Faculty

Karen E. Pollok, PhD

Karen E. Pollok, PhD

Associate Professor of Pediatrics

Phone: 317-944-8784
Email: kpollok@iu.edu
Address:
1044 West Walnut, R4 302
Indianapolis, IN 46202

Bio

Areas of Interest

Building upon standard-of-care therapy for glioblastoma and neuroblastoma by modulation of dysregulated signaling networks.

Bio

Dr. Pollok is an Associate Professor of Pediatrics with a secondary appointment in the Department of Pharmacology and Toxicology. She serves as Director of the In Vivo Therapeutics core for the Indiana University Simon Cancer Center and the Basic Science Leader of the Brain Tumor Working Group.

Education

1983 BS, College of William and Mary
1990 PhD, University of Kentucky

Honors & Awards

  • 1985-90 Lucille P. Markey Predoctoral Fellowship
  • 1989 1st Place; Graduate Research Award-Mid-West Autumn Immunology Conference, St. Louis, MO.
  • 1992 2nd Place; Fellow Research Award-Mid-West Autumn Immunology Conference, Chicago, IL
  • 1993-94 National Research Service Award (NRSA) fellowship, NIH
  • 1995-96 American Cancer Society Institutional Junior Investigator Grant
  • 10/08 Ad hoc reviewer, External site visit team for the NIH/NCI-Experimental Transplantation & Immunology Branch.
  • 6/09 Ad hoc reviewer, RC1 Challenge grants, ZRG1 OTC-K (58) in Oncology-2 Translational Clinical IRG
  • 2013 selected nationally to attend the National Mid-Career Women Faculty Professional Development Seminar, Austin, TX
  • 2014 Ad hoc reviewer, NIH BMCT study section

Clinical


Research & Grants

There are currently no effective cures for pediatric cancers such as glioblastoma multiforme (GBM) and metastatic neuroblastoma.  Additionally, conventional therapies can result in severe toxicity to normal tissues and organs. In Dr. Pollok’s laboratory, treatment strategies that effectively target key survival signaling networks in GBM and neuroblastoma are being pursued. Dr. Pollok’s NCI-funded research is using orthotopic humanized adult and pediatric tumor models to evaluate therapeutic potential of novel DNA crosslinking agents and blocking the MDM2 signaling network to sensitize tumor cells to DNA-damaging agents. We are investigating the pharmacokinetic and pharmacodynamic characteristics of innovative and unexplored combination treatments at both the molecular and cellular level. In our GBM research, we are working in a collaborative effort to identify compounds that have the potential to block MDM2-mediated signaling but also may have a higher propensity to cross the blood-brain-barrier (BBB) and the blood-tumor-barrier (BTB). There is an unmet clinical need to identify and characterize new therapeutics with increased ability to be delivered at biologically effective doses to the brain to treat cancers of the central nervous system. Additionally, we continue to develop novel ways to assess off target toxicity. We recently developed a humanized bone-marrow mouse model to screen for regimen-induced toxicities to the hematopoietic compartment.  We are continuing to validate the predictive value of this model with industry partners with the goal of utilizing this as an additional screen for normal tissue toxicity of novel scaffolds and anti-cancer regimens.

R01 CA138798-03 (Pollok) 07/15/10-05/31/15 4.0 calendar months
NIH/NCI $202,809
Dual Targeting of DNA Repair and p53 pathways for treatment of brain cancer
Goals: evaluate in vivo therapeutic efficacy of HDM2 inhibition in combination with temozolomide/irradiation as new treatment for glioblastoma.

P30DK090948-03/CEMH (Broxmeyer) 09/30/10-06/30/15 1.8 calendar months
NIH/NIDDK $155,656
Regulating hematopoietic stem cells and hematopoiesis for clinical efficacy
Goals: to provide specialized colonies of mice to all investigators, technical support, and expertise for irradiations and hematopoietic transplant experiments
Role: Core Leader, Core 3: Experimental Mouse Core

IUPUI Signature Center Initiative: Pollok/Cohen-Gadol (Directors) 07/01/13-06/30/16
$300,000 No Salary Support
Indiana University Purdue University Signature Center Initiative Funds
Center for the Cure of Glioblastoma
Goal: To interrogate molecular mechanisms of glioma cell growth and development new therapies for GBM.
Role: Co-Director

Pilot project for collaboration in brain tumor research (Pollok) 06/01/12-12/31/14
$100,000 No Salary Support
The Neurosurgery Foundation at Goodman Campbell and SRI/IUSCC
Identification of brain-permeable MDM2 antagonists and characterization of primary glioblastoma multiform patient cell lines
Goals: to select and characterize HDM2 inhibitors with improved delivery to brain tumors.

(Ivan/Pollok) 01/01/13-12/31/14 No Salary Support
CTSI program development team/ IUH/IUSM Strategic Research Initiative in Neurosciences Program $29,700
Overcoming Resistance to Anti-angiogenic Drugs in Glioblastoma Multiforme by Interfering with Tumor Metabolism
Goals: to determine metabolic molecular signatures of avastin-resistant GBM using in vivo models

IU Simon Cancer Center Pilot Project: Pollok (PI) 06/01/14-05/31/15
$20,000 No Salary Support
Dose finding studies for development of novel combination therapy for disseminated
Neuroblastoma: building upon frontline therapy by blocking MDM2 function
Goals: Validate orthotopic models of neuroblastoma and test efficacy of novel MDM2 inhibitors in the context of standard-of-care therapy

IU Simon Cancer Center Pilot Project: Pollok (PI) 04/01/13-03/31/14
Medicinal and Synthetic Chemistry Core $12,271 No Salary Support
Inhibition of MDM2/MDMx function for the treatment of cancers of the brain in adults and children
Goals: Synthesize novel MDM2/MDMx inhibitors

Indiana CTSI Cores Pilot (Pollok) 09/01/13 – 08/31/15 No Salary Support
Indiana Clinical and Translational Sciences Institute $10,000
Therapy-induced DNA Damage Response Kinetics in Nervous System Tumors measured by imaging flow cytometry using the ImageStreamX Mark II.
Goals: Utilize novel technology to monitor mechanisms of cell death in glioblastoma and neuroblastoma

IU Simon Cancer Center Core Pilot Project (Pollok) 10/01/13 – 9/30/14
Utilizing IUSCC Shared Facilities $20,000 No Salary Support
Analysis of human glioblastoma stem-like cells by multi parametric flow cytometry
Goals: Compare gliomablastoma stem cell frequency in primary patient samples and established GBM cell lines

Astra Zeneca Pharmaceuticals – Division of Global Safety Assessment, (Crosby/Pollok)
$50,000 No Salary Support
Pilot study to assess compound safety profiles in human versus murine hematopoietic transplantation models
Role: co-PI

(Kelley/Murray) 07/01/11-06/30/14 No Salary Support
IUPUI Signature Center Initiative $150,000
Center for Pancreatic Cancer Research
Goals: Improve standard-of-care therapy for pancreatic cancer by investigation of novel small molecule inhibitors that therapeutically modulate newly identified targets in pancreatic cancer cells
Role: Co-Investigator


Publications

E.L. Kreklau, K.E. Pollok, B.J. Bailey, N. Liu, J.R. Hartwell, D.A. Williams, and L.C. Erickson. Hematopoietic expression of O(6)-methylguanine DNA methyltransferase-P140K allows intensive treatment of human glioma xenografts with combination O(6)benzylguanine and 1,3-bis-(2-chloroethyl)-1-nitrosourea. 2003. Molecular Cancer Therapy. 2:1321-1329. PMID: 14707273

S. Cai, Y. Xu, R.J. Cooper, M.J. Ferkowicz, J.R. Hartwell, K.E. Pollok, and M.R. Kelley. Mitochondrial targeting of human O6-methylguanine DNA methyltransferase protects against cell killing by chemotherapeutic alkylating agents. 2005. Cancer Research. 65(8): 3319-3327. PMID: 15833865

S. Cai, J.R. Hartwell, R.J. Cooper, B.E. Juliar, E. Kreklau, R. Abonour, W.S. Goebel, and K.E. Pollok. In vivo effects of myeloablative alkylator therapy on survival and differentiation of MGMTP140K-transduced human G-CSF-mobilized peripheral blood cells. 2006. Molecular Therapy. 13(5):1016-1026. PMID: 16426896

J.L. Fischer, M.A. Suresh Kumar, T.W. Day, T.M. Hardy, S. Hamilton, C. Besch-Williford, A. R. Safa, K.E. Pollok, and M.L. Smith. 2009. The Xpc gene markedly affects cell survival in mouse bone marrow. Mutagenesis. 24:309-316. PMCID: PMC2701989.

S. Araki, J.A. Eitel, K. Bijangi-Vishehsaraei, X.-J Xie, D. Danielpour, K.E. Pollok, D.A. Boothman, and L.D. Mayo. TGF?1-induced expression of HDM2 correlates with late stage metastatic breast cancer. 2010. Journal of Clinical Investigation. 120: 290-302. PMCID: PMC279868.

T. Mani, F. Wang, W.E. Knabe, A.L. Sinn, M. Khanna, I. Jo, G. E. Sandusky, G.W. Sledge, D.R.Jones, R. Khanna, K.E. Pollok, and S.O. Meroueh. Small-Molecule Inhibition of the uPAR-uPA Interaction: Synthesis, Biochemical, Cellular, in vivo Pharmacokinetics and Efficacy Studies in Breast Cancer Metastasis. 2013. Bioorganic & Medicinal Chemistry. 21(7): 2145-2155. PMCID: PMC3625246

S. Cai, H. Wang, A.R. Baluyut, A. Ernstberger, B. Juliar, A.L. Sinn, L.D. Mayo, W. S. Goebel, and K.E. Pollok. Humanized bone-marrow xenograft model as a pre-clinical tool to assess therapy-mediated hematotoxicity. 2011. Clinical Cancer Research. 8:2195-2206. PMCID: PMC3078977

J.A. Mund, H. Shannon, A.L. Sinn, S. Cai, H. Wang, K.R. Pradhan, K.E. Pollok, and J. Case. Human Proangiogenic Circulating Hematopoietic Stem and Progenitor Cells Promote Tumor Growth in an Orthotopic Melanoma Xenograft Model. 2013. Angiogenesis. 16(4):953-962. PMID: 23877751

C.A Campos, J.B. Gianino, B.J, Bailey, M.E. Baluyut, C. Wiek, H. Hanenberg, H.E. Shannon, K.E. Pollok and B.L. Ashfeld. Design, synthesis, and evaluation of curcumin-derived arylheptanoids for glioblastoma and neuroblastoma cytotoxicity. 2013. Bioorg Med Chem Lett. 23(24):6874-8. PMID: 24183537

H. Wang, S. Cai, A. Ernstberger, B.J. Bailey, M.Z. Wang, W. Cai, W.S. Goebel, M.B. Czader, C. Crean, A. Suvannasankhah, I. Shokolenkoc, G.L. Wilson, A.R. Baluyut, L.D. Mayo, and K.E. Pollok. 2013. Temozolomide-mediated DNA methylation in human myeloid precursor cells: differential involvement of intrinsic and extrinsic apoptotic pathways. 2013. Clinical Cancer Research. 19(10): 2699-2709. PMCID: PMC3711223