OHSU Doernbecher Pediatric Cancer Program will represent Oregon on StoryCorps’ National Day of Listening, Nov. 26

Sarcoma patients, their families, physicians, nurses and volunteers will gather at OHSU Doernbecher on the day after Thanksgiving to preserve their stories for future generations. 

StoryCorps, one of the largest oral history projects of its kind, has asked the Pediatric Hematology/Oncology division at OHSU Doernbecher Children’s Hospital to be an official representative in Oregon for the 2010 National Day of Listening.

About 25 OHSU Doernbecher patients, family members, volunteers, nurses and physicians will preserve their stories of courage, strength and hope for future generations by recording an interview with someone they care about. All of the patients have, or have had, sarcoma, a cancer that occurs in the muscle, fat, fibrous tissue, blood vessels or other supporting tissue of the body. A synopsis of their stories will be posted on the “Wall of Listening,” on the National Day of Listening Web site and recorded on a free CD to share.

“We hope to eventually expand on StoryCorps’ ‘National Day of Listening’ and allow all of our patients to be interviewed,” said Rae Acosta, R.N., research nurse coordinator in the Division of Pediatric Hematology/Oncology, OHSU Doernbecher Children’s Hospital.

WHERE:        OHSU Doernbecher Children’s Hospital first-floor lobby, 700 S.W. Campus Drive, Portland

WHEN:           Friday, Nov. 26, at 9 a.m.

DETAILS:      The 2010 “National Day of Listening” marks the first time StoryCorps has had "official state representatives." To become an official state representative, organizations must conduct at least five National Day of Listening interviews with members of their organization or others in their community and post a summary of those interviews on the "Wall of Listening."

This outreach initiative was made possible through a National Cancer Institute grant resulting from the Carolyn Price Walker Act. The grant, awarded to Charles Keller, M.D., F.A.A.P., and Melissa Hill of the Northwest Sarcoma Foundation, specifically allocates resources for a StoryCorps Outreach Initiative.  Credit for the project concept goes to Dr. Linda Stork, Division Chief of Pediatric Hematology/Oncology.  The Co-organizing the StoryCorp project with Acosta is Keller laboratory research scientist Jennifer Alabran.

The National Day of Listening is a new national holiday started by StoryCorps in 2008. On the day after Thanksgiving, StoryCorps asks all Americans to take an hour to record an interview with a loved one, using recording equipment that is readily available in most homes, such as computers, iPhones, and tape recorders, along with StoryCorps’ free Do-It-Yourself Instruction Guide. StoryCorps is an independent nonprofit whose mission is to provide Americans of all backgrounds and beliefs with the opportunity to record, share, and preserve the stories of our lives.

This information is also at:  http://www.ohsu.edu/xd/about/news_events/news/2010/2010-11-24-ohsu-doernbecher-pe.cfm   

OHSU Doernbecher Children’s Hospital Development Therapeutics Program

The principal aim of the Doernbecher Children’s Hospital Development Therapeutics program is to evaluate novel agents for the treatment of pediatric cancer through early phase clinical trials. We conduct Phase I and Phase II trials of potentially promising new drugs for the treatment of all types of childhood cancer.  Doernbecher is one of 21 select institutions throughout North America who comprise the NCI-funded Children’s Oncology Group Phase I Consortium.  Through our participation in COG early phase trials, industry-sponsored trials, and investigator-initiated studies, we hope to find better therapies for the treatment of childhood cancer.

  

The principal investigator of the Doernbecher Children’s Hospital Development Therapeutics program is pediatric hematologist-oncologist, Dr. Suman Malempati.  For a recent discussion by Dr. Malempati on a targeted therapy for childhood sarcomas, see the November 16th  NCI Cancer Bulletin.  Integral, too, to the Development Therapeutics program is Rae Acosta, RN.  

Why we do what we do!

From my earliest days on the wards as a medical student, I was struck by the courageousness of children and adolescents with cancer - and the inability of current medical practices to offer long term survival to such a large fraction.

Later, as a new pediatric hematology oncology fellow, I cared for a vibrant adolescent/young adult with rhabdomyosarcoma, a type of muscle cancer. In the space of one year, I attended both her engagement party and her funeral. This result repeated itself year after year for patients with the same disease.

I was sure someone would make a breakthrough, but in stepping back from the situation I realized that the lack of breakthroughs dated from 1972. If there were to be a change, I needed to be the catalyst for that change. With my love for research (as well as some luck in being in the right environment at the right time), I knew what my mission should be: Unravel the biology of these kinds of tumors and bring tangible, effective new treatments to the clinic.

Almost a decade after caring for that young woman with rhabdomyosarcoma, I find myself the inaugural leader of the Pediatric Cancer Biology Program at OHSU. Our program’s mission is to understand refractory childhood cancers.

In its first phase, our Program will address not only soft tissue and bone sarcomas, but also brain tumors and neuroblastoma.  My own laboratory anchors the Program with study of rhabdomyosarcoma as well as medulloblastoma, the most common malignant childhood brain tumor of childhood. Using genetically modified mice and other tools, my laboratory’s research team seeks molecules in tumors that can be directly turned on or off by drugs, so that the tumor stops growing & spreading.

We pursue these goals with urgency and accountability, and importantly, through collaboration with colleagues in the physical sciences. Our belief is that new treatments should be made available in the next one to four years, rather than 25 to 50.  Said simply, we hope to develop personalized, non-chemotherapy treatments for children with cancer.

Why Portland, and why now? OHSU is a fantastic place to be. I believe that in the next three to seven years that Brian Druker, M.D., Director, OHSU Knight Cancer Institute, will be increasingly recognized not only for developing a non-chemotherapy treatment for Chronic Myelogenous Leukemia, but also as an international leader for personalized medicine.

I have seen how transformational this kind of recognition can be for an institution, and rest assured all the world’s eyes will soon turn to OHSU.

What they will find is something very special:  a community of citizens and researchers working side by side building the infrastructure and creating the discoveries that pioneer personalized cancer care in the here and now.

Charles Keller, MD

Leader, Pediatric Cancer Biology Program

OHSU

[ this post is also available here . ]

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) ]