Room: R4 302D
Karen E. Pollok, PhD
Associate Professor of Pediatrics
Adjunct Associate Professor of Pharmacology & Toxicology
Director In Vivo Therapeutics Core
Co-Director Signature Center Initiative for the Cure of Glioblastoma
Basic Science Leader Brain Tumor Working Group
- B.S.: College of William and Mary
- PhD: University of Kentucky
- Fellowship in Microbiology & Immunology: Indiana University School of Medicine
- Fellowship in Pediatrics: Indiana University School of Medicine
Current Research Interests:
Dr. Pollok has over 15 years of experience in hematopoiesis, experimental therapeutics, toxicology, in vivo imaging, and orthotopic cancer xenograft modeling. Dr. Pollok’s research program focuses on the development of new treatments and refinement of existing treatments for solid tumors such as glioblastoma (GBM), neuroblastoma, sarcoma and other relapsed, refractory disease.
Dr. Pollok has built a solid infrastructure at IU in studying relapsed and refractory cancers, especially in the brain. She is the leader of an institutional Brain Cancer Translational working group with a diverse group of health professionals in an effort to further influence the field of brain cancer research. She was instrumental in building this team from the ground up. This group received just one of two awards given in 2013 by Indiana University Purdue University (IUPUI) which provides funds to disease-focused research teams showing potential to truly make an impact in biomedical research and patient care. The IUPUI Signature Centers Initiative, an intercampus collaborative group of 50 clinicians and researchers, seeks to understand both primary and secondary brain tumors in adults and children. At this time, her group’s primary focus is GBM as a primary or secondary tumor. GBM is among the most difficult-to-treat brain tumors, and there are currently no effective cures for highly invasive solid tumors such as GBM.
The overall therapeutic strategy is to study the therapeutic effect of blocking DNA damage and repair pathways in the context of front-line therapies. The use of primary patient specimens and clinically relevant human tumor models is a priority. The cancer research projects build upon standard-of-care regimens currently used in the clinical setting at Riley Hospital for Children and incorporate small molecule inhibitors that target aberrant cell survival pathways in these devastating cancers. Orthotopic humanized adult and pediatric tumor models are being used to evaluate therapeutic potential of standard-of-care cytotoxic agents in combination with small molecular inhibitors that block the Akt and Mdm2 signaling networks since there is regulatory crosstalk between these signaling pathways. The use of intermittent dosing regimens that minimize therapy-mediated bone-marrow toxicity as well as the pharmacokinetic and pharmacodynamic characteristics of these innovative and unexplored combination treatments are being pursued. Furthermore, there is an urgent need to identify and characterize new therapeutics that can be delivered at biologically effective doses to tumors in the brain. In collaborative efforts, in vitro and in vivo screening assays are being used to identify compounds that have the potential to block Akt- and Mdm2-mediated signaling but also may have a higher propensity to cross the blood-brain-barrier and the blood-tumor-barrier. Her research team is poised to significantly contribute to the field of brain cancer research.
Because of her strong hematopoiesis background, Dr. Pollok’s lab also continues to develop novel ways to assess normal bone-marrow toxicity since this compartment is particularly sensitive to anti-cancer therapies. A humanized bone-marrow mouse model to screen for regimen-induced toxicities is being studied with an industry partner to determine the predictive value of this model with the goal of utilizing this as an additional screen for normal tissue toxicity of novel scaffolds and anti-cancer regimens.
Dr. Pollok is also heavily involved in driving the ‘bench’ studies for the new Riley Children’s Hospital Precision Genomics in Partnership with IU Health - a pediatric-specific clinical program in collaboration with Dr. Jamie Renbarger, MD, MS. The Riley Hospital for Children at IU Health and the Department of Pediatrics at IU School of Medicine have an exciting opportunity to be leaders in growing the scope and services of pediatric cancer treatment in the establishment of a pediatric-specific clinical program. Cutting-edge research and a pediatric-specific tumor platform will be developed in collaboration with Paradigm, a next-generation and CLIA-approved cancer diagnostic designed to provide patients and physicians with a blueprint of the underlying mechanisms of a patient’s disease, potential treatment approaches, and comprehensive inventory of relevant clinical trials. The Riley Center for Pediatric Precision Genomics will use changes in tumor genetics or gene expression in combination with germ line genetics to provide individualized treatment recommendations for children with aggressive cancers. This personalized medicine approach calls for choosing a treatment plan based on the patient’s underlying mutations, rather than the one-size-fits-all approach of standard chemotherapy. The center’s process includes a combination of sophisticated genetic sequencing of tumor tissue, germ line (host) genetic testing, and bioinformatics, and assessing efficacy and toxicity of a particular drug in recommending therapeutic options to a patient. There remains a subset of patients who have a very poor prognosis due to tumor type or stage at presentation, or who have a dismal prognosis with relapse or recurrence. As such, innovative approaches to therapy are clearly needed. Because her lab is intricately involved in researching therapies for metastatic forms of neuroblastoma and sarcoma coupled with her strong expertise, Dr. Pollok will direct the bench efforts of building an infrastructure, including patient-derived and molecularly characterized cell lines as well as humanized models similar to what she has done in her own research lab, to begin to define important biologic and genetic components of childhood cancer that can guide research and therapy in collaboration with Dr. Jamie Renbarger and other Pediatric Oncologists working on Pediatric relapsed and refractory disease. Specific research areas include:
- Development of adult and pediatric GBM intracranial models (in collaboration with Dr. Aaron Cohen, MD, MS)
- GBM Molecular Signatures and Personalized Medicine
- • Targeting and Optimizing Cancer Therapy to the Individual including clinical pharmacology of anti-cancer drugs, genetic assessment of each patient’s ability to tolerate treatment and identification of genetic biomarkers in DNA and proteins that predict therapy response (in collaboration with Dr. Jamie Renbarger, MD, MS, Pediatric Hematology/Oncology)
- Identifying the underlying mechanisms regulating cancer stem cells (drug resistance)
- Tumor model development including tumorspheres and humanized orthotopic animal models for pediatric relapse and refractory disease (neuroblastoma, sarcoma)
- Novel therapeutic approaches that combine front-line low-dose alkylating and platinum agents and targeted therapies to treat solid tumors – brain cancers, neuroblastoma, and sarcomas
- Mechanisms of therapy-induced cytotoxicity in normal hematopoietic bone marrow cells
- Protection of bone marrow cells from therapy-mediated cytotoxicity
- Assessment of drug delivery to brain tumors (Blood-Brain-Barrier Permeability)
Molecular targets and signaling pathways of interest:
- DNA damage response
- DNA repair pathways – direct reversal repair/MGMT, base excision repair (BER), nucleotide excision repair (NER)
- Mdm2 (p53-dependent and p53-independent functions)