Basic science research spotlight: Dan Peltier, MD, PhD

For Dan Peltier, MD, PhD, the motivation to pursue a career in pediatric hematology-oncology started on a very personal level as he witnessed cancer’s toll on family and friends. Today, Peltier is working to change the trajectory for patients and families as a stem cell transplant specialist at Riley Children’s Health and an immunologist in the Hematologic Malignancies and Stem Cell Biology group in the Herman B Wells Center for Pediatric Research at IU School of Medicine.

“I was particularly attracted to the dynamic, collaborative, cutting-edge research environment in the Department of Pediatrics and the Wells Center,” said Peltier, who joined the IU School of Medicine in 2022. “The environment here is incredibly supportive, and I have benefited from learning and collaborating with researchers outside and within my field who have expertise beyond what I was previously able to draw upon.”

With a research interest in graft-versus-host disease (GVHD) and funding awards from the National Institutes of Health, Peltier studies long non-coding RNA (IncRNA), biology that is emerging as important cell- and context-specific regulators of immune responses. Specifically, his research aims to determine whether any undescribed long non-coding RNA genes may regulate the T cells that drive GVHD.

How did you become interested in research related to GVHD?
I’ve developed a fascination with the immune system’s potential to both heal and cause disease. The effects that donor T cells have after bone marrow transplantation are a stark example of this. Bone marrow transplantation offers a cure for many high-risk blood cancers. Part of its curative potential relies on the beneficial action of donor T cells called the graft-versus-leukemia effect (GVL). In GVL, donor T cells kill any remaining blood cancer cells. This effectively represents one of the first, although imprecise, forms of cancer immunotherapy. However, donor T cells can also damage healthy host tissues causing acute graft-versus-host disease—a severe and often life-threatening complication. Unfortunately, I have witnessed far too many children trade their life-threatening cancer diagnosis for severely debilitating or even life-threatening GVHD. This motivated me to pursue research in this field trying to identify novel regulators of T cells that drive GVHD.

Do you have any recent findings to share or any publications on the horizon related to your work?
We have been studying a particular lncRNA associated with GVHD and have since determined its function in mouse models of GVHD and identified its ability to decrease a particular type of T cell activity after bone marrow transplant that is known to increase GVHD severity. We hope to see this work published soon. Perhaps even more exciting, we surprisingly found that this lncRNA also produces a previously unrecognized microprotein. We have since discovered that this microprotein is functional and its function is separate from that of the lncRNA molecule that encodes it. This is interesting because it is a rare demonstration of a human gene producing two separate functional products, a protein and an RNA molecule.

How have the IU School of Medicine, the Department of Pediatrics and Riley supported your research efforts?  
I have received excellent mentorship from senior faculty in both the Wells Center and other departments, including medical and molecular genetics, informatics, and microbiology and immunology. This has been fundamental to my success, and I am extremely grateful. I am also fortunate to have ample protected time and start-up support from the Department of Pediatrics, the IU Simon Cancer Center and the Riley Children’s Foundation. I was also honored to be named the IU School of Medicine Nalepa Endowed Scholar of Pediatric Research.
What are your plans for future research?
We are excited to explore how lncRNA and microprotein influence T cell responses in other diseases such as cancer, autoimmunity and infection. We are also building collaborations to examine other uncharacterized microproteins and lncRNAs important for bone marrow transplant outcomes and engineered T cell responses.

What do you find most rewarding about your work as a physician-scientist?
The most rewarding aspect is being able to not only help care for patients in the clinical setting but also help drive knowledge forward that may lead to improved clinical outcomes for my patients.