Grant: Foundation Grant

For the past 25 years, my laboratory focused on elucidating the function of a family of genes named "protein tyrosine phosphatases" (PTPs). The PTP family contains 107 different genes in humans that control a plethora of normal cell functions. PTPs have one common property: to remove a phosphate molecule added to specific tyrosine residues present in many cellular proteins, which confer, or deny, various properties to proteins. Our main purpose is to understand PTP function and to transfer this knowledge into common scientific knowledge and towards clinical applications. Herein we propose three experimental sections. Section 1 is a continuation of our recent work on PTPN1(also known as PTP1B) and PTPN2 (also known as TC-PTP) in characterizing their roles in the immune system. We plan to examine their function in a type of immune cells named "T-cell ". These comprise several subsets of T-cell with different function that kill tumor cells and maintain surveillance against cancer cells. Our proposal is to use small molecule inhibitor of PTPs to reactivate patients T- cells or improve the novel cancer immunotherapeutic approaches of CAR-T cells. Section 2 is pursuing a new system of proteins (the PRL-CNNM proteins) that we first reported in 2014. Involved in the supplies of magnesium to all higher organisms, PRL PTPs are upregulated in almost all cancers to sustain growth and invasion. By understanding their roles and preventing their binding to CNNMs, we intend to develop a novel class of anti- cancer drugs. Finally, section 3 has for objective to explore further this large and relatively still unknown gene family. Our previous data showed that most PTPs are involved in the immune system. We plan to assess the function of each one of the entire gene family towards inhibiting or activating the immune system response against cancer. We are confident that this program will contribute original and important scientific advances and novel clinical applications.