|Awarded On||September 14, 2022|
|Title||Understanding the impact of immunity on pre-malignant somatic mosaicism and cancer prevention|
|Award Mechanism||High Impact/High Risk|
|Institution/Organization||The University of Texas Southwestern Medical Center|
|Principal Investigator/Program Director||Hao Zhu|
|Cancer Sites||Gallbladder, Liver and Intrahepatic Bile Duct|
*Pending contract negotiation
Sequencing of normal tissues has now established that aging cells in the blood, skin, liver, bladder, and esophagus accumulate a high abundance of somatic mutations prior to cancer. While our work on somatic mutations in the liver supports the possibility that some mutations are beneficial, the development of cancer is generally correlated with increased mutation burden. Immunosurveillance is clearly important for the suppression of tumor initiation and progression, but it is unknown if it exerts selective pressure on mutant clones prior to tumor initiation. Furthermore, if immune hyperactivation is able to selectively cull mutant clones destined for cancer, then it is possible that cancer r...