OHSU

Bill Chang Lab

Laboratory Overview

IDENTIFICATION AND DEVELOPMENT OF NOVEL THERAPIES FOR PEDIATRIC LEUKEMIAS

The Chang Lab focuses on developing novel targets for therapies in pediatric leukemias. The lab 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.

Division of Pediatric Hematology and Oncology

chang-lab-figure

Research Profile

Leukemia is the most common cancer in children and remains a leading cause of disease related mortality in children.  Although pediatric Acute Lymphoblastic Leukemia (ALL) has been hailed as one of the success stories of modern medicine, there remain subsets of leukemias that continue to have a poor prognosis.  Unfortunately, these subsets continue to have highly resistant disease that may not be overcome even with myeloablative therapy and hematopoietic stem cell transplant.  These diseases may have approached the limit of treatment by standard chemotherapeutic regimens.  Therefore, new targets for therapy are needed in hopes to further therapy.

The focus of our research is to use novel techniques such as RNA interference (RNAi and siRNA) to identify new targets for therapy in pediatric leukemias.  Working in collaboration with the Druker Lab and Dr. Jeffrey Tyner, we have been able to identify several novel targets in different subsets of pediatric leukemias.  We are now using this data to develop the biochemical knowledge needed to utilize these targets for therapy.

  1. Screening pediatric leukemias for novel targets.  Currently, we are utilizing a RAPID siRNA assay developed by Dr. Tyner to screen bone marrow samples from pediatric leukemias.  Bone marrow or peripheral blood from patients who are diagnosed with pediatric leukemias (including ALL, AML, CML, MDS, etc) are obtained for screening on this assay.  A new assay developed by Dr. Marc Loriaux using small molecule inhibitors is also utilized on these samples for further validation and development.  Results of these assays on patient samples will eventually lead to a database that can be utilized to understand the biology of resistant disease as well as develop individualized therapies for these diseases.
  2. Survivin as a target for therapy in high risk and very high risk ALL.  Survivin is a small protein that is known to be an inhibitor of apoptosis and a member of the chromosome passenger complex that is crucial for cell cycle progression.  We have recently identified that certain subsets of pediatric ALL are sensitive to inhibition of expression of survivin.  We are currently pursuing further research to understand this mechanism and develop this protein as a target for therapy in these diseases.

 

Contact Us

Doernbecher Children's Hospital
Mailcode: CDRCP
3181 SW Sam Jackson Park Rd
Portland, OR 97239
Phone: 503-494-1543
Fax: 503-494-0714
Email: changb@ohsu.edu