Paying it forward
Recalling how Randy Schekman, PhD, a future Nobel laureate, made time to help him while he was an unfocused UC Berkeley undergraduate, Negrin today likes paying it forward in hopes of “helping somebody launch their career and then watching that career really unfold in beautiful ways.
“I’ve had the privilege of helping to educate or launch the scientific and medical careers of extraordinary, gifted trainees from all over the world. Many of them are now in leadership roles at their various institutions.
“And that’s what we get to do. We get to interact with young people. They’ve had an incredible impact on my life and my science, and we built something together. To me, that’s the essence of what academia is about,” he says.
Whether working with junior or senior colleagues, Negrin is passionate about science and has led a program project grant titled “Bone Marrow Grafting and Cellular Therapy for Leukemia and Lymphoma,” a program that Blume started and that Negrin has directed since 2000. Recognizing the program’s importance, the National Cancer Institute recently renewed it for another five years.
“That funding has been the engine of our science, providing resources for our division,” says Negrin, who was chief of BMT-CT from 2000 to 2020.
“It allows us to bring a number of investigators together to work on common problems from different angles. And many things have come out of that program project grant, including a deeper understanding of the biology of transplantation and cellular therapy and practical applications for overcoming some of the challenges of treatment.
“A major focus of my laboratory has been the study of the biology of GVHD, a terrible problem resulting from a bone marrow transplant. However, the major benefit of the transplant is that the immune system from the donor can reject the underlying cancer — something we call the graft versus tumor (GVT) effect that is also a result of donor T cells among other cell populations. So the fundamental question that my laboratory has been focused on for a long time is how do you get this beneficial GVT effect without the harmful GVHD,” he explains.
The Negrin laboratory has been building off the work of Japanese Nobel laureate Shimon Sakaguchi, MD, PhD, and Stanford colleague Samuel Strober, MD, who identified specific populations of cells called regulatory T cells that help regulate human immune systems. Negrin’s team demonstrated that GVHD can be avoided while retaining the graft versus tumor effect by giving the right combination of cells with the right timing.
Collaborating with industry
The team developed the idea in the laboratory based on fundamental biological principles. Fortunately, the Negrin lab was able to collaborate with a company called Orca Biosystems to move the concept forward. Orca Bio brought resources to perfect the process and to export it to multiple sites around the country. The collaboration with Orca Bio resulted in a number of important studies that were led by Everett Meyer, MD, PhD, associate professor of Blood and Marrow Transplantation and Cellular Therapy in the Department of Medicine and of Stem Cell Transplantation in the Department of Pediatrics. Orca Bio recently completed a phase III registrational trial that will be published this year.
“That trial really validates this whole concept and led Orca Bio to apply to the FDA for product licensing. In a crazy turn of fate, the day the Nobel Prize was awarded to Shimon Sakaguchi was the same day that Orca Bio received their PDUFA (Prescription Drug User Fee Act) date, which is the date that the FDA will decide on product licensing,” Negrin says.
Relying on fate for one’s success violates a crucial tenet of Negrin’s work ethic. Asked what advice he would offer to those who are early in their careers, the veteran physician scientist talks about persistence.
“If you think an idea has merit, keep at it and try to overcome all the disappointments that will come, all the papers that will be rejected, and all the grants that aren’t going to get funded. That’s just part of the process, and you have to have a long view and a bit of a thick skin to learn from those experiences.”
Taking the long view has clearly worked out for Negrin, who is relishing his annus mirabilis.
