Skip to main content

Uncovering the dysregulated RNA binding protein network in normal and malignant hematopoiesis

Michael Kharas

Michael Kharas

PhD

Sloan Kettering Institute for Cancer Research

Project Term: July 1, 2017 - June 30, 2022

The research focuses on discovering the driving factors in leukemia cells that control translation of RNAs into protein. Our studies explore these RNA regulators with a myriad of approaches including genetic mouse models, human leukemia cell lines, and human acute myeloid leukemia samples. Our ultimate goal is to discover new mechanisms and targets that are essential for leukemia cell survival and thus creating new therapeutic strategies for patients with myeloid leukemia.

Lay Abstract

Although molecular targeted therapy has dramatically changed how we treat cancer, the treatment for acute myeloid leukemia (AML) remains focused on the use of cytotoxic drugs with many patients eventually relapsing with their disease. One of the major drivers of resistance is the persistence of cells that retain the immature properties of stem cells. Cancer cells are made up of proteins expressed by the genes in the nucleus of the cell. Many RNA molecules comprise the information that is the intermediary between genes and proteins. An emerging focus of study is how these RNA molecules may be involved in disease processes. Our laboratory and others have identified that there are specific RNA binding proteins that regulate gene expression programs that are essential for the survival and immature state of acute myeloid leukemia cells. This network of RNA binding proteins is engaged in the most aggressive leukemias and predicts a poor outcome. We developed a screening strategy to identify other RNA binding proteins that contribute to the leukemic state. Using this novel approach, we identified an RNA binding protein called SYNCRIP that we found to be critical for myeloid leukemia and the response of leukemia patients to therapy. Our studies will further explore SYNCRIP’s role in genetic mouse models, human leukemia cell lines, and primary AML patient samples. We plan to understand the mechanism for the regulation of the dysregulated RNA binding protein network in leukemia and to develop therapeutic strategies for treating this aggressive and devastating disease.

Program
Career Development Program
Grant Subprogram
Scholar
To All Projects