An Out of Breath Conversation

In this exclusive interview, RAY_ANURADHA_PhD_PULMDr. Anuradha Ray, a reputed Professor of Medicine and Immunology in the Department of Medicine at the University of Pittsburgh shares her passion and contribution toward asthma research with the NGSF Team. She completed her PhD in Molecular Biology at Calcutta University and then went on to do her postdoctoral training at Cornell University and Rockefeller University. She was on the faculty at Rockefeller University and Yale University before moving to Pittsburgh in 2001.

Can you briefly describe the evolution of asthma research and where it is at now?

In the 1950s, asthma was not thought to be an inflammatory disease. It was merely considered to be a disease in which airway smooth muscles constrict in response to cold, allergens or exercise.  Then it was suggested that there was an underlying inflammation involved in the disease. The advent of corticosteroids that could be inhaled and therefore localized to the airways revolutionized the field. Slowly, people realized that not all asthma conditions are alike.

This is where we are at now – trying to understand the mechanisms of the different types of asthma. About 5-10% of patients diagnosed with severe asthma are found to be unresponsive to corticosteroids. To determine why this is, investigators have looked into the cell types in these patients and discovered that even inflammatory cells look different among them. The concept of heterogeneity, what we call the endotypes of asthma was coined.

How has your own research evolved since you came to the University of Pittsburgh?

My husband Dr. Prabir Ray and I were at Yale for 10 years where we worked on asthma. During that time, news broke out that T cells were important, particularly T helper 2 (Th2) cells. Our question was to determine what caused a naïve T cell to become a Th2 cell. Our lab and another lab concluded using very different approaches that when a transcription factor GATA-3 is upregulated, it pushes a T cell to Th2 lineage. Importantly, we found that GATA-3 was also upregulated in human asthmatic patients. GATA-3 was also targeted in allergen-induced mild asthma as a treatment in humans which resulted in suppression of Th2-associated inflammatory responses.

We realized that the availability of human samples was greater in Pittsburgh and we wanted to find a way to do more human based research. This led to a collaboration with Sally Wenzel who was one of the first investigators to identify severe asthma as a separate category of asthma. We are now looking at multiple markers in a few cells from human patients using mass cytometry (CyTOF) in combination with an RNA sequencing approach. It’s exciting to write this manuscript with many authors as this approach has not been used before.  We have already started finding sub-groups in asthmatics within this small cohort.

“Many people have asked me how I managed to advance in my career. Here’s what I would say to aspiring young scientists: You do have to work very hard but you also have to be extremely strategic in terms of networking – be at the right place at the right time and never miss an opportunity. Take the appropriate approach to take advantage of opportunities presented to you. “

Your lab uses mouse asthma models to study potential mechanisms. What are the drawbacks or issues that we should be aware of when using mice for this kind of research?

Mice are easy to use and there exists several reagents and strains to investigate specific questions. The limitations include the structural difference in the airways between the mouse and human. The human airway branches into many more divisions than in the mouse. Immunologically, many of the cell types seem to be similar though there are differences in the structural cells. Fortunately, the pathway involving Th2 cells is exactly the same between mouse and human.

You hold several titles: Lung Immunology Endowed Chair, Associate Editor of the Mucosal Immunology, Elected member of Faculty of 1000 Biology in Immunology Discipline to name a few. How do you balance all these positions?

It has been a learning experience. As the Chair, I do not have many administrative responsibilities. I am involved in the training of physician scientists as well as basic scientists and work closely with Division and Departmental leadership. Having administrative titles was never my primary goal. My first and foremost goal is to do the best science possible. Choosing the right people in the lab is crucial since they are the ones doing the work.

Looking back, what would be your advice to your graduate student self?

I always stress on collaborations especially in this day and age. That is how we are able to do what we do in our own lab. My advice would be to look around you for collaborators with whom you can share data that could then lead to mutually beneficial work relationships.

Everything is technology-driven now. The best journals ask for complementary approaches to arrive at the same answer so if you want to do good research, sit back and think of which tools must be used to solve the problem. It will give you satisfaction and confidence when you know that you have vetted it in many different ways. I would also advise everyone in biomedical research to acquire some basic expertise in bioinformatics.

What would you like to see happen differently in terms of training for science students in India?

I would really love for top institutions such as Indian Institute of Technology (IIT), National Center for Biological Sciences (NCBS) etc, to open up their bioinformatics labs and train people. Since it is not wet bench research, a lot of students would be attracted to apply. Even in the US, the number of people with such a skillset is low. When you arm yourself with bioinformatics or related computer skills, you will find that it will help you to be highly competitive for postdoctoral research positions in reputed research labs.

India can easily do this as the strength is huge and it should not involve too much financial investment either. All that is needed is good leadership and an increase in the number of training opportunities.

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