Get to Know …  John DiPersio, MD, PhD 

By Cecilia Brown - Last Updated: August 21, 2023

John DiPersio, MD, PhD, the Virginia E. and Sam J. Golman Professor in Medicine and Director of the Center for Gene and Cellular Immunotherapy at the Washington University School of Medicine in St. Louis, discusses the key events that shaped his career, his lab’s most transformative research, and the future of transplant. 

Where did you grow up and when did you know you wanted to be a physician-scientist? I was born in the north end of Boston. I lived in Belmont and Brighton. Then I moved to Scituate, a town south of Boston, where I grew up through high school. I went to a large Catholic high school in Braintree, Massachusetts.  

 I was interested in science, mostly physics and astronomy. My dad was a pilot who worked for the US Air Force. When I was in high school, I wanted to go into aeronautical space engineering, but I lost my left eye playing hockey, so my flight career was terminated. I couldn’t become a pilot or an astronaut.  

I went to Williams College, and I decided to regroup. I majored in biology with a minor in chemistry and did some research projects. I was interested in medical school and pursuing a career as a physician-scientist. 

What led you to specialize in hematologic oncology and hematopoietic stem cell transplantation (HSCT)? I did a research project and thesis in college with Bill DeWitt, PhD, who studied red blood cell production in the frog. 

When I went to medical school, I did an MD-PhD. My doctoral advisor was a hematologist, and we were trying to identify a protein that stimulated white blood cell production. My project was to purify and characterize the first white blood cell growth factor. We made a lot of progress. Although I didn’t identify it when I was a graduate student, it turned out to be a cytokine called GM-CSF. It was later cloned by a pharmaceutical company.  

When I finished my residency in medicine at the University of Texas (UT), I was interested in a hematology-oncology fellowship and went to the University of California, Los Angeles (ULCA). I joined a lab that focused on hematopoietic growth factors, stem cell biology, and the genes involved in progression to acute leukemia. I continued working to identify growth factors, and we finally succeeded.  

After my postdoc at UCLA, I got a job there as an attending in hematology-oncology. Then I went to the University of Rochester as the first director of its Bone Marrow Transplant Program.  

I was recruited to Washington University in 1994 as the head of the Transplant Division. A year or two after I arrived, I was appointed chief of the Division of Oncology, which included bone marrow transplant and solid tumor oncology. We had only six or seven faculty at that point. Now we have 150 faculty. We started with about 16 employees. Now we have 1,600 employees. 

Was there a particular mentor or group of mentors who shaped your career path? Dr. DeWitt got me involved with blood cell production research when I was in college. Marshall Lichtman, MD, was my major mentor in medical school. He became the President of the American Society of Hematology and the Dean of the University of Rochester. He’s a great colleague and friend.  

Don Seldin, MD, who was the Chairman of Medicine at UT Southwestern at Parkland Hospital, always reminded me that academic medicine was what I wanted to do. He was supportive of me pursuing a career as an academic physician-scientist. 

When I got to UCLA, Judy Gasson, PhD, was my mentor, and I worked in her lab. She became the Cancer Center Director at UCLA. I was also under the mentorship of David Golde, MD, who was the Head of the Hematology Division at that time.  

When I started as a junior faculty member at the Washington University School of Medicine in St. Louis, my great colleagues and mentors included Tim Ley, MD, who was a well-known expert in the field of acute leukemia; Stan Korsmeyer, MD; and John Atkinson, MD, Chairman of Medicine. They were great supporters. Even though they were my colleagues, they were my mentors as well.  

What are some of your current research projects? My lab is broken up into multiple areas. One area works on the genetics and genomics of acute leukemia. It’s a collaborative effort with Dr. Ley and his colleagues to understand mutations associated with acute leukemia and how to overcome resistance for patients who receive treatment and transplant for acute myeloid leukemia (AML). That work has been translated into several novel immunotherapies for AML, including chimeric antigen receptor T-cell therapies and bispecific therapies that we either helped develop or are developing on our own. 

We also work on improving transplant therapies and identifying ways to more efficiently mobilize stem cells. In that regard, we’ve been leaders in the world. We were involved with the approval of the first small-molecule mobilizing agents, and we were involved with a CXCR4 inhibitor that hopefully will be approved soon by the US Food and Drug Administration (FDA). We’ve also developed our own completely novel approach, and we are in the process of licensing it. We’ve been a major player in that area.  

Along with mobilization, we’re interested in how stem cells interact with the hematopoietic niche and how they traffic outside of the bone marrow, as well as understanding the factors and tethers that pull stem cells into bone marrow.  

Another area of interest is developing transplant conditioning regimens that don’t involve chemotherapy or radiation. We’ve developed antibody-based conditioning regimens for stem cell transplant that are effective across histocompatibility barriers in a mouse. We’re trying to carry those forward into the human setting. This work has broad implications for patients with malignancies, as well as patients with nonmalignant diseases like thalassemia or sickle cell anemia. It would be a huge step forward. We’ve made a lot of progress and we’re excited about that. 

We also study graft-versus-host disease (GVHD). We identified Janus kinase inhibitors as a way to prevent GVHD. Ruxolitinib was the first drug the FDA ever approved to treat acute GVHD. 

Additionally, we’re interested in enhancing treatment for patients who relapse after transplant. We’ve focused on immunotherapy targeting for AML, T-cell acute lymphoblastic leukemia, and multiple myeloma. 

I was also involved with cofounding two companies, Magenta in Boston and Wugen in St. Louis.  

How have you seen HSCT evolve throughout your career? It’s evolved in a few major ways. It has become better and safer, so we can transplant older patients with less toxicity and better outcomes. We’ve also found ways to improve conditioning regimens and GVHD treatment.  

We are excited about measures to prevent GVHD while maintaining good graft-versus-leukemia effect. That has changed the playing field a bit. By manipulating the cells, by reducing the number of conventional T cells, by increasing the number of regulatory T cells, by manipulating the grafts, the GVHD complications have decreased, and the engraftment rates have improved.  

I think the next big phase will be antibody-based conditioning regimens that don’t involve chemotherapy or radiation. That will make it easier for patients with malignant or nonmalignant disease to receive a transplant. 

We haven’t fixed everything yet. People still relapse. The final frontier will be addressing relapse after transplant by using targeted therapies, immunotherapies, and a safer transplant platform for gene therapy. If you had the perfect model for gene therapy, you would not give chemotherapy or radiation therapy before you infuse genetically modified stem cells. You would give an antibody. But that option has not been possible traditionally. However, I think we are finally seeing it come to fruition. 

We can also use these antibodies to work across histocompatibility barriers. I could do an allogeneic transplant with just antibodies and no chemotherapy or radiation therapy. Just a year ago, that was unheard of.  

Those approaches can be used to transplant genetically modified cells. Genetically modified cells can be used to cure sickle cell anemia, thalassemia, and genetically inherited diseases. However, that has been difficult due to the need for transplant conditioning and all its associated risks. If we figure out how to reduce the risk of the conditioning, then everything would be better. 

What would you tell someone who is just starting out in the field of hematologic oncology? It’s a rapidly evolving field. There’s lots to do. We now have a lot of great tools to look across the entire genome in an unbiased way. 

In the past, I’d have an idea and test that idea. We would only discover things we were looking for. Now, we can do big screens to look at mutations or epigenetic changes and see if there’s any common thread. You can do these big experiments now that you could never do before. Instead of just testing a single hypothesis, you can do hypothesis-generating experiments. It’s exciting. 

We think we know what’s going on, but we have no idea what’s going on. The smarter we are, the dumber we are. We have just scratched the surface. There’s so much more to learn, and the tools we have to interrogate areas of basic and translational science now are fantastic. That’s the advantage that kids today have. We have amazing tools to look at these biologic processes. The acquisition of new knowledge will increase exponentially over time. 

What are your favorite hobbies and activities outside of work? I love art, mostly modern art. I doodle and paint for fun. I sell something occasionally. I also love music, in particular jazz. I’ve been listening to jazz my whole life. I have around 3,000 jazz albums and CDs. I love jazz. My family hates it, but I love it. 

I’ve played hockey my whole life. I played in high school, and I played National Collegiate Athletic Association hockey in college. I’m a hockey nut. I have season tickets to the Blues, even though they’re doing terribly this year. I also love golf and being outdoors. 

What brings you joy in life? I have a great family. I got married late in life. I have a great wife who’s an academic hematologist and oncologist working in pediatrics.  

I have twins, a boy and a girl, aged 12. They’re good kids. When you’re an older parent, you’re just happy that they’re alive every day, and they seem to be happy. I think as a younger parent, you’re worried that they’re not writing poems and doing multivariate calculus by the time they’re four years old. For me, if they’re happy and normal kids, and they’re kind to other people, that’s all I care about.  

I have lots of great friends and colleagues. I came here and started with just a few people, and now there’s a massive army of characters involved with the cancer center. I am proud and happy to have contributed in a small way to our success as a Division of Oncology and a National Cancer Institute Comprehensive Cancer Center even though my exceptionally talented colleagues did all of the heavy lifting. It’s been a great experience for me here. I have great friends, great supporters, and terrific colleagues. That’s the best part of life. 

John DiPersio, MD, PhD, is the Virginia E. and Sam J. Golman Professor in Medicine and Director of the Center for Gene and Cellular Immunotherapy at the Washington University School of Medicine in St. Louis. 

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