Ravi Majeti and the Elusive Cells
After undergraduate education at Harvard University, Ravi Majeti earned his MD and PhD at University of California San Francisco. He took an interest in acute myeloid leukemia (AML) in medical school and cared for patients with AML during his residency in internal medicine at Brigham and Women’s Hospital in Boston and Hematology fellowship at Stanford University.
“At that time, there were not a lot of treatment options,” he says. “We had chemotherapy, and bone marrow transplants for patients who were physically capable, but otherwise there wasn’t much for them beyond supportive care.”
Starting his postdoctoral fellowship in the Stanford University lab of Irving L. Weissman, MD, FAACR, Majeti wanted to find a better way to attack AML and other hematological malignancies. A molecule called CD47 on the surface of AML stem cells kept coming up in his research. To support further investigation, he successfully applied for the 2008 AACR Centennial Postdoctoral Fellowship in Cancer Research.
“The AACR grant, and other sources of support, were very important to me,” he says. “It’s difficult to get support when you are a fellow, so the grant was very important. It allowed me to stay in the laboratory and conduct my research. And we started making discoveries.”
Majeti made the seminal observation that CD47 acts as a “don’t eat me” signal on leukemia stem cells, and contributes to leukemia development by blocking ingestion and removal of the leukemia cells by macrophages.
Under the mentorship of Dr. Weissman, a Fellow of the AACR Academy, he and his colleagues obtained anti-CD47 monoclonal antibodies and demonstrated that blocking CD47 enabled phagocytosis of AML and leukemia engraftment in vivo. Their findings were published in a groundbreaking paper in Cell in 2009.
A humanized anti-CD47 monoclonal antibody, magrolimab, for the treatment of newly diagnosed high risk myelodysplastic syndrome and AML, developed by Weissman and Majeti, recently received “breakthrough therapy” designation from the U.S. Food and Drug Administration (FDA) and is in late stage clinical trials, 11 years after he and his colleagues published their initial findings. CD47 is being investigated in several cancers and other diseases as well, attracting a large number of pharmaceutical companies to develop CD47-targeted therapies.
“I never could have imagined that our research would lead to where we are now,” Majeti says. “The ‘return on investment’ in scientific and medical terms has been huge,” he adds.
Majeti pays tribute to the leadership of Weissman, a renowned researcher who is director of the Stanford Institute for Stem Cell Biology and Regenerative Medicine.
“None of this would have been possible without him,” Majeti says. “He’s an amazing mentor. The world of stem cell biology is filled with investigators who trained under him.”