Dinesh Rao, M.D., Ph.D. 

Dinesh Rao, M.D., Ph.D., studies how gene regulation – the mechanisms by which genes in a cell's DNA are turned on and off – influences blood-forming stem cells as they differentiate to create all the cell types that make up the blood and immune system. His research focuses on post-transcriptional gene regulation, which occurs in the period after genes have made RNA and before that RNA is converted into proteins. RNA messages are copies of small snippets of DNA that move out of the cell nucleus to be converted into proteins. Certain proteins cause cells to grow and divide when needed. Too little or too much production of these critical proteins can cause disease. Rao aims to identify how post-transcriptional gene regulation causes blood-forming stem cell differentiation to go awry, which can lead to cancer and other diseases, in order to develop new treatments.

As a physician, Rao treats patients with blood cancers, including leukemia, which is a cancer of the blood-forming tissue. His clinical practice drives his desire to better understand how these blood cancers arise and to use that understanding to develop better treatments. Rao has identified a set of non-coding RNAs – RNA molecules that are not translated into proteins – that are dysregulated in leukemia. As he studied these RNAs, he discovered that they regulated a variety of proteins that play a role in leukemia and are also critical to blood cell development. These findings laid the groundwork for two ambitious goals in his lab: to develop these molecules into therapies for patients with leukemia, and to understand the basic biology of how these molecules influence the development of blood-forming stem cells.

One of the non-coding RNA discovered by Rao is BALR-2, which regulates how responsive leukemia cells are to steroid therapy. Steroids are often given with chemotherapy to help destroy leukemia cells. Observing that patients who do not respond to steroid therapy often have a poor prognosis, Rao sought to uncover how steroid resistance occurs. He discovered that high expression of BALR-2 correlated with poor overall survival and diminished response to steroid therapy. He is now working to develop a drug to block BALR-2 to make steroid therapy effective for patients whose cancers have resisted treatment.

Rao also uncovered how a cellular protein, IGF2BP3, contributes to the most common cancer in children, B-acute lymphoblastic leukemia, also known as B-ALL. While major strides have been made in the treatment of B-ALL, certain subtypes of this cancer resist current therapies. One such subtype is MLL-rearranged B-ALL, which develops in infants, often recurs after treatment and is associated with poor survival rates. Rao and his lab discovered that IGF2BP3 plays an important role in the development of MLL-rearranged leukemia by regulating various RNA messages that contribute to the disease. His lab is now working to determine whether the IGF2BP3 protein plays a role in other types of leukemia, and developing methods to inhibit the protein and effectively kill leukemia cells in patients.

Rao earned a medical degree from Case Western Reserve University and completed a research fellowship in cancer biology at the University of Michigan, Ann Arbor. He then completed a residency and clinical fellowship in pathology and hematology at UCLA and earned a doctorate in biology at California Institute of Technology.