Starting this month, we will be beginning a monthly spotlight series of “People in ME/CFS Research.” The first spotlight for January 2018 is on Derya Unutmaz, M.D. Derya is a Professor of Immunology and the Principal Investigator for The Jackson Laboratory ME/CFS Collaborative Research Center. His lab researches the mechanisms of the human immune system in the context of infectious or chronic diseases, cancer, and aging. Recently, I (Courtney) sat down with Derya to ask him some questions about his background and his involvement in ME/CFS – below are his candid responses.
Hey, Derya! Thanks for taking the time to speak with me today. First of all, tell me a little bit about yourself and how you got involved in researching ME/CFS.
Thanks for talking with me, Courtney! I’m currently a Professor of Immunology at The Jackson Laboratory for Genomic Medicine. I’m also affiliated with the UCONN School of Medicine, and I study the human immune system. Before coming here, I was a Professor at the NYU School of Medicine, where I worked for about 8 years. I originally started my lab at Vanderbilt University in Nashville, TN about 20 years ago. Throughout my career, I’ve always been interested in understanding how the immune system works, and specifically trying to understand the immune system in the context of different diseases.
For many years, my lab has studied HIV infection and immunopathology in infected individuals. More recently, we have been studying cancer and other chronic diseases. I first became interested in ME/CFS about four years ago, mainly because there were indications that this disease has some kind of immunological perturbation and was very poorly understood. What jumpstarted this interest was meeting Dr. Suzanne Vernon, who was then at Solve ME/CFS Initiative. She provided some initial samples to us from ME/CFS patients and their controls, to do what we call immune profiling, which is determining different populations of immune cells and their functionality. Even though this was a small subset of patients, we were able to generate some interesting results that led to an NIH funded grant. When NIH issued a request for grants for ME/CFS Centers, we were already becoming more and more interested in this terrible disease, so we applied for the grant to expand our studies from the immune system to also looking at the microbiome and metabolism.
What exactly are the research questions you’re currently setting out to address, and how are you planning on answering them?
In the context of the collaborative research center for ME/CFS, there are two major layers of research questions. The first layer is all about generating data. We want to determine different biological parameters in these patients in an unbiased fashion, and that has three main areas of focus, or arms. The first arm is the immune system. As I mentioned, we are going to be doing detailed analysis of different immune populations and their functionality in patients over time. The second arm is the microbiota, or the trillions of bacteria that live in our gut. We will be analyzing if there are particular changes and differences in patients versus healthy controls. And then the final arm is the metabolism.
So after this first layer, which is a focus on systems biology, the second layer is using all of the data we generate in the hopes of achieving two things. One is to generate new hypotheses about ME/CFS, and determine the mechanism that results in this disease. If we can understand the mechanism and what’s going wrong at the biological level, we can then develop treatments to address that. And second is to come up with a variety of biomarkers to enable the diagnosis of these patients using biological markers rather than just clinical symptoms. There is a great unmet need for many patients and physicians to establish objective diagnostic criteria.
In terms of the three arms that you’re focusing on with the immune system, microbiome, and metabolism, how are you planning on combining all of the data?
This is actually a very important part of the project. We have built into our center a very strong computational component. We’re lucky to have one of the leaders in the field, Peter Robinson, as well as several others in the field, including Alison Motsinger-Reif at NCSU, whose task will be to analyze all of this data. The plan is to not just look at it from statistical perspectives, but to focus on integrating the three datasets into one component that will hopefully put the parts together in a holistic manner. This will be done through developing some novel tools, including machine learning and deep learning methods that Peter has been developing.
In addition to machine learning, what are some of the technologies you use in your work, and what power do they have to help us understand more about ME/CFS?
We have quite a few technologies, and I think that technology is advancing very fast. Things that we can do now weren’t even possible 5 or 10 years ago. First of all, we have a tremendous capability to sequence bacteria – trillions of bacteria and thousands of species. You need very sophisticated methodology not just to sequence their genomes, but also to bioinformatically analyze them. We’re very fortunate to have that expertize here – our Associate Director of the center, Julia Oh, is responsible for doing that. She is a leader in the field in skin and gut microbiome analysis, and she has the bioinformatics capabilities to do that research. Another key technology that we’re employing is flow cytometry, which enables us to determine differences in the immune system in a high-resolution manner. We have the capability to look at many populations at the same time, many more than was feasible even a few years ago. We also will be using mass spectrometry to look at thousands of metabolites in human blood.
What do you hope to achieve during the first year of the RFA study?
We’re beginning to recruit patients through our collaborators in Utah at the Bateman Horne Center. We have decided to focus on a subset of patients that we call early-onset; in other words, they have just begun to show symptoms within the last 3 years. This is a relatively smaller group of patients to recruit, however we feel it is very important to start looking at the changes from early on in the disease since this is a longitudinal study where we will be following the patients for the course of the center over the next 5 years. So, one achievement for the first year would be to reach our milestone for recruiting a sufficient number of patients for the study. We are hopeful that we will reach this goal, as the patient community is very enthusiastic. We’re also thinking about how we can expand the patient population to include different groups – for example we’re discussing doing a study with a younger pediatric and teenage group locally through our colleagues at UConn Medical School.
In terms of scientific achievements for this first year, we’re hoping to begin generating data from the patients that we recruit, and that the quality of the data is high, as this is critical for making sense of the results. We also hope to build a good relationship with the patient community over the next year, as an important part of our mission is to keep the community in the loop and provide as much educational and scientific updates as we can. I believe this blog is going to be instrumental in that!
Those sound like great goals! What do you think some of the most promising areas of research in the ME/CFS field are right now?
Of course, I have my own biases. I think that the immunological perspective is very important, however that does not exclude the importance of other areas of research. It’s difficult to know what’s a priority and what’s important since we’re dealing with the unknown. As I always say, we don’t know what we don’t know with this disease, so it’s important that different aspects of it are studied. I think that the link between the immune system and what’s happening in the nervous system of these patients is very important. Also, the physiology of the disease in terms of the effects on the nerves and the muscles, as well as the physical aspects like the imaging of the brain, are very important as well. I think the work that we and others are doing in terms of the metabolism and microbiota are important areas, but I’m very excited to hear about new ideas in the field too.
As a follow-up to that, do you think there are any research areas that need more emphasis?
I think, as I mentioned, the ME/CFS field still has too many unknowns, so we won’t know which areas need more emphasis until we are able to see the data that we generate. So, it really should be about the results, and letting the data drive the next stages of research in this field. If the data suggests we should dig deeper into the immune system, then that’s what we’ll do. If not, we need to shift to other hypotheses.
This is more of a personal question – who is your role model and why?
Such an easy question! My number one idol, by far, is Steve Jobs! I greatly appreciate his philosophy, which in the most simple terms is about focusing on the values. My principle philosophy is also in line with that, that the value we bring to the world is what really matters in life, much more so than our personal accomplishments and successes, and that the end users, in this case, the patients, are really what we have to focus on. Of course, having good ideas and satisfying our own curiosity is a tremendously fun part of doing science that I also enjoy greatly, but in the end I always think and focus on challenges that can have a positive impact on the patients and enable paths to fix the problems. Can we leave good trails behind that others can also follow and make the world a better place? And I think that’s the overall philosophy that Steve Jobs had, that as he was coming up with the products at Apple, he wanted not just good products but insanely great ones that are easy to use, user-friendly, transformative, and of high quality that the users would want. But again, I am highly biased on my love of Apple products!
It sounds like you’re quite the fan! Are there any other comments about yourself or your research that you would like to share with the readers of the blog?
The last comment I can make is that in the past several months, we have tried to engage the community through the opportunity of the center, both through social media as well as through the blog. We hope to increase these efforts. I have to say that the response and feedback I have gotten has been overwhelmingly positive, and we hope that the community continues to appreciate our efforts to provide insights into our scientific process and progress. We also love the feedback we get – both the critical feedback as well as the ideas about the research. I have received several ideas from patients that we have actually decided to incorporate into our work. We learn from the patients and the community, so it is a very beneficial relationship for us as well that we hope we can cultivate. And thanks so much for your efforts, interesting questions, and for maintaining this blog, Courtney!
No problem at all, Derya! Thanks for taking the time to talk with me so that our readers can learn more about you and the projects happening at the center!