DK: I wanted to start out by talking a little bit about your background, your story: your research, but also how you grew up, where you came from?

LG: I grew up in Brookline, and my dad was a professor of orthopedic surgery at Harvard Medical School. He shared the Department of Orthopedic Surgery at MGH and then at Children’s. But he, like me, was a physician-scientist, and he was really a biophysicist and a biochemist. He basically founded the orthopedic research labs at both places. So he was certainly an influence in my life.

I went for high school to the Winsor School. And then I went to Harvard undergrad and Harvard Medical School. At HMS, the immunology block was at the end of the first year and that’s when I fell in love with immunology. That was it. I spent my fourth year at medical school in a laboratory here at Dana-Farber – Harvey Cantor’s laboratory – where I learned about immunology, did immunology research, and then I trained at Massachusetts General Hospital in Internal Medicine followed by subspecialization in Rheumatology. After a postdoctoral fellowship at NIH in immunology, I returned to Harvard to become an Assistant Professor and start my own laboratory, in the Longwood Medical Area. My lab was at the Harvard
School of Public Health with a joint appointment at Harvard Medical School where I rose through the ranks, and received tenure at the School of Public Health and the Medical School in 1990.

Immunology is something I’ve always loved, but I’ve also drifted into different fields, I’ve gone where the science takes me.

Basically, I have spent my life in Boston. At some point, I decided that it would be interesting to live somewhere else and do something different. When I was asked if I would consider being the Dean at Weill Cornell, I thought I should look at this opportunity, because I could perhaps have a greater impact by enabling other people’s science and other people’s careers if I were Dean, rather than just focusing on my own laboratory. And I just thought it would be fun to have two different careers in one’s life. My first career was primarily as a basic researcher, also as a physician, although I didn’t spend a lot of time in patient care. And I’ve been very fortunate to have a rewarding scientific career – far better than anything I would have ever dreamt I could have – so I figured it was time to give back. I had a fairly large research lab. When I moved to Weill Cornell, it got smaller. I decided to focus on just a couple of things. That’s how I ended up at Weill Cornell. Which was great – I had a great time there, it was a huge job, much of which I was not prepared for, so there was a very steep learning curve which I always like. My intent was to stay at Weill Cornell another five years, but when Dana-Farber asked me if I would consider the position of CEO and President, I just couldn’t resist because it’s such a fantastic institution. And it brought me back to Harvard, to Boston. Which was always my intention; I was always going to come back here at some point. Two of my three kids are here; my older son went to Harvard Medical School. He’s a cardiothoracic surgeon at MGH. My younger son went to Harvard undergrad and thence to the Marine Corps where he was a Captain in the Marine Corps in Force Recon. , He then went to MIT business school, and now he’s in business and politics. So two of my three kids are here and my daughter is in Washington, D.C. So there were a lot of reasons to come back. And I think Boston is an amazing place for the life sciences. It clearly still is the premiere place for the biomedical sciences. And it’s not just that it has a plethora of top-notch academic medical centers, and research institutes, but it also of course has the whole venture capital biotech pharma environment which works nicely with academia.

DK: You’re considered a pioneer, a champion of the field of immunology. Is there any direction you see the field going, either in cancer therapy or implications for other fields that really excites you? Or, could you tell us a little bit about what that search was like in the past, in your previous research – finding markers like Nk1.1?

LG: (laughing) That was so long ago!

But I’ll tell you what my philosophy is. And I decided this when I started out: that I did not want to do humdrum science. I wanted to have the chance to make big contributions and the only way you can do that is to be a risk taker. And I kind of have a risk-taker phenotype anyway, so I decided I would just aim very high, and if I crashed, I crashed! Being a physician opens lots of avenues for various careers.

I decided that when I set up my own lab that I would try to figure out the relationship between the major histocompatibility complex and how that related to activating T cells by the T cell receptor. Then I became interested in gene regulation, which has really been my love, and wanted to figure out why an uncommitted progenitor cell, a naïve, T lymphocyte – decided to become one kind of T cell or another kind of T cell. And so we isolated several of the transcription factors that really controlled lineage commitment. Whether a T cell became a type 1 T cell, type 2 T cell, helper cell or killer cell. Probably what I’m best known for is identifying the master regulator transcription factor for type 1 immunity. This was T-bet. And then we also discovered the first transcription factor that controlled a key step in B lymphocyte development- from a B cell into an antibody-secreting plasma cell. And that led us into the ER stress response... We kind of go where the science takes us, and we’ve been fortunate to make some major contributions.

To be a scientist, you have to tolerate highs and lows. The highs are great, when you make a big discovery; but there are a lot of lows. It requires emotional stamina. Everybody’s experienced lows. Everyone is going fail at times. If you’re not failing in some projects, you’re not taking enough risks. That’s the bottom line. So you have to fail at some projects. But if you’re lucky, you’ll succeed in a few, and that’s all you can hope for. And we were pretty lucky.

Also, it’s good to have an open mind. If you get an unexpected result, don’t just ignore it. We isolated a gene called Shnurri-3 that we thought might be important in the immune system. But it turned out to not affect the immune system but instead had an enormous effect on the skeletal system. That led to a sustained interest in skeletal biology, and identification of new proteins that control bone mass. Osteoporosis (low bone mass) is a very common disease and we don’t have ideal treatments for it. So, one goes where the science takes you; at the same time, it’s important to focus on two or three different areas so that after the initial discovery one can pursue it in depth.

So where do I think cancer [therapy] is going? It truly is an amazing time for cancer. It really is. Two revolutions have occurred in the last decade – precision or targeted medicine which identifies unique genetic mutations in each patient’s tumor and immuno- therapy which has finally seen some astonishing successes for some tumors. My own lab has focused on the role of endoplasmic reticulum (ER) stress both in the tumor and also in the immune system with some interesting results. We predicted that if you manipulated ER stress pathways in the tumor cell, it should lead to increased tumor death. And we were right about that. What we didn’t predict was that if you block the pathway in the immune system, you would actually activate antitumor immunity in multiple immune cells. It’s like a double whammy, which is why we founded a company about a year and a half ago, to develop small molecule inhibitors of this key enzyme and its substrate because one would predict that such inhibitors would simultaneously activate antitumor immunity and also directly kill the tumor.

DK: I could talk about research all day, but it would be great to switch gears because there is another side to all of this in your life, that I would feel remiss if I didn’t mention, and that’s that you’re considered somewhat of a champion in also women’s rights in the STEM-related fields. Could you tell us a little more about initiatives that you’ve started, or become involved in recently?

LG: I realized fairly early as my lab grew bigger that we needed to level the playing field for women. Too many women get discouraged and drop out early on because achieving an acceptable work/life balance is challenging to say the least. By the time you’re a postdoc, you’re thinking about having kids... I mean, I had my three kids when I was 28, 30, and 36. I started my own lab when I was 31. And it was very tough! I wanted to make it easier for my graduate students and postdoctoral fellows. If you provide a technician to a postdoctoral fellow who has young kids, then the work can continue if you have to run out and go to the kids’ school, kid’s ball game because there is a pair of hands carrying on with the experiments. If your hours are 8 to 6 or 8 to 5, because you have to pick up the kids at daycare or whatever, it’s good to have somebody else to continue the experiment. My lab was well-funded, so I was able to provide that for the female grad students and postdocs who had childcare responsibilities. And it worked! They were productive, and a lot of them are in very wonderful positions now. So then I convinced the NIH – the NIAID, in particular, to pilot this program, which they call PCTAS. I was on the Summers’s task force for women in science and engineering and was able to suggest some programs that would help support women there as well.

When I arrived at Weill Cornell, I was able to build an excellent childcare center, and made sure we had paid maternity leave and automatic suspension of tenure. It was a pleasure to look for really talented women to develop at Weill Cornell – and there were plenty of them. I found talented junior and senior women faculty whose talents had been unrecognized, and promoted them. It’s important to provide intellectual and emotional support, but one also has to provide financial support. I raised a fund for young female faculty who were assistant professors. They had a great idea, they had a great discovery, they needed to push it for all it’s worth, they don’t have time to wait to get a grant from the NIH. Give them money now so they can hire another postdoc, so that they can push that discovery further, faster. Put them in positions of leadership, because we don’t have enough senior leaders who are women who can serve as role models.

DK: So you kind of facilitated that.

LG: Yes, this has been a big priority for me. And not just women – men too. But a special place for women – because I know how hard it was when I went through it. My first husband was a surgeon so I was the primary childcare parent. Three kids, you really learn how to manage your time for sure, but I didn’t want the people I trained to have to go through what I went through. At that time I really didn’t have a mentor, nobody really helping me – it was tough, it was really hard.

DK: One last question: I was wondering what your thoughts were on how to help before – because a lot of your work has centered on doing great things for women professionals, people who are already established, and I was wondering: do you have any advice for young women who might be struggling with their identity, within the phase of education, within their field of interest, before they become established as a professional? Any dreams or advice you have for female students who might feel gender-based pressure?

LG: I think having self-confidence is a very big part of it. And women tend to have less self-confidence, even though it is not deserved. I saw this over and over again in my grad students and postdocs. Certainly in college students as well; I’ve had a lot of undergraduate students over the years. Women just tend to have less self-confidence. One piece of advice is: act as if you’re self-confident, even if you aren’t. You have to believe in yourself. And you have to be willing to put yourself out there. Take risks and speak up, for yourself. Men – and this is a gross generalization – but men tend to think they are better than they actually are, and women tend to think that they are not as good as they in fact are. And that’s something that has to be worked on, the younger the better.

DK: Thanks for your time.

LG: You’re welcome.