University of Texas Southwestern Medical Center at Dallas

University of Texas Southwestern Medical Center at Dallas

5323 Harry Hines Blvd.

Dallas, TX 75235

United States

The Role of Pyruvate Dehydrogenase in Leukemia

Different cancers start from different types of normal stem and progenitor cells in tissues. This raises the possibility that the molecular makeup of cancers, and how vulnerable they are to therapies, is to some extent inherited from their cell types of origin. We recently developed a new technique that can measure the small molecules of cellular metabolism in rare cell types isolated from tissues. This allows us to compare the metabolism of cancer cells with the metabolism of their normal cells of origin.

Genetic Models of Ewing sarcoma

Ewing Sarcoma

Background

Ewing’s sarcoma occurs when pieces of two chromosomes break and abnormally fuse together, creating a novel, aberrant protein called EWS-FLI1. EWS-FLI1 then acts in an unknown way to cause the cell to become cancerous, starting the process that leads to a Ewing's sarcoma tumor. Current treatment of children with Ewing's sarcoma, including chemotherapy, radiation and surgery, can be very successful but at the price of causing severe side effects. Clearly, there is a tremendous need for better approaches.

DICER1-Driven Cancers: Models, Mechanisms and Therapies

Wilms Tumor

Background

We recently sequenced Wilms tumors, a childhood kidney cancer. We discovered a novel type of missense mutation at position G1809 in the enzyme DICER1, a critical part of the microRNA biogenesis machinery. This mutation, which appears to distort the geometry of the DICER1 active site, destroys the ability of DICER1 to produce the let-7 class of tumor-suppressing microRNAs.

The Role of MiRNA Impairment in Wilms' Tumor Formation

Wilms Tumor

Background

Wilms' tumor is the most common pediatric kidney cancer. While many patients are cured, children with high-risk disease continue to have poor outcomes. No alternative, targeted therapies have proven effective in Wilms' tumor. One-fifth of Wilms' tumors harbor mutations in the enzymes are responsible for producing microRNAs, small RNA molecules that regulate expression of target genes. These mutations drive tumor formation; leading to a worse prognosis.

Alex's Lemonade Stand Foundation for Childhood Cancer