With the goal of harnessing the untapped potential of Iranian-Americans, and to build the capacity of the Iranian diaspora in effecting positive change in the U.S. and around the world, the Iranian Americans’ Contributions Project (IACP) has launched a series of interviews that explore the personal and professional backgrounds of prominent Iranian-Americans who have made seminal contributions to their fields of endeavor. We examine lives and journeys that have led to significant achievements in the worlds of science, technology, finance, medicine, law, the arts and numerous other endeavors. Our latest interviewee is Reza Dana.
Professor Reza Dana holds the Claes Dohlman Chair in Ophthalmology at Harvard Medical School where is Vice Chairman and Associate Chief of Ophthalmology for Academic Programs. He is also Director of the Cornea Service at Massachusetts Eye and Ear, Senior Scientist and W. Clement Stone Scholar at the Schepens Eye Research Institute, and a faculty member in the Immunology graduate program at Harvard Medical School. A graduate of Johns Hopkins and Harvard universities, his work focuses on the molecular and cellular mechanisms of eye inflammation with applications in autoimmunity, transplantation, dry eye disease, stem cells, and bioengineering.
Dana has authored over 400 publications, books and reviews, and his scientific work has been cited more than 19,000 times. He has been the recipient of numerous national and international scientific awards in the fields of ophthalmology, transplantation, and neuroscience, and is recognized internationally as a leading vision scientist and ocular immunologist whose work has transformed the fields of corneal transplantation and ocular autoimmune diseases. He has delivered more than 200 invited lectures worldwide and is an editor of several scientific journals and textbooks. Among his most significant contributions has been his training and mentoring of over 120 physicians, scientists and students from more than 30 countries in his laboratory, many starting their own leading academic programs around the globe. In 2014, Dana received the A. Clifford Barger Excellence in Mentoring Award, the highest mentoring award bestowed at the Harvard Medical School.
Can you tell us about your personal and family background? Can you outline your journey beginning as a student to your appointment as a professor at Harvard University?
I grew up in a family for whom education was paramount. My parents themselves came from highly educated families, and had older siblings who were quite accomplished, including writers, journalists, scholars, and lawyers. This focus on education, in the broad sense of the word that meant understanding the world and not simply learning a trade, was a current that was quite strong in our family. My parents met across a balcony wall that separated their apartments near the Tehran University campus. My father completed his studies in architecture, and received his graduate degree in the US; my mother completed her degree in child psychology. They belonged to the professional and educated class in Iran, and like many of their peers sent their children to Europe and the US for their education.
I attended the Tehran International School where we had students from over 50 countries, many from the large community of mostly Americans and Europeans who lived in Tehran. My parents had already planned on sending me to study overseas for high school, but the start of the Iranian revolution and social unrest that led to the closure of many schools, and departure of the international faculty, compelled them to send me abroad early. I completed my high school years in a boarding “prep” school in New Hampshire, followed by my university studies and medical degree at Johns Hopkins University. I made my way back to New England in the 1990s to complete my ophthalmology subspecialty training at Harvard in my field of ocular and transplantation immunology. After completing my studies here, I had the opportunity to stay and develop my own program as a faculty member, and I haven’t left since.
What brought you to Ophthalmology? Was there a particular person, place or event that you count among your key influences to date?
That’s an interesting question; I don’t think life is merely a game of chance, but at least in my life, unplanned events have had a major impact on how things transpired, including my choice of specialty. My initial draw to medicine came from a deep conviction in doing something that had social, not just career or monetary, value, and this is one reason I pursued a degree in public health as well. I also wanted to pursue a career that had value for people anywhere in the world. These priorities drew me to medicine. During medical school, I became very interested in the concept of organ transplantation and transplant immunology. One day during a random conversation with a friend, I learned about corneal transplants, and how they can restore vision to many people blind from corneal diseases— say from infections and injuries. Honestly, until that time I had not given ophthalmology much serious consideration. But I arranged a couple of interviews with laboratories that were doing research in the area. The more I learned about the possibilities of transplantation, including use of stem cells, whose applications were just being appreciated in medicine at the time, and the issues of immune mediated transplant rejection, the more I was drawn to the idea of doing my work in corneal transplantation. The idea of merging transplantation with restoring vision totally captivated me, and so I signed up to work in a corneal transplant lab. So, a seemingly random conversation launched my life’s professional pursuit.
Who has been your greatest mentor and why?
My studies and research in transplant immunology drew me to the work of Wayne Streilein in the 1990s, who at the time was the head of the Department of Immunology at the University of Miami. He was pursuing a line of research that was initially launched by Sir Peter Medawar, a British immunologist whose work on transplant tolerance led him to receive the Nobel Prize in 1960. Streilein and his coworkers had shown that while corneal transplants are susceptible to immune rejection, the eye onto which they are grafted, leads to a “deviant” form of protective immune response that is unique and not shared with other transplants, such as kidney or heart grafts. They termed this “corneal immune privilege” to capture how the immune system can be actively protective of grafts rather than just rejecting them. While some of the mechanisms of immune privilege had been worked out, many issues remained unanswered, and I found this whole area fascinating. I remember the day I read one of his papers on the topic vividly. I called Wayne Streilein the following week, and was honestly surprised that he took my call. I told him I wanted to work with him, and he informed me that he had just accepted a position at Harvard, and invited me to join him there after a hastily arranged interview. That was 20-some years ago.
Of all the teachers and colleagues I have had, there is no question for me that Wayne was the most influential mentor I’ve had. It wasn’t just his knowledge of the field, which in of itself was immense and extremely helpful for me as I pursued my research as a beginner student in the field of immunology. It was also his wisdom, and the way that he dealt with people and problems. We would meet every week, review scientific problems, and then talk about everything from culture to politics, and I found that extremely gratifying. He was also an immensely gracious person, since some of the findings that I made years later contradicted conclusions people had made based on his earlier work, and yet he always remained supportive and encouraging. So he exemplified the ultimate mentor to me. Unfortunately, in 2004, he died after a very brief acute illness.
You have developed one of the leading translational research programs in ophthalmology. Can you please tell our readers about it, and steps you’ve employed to develop such a program?
Translational science refers to efforts that bridge the gap between what science can do and how it is being practiced. Of course, science, in of itself, is highly valuable as a human pursuit for any civilized society, whether it is applied science, theoretical science, or fundamental basic investigation that does not have any obvious direct applicability to human disease. However, from a social value standpoint, translational investigations that apply learnings gained in the laboratory to human diseases through carefully conducted controlled studies are critical if we are to successfully bridge the ever-expanding divide between the state of the art in science and the standard of care in clinical medicine. Just as the automobiles we drive often do not operate based on the latest technological and engineering marvels possible, the clinical care we provide our patients is often many years behind what our scientific investigations suggest we can do. There’s no magic recipe for conducting translational science, but I have always tried to build my work on three pillars: innovation, impact and talent that we can recruit to a project. Novelty is important, but in of itself is inadequate; there are lots of innovations that don’t get anywhere, so it’s important to keep the potential impact of a program in mind. And of course, having the best people possible engaged is not only critical for advancing a project, but also makes it more fun.
You have made fundamental contributions to our understanding of ocular inflammatory disorders in the areas of transplant rejection, growth of blood vessels, autoimmunity and dry eye disease. Can you share the highlights of your work and also tell us a bit about your contributions that have earned you the most recognition?
I started my research career focused almost exclusively in determining the basic cellular mechanisms of transplant immunity—essentially understanding how immune cells are mobilized and activated to attack transplants. While our work was focused primarily on corneal transplants, which by the way account for the most common form of transplantation, our studies were designed to better understand immune mechanisms that have broader applications. The cornea is the transparent dome in the front of the eye whose clarity is essential for vision. In our quest to understand better how our immune system has evolved to protect our eyes from unwanted inflammation, our group first discovered, and then classified, several unique populations of immune cells that specifically reside in the cornea and have high capacity to change their function in response to different stimuli—what we call plasticity. Similar cells have also been identified around certain tumors, and it is believed now that some of the same mechanisms by which many tumors protect themselves against immune attack are similar to the mechanisms we identified for the eye.
Around this time, in the early 2000s, I had the incredibly good fortune of meeting Ralph Steinman at a scientific conference in Keystone Colorado. He was known as the founder of the field of dendritic cells, specialized immune cells that are critical in immune surveillance and tolerance. We happened to be sharing a breakfast table, and after introducing ourselves we sat there for more than an hour talking science and I told him about my work. He was very interested and kept asking me questions that were both provocative and insightful. I felt extremely lucky as a young scientist working in a narrow area to have connected with a senior world-class scientist of that caliber. While we never formally collaborated on a project, we stayed in touch for years, and I invited him to Boston to visit my lab and meet my students. The most important lesson I learned from him was to focus my work on immune ‘function’ and not on simply describing the various features of the cells we had discovered. While this may sound trivial or semantic hair splitting, it had a major influence on how we pursued work in our lab. Parenthetically, about a decade after we first met, in 2011 Steinman was awarded the Nobel Prize in Medicine for his contributions to immunology.
Apart from our work in the field of transplant immunology, my laboratory developed a major focus on mechanisms that regulate the growth of new blood vessels, what is called angiogenesis. The cornea, along with cartilage, is the only tissue that is entirely free of blood vessels—for good reason, since growth of blood vessels would take away its transparency and thus impact vision. This happens commonly after infection and inflammation. The cornea thus offers a wonderful model system for studying how blood vessel development is controlled, and my lab made discoveries regarding the unique systems employed by the cornea to maintain its clarity under normal circumstances. The other area that we have been actively pursuing is to better understand the mechanisms that underlie autoimmunity, namely how our immune system can go awry and cause unwanted chronic inflammation in our various tissues including the eyes. Common autoimmune conditions of the eye include dry eye disease and inflammation of the inside of the eye called “uveitis.”
What are some of the biggest challenges that you have faced in your career, and what lessons have you learned as a result?
Science is challenging. That’s why many of us are drawn to it. We want to explain how the world functions, and what mechanisms underlie the problems and phenomena we observe, whether in our health, environments, economies, or the universe. And establishing a career in science is no trivial process, given the intense competition for receiving grants and publishing our work. These are challenges we face on literally a weekly basis, as we strive to retain the vitality of our research and educational programs.
Other major challenges I have witnessed relate to organizational and group dynamic conflicts. Our research and teaching institutions were for a long time relatively protected from socioeconomic pressures, which led to a false feeling of long-lasting security for many academics. No longer. Today, we are all challenged by a variety of factors: macroeconomic issues and fast-changing technologic innovations that affect work flow, an ever-increasing regulatory environment that stresses set organizational structures, and leadership dynamics that can’t always keep pace and respond nimbly with the ever-changing funding landscape. Not surprisingly perhaps, these challenges can sometimes lead to organizational behavior trends that stifle growth, cause dissatisfaction and amplify insecurity. Add to this mix the occasional intransigent colleague and you can imagine the conflicts that can arise in such a charged environment.
What have I learned as a result that impacts my leadership style? The Pareto Principle, or the “80-20 rule” in management essentially means that 80% of issues emanate from 20% of factors. The converse of it means that changing a few critical factors can make a huge difference. I believe that real commitment to a few principles, such as open communication and creating a culture of collaboration and pure meritocracy, can go a long way in developing a nourishing environment that can lead to growth, and alleviate much of the insecurities that many people sense in their workplace. That doesn’t mean there will never be conflict, since our responses to workplace realities will never be identical. It’s axiomatic that we are driven by different visions and fears, and these lead to differences in temper, incentives, and communication styles. I try to focus on shared positive interests and the concept of professionalism. When you sit in a plane as a passenger, you don’t worry about how much the pilot and copilot like each other because you take it as a given that they are professionals. You assume that whatever they think of each other, their professionalism will supersede all other factors, and they automatically focus on shared goals. Similarly, razor sharp focus on shared goals in a positive and collaborative environment is essential for group success.
How do you see your field changing? What excites you most about the future of your field?
This is an extremely exciting time for biomedical research. The increasing focus on mechanisms of disease development and progression rather than simply describing and classifying diseases has led to a revolution in multiple fronts. As we have made progress in better understanding the mechanisms that underlie autoimmunity, cancer, microbial diseases, transplant rejection and other pathologies, a second important trend has appeared. Rather than focusing on tissue-specific manifestations of a disease (say rheumatoid arthritis in the joints or multiple sclerosis in our central nervous system), most of the field is now focused on shared critical paths that lead to disease. I personally see this development as very positive. Since most eye diseases can be directly visualized, the field of ophthalmology grew in the past few centuries with layer upon layer of descriptive findings detailing the appearance of various pathologies. Students of our field, like many other specialties, have had to memorize these minutiae without fully understanding the reason behind why the diseases would manifest a certain way. That is all changing now.
Alongside this scientific trend, we are witnessing the age of regenerative medicine. Harnessed with information emanating from disparate fields of cell biology, immunology, genetics, microbiology, and stem cells among others, we are at the cusp of reversing and restoring function to many tissues that until recently we thought were irreversibly damaged from chronic diseases. Restoring function to the brain or eye that has degenerated due to diseases of “aging”, or the gut or joints by the ravages of autoimmune inflammation, or the heart that has lost pump function due to vascular disease, is no longer simply just a dream.
In your opinion, what are the main challenges currently facing biomedical research and biotechnology?
From a purely scientific standpoint, it’s honestly mindboggling how much farther ahead we are today than just even a decade or two ago. Whether based on limited clinical studies or novel concepts applied to laboratory models of disease, we know that many of our goals in treating or preventing disease are possible. However, getting these possibilities into a realm where as a society we can benefit from them is not only a scientific issue but also a socio-economic matter. Regardless of where we live, we are confronted with major challenges. Health care, education, roads and infrastructure, security matters, and among many others all vie for our attention and commitment. I personally believe that while private foundations play an important role in promoting education and research in several specialty areas, say muscular dystrophy or multiple sclerosis, broad and fundamental advancement of the sciences requires major public financing. For example, the National Institutes of Health is one of the jewels of biomedical research, and is seen by scientists and administrators all over the world as the model organization to emulate. There is no question in my mind that the leadership position of the US in the biomedical sciences owes much of it to the NIH, which enables application of top talent in academic labs to answering innovative and high-impact areas in science. As long as we can foster this growth in scientific discovery, the prospects are bright.
How has your background affected you? And what challenges and opportunities does your background provide you with?
On an intellectual level, I am aware and proud of my Persian heritage, linked to more than 5,000 years of civilization. However, while I realize that it may be convenient to label ourselves or others based on our cultural and ethnic heritage, I honestly don’t see my identity simply fitting any one particular designation. Of course, in many ways I have a deeply personal link to my past in what I suppose you could call a Proustian recollection of my childhood, personal experiences mixed with images, smells, and people that have long passed.
I came to the US in my early teenage years, after having gone to an international school in Tehran, having spent a lot of time before that in Europe and having grown within a family with strong international roots, so I can’t say that my principal challenges moving to the US were primarily cultural. Rather, they were personal—I didn’t have my family around, and so basic childhood experiences like showing your school report cards to your parents, going home for the holidays, or having your parents visit the school during parents’ weekend, were totally different experiences for me than for my peers.
From an opportunity standpoint, the positive side of growing up in a culturally diverse or perhaps even fragmented way, is that you end up having the luxury of picking various elements of a given culture that you like without necessarily assuming the full identity of that cultural macrocosm. That fluidity and capacity to adapt has been helpful to many of us. It’s apparent now that with the progress of history, ethnocentric cultural identities, for better or for worse, are also melting away as our societies are becoming increasingly defined by a mix of Asian, Latin, Anglo-Saxon, African and other cultures, that define how we live, and what we eat and listen to. And this amalgamation of various cultures is becoming a universal phenomenon now, not just here in the US, but also in many other countries that are being economically and socially (through immigration) assimilated into the global fabric. That’s one reason the young in the particular all over the world are looking and behaving so similarly to one another. I’ve been fortunate that through my work as a researcher-educator, I get to work with people from all over the world who train with me, and I also get to travel to many countries for work. This exposure to a mélange of cultures makes me feel that I have an element of each within me, though of course my Persian heritage, tempered by my Anglo-European centric education and experiences, outline the concoction that defines me today.
Do you have any last words of advice to young students who are building a passion for medicine and biomedical research? Are there specific strategies that you think have helped you in achieving success in your professional life?
Achieving success is not formulaic. First, I certainly don’t take most of the credit for whatever success I have achieved. The emotional and financial and other types of support I received from my family in pursuit of my education were critical. Second, no matter what you do, the role of luck or chance, pure and simple, cannot be overemphasized. I can think of many twists and turns in our projects, and in my own life and those of other people I know well that were impacted significantly by apparently chance events such as people and situations you run into. In terms of what we can do to increase the odds of success, in anything we do, there are several principles I follow. Discipline and focus are perhaps the most important. Discipline without focus can turn us into a compulsive taskmaster, and focus without discipline or an overarching aim, can turn us into an automaton. So both are necessary. Finally, one principle that I remind our students and my kids is that we need to push ourselves to get to, and then stay, beyond our comfort zones. We all hear the constant drone of “being ourselves”, an irony given the commodification and conformity of nearly every human endeavor in our global society. While I’m all for authenticity, I do think that we can’t approach learning with a sense of entitlement. It’s important to push the boundaries and get ourselves to operate at a level that is beyond our immediate comfort zone. Any top athlete knows this, and the same applies to the world of science and research.