Jun 12 2018 Posted: 00:00 IST

David Mooney Interview: June 12th 2018

Prof. Mooney is the Robert P. Pinkas Family Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences. He plays an active role in the major biomedical and chemical engineering professional societies, serves as an editorial advisor to several journals and publishers, organizes and chairs leading conferences and symposia, and participates on several industry advisory boards. His current projects focus on therapeutic angiogenesis, regeneration of musculoskeletal tissues, and cancer therapies. In 2009, his team developed the first vaccine ever to eliminate melanoma tumors in mice. It is a tiny bioengineered disc filled with tumor-specific antigens that can be inserted under the skin where it activates the immune system to destroy tumor cells. While typical tissue engineering involves growing cells outside the body, his novel approach reprograms cells that are already in the body.

How did you choose and start off your career?

Early on I had some people who were influential and at least explained to me what the possibilities were. I do not come from a technical background. My parents did not attend college, but all my siblings did, but when I went to college I had no idea what I wanted to do. I did not have one of those planned out careers. I went to a large public university, the University of Wisconsin and I had a great advisor in first year and on the tests he said ‘well you did really well in chemistry and math and have you ever thought of chemical engineering?’ At that stage I did not really know what that was, but his question led me down that path and I ended up realising that I really enjoyed chemical engineering, learning chemistry and particularly how to apply the sciences which I found very exciting.

In my undergrad I was a co-op student, which means that you alternate semesters spending one going to school and the next working for a company. I did that also for financial reasons, I needed to pay my own way through college. I had planned to go to work for the company that I was co-op for, but in my last year one of my professors asked me to stay after class one day and asked if I had thought about graduate school. He explained what it was and said that he thought that I might enjoy it. He convinced me to apply and so that led to me enrolling at MIT.

I originally intended just to stay for a Masters, but in that time I got exposed to a lot of research and in particular learned of this emerging field of tissue engineering, that was really just getting started and I got really enthused about the possibility of working in that space.

The idea of being able to use my engineering background not to just make some product maybe faster and cheaper, but to actually have an impact on people’s lives was very compelling to me. So I decided to go into that research area.  I still had no intention of becoming a professor at that time, I assumed I would just go and work in industry when I was done, but near that end of my time at graduate school I got a couple of phone calls from Universities that were interested in my general research space had heard me give a talk at a conference. They wanted to know if I would be interested in applying for a faculty position. I did apply but was also looking at positions in industry because I had really enjoyed my time in industry, but I decided that the freedom to pursue my own ideas in academia was the main draw for me.

I have stayed in an academic position where I do a lot of teaching because I found that I really enjoy engaging with the students. One of the things I like about academia is the diversity of activities, so I will walk into a classroom for an hour, engage with brilliant undergraduates and get a chance to see their excitement and enthusiasm and help them see some opportunities, and then you might engage with your PhD students and talk about the research projects you have underway, or talk to collaborators,  do some consulting for governments, have a chance to learn what is happening in other universities, companies and settings, so the diversity of experiences and the ability to work with young people and to teach, has been a lot of fun.

Tell us a little about the research you are currently working on?

We work in a lot of different areas but what holds all the work together is that we design materials that act to control biology in the body. At the end of the day we are trying to direct biology down certain pathways and we use these materials as our tool to try and achieve that goal. It ends up taking a lot of different directions and themes.

One theme that has been very important in the laboratory for the last several years has been the idea of being able to pursue cellular therapies and the ability of cells to be very potent agents to address disease and to do this where we interface with those cells directly in the body. Really we’re trying to bypass the need to do ex-vivo cell manipulation which is a big issue in terms of cost and complexity and in making cell therapies broadly useful in the treatment of disease. So we are trying to simplify that by using materials to do that in-vivo. One way to think of it is as making cell factories within the body where we have a material and we bring in cells that already exist in the body and we manipulate those cells and then let them loose to go someplace else and do something useful. A big context for this has been in the area of immunotherapy, particularly cancer immunotherapy, where we’ve been trying to develop materials that can function as therapeutic vaccines to generate immune responses against pre-existing cancer. In that activity we are really targeting a particular kind of immune cell called the dendritic cell and now, we are increasingly beginning to target T-cell biology as a means of regulating immunity. 

Another theme that’s been in existence in the laboratory for quite a while is the use of stem cells in trying to induce regeneration. We are now beginning to look at the intersection of immune cells and stem cells and how cells of the immune system, T cells, regulate regeneration. Another prominent area that we do research in is what I would call ‘mechano-regeneration’, which is where instead of using chemical cues or signals like drugs, we use mechanics to drive regeneration. So we are studying how mechanical properties of tissues vary in disease and how we can then make materials that have specific types of mechanical properties to enhance regeneration. These studies look at the intrinsic mechanical interaction between a cell and a material, how when a cell attaches it pulls and feels how stiff its surroundings are, but we are also then using materials to impose forces on cells to try to induce regenerative situations.

How do you see it developing in the future?

In ten years, the ideal scenario is that some of our immunotherapies, in the context of cancer will be established as effective means to treat cancer in patients. We’re at the very early stages of that now, at first clinical trials at this point in time. In ten years hopefully that’s enough time for us to understand if these really are effective in humans. For some of our stem cell therapy approaches, my hope is that in ten years we would be in the midst of clinical trials, evaluating. We will not know in ten years, but at that point we are at least on the path to figuring that out.

What do you see as the key strength of a centre like CÚRAM?

I’ve been really impressed with the ability to couple an understanding of biomaterials and fundamental biological principles with medical devices. It’s very exciting and clearly where the field is headed. I think CÚRAM has also done a wonderful job of bringing together the right players, many places cannot do that because they don’t have such a strong medical device industry presence or they do not have the combination of engineering, life sciences and clinical sciences but here you have all of the different facets you need to have an impact. I have been really impressed with the leadership at CÚRAM in terms of its vision of where this field can go and how you bring people together to make it happen.  So the intellectual part is there, the different players are there and then it seems that the infrastructure both in terms of facilities and the financial part has come together with the Irish Government engaged and recognising the importance of the work. I have been very enthused about how all the different components you need for a recipe to be successful are here and I think CÚRAM is seeing a lot of success. I have also met with some of the students and they are doing some really exciting projects that have both a lot of basic science implications but which could also potentially lead directly to new types of medical devices and therapies.

What do you think is the key to successful collaboration?

Finding common goals, often different types of researchers have very different objectives for their research. For collaboration to work you need to find a common ground where there’s something everyone is excited about, for example a new materials system being developed here, that then allows different applications and needs to be met depending for a variety of perspectives. I think this ability to bring people together and find common interests is really important and then having a forum to train the students in the different fields is critical. If the students aren’t appropriately exposed and trained in a multidisciplinary style approach, then it’s not going to work for the future as they are the ones doing the research.

What is the greatest challenge in your area of research?

The biggest challenge is that there are a lot of things you could do and so it’s trying to figure out what the most important thing to do is and where you should really invest your time. A very important skill to learn as part of that is learning to fail quickly. It is impossible, at least for me, to predict what’s going to be the most important thing to do, but if we can learn to quickly screen ideas to figure out which ones are not going to be useful , do the definitive experiment quickly, fail that and then know to move on and spend your time someplace else.

What areas of research would you like to see tackled in the future?

We’ve come a long way in translational research but there is still a long way to go. I think the funding mechanisms are not that well aligned and perhaps even the reward structure in academia is not set up to allow people who spend all the time and effort in translational work, collaborative work in these teams, to get the credit that they need to get. At this point in time this research in the US anyway, is largely a luxury for senior faculty members. Junior faculty members have to be very careful, because it does not result in papers or publications and that’s what the academic reward structure is set up around. We need to find the right way to not only foster but reward people who do this type of collaborative, multidisciplinary research.

What advice would you give to a secondary school student who is unsure what career path to choose?
There are two things I would say. The first is to do what you are excited about. Don’t do what people tell you is the right thing to do just because this area or that area will be important in the future. At every stage of my career I have just done what I was excited about at that stage and at least for me it’s worked out OK. The second is to realise that you are not making an irrevocable choice! You are probably going to go in a lot of different directions in your career, so do not get too worried or stressed about making this choice.

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