Stanford Cancer Institute

SCI Innovation Awardee

October 2023

Sydney Lu, MD, PhD, assistant professor of medicine (hematology), was awarded a $50,000 SCI Innovation Award. His proposal is entitled “Regulation of mRNA 3’ end formation by recurrent RNA splicing factor mutations.” Lu is a hematologist and medical oncologist who is interested in how processes regulating RNA expression impact immunity and cancer. His previous work demonstrated that the targeting of RNA regulators may be exploited to promote immune activity against cancer cells.

A complex and intricate machinery transcribes DNA into RNA, and then translates RNA into protein. Each of these operations entails multiple regulatory steps that impact the final shape and amount of protein produced. RNA molecules, for example, are processed via splicing to remove regions that don’t code for proteins. If RNA splicing regulators malfunction, the resulting RNA blueprints are distorted and produce abnormal proteins that can promote cancer. This is commonly observed in myelodysplastic syndrome and related leukemias. Lu recently discovered that mutations impacting splicing regulators also affect another RNA processing step, the addition of an RNA tail. The tail controls how much protein is made from the RNA, where the proteins are made within the cell, and how the proteins ultimately function. Lu found that mutations in splicing regulators also alter the RNA tail, including where in the RNA the tail starts and its length. Through the support of the SCI Cancer Innovation Award, Lu plans to study whether these tail alterations contribute to driving cancer growth and which ones may be targets for new therapies in leukemias.