Mouse Models

The strength of the PPTI is its use of genetically engineered mouse models to study the effect of drugs on particular kinds of cancer.   In the past, cancer models used mice with weakened or missing immune systems that added in cancer cells to watch their growth (xenografts).  This method has yielded many great results but we know that cancer interacts heavily with the immune system interact so this is a major drawback of the model to consider.  Another concern is the location of the tumors that grow – the cancer cells are added in places that are easy to get to and are not necessarily the natural site of development.  

Both of these issues are addressed in the PPTI models of cancer in that the mice have normal immune systems and are genetically modified so that their tumors begin and expand in the places that are found in patients.  Combined with other changes that allow us to “see” these tumors as they develop we believe that we have a unique opportunity to find effective treatments faster than ever before.

A Word from Charles

             As a physician-scientist, my laboratory is devoted to the development of novel molecular therapies for advanced childhood solid tumors associated with high morbidity or mortality. To achieve this goal, my laboratory utilizes physiologically-accurate, genetically-engineered mouse models (GEMMs) of three related pediatric small round blue cell tumors: medulloblastoma, alveolar rhabdomyosarcoma and embryonal rhabdomyosarcoma. Medulloblastoma is a childhood brain tumor with a predilection for leptomeningeal metastasis for which radiation-sparing treatments are needed, whereas alveolar and embryonal rhabdomyosarcoma are aggressive muscle cancers that are difficult to cure if not completely resected or if metastatic. The long-term emphasis of my laboratory’s research is the investigation of tumor progression, since advanced disease remains the greatest challenge in the treatment of children with these cancers. The ultimate goal of my research program is to develop pre-clinically tested, molecularly-targeted therapies to halt progression or induce regression for gross residual disease, metastatic disease and relapsed disease.

Accelerating Drug Discovery

We are very excited to welcome the newest member of our equipment crew:  the Eppendorf epMotion 5075!  (Shown here with Jinu Abraham, PhD, our Scientific Manager.)  This machine will give us high throughput capabilities that will be critical for getting drugs into the testing process and out into trials as fast as possible (with the least amount of human error!)  This instrument is also central to the forthcoming Personalized Medicine effort for childhood cancer at OHSU.    Check back to see it in action!

Scientific and Operational Managers: Jinu Abraham and Elaine Huang

Jinu Abraham, PhD earned his doctoral degree in Molecular and Cellular Biology and as a postdoctoral researcher in the Keller laboratory has been investigating how rhabdomyosarcoma can, over time, begin to develop resistance to treatment by a class of drugs called tyrosine kinase inhibitors.  He is the driving force behind the analysis and selection of novel therapeutic agents to be tested by the PPTI. 

Elaine Huang, MSc received her M. Sc. in Immunology and begain working in an industry-sponsored GLP/GMP clinical cell and vaccine production facility.  More recently she has been employed in a facility dedicated to generating genetically modified mice for the research community of OHSU.  The PPTI will utilize her experience with animals and familiarity with industry standards to streamline the testing and analysis of drugs.

Good times with the Papé Family Pediatric Research Institute and the Oregon Stem Cell Center!

Many thanks to the Papé Institute and the OSCC for a fun filled picnic/barbeque/potluck yesterday evening!  Laboratory and administration members and their families all gathered to enjoy food, music, games and each others' company in Gabriel Park on a picturesque Portland summer evening.  With two grills firing and the loads of homemade treats that were brought in, no one left hungry!

Introducing Charles

Dr. Keller is a board-certified pediatric oncologist and NIH R01-funded investigator specializing in the development of more effective, less toxic therapies for the childhood muscle cancer, rhabdomyosarcoma, and the childhood brain tumor, medulloblastoma. His special interest is advanced disease that has spread beyond the initial location of the cancer. Dr. Keller is investigating whether the genes thought to be responsible for the initial tumors are also important when the disease progresses, thereby identifying targets for new medical therapies. To address these diseases, Dr. Keller's laboratory encompasses a multidisciplinary team with expertise in genetically-engineered mouse models, biochemistry and biomedical engineering. Dr. Keller is a Full Member of the Soft Tissue Sarcoma Committee of the Children's Oncology Group (COG) and a participant in the COG Central Nervous System Biology Committee (groups which identify new opportunities for diagnosis and treatment of childhood sarcomas and brain tumors). Dr. Keller is also a Consultant to the Pediatric Preclinical Testing Program sponsored by the National Cancer Institute. Dr. Keller has authored more than 35 scientific publications.

Dr. Keller joined the Pape' Family Pediatric Research Institute, Department of Pediatrics, as Leader of the Pediatric Cancer Biology Program in June of 2010 as an Associate Professor and the Tarshis Professor of Pediatric Hematology-Oncology. Dr. Keller also directs the Pediatric Preclinical Testing Initiative in the Pape' Family Pediatric Research Institute. Dr. Keller is also a Member of the Knight Cancer Institute and the Oregon Stem Cell Center. Dr. Keller was previously a Founding Principal Investigator of the Greehey Children's Cancer Research Institute at the University of Texas Health Science Center in San Antonio. For his education, Dr. Keller attended Tulane University where he received a degree in Biomedical Engineering prior to attending Baylor College of Medicine where he received his M.D. degree. After completing his internship and residency in Pediatrics at Texas Children's Hospital Dr. Keller trained in Pediatric Hematology-Oncology at the University of Utah and as a K08-funded postdoctoral fellow in the laboratory of 2007 Nobel laureate, Mario R. Capecchi.

Strengths
- Expertise in growth factor biology as a therapeutic target in pediatric cancers
- Specialization in the development of state-of-the-art genetically-engineered mouse models of human disease
- Interests in both basic science and therapeutic approaches for childhood cancer (that is, defining the cell of origin of a cancer then developing a treatment approach which best stops growth of a tumor based on this knowledge)
- Firm commitment to training the next generation of physician-scientists and multidisciplinary pediatric cancer biologists

Welcome

The Pediatric Preclinical Testing Initiative (PPTI) at the Papé Family Pediatric Research Institute of the Oregon Health and Science University (OHSU) has been established with the mission of identifying novel targeted therapies for childhood cancer and other diseases using genetically-engineered mouse models. For childhood cancers, the PPTI works in partnership with the Cancer Therapy Evaluation Program (CTEP) at the National Cancer Institute (NCI)to discover new, molecularly-targeted therapies that are more effective and less toxic than traditional chemotherapy.

We are a team of scientists from diverse backgrounds - biomedical engineering, biochemistry, immunology - who are dedicated to the performance of leading-edge research that will improve the outcomes of children who find themselves battling pediatric illnesses. For the childhood cancers rhabdomyosarcoma and medulloblastoma, the last three to four decades of research have not resulted in a significant improvement in children diagnosed with advanced forms of these cancers despite the earnest efforts of scientists across the globe. The PPTI will directly test the effect of newly developed drugs in these and other childhood diseases in collaboration with other universities and pharmaceutical companies alike in order to identify treatments that have the best chance of making a difference in a child's life.