Pollok Lab

The research laboratory of Karen E. Pollok, PhD, focuses on the development of new combination therapies for solid tumors such as glioblastoma and pediatric sarcoma. The overall strategy is to use precision genomics to guide prioritization of targets for study. Emphasis is on investigations that evaluate the therapeutic effect of blocking DNA damage and repair pathways in the context of front-line therapies.

The Pollok Laboratory is heavily invested in team science that integrates bench research with the clinic. The research team represents a highly integrated, collaborative, and dynamic training environment to advance discovery and create pathways cures of adult and pediatric cancers.

Pollok’s expertise and many designations are a strong foundation for synergistic study. She serves as the basic science leader of the Brain Tumor Working Group (BTWG) and the director of the In Vivo Therapeutics (IVT) Core for the NCI-designated Indiana University Simon Comprehensive Cancer Center. She is also the co-director of the Indiana University Purdue University-Indianapolis (IUPUI) Signature Center for Brain and Neurological Tumors.

In addition, Pollok is the associate director (Administrative Core) and an MPD/PI for Project 1 of the U54 Eunice Kennedy Shriver NICHD Specialized Centers in Research in Pediatric Developmental Pharmacology, the co-leader for the summer enrichment program and project leader of the Experimental Mouse Resources Core on the U54 NIDDK Cooperative Centers of Excellence in Hematology. She has also directed the development of ectopic and orthotopic models (brain, ovarian, breast, sarcoma, lung and pancreatic cancers) at IU School of Medicine to streamline resources and processes for multiple investigators.

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Active Research

The Pollok Laboratory is integrating genome, transcriptome and proteome data to discover and validate emerging treatment response networks that can be targeted to prevent tumor resistance to therapy. The laboratory has more than 15 years of experience in preclinical pharmacokinetic and pharmacodynamic (PK/PD) studies, in vivo efficacy studies using tumor xenograft models and toxicology with an emphasis on assessment of therapy-mediated bone marrow toxicity. These studies utilize ectopic and orthotopic humanized adult and pediatric solid tumor models to develop and validate strategic drug sequencing and multiphase treatment strategies to improve therapeutic efficacy.

Currently the laboratory is exploiting mechanistic links between signaling networks that modulate the DNA damage response and DNA repair (Chk1, EZH2, PI3K/Akt, and Mdm2/p53/p73 signaling networks) in GBM and pediatric sarcomas.

Research Funding

Indiana University Center for Pediatric Pharmacology and Precision Medicine (ICPPPM)

Programmatic Goal/Theme:  Biomarkers that predict the efficacy and toxicity of chemotherapies for children with cancer to optimize treatment of individual pediatric patients.

Goals Project 1:  Using a precision medicine approach (incorporating focused NGS based tumor therapeutic strategies to relapsed and refractory pediatric sarcomas

The Development of Thermally-activated Metalloenediynes for Cancer Therapy

Goals: The major goals of this project is to select and characterize Metalloenediyne derivatives using PK/PD and efficacy studies in tumor xenografts.

Development of SHP2 inhibitors for targeted anti-cancer therapy

Goal: screen prioritized SHP2 inhibitors using in vitro and in vivo models of lung and brain cancer.

Preclinical Assessment of Therapeutic Response-Related Molecular Biomarkers in Pediatric Osteosarcomas

Goal: Evaluate novel multi-targeted therapy based on precision genomics data mining of CNVs in osteosarcoma.

Development of a Novel Oncolytic Therapeutic to Treat Glioblastoma

Goal: test novel mammalian reoviruses with increased capacity to induce cell death in models of GBM

Recent Publications

For a full list of Pollok’s publications, find her on PubMed.

J. Carter, L. Cheng, J. Zucker, M. Marshall, K.E. Pollok, M. Murray, L. Li, and J. Renbarger. (2017) Use of Precision Medicine Molecular Profiling of Baseline Tumor Specimen May Not Benefit Outcomes in Children with Relapsed, Refractory, or Rare Pediatric Sarcomas. Clin Pharmacol Ther. Mar;101(3):328-330. PMCID: PMC5511378.

H. Wang, S. Cai, B.J. Bailey, M.R. Saadatzadeh, E. Tonsing-Carter, J. Ding, T.M. Georgiadis, T.Z. Gunter, E.C. Long, R.E. Minto, K.R. Gordon, S.E. Sen, W. Cai, J.A. Eitel, D.L. Waning, L.R. Bringman, C.D. Wells, M.E. Murray, J. Sarkaria, L.M. Gelbert, D.R. Jones, A. Cohen-Gadol, L.D. Mayo, H.E. Shannon, and K.E. Pollok. 2017. Combination therapy in a xenograft model of glioblastoma: enhancement of the antitumor activity of temozolomide by an Mdm2 Antagonist. J Neurosurgery. 126(2):446-459. doi: 10.3171/2016.1.JNS152513. Epub 2016 May 13; PMID: 27177180.

K. Bijangi-Vishehsaraei, M. Reza Saadatzadeh, H. Wang, A. Nguyen, M. M. Kamocka, W. Cai, A.A. Cohen-Gadol, S. L. Halum, J. N. Sarkaria, K. E. Pollok*, and A. R. Safa. (*co-corresponding authors). 2016. Sulforaphane suppresses growth of glioblastoma (GBM) cells, GBM stem cell-like spheroids, and tumor xenografts through multiple cell signaling pathways. 2017. Journal of Neurosurgery, Epub 2017 Jan 6.

E. Tonsing-Carter, A.L. Sinn, J. Silver, K.M. Peterson, B.J. Bailey, C.M. Eischen, H. Wang, H.S. Shannon, J. Ding, S. Cai, P.R. Territo, G.E. Sandusky, L.D. Mayo, J. Li, C.B. Marchal, H. Hanenberg, and K.E. Pollok. 2015. Potentiation of carboplatin-mediated DNA damage by the MDM2 modulator Nutlin-3a in a humanized orthotopic breast-to-lung metastatic model. Mol Cancer Ther, 14(12):2850-63. PMCID: PMC4674357 Featured Highlight Article.

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.

Faculty Research Team

13544-Pollok, Karen Karen E. Pollok, PhD

Karen E. Pollok, PhD

Caroline Symmes Professor of Pediatric Cancer Research

4951-Saadatzadeh, Mohammad Mohammad R. Saadatzadeh, PhD

Mohammad R. Saadatzadeh, PhD

Associate Research Professor of Pediatrics

17201-Pandya, Pankita Pankita H. Pandya, PhD

Pankita H. Pandya, PhD

Assistant Research Professor of Pediatrics

Additional Research Team Members:

The research team also includes Adily Elmi, MS (Research Associate), Barbara Bailey (Senior Research Technician, Lab Manager), and Courtney Hemenway (Research Technician). Research staff within the In Vivo Therapeutics Core include Dawn Bullock (Research Technician), Melissa Trowbridge (Research Technician), and Tony Sinn (Core Manager). Within the Angio BioCore, research staff includes Matt Repass (Research Technician) and Emily Sims (Core Manager).