Faculty Spotlight: Exploring Experimental Pathology with Wayne Hancock, MBBS, PhD

Editor’s Note: Meet the diverse, dedicated, and distinctive faculty who are discovering and developing pediatric life-changing solutions at Children’s Hospital of Philadelphia Research Institute, in our monthly Faculty Spotlight series. This year, we’re celebrating our internal grant recipients who are pursuing new avenues of research with this dedicated funding support. Although we cannot feature all the award recipients in this series, we congratulate their continued hard work and scientific contributions to pediatric research. In this Q&A, we meet Wayne Hancock, MBBS, PhD, chief of the Division of Transplantation Immunology and recipient of the Add-an-Aim Thematic Accelerator Grant Program. Stay tuned for more from our Faculty Spotlight series throughout the year.

How long have you been at CHOP?

I came to CHOP in 2001 from Boston where I was working in the biotech field. A friend organized a going away party for me on Sept. 11 — the day before I was supposed to move. That morning I learned far more important events had intervened, so I held off moving to Philadelphia for a couple more weeks, then started working at CHOP that October. 

Can you tell us why you chose to become a scientist and focus your research on experimental pathology?

I am an odd duck and so I don’t suggest others try replicating my version of becoming a scientist, but when I was 4 years old, I asked my dad, “Who earned the most money?” No one in my family had ever gone to university but after hearing his answer, I eventually trained as a doctor and did a PhD. However, along the way others advised me that if I wanted to become head of a laboratory in some institution, I’d better study pathology or some lab-related field of medicine.

I did my doctorate studies in Australia and my postdoctoral program in Boston. After completing all my training and certifications and running a pathology lab in Australia, my career was not all I had hoped it would be. But my time in Boston as a postdoc with Ramzi Cotran, MD, had given me the sense that being an experimental pathologist was a respectable career option. 

So when I received a call a few years into living in Australia, asking me to return to Boston, I jumped at the chance. After several years at Harvard, I moved to industry and eventually to CHOP. Each step was driven by the science, whose intoxicating attractions are hard to appreciate until you are in it, and then it becomes obvious and irresistible.

What is a new avenue of research you’re able to explore as result of the Add-an-Aim Thematic Accelerator Grant Program? 

The Add-an-Aim work builds on long-standing interests in the actions of enzymes called histone deacetylases, or HDACs, that regulate the opening and closing of chromatin, thereby turning gene expression on and off. This area of research is included in the broader field of epigenetics. Moreover, these enzymes also affect the function of individual proteins, including those important to immune responses. My lab focuses on that latter aspect and how variations in levels of those enzymes can have implications for human disease. 

A brilliant investigator in my lab, Tatiana Akimova, MD, PhD, went on to show that differences in the levels of one enzyme, HDAC6, could markedly affect outcomes of patients undergoing lung transplantation. The use of a selective inhibitor, an HDAC6i, might be of practical benefit in the management of such patients. With support from the National Institutes of Health, we are currently exploring this possibility in lung transplant recipients with University of Pennsylvania colleague Jason Christie, MD, MSCE, and in the management of injury of other organs, such as the liver, with another University of Penn colleague, Matthew Levine, MD, PhD. 

We realized there are differences between outcomes in males and females undergoing lung transplantation. In aggregate, females tend to do worse in the early period post-lung transplant. Our focus on a particular immune population, regulatory T cells or Treg cells, was consistent with this, in that the suppressive activities of Tregs from women as well as female mice are decreased compared to that of corresponding males. This led us to consider the roles that estrogen receptors, of which there are several types, might play in control of Treg function.

Work by a talented postdoc in my lab, Lana Christensen, PhD, narrowed receptors down to two types and showed that deletion of either one improved Treg suppressive function. Such data are consistent with the known major predilection of most forms of autoimmunity to occur in females versus males. Interestingly, it seems that HDAC6i can reverse matters and boost Treg function, even more in females than in males, and we are currently exploring how estrogen receptors and their signaling functions are modulated by HDAC6i.

Can you tell us about a current or recent research project that you are excited about?

At any one time, my lab is immersed in exciting projects that all bubble along. What keeps me alive and happy is seeing the data, realizing we are making progress, and that all of us — trainees, young scientists, and experienced investigators — are contributing to the field and drawing satisfaction from their work.

What are the long-term research questions you hope to answer?

The scientists I know are asking the same fundamental questions: Why are things the way they are? How can things be made better? This sort of translational approach is not for everyone, but it drives me, the people in my lab, and my collaborators. There is a place for science for science’s sake, especially since you can never know what will turn up and how it may lead to new applications — whether diagnostic, therapeutic, or simply new understanding — but the potential translational applications drive our work.