Histio Heroes Research Fund -- Research Goals

What is the goal of the research that Histio Heroes Research Fund is supporting?

The overall goal of the Histiocytosis Research Program at Texas Children’s Cancer Center is to comprehensively identify essential genes critical to the growth and development of Langerhans Cell Histiocytosis (LCH). Identifying these genes will lead to an understanding of the key proteins that regulate cell function and the pathways they control. The knowledge gained will lead to a complete understanding of how LCH lesions are formed and how they progress. This complete understanding will ultimately lead to better treatments and a cure for this disease.

What types of research activities will the Histio Heroes Research Fund be supporting over the next five years?

The Histiocytosis Research Program at Texas Children's Cancer Center has four areas of focus:

Comprehensive Analysis of Cell-Specific Gene Expression in LCH Tumors

This project is the core of our research program. It is based on the idea that we cannot improve treatment of patients with LCH until we understand the fundamental nature of the cells that comprise LCH lesions. These lesions can arise in almost any organ system, and their severity can range from a rash to systemic disease that obstinately resists chemotherapy.

Data from our cell-specific microarray experiments do not support the current concept that LCH arises from clonal proliferation of activated-immature Langerhans’ cells (LCs) from the skin. We propose an alternative hypothesis that LCH tumors arise from pathologic myeloid dendritic cells that affect lymphocyte activation, migration and accumulation.

Developing Unique Models for Preclinical Drug Screening

A significant obstacle in developing novel therapies for LCH has been the lack of a preclinical model that accurately mimics LCH in humans to predict clinical response. The large number of samples acquired by our laboratory now makes it possible to attempt development of cell culture and animal models that may be used to study disease progression and test therapies.

Developing a Comprehensive Genomic Database

We also plan to develop a comprehensive genomic database for LCH, JXG, RDD, ECD, and malignant histiocytosis that will be used by Texas Children’s investigators and also by collaborators from various institutions in the United States and around the world. This genomic database will help identify novel therapeutic targets based on the genetic changes unique to histiocytic diseases.

Implementing High Throughput Therapeutic Drug Validation Strategies

Once we have identified potential drug targets using the gene profiling studies described above, we will perform high-throughput studies to validate these possible targets. For this crucial step, we have the special advantage of being able to use highly sophisticated technologies now available to us through the recent establishment of the John S. Dunn Gulf Coast Consortium for Chemical Genomics. Using this state-of-the-art facility, we propose to use siRNA approaches to independently validate the function of the candidate genes and pathways by either targeted inactivation or by using whole genome siRNA libraries.

We will also use the chemical genomics approach as part of the target validation process. The compounds identified at this stage could be used both as chemical probes to further dissect the pathways and as potential lead compounds in the subsequent drug development phase of the project.

Why should you get involved with HHRF and support this research?

Establishment of a focused, intensive LCH research program will improve our understanding of the biology of LCH and other histiocytic diseases and facilitate identification of new molecular targets. Most importantly, this unique program—if funded and executed as planned—will lead to more effective treatments and potentially a cure for Langerhans’ Cell Histiocytosis.

You can learn more about this research and how to become involved by going to the Histio Heroes Research Fund page on Facebook --

http://apps.facebook.com/causes/424806

Please feel free to post any comments or questions about HHRF or this research.

The HHRF Parental Advisory Board

Betsi Burns

Bridget & Patrick Colby

Mike Golding

Toby & Billi Jo Hausman

Darci Moon

Donna & Don Johnson

Pam & Tom Sanger

Melissa & Jeff Thompson

Colleen McPeek & Ron Bechtold