNA expression (publication 1), and my lab went on to show that the loss of MGMT mRNA expression was in turn related to alterations in DNA cytosine methylation (publications 2-4). These studies formed the basis for further developments that eventually led to the identification of MGMT promoter methylation as one of the strongest prognostic factors for patients with newly diagnosed GBM and the only biomarker to date of drug action in cancer.

  1. 1.Pieper RO, Futscher BW, Dong Q, Ellis TM, Erickson LC. Comparison of O-6-methylguanine DNA methyltransferase (MGMT) mRNA levels in Mer+ and Mer- human tumor cell lines containing the MGMT gene by the polymerase chain reaction technique. Cancer Commun. 1990;2(1):13-20. PMID: 2369549
  2. 2.Pieper RO, Costello JF, Kroes RA, Futscher BW, Marathi U, Erickson LC. Direct correlation between methylation status and expression of the human O-6-methylguanine DNA methyltransferase gene. Cancer Commun. 1991 Aug;3(8):241-53. PMID:1716139
  3. 3.Costello, J.F., Futscher, B.W., Kroes, R.A., Pieper, R.O. Methylation-related chromatin structure is associated with exclusion of the O-6-methylguanine DNA methyltransferase (MGMT) gene in human glioma cell lines. Molecular and Cellular Biology 14:6516-6521, 1994. PMCID: PMC359181
  4. 4.Costello, J.F., Futscher, B.W., Tano, K., Graunke, D.M., Pieper, R.O. Graded methylation in the promoter and the body of the O-6-methylguanine DNA methyltransferase (MGMT) gene correlates with MGMT expression in human glioma cells. J. Biol. Chem. 269: 17228-17237, 1994. PMID: 8006031

Contribution 2: The development of an in vitro model of human gliomagenesis
In 1999 the Weinberg lab demonstrated that a limited number of genetic alterations could convert normal human fibroblasts into tumorigenic cells. To address the question of whether human astrocytes could be converted in vitro into glioma-producing cells, my lab initiated a series of studies to determine if introduction of defined genetic alterations into human astrocytes could drive gliomagenesis. The results of the studies (publications 1 and 2) defined four events as critical for gliomagenesis (loss of p53, loss of Rb, TERT reactivation, and Ras-mediated growth factor pathway activation), all of which were verified by TCGA-based studies a decade later. More importantly, the cellular system created has been widely distributed and used, and has played a critical role in helping the brain tumor community unravel how other genetic alterations, including most recently mutant IDH (publications 3 and 4), contribute to brain tumor formation.

  1. 1.Sonoda, Y., Ozawa, T., Hirose, Y., Aldape, K.D., McMahon, M., Berger, M.S., and Pieper, R.O. Formation of intracranial tumors by genetically modified human astrocytes defines four pathways critical in the development of human anaplastic astrocytoma. Cancer Res. 61: 4956-60, 2001. PMID: 11431323
  2. 2.Sonoda, Y., Ozawa, T., Aldape, K.D., Den, D.F., Berger, M.S., and Pieper, R.O. Akt pathway activation converts anaplastic astrocytoma to glioblastoma multiforme in a human astrocyte model of glioma. Cancer Res. 61:6674-6678, 2001. PMID: 11559533
  3. 3.C Lu, PS Ward, GS Kapoor, D Rohle, S Turcan …Thompson, CB. IDH mutation impairs histone demethylation and results in a block to cell differentiation. Nature 483 474–478, 2012.
  4. 4.S Turcan, D Rohle, A Goenka, LA Walsh, F Fang…Chan, T. IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype. Nature 483: 479–483, 2012.

Contribution 3: Identification of the role of cell cycle arrest in the mechanism of action of temozolomide (TMZ)
Temozolomide is a DNA methylating agent that is widely used in the treatment of brain tumor patients. The action of TMZ is dependent on the MGMT levels in tumor cells as described above, although even cells that undergo TMZ-induced DNA damage can escape from TMZ-induced cytotoxicity. My lab was the first to demonstrate that TMZ-induced DNA damage causes a G2 arrest, the elimination of which sensitizes cells to TMZ (publications 1 and 2). These studies not only increased our understanding of TMZ action but have also led to a clinical trial of agents that target key points in the G2 arrest pathway (WEE1 Inhibitor MK-1775, Radiation Therapy, and Temozolomide in Treating Patients With Newly Diagnosed or Recurrent Glioblastoma Multiforme, NCT01849146).

  1. 1.Hirose, Y., Berger, M.S., and Pieper, R.O. Abrogation of the Chk1-mediated G2 checkpoint pathway potentiates temozolomide-induced toxicity in a p53-independent manner in human glioblastoma cells. Cancer Res. 61: 5843-5849, 2001. PMID: 11479224
  2. 2.Hirose, Y., Katayama, M., Stokoe, D., Haas-Kogan, D.A., Berger, M.S., and Pieper, R.O. The p38 mitogen-activated protein kinase pathway links the DNA mismatch repair system to the G2 checkpoint and to resistance to chemotherapeutic DNA-methylating agents. Mol. Cell. Biol. 23:8306-8315, 2003. PMCID: PMC262371

Contribution 4: Identification of immune checkpoints as contributors to gliomagenesis
Effective cancer immunotherapy relies on using the patient’s own immune system to fight their disease. The effectiveness of immunotherapy-based approaches, however, is limited not only by sub-optimal immune stimulation, but also by the ability of tumors to create a hostile immune microenvironment. Studies from my lab, in collaboration with that of Andrew Parsa, MD, PhD, were the first to show that the same genetic alterations that lead to tumor formation also activate the pathways that create an immunosuppressive microenvironment. These studies in particular linked PTEN loss to activation of the immune checkpoint protein B7-H1 in glioma as well as in several other cancers, and have contributed to the initiation of clinical trials of so-called “immune checkpoint” modulators including those targeting B7-H1.

  1. 1.Parsa A.T., Waldron J.S., Panner A., Parney I.F., Stokoe D., Tihan T., Jensen M.C., Mischel P.S., Cachola K., Murray J.C., Sison C.E., and Pieper R.O. A novel link between PTEN loss and cancer immunoresistance. Nat. Med. 13(1):84-88, 2007. PMID: 17159987
Link to MyBibliography:

D. Research Support


P50 CA097257 (Berger)              05/01/2013 – 04/30/2018
Brain Tumor SPORE Grant
This continuation SPORE proposal includes 4 translational research projects and 4 Cores - Administrative Core, Tissue Bank Core and a Pre-Clinical Animal Core - and represents the efforts of interdisciplinary teams of investigators from the Neuro-Oncology Program of the UCSF Cancer Center to apply their knowledge and expertise to translational research focused on brain tumors.
Admin Core (Berger/Prados/Pieper)
The Administrative Core, through the SPORE Executive Committee, the SPORE Steering Committee, and the SPORE External Advisory Board, will be responsible for evaluating the progress of projects and making decisions regarding the continuation/replacement of projects and to provide fiscal management.
Role: Core Co-Director
Developmental Research Program (Pieper)
The Specific Aims of the UCSF Brain Tumor SPORE DRP are to implement new technologies and resources for translational brain tumor research, to help develop collaborations among scientists within UCSF and at different institutions and to develop new ideas as pilot projects to replace SPORE projects.
Role: Program Director
Career Developmental Program (Pieper)
The Specific Aims of the UCSF Brain Tumor SPORE Career Developmental Program are to identify, support, and mentor individuals with promising careers in translational brain tumor research, to encourage new and established investigators to develop careers in translational brain tumor research and to encourage women and minorities to pursue careers in translational brain tumor research.
Role: Program Director
P01 CA118816 (Chang)               08/1/2013-07/31/18
NIH Imaging and Tissue Correlates to Optimize Management of Glioblastoma
The overall goal is to integrate advances in physiologic and metabolic imaging with tissue biomarkers in order to optimize the management of patients with glioblastoma. This will be achieved by characterizing the evolution of changes in imaging, genetic and epigenetic profiles from the time of initial presentation until presumed tumor progression.
Project 3(Pieper/Ronen)
Hyperpolarized 13C MRSI Monitoring of Pyruvate Metabolism to Assess Drug Action
The goal of this project is to determine if treatment-induced alterations in pyruvate metabolism detected by hyperpolarized 13C magnetic resonance spectroscopic imaging (MRSI) can be used as a biomarker to assess target inhibition and early response to treatment in recurrent glioblastoma (GBM).
P30 CA082103(McCormick)             09/19/2012-05/31/2017
Cancer Center Support Grant
The Cancer Center Support Grant provides support for administration and infrastructure for the UCSF Helen Diller Family Comprehensive Cancer Center.
Role: Neuro-Oncology Program Co-Leader
R01 CA171610(Pieper)               02/01/2013–01/31/2018
Understanding the role of altered metabolism in gliomagenesis
The long term objective of this proposal is to improve the therapy of glioma by better understanding the role altered metabolism plays in gliomagenesis.
Role: Principal Investigator
R01 CA172845(Ronen)               02/05/2013-01/31/2018
Metabolic Reprogramming in Brain Tumors
The objective for this project is to test the hypothesis that the neomorphic activity of mutant isocitrate dehydrogenase (IDH) results not only in production of the oncometabolite 2-hydroxygluatarte (2-HG), but also in a wider metabolic reprogramming which is essential for tumor progression and therefore can be targeted in the treatment of IDH-mutant gliomas. A secondary goal is to identify novel imaging biomarkers for monitoring the normalization of this metabolic reprogramming with treatment.
Role: Co Investigator
No number(Berger/Costello/Pieper)        10/1/2015- 9/30/2018
The loglio Collaborative
The loglio Collective is a privately funded effort involving over 20 investigators from 6 different institution with the goal of developing better understanding and better therapeutics for lower grade glioma.
Team 3: The Development of Therapeutic Approaches based on the Unique Properties of Lower-grade Gliomas (Pieper)
The objective of this proposal is to develop new therapeutics for lower grade glioma based on the unique properties displayed by lower grade glioma.
Role: Team leader
Project 3b:
The Development of Therapeutic Approaches targeting mutant IDH-driven lower grade glioma (Pieper)
The objective of this proposal is to develop new therapeutics for lower grade glioma based on the unique properties displayed by mutant IDH1-driven alterations in cell metabolism.
Role: Project leader