Cytocentric Visionaries: Dr. Heather O’Leary
Part One: Extraphysiologic Oxygen Shock
This is a three-part series of blog posts containing excerpts from an interview that Dr. Alicia Henn, Chief Scientific Officer of BioSpherix, conducted with Dr. Heather Ann O’Leary. Dr. O’Leary has finished up a post-doc in the laboratory of Hal Broxmeyer and is starting up her own lab at Indiana University. Her talk was a highlight of ISSCR 2015 where she reported on a landmark paper published in Cell.  Our conversation was edited for length and clarity. Continue reading the interview transcripts to learn more about her findings regarding how hematopoietic stem cells are affected by EPHOSS.
You gave a fantastic talk in Stockholm, relating that unbroken oxygen control dramatically increased hematopoietic stem cell yields. The term in that paper was Extraphysiologic Oxygen Shock, or EPHOSS, for the effect on cells when exposed to room air. There was a lot of excitement at the meeting about your findings. What are the implications of this work for the stem cell field?
HAO: From a basic science perspective, it will help us think more broadly about how we do experiments and how we interpret our data. I expect there will be implications not only for HSC, but potentially for other stem cell types, both at a phenotypic and a functional level.
Additionally it highlights that there may be a disconnect between phenotype and function of knockout animal models harvested in air vs. hypoxia. Some of the knockout models that we used in the paper in air had a different phenotype than what we saw in hypoxia. From a clinical standpoint, we hope it may help us understand how to enhance the number of HSC for transplantation. Overall it suggests the need to be more careful interpreting data in that there may be some cell types that are more or less sensitive to this oxygen shock and stress.
Were your results surprising to you?
HAO: I think the most surprising part for me was how quickly it happens. The magnitude in some of the cases was more than I expected, but the short timeframe was the most surprising thing.
Within 10 to 15 minutes, we see the cells start to change. That was as quickly as we could process the cells, but it might be happening even faster than that and we would hypothesize that it is. It made me not as surprised that other people had not seen it, because 10 to 15 minutes is a very quick timeframe.
There are findings in the HIF literature that room air exposures of just a few minutes can have an effect, but most people don’t take the steps needed to protect cells. What made you want to investigate the effects of room air?
HAO: It was something we had discussed as a laboratory in general for awhile. My background is bone marrow and it is well known that the microenvironment there has oxygen ranges between 1 and 4%.
If you could look back on your career from 99 years old, what would you want your impact to be on the stem cell field?
HAO: I want to do work that is meaningful to the field and that someday may lead to enhanced treatment of patients. Not every paper is going to be a Nature/Science/Cell paper, but you want to consistently do work that is valuable, that you can be excited about and that makes you want to consistently work hard. I think that is important. To have the chance to be excited to go to work every day, enjoy training the people around you and learning from and interacting with them in a collaborative fashion is part of what makes science as a career amazing.
Obviously, everyone wants to say that they discovered something that could help somebody and trained great people. If I could say that I helped to discover something that could translate into the clinic and help patients that otherwise would not have many options and made a difference in the life of the people I trained, I think those are the ultimate ways to look back on your career and say it was worthwhile and amazing.
What, in the beginning, made you enthusiastic about coming to work every day?
HAO: I grew up in a culture with the intellectually challenged. My aunt is intellectually challenged and I’ve volunteered with the intellectually challenged and disabled since I was 17. They have a ton of health issues, such as a higher incidence of leukemia and heart problems. We don’t know why other than some chromosomal instability and not knowing why has always bothered me. So that initially was part of it, and when I got a little older, I thought I wanted to do an MD/PhD program.
I shadowed a doctor in the pediatric oncology/bone marrow transplant program. It turns out I am a poor detacher, getting upset about the patients. So medicine was not going to be my avenue. Research was another way to say “What can I do that may help people broadly?”
If you make a discovery in the lab, it has such a broad spectrum applicability to help so many people and that made science seem like a really exciting opportunity to me.
In the next post, Dr. O’Leary talks with us more about the practical challenges in working in low-oxygen environments with cells.
1. 1. Mantel, C.R., et al., Enhancing Hematopoietic Stem Cell Transplantation Efficacy by Mitigating Oxygen Shock. Cell, 2015. 161(7): p. 1553-65.
About the Author
Alicia D Henn, PhD, MBA
Alicia Henn has been the Chief Scientific Officer of BioSpherix, Ltd for two years. Previously, she was a researcher at the Center for Biodefense Immune Modeling in Rochester, NY. Alicia obtained her PhD in molecular pharmacology and cancer therapeutics from Roswell Park Cancer Institute in Buffalo, NY and her MBA from the Simon School at University of Rochester in Rochester, NY.