Kiwanis Childrens Fair in St Helens

The Pediatric Cancer Biology Program was honored to participate in the Kiwanis Children's Fair in St Helens, Oregon.  This event raises awareness of child safety issues as well as educates and entertains.  The Pediatric Cancer Biology Program had a booth with 3D images of scientific topics.  We sincerely thank the Kiwanis for activities like this one that support the Pediatric Hematology Oncology Fellowship Program at Doernbecher Children's Hospital (OHSU).

Upcoming Talk by Dr. Robert Krauss

Robert Krauss, P.h.D. will be speaking as a PCB invitee for the Knight Cancer Institute Seminar Series on November 30, 2010 in the OHSU Main Hospital 8th Floor Conference Room (8B60).  Dr. Krauss, Professor of Developmental and Regenerative Biology at Mount Sinai School of Medicine, is a developmental biologist with interests in the Sonic Hedgehog pathway.  His work is relevant to cancer as well as neurology and neuroscience. Dr. Krauss will be presenting a seminar titled: “Modeling the Holoprosencephaly Spectrum in the Mouse: Regulation of Sonic Hedgehog Signaling by Co-receptors.”

  

more about Dr. Krauss' research:

 

The Krauss lab is interested in regulation of cell adhesion and signal transduction pathways during development and how such processes may go awry in disease. We have focused much of our effort on a small group of complex and multifunctional receptor-like proteins of the Ig superfamily. Cdo and Boc have Ig and FnIII repeats in their ectodomains and long, divergent cytoplasmic tails. Cdo and Boc function as components of cell surface protein complexes to influence signaling by cadherins, netrins and Sonic hedgehog (Shh). Cdo promotes skeletal myogenesis in vivo and in vitro. Cdo binds in a cis manner (in the plane of the same cell membrane) to the cell-cell adhesion molecule N-cadherin. N-cadherin ligation during myoblast differentiation stimulates binding of Bnip-2/Cdc42 and JLP/p38a/b complexes to the intracellular region of Cdo and thereby links extracellular cell-cell contact to activation of a pathway (p38a/b) that controls a cell-type specific transcriptional program. In addition, Cdo binds in a cis manner to the netrin and RGM receptor, neogenin to influence netrin-mediated signaling during myogenesis.

 

Cdo and Boc also function as both components and targets of the Hedgehog signaling pathway and feedback network. Cdo and Boc bind directly to Sonic hedgehog (Shh) and promote Shh signaling. Mice lacking Cdo or Boc display tissue-specific loss-of-Shh function phenotypes. Cdo-null animals display holoprosencephaly (HPE). HPE is one of the most common human birth defects and is associated with haploinsufficiency for genes encoding Shh pathway components. Clinical expression of HPE is extremely variable, but it is rarely associated with defects in other Shh-dependent structures, such as the limbs. Mice lacking Cdo display HPE with strain-specific severity and without limb defects, modeling human HPE and implicating silent modifier genes as a cause of variability. Boc-null mice are viable, but removal of Boc from Cdo mutant mice worsens the latter’s HPE phenotype. We have used these mice to develop additional models of HPE that include gene-environment interactions and recapitulate the major features of human HPE.

The Neuwelt Laboratory

Dr. Edward Neuwelt is a neurosurgeon and leader of the Blood Brain Barrier and Neuro-Oncology Program at OHSU, as well as organizer of the Blood-Brain Barrier (BBB) Consortium.  Dr. Neuwelt's large and active laboratory investigates not only novel methods for imaging primary brain tumors and their leptomeningeal metastases, but his group has developed leading preclinical models for testing therapeutic strategies for pediatric metastatic brain tumors, including medulloblastoma. 

The Grompe Laboratory

The laboratory of Markus Grompe investigates the biology of liver and pancreas stem cells.  This work has important implications for the development of embryonal (pediatric) and adolescent cancers, namely hepatoblastoma and hepatocellular carcinoma.  Dr. Grompe is a medical geneticist with expertise in metabolic disorders and Fanconi Anemia.  He is also Director of the Oregon Stem Cell Center and the Pape' Family Pediatric Research Institute.   
  
[ right:  an exciting recent study published in Nature, describing an unprecedented biological process whereby normal liver cells are capable of increasing their chromosome number, without apparent predisposition to cancer developing. ]  
   

The Fleming Larboratory

The laborator of Dr. W. Harv Fleming investigates the factors related to normal and abberant myelopoeisis and the interaction with the microenvironment (vascular endothelium), specifically in the context of acute myelogenous leukemia. 
 

[ left:  human leukemia cells integrating into the vascular endothelium in  a NOD/SCIDg-/- mouse ]

The Druker Laboratory

The Druker Laboratory  at OHSU is distinguished for its work in developing molecularly-targeted, non-chemotherapy treatments of leukemia.  Dr. Druker is the recipient of the 2009 Lasker-DeBakey Award for this pioneering work, which opens the door to personalized therapy for a wide range of cancers. 

Current projects in collaboration between the Keller laboratory and the Druker complement ongoing childhood cancer research programs within the Druker laboratory, including that of:

Dr. Jason Glover (pediatric hematology-oncology fellow) studies the role of kinases in cell signaling of pediatric cancers.  Dr. Glover's project takes the approach of using high throughput siRNA technology and small molecule inhibitor panels to understand the processes of tumor initiation, maintenance and progression.  Dr. Glover's primary area of focus is the pediatric solid tumor, neuroblastoma, which is among the 5 most frequent causes of mortality in childhood cancer.

Dr. Bill Chang (Assistant Professor, pediatric hematology-oncology) is investigating novel targets for therapies in pediatric leukemias. Dr. Chang utilizes a translational approach using RNA interference technologies to screen and identify functional biochemical targets from patient samples that have the potential to be developed for therapy.

The Kurre Laboratory

The Kurre Laboratory is interested in understanding the process by which leukemia cells actively alter the bone marrow microenvironment to promote chemotherapy resistance and relapse. 
 

The Keller Laboratory

The Keller Laboratory  at OHSU  studies the driving mechanisms and therapeutic targets in the childhood muscle cancers, alveolar rhabdomyosarcoma and embryonal rhabdomyosarcoma, and the childhood brain tumor, medulloblastoma.

You Can Participate in our Novel Therapeutics Studies !

One would like to think that tangibly better treatments for rhabdomyosarcoma, medulloblastoma and other childhood cancers can be found in a matter of years, instead of tens of years. Finding new treatments starts with research, perhaps even a new research approach to identifying effective new treatments. The Pediatric Preclinical Testing Initiative (at the Pediatric Cancer Biology Program, Pape' Family Pediatric Research Institute, Oregon Health & Science University) focuses on finding molecules in childhood cancers that can be directly turned off or on by drugs so that the tumor stops growing. Behind our novel approach is the use of genetically-engineered mice. Our Pediatric Preclinical Testing Initiative uses mice modified from before birth so that at a certain age, and in a certain tissue, the same mutations found in a child’s cancer are activated in the mouse. These special mouse models of childhood cancer can be used to test a treatment to see whether the tumor growth and spread (metastasis) can be reversed. The specific aspect of these mice having normal immune systems is a real plus, too, because white blood cells play an important role in how tumors evolve and respond to therapy.

Our program is designed around community participation. Through the Doernbecher Children's Hospital Foundation at OHSU, you can contribute directly to this grass-roots initiative. Donations through small gifts or grants will assist in studying compounds that may be effective in treating such childhood cancers as alveolar rhabdomyosarcoma, embryonal rhabdomyosarcoma, or medulloblastoma (the alveolar rhabdomyosarcoma model was featured by Dr. Keller's long time collaborator and former mentor, 2007 Nobel laureate Mario Capecchi, in his Nobel Prize lecture.) For example, a grant of $10,400 enabled the PPTI to study a promising multi-kinase inhibitor in mice with alveolar rhabdomyosarcoma.

For additional information regarding supporting this program please contact Ms. Sue Nicol, Doernbecher Children's Hospital Foundation, at nicols(at)ohsu.edu . For additional information on this program, please contact PPTI leader Dr. Charles Keller at keller@ohsu.edu. Results obtained through these studies will be shared with the National Cancer Institute’s Cancer Therapy Evaluation Program, as well as the Children’s Oncology Group, which designs clinical trials for childhood cancer.

Organizational Structure of the PCB Program

Pediatric Cancer Biology is a program of the Pape' Family Pediatric Research Institute at the Oregon Health & Science University (OHSU).  We are within the Department of Pediatrics but closely affiliated with the Knight Cancer Institute.  We have basic science laboratories, as well as a preclinical therapeutics program (the Pediatric Preclinical Testing Initiative) which is affiliated with the National Cancer Institute's cancer therapy evaluation program that investigates new drugs for treating childhood cancer.  
  
[ org chart updated 2/16/2011 ]
  

 

Strategic Plan

Our goals in the first 5 years are:

to successful partner basic science laboratories with the OHSU Pediatric Oncology Phase I Clinical Trial Program in order to develop 4 or more effective, molecularly targeted therapies,

to recruit 2 additional basic science laboratories in the areas of brain tumor (glioma) and neuroblastoma biology,

to  develop a $100M endowment as a key element to the second phase of recruitment and program building.

Welcome from the Program Leader

Tremendous progress has been achieved in childhood cancer long term survival since the initial pioneering work of Don Pinkel and Joe Simone.  The cure rate for childhood cancers as a group is approaching 80% *.  The challenge for our Program is to address the causes of mortality in the the remaining 20% of children, with a sense of urgency and accountability, and through multidisciplinary collaboration.  The cornerstone of our program is our institution’s expertise in sarcomas and hematological malignancies.  We will expand the scope of our endeavors strategically over the next 5 years, and community participation and relationships with the pharmaceutical industry will be driving forces in our enterprise.


Charles Keller, MD
Leader, Pediatric Cancer Biology program
Oregon Health & Science University

Please see also our Organizational Structure, and our Five Year Strategic Plan.

* American Cancer Society Facts & Figures 2009

[ below:   Causes of Childhood Cancer Mortality.   adapted from  cdc.gov/mmwr/preview/mmwrhtml/mm5648a1.htm (2004) ]