Dr. Luis Montaner - A Career in HIV Research

In this episode The Wistar Institute’s podcast, we take a deep dive with Dr. Luis Montaner, one of Wistar’s longest-serving scientists. Listen today as he discusses his lab’s groundbreaking HIV cure research and how he decided to dedicate his life to the cause of searching for an HIV cure.

Transcript

Dr. Maureen Murphy: This is Wistar Science Up Close, where we tell the stories of researchers who are global leaders pushing the boundaries of what's possible in biomedical research. I'm your host, Dr. Maureen Murphy. I'm the Deputy Director of Wistar's Ellen and Ronald Caplan Cancer Center. I'm also a teacher and I love to learn. In each episode of Wistar Science Up Close, we'll take you into the labs and lives of our scientists to learn about their special expertise in fields like vaccine development, immunology, infectious diseases, and the fight against cancer. We'll also get to know a bit about our scientists outside of the lab, hear the stories of their professional journeys, and find out why they do what they do. My guest today is Dr. Luis Montaner. Dr. Montaner joined Wistar in 1995, which makes him one of the organization's longest serving scientists. We discuss his lab's groundbreaking HIV research, hear about how he got his start in science, and Dr. Montaner shares a few lessons he's learned from doing this work for over three decades.

So welcome everyone, I'm here with Dr. Luis Montaner, the Herbert Kean Family Professor and director of HIV Immunopathogenesis Laboratory and leader of the HIV Research Program here at The Wistar Institute.

So let's say that you meet someone at a party and they don't work in science. How do you describe what you do for a living to them? 

Dr. Luis Montaner: Usually open up by saying that I work on how to manipulate the immune system in order to make it work for us in regards to people living with HIV, how to get rid of residual virus after they go on treatment or regarding cancer, how to get the immune system to better engage a cancer and clear it. 

Dr. Maureen Murphy: Wonderful. Now I know a little bit of your story, that your dad was a healthcare professional and at first you thought that you might want to follow up in his footsteps, but then you caught the science bug. But tell me three things that I don't know about you. 

Dr. Luis Montaner: Well, I used to get up at 4:30 or 5 for a paper route back before the internet where people used to get their news in the morning. I also was heavily involved in drama in high school, so I thought I was going to be an actor. I really enjoyed it. And actually, to be honest, there are skills that you use throughout science. And third, really a big legacy of what I was able to leave the university - Kansas State University - was I was unfortunately part of a racially charged incident. So this was back when I was in veterinary school and in Puerto Rico we celebrate San Juan Night, which is St. Joseph, St. John is San Juan is the capital. So we all got together into this commercial sort of place, a bar, and unfortunately the people in the bar kind of took it to themselves to go after our group in a very not productive way by putting up signs and all this stuff.

And so we then kind of coalesced the awareness that this was really not acceptable and that it really needed some attention from all the local entities that students needed to have a safe haven within the town that actually was right proximal to university without this type of activity. And then interestingly, all the other international students joined in, it was almost like you spark a nerve that there was something that was amiss that we experienced, but others must have too. Because as soon as we stood up and said "This needs to change," then everyone joined in. And that created enough attention from the university that they basically took it as an opportunity to redirect that in a productive manner. And they did so because they established a whole program around community harmony and outreach and cultural awareness and to this day is still there. 

Dr. Maureen Murphy: And so this is a week long event where different cultures are celebrated and information is dispersed. 

Dr. Luis Montaner: Correct. I mean, it started from an unfortunate event, but it really turned into a positive force into the future that to this day is still there 25 years later under cultural harmony week. 

Dr. Maureen Murphy: Oh, that's wonderful. So you have a lasting influence everywhere you've been. So go back and walk me a little bit through your journey as a scientist. Where did it begin? When did you catch the science bug? 

Dr. Luis Montaner: My family's in science. My father's a pediatrician, so I sort of grew up with him sort of dealing with vaccinations and hanging out at his office. And interestingly, from a child's perspective, it always seemed kind of simplistic because it was sort of a primary care place. So people came with pretty standard type of needs. So I always thought, well, I want to do something much more complicated than this. I want to do research. And then I started thinking, well, medical school sounds kind of simplistic. It's only one system. So I want to be able to understand multiple systems and if I'm going to go to research, I want to know more about the heterogeneity of biology as opposed to just the human system. So that's why I went to veterinary school because I wanted a broader physiological type of awareness. So I did research, I didn't do my clinical rotations, I did research rotations instead.

And that's when I was introduced to SIV, the Simian Immunodeficiency Virus. I was able to work at the Harvard Primate Center at the time and sort of start working with the whole dynamic of immunodeficiency virus in the context of the simian model. And then after that, I was fortunate enough to go to Oxford under Marshall Scholarship to work on HIV at the time. And then I came back to Wistar to start a lab and it became clear that I could interface with clinical centers. And once you start having a vision about what you want to contribute and you can articulate that, people join. So physicians joined, we did trials, and those trials led to international trials and international trials led to a global coalition. And then at some point the veterinary degree becomes almost like a Bachelor's. It was something on your background that gave you some insight, but it's not what I do today.

It's funny because people are like "Oh, you're a vet. Can you look at my cat?" And I'm like, "I'm sorry, I would not touch your cat. You don't want me to touch your cat. I do a different type of science." Or they say, "Well, how come you're not an MD if you're doing clinical trials?" And it's like, because science is a team effort and you can lead the science with colleagues that take care of the clinical setting, but that doesn't mean that your degree defines what your contribution is. So anyway, so it's interesting that it's always a topic of conversation saying, wait, you're a vet. 

Dr. Maureen Murphy" It's funny, the word I hear from you is vision. And the beauty of Wistar I find is that each scientist doesn't just have a little silo of research. You actually think about your vision of a collaborative environment, a group effort targeted at a particular question, and you really achieve that. And I think that, to me, is the message we need to get to younger scientists. Don't just ask an interesting scientific question. What's your vision for making the world a better place? And in 20 years, where will you be? What kind of team will you have accrued? What are the important questions that you'll have asked? And you've done that. We're going to go to your research now. What's the main questions you're trying to answer with your research? 

Dr. Luis Montaner: I think we're really trying to understand in the context of HIV disease, how to get rid of the residual virus burden in someone that goes on treatment. As you know, treatment is for life. The burden of treatment can spill into toxicities. It can spill into an economic dependence on health infrastructures. It can spill into access relative to how people can get the sustained and maintained access throughout their entire life. And in addition to that, because it's an incurable disease that is dependent on treatment, unfortunately society has placed stigma onto the disease for which even today there's a lot of criminalization laws in the US that are really because HIV is not curable. So trying to understand how to get rid of the residual virus will have multiple benefits to society as well as to the individual. 

Dr. Maureen Murphy: Can I ask, for some context, how many people in the United States are currently living with HIV and have there been any cures? And if so... 

Dr. Luis Montaner: I think there's approximately about a million and a half, 1.2 to 1.5 million people living with HIV in the United States. The infection rates are still sustained, and there have been cures actually, and these have been individuals that have been treated for their cancer, but because the treatments - specifically for leukemia where they basically get rid of your whole immune system through irradiation of your entire body, and they give you a new immune system through what they refer to as a bone marrow transplant. And the individuals that were chosen for the bone marrow transplant had a particular mutation in one of the molecules that HIV requires to enter a cell. And it was that choice of a person with this mutation that basically avoided the HIV of an individual to populate the new immune system. Now, this is not a treatment because there's a 30% mortality as a consequence of these procedures, and you can go on therapy now for HIV and live without this mortality risk. But importantly, it showed us that a cure was possible, and that has really galvanized the scientific community to really go after the cure because we have treatments, people can live on treatment as we speak, but if we were able to achieve a cure, I think that we would serve many benefits, as I mentioned, across both the US and globally. 

Dr. Maureen Murphy: So the potential there is for the roughly 2 million people in the United States to now be cured like the very small handful of people have been cured already. That's the goal of your research. Is that fair to say? 

Dr. Luis Montaner: Yeah, to make possible a cure to most people living with HIV. Yes. 

Dr. Maureen Murphy: Tell me a little bit about healthcare disparities in HIV treatment. Are there systemic issues with healthcare disparities? Do you have a vision for how we can make care and treatment more accessible and inclusive? 

Dr. Luis Montaner: I think health disparities is a critical component of our current health awareness of access to care and therapy in the United States and globally. We know, for example, that incidents of both HIV disease and cancer disproportionately affects populations that lack greater access to health infrastructure. So when we talk about health disparities, we talk about both gaps in access to the services, but we also have to acknowledge a gap in information that's available to the populations. So I think Wistar can contribute in the context of being able to lay out information for groups that otherwise may not have access. For example, our outreaches in people living with HIV within our community, our seminars that we sponsor for communities at large, our campaigns for community advisory boards that bring in feedback from the community into the research process. But all of these forums clearly highlight that health disparities remains one of the critical barriers to our ability to anticipate that even our research findings will be accessible to everyone equally. So we have to continually, I guess, demand greater attention to this topic at all levels. Our contribution could be at the information level, but it's really a societal objective. And I'm hoping that this someday will be addressed. But at the moment, I think what we all can do is advocate strongly for awareness and change. 

Dr. Maureen Murphy: Wonderful, wonderful answer. You were really a pioneer. You spearheaded this Delaney Collaboratory; BEAT-HIV Delaney Collaboratory where 85 different laboratories have come together to galvanize and try and find a cure, to try different cures. What do you think will be the keys for this effort to cure HIV? What will be the keys for success? 

Dr. Luis Montaner: I think we've had success even as we speak. I mean, we've been able, as you mentioned, to bring together an entire global coalition of scientific talent that really brings multiple dimensions of the scientific work into the same tent. Because before this initiative, we all were kind of raising our own individual projects that would contribute to the larger goal, but it's very different to bring everyone on the same project. And here the dimension, the scale of it becomes also a really attractive feature because we basically can, as you mentioned, join multiple teams and move within and between teams within the ease of having the resources to support the science as it emerges. And that really creates an opportunity for collaboration, which is key and an opportunity for innovation and taking the talent from other teams into your own research and vice versa. And also a unique opportunity for community engagement, meaning that to bring the community into the process. As our community members like to say, they don't want to be served the dinner, they want to be in the kitchen, and we provide an environment where that is actually the reality. They are part of the process and there's many examples where their contributions have actually moved the scientific effort independently of our own initiative. And I think that that synergy is one of the biggest benefits of the BEAT-HIV program. 

Dr. Maureen Murphy: Wonderful. I know you personally, and I know you're very passionate about an HIV cure, you're passionate about community engagement. What makes you so passionate about this particular area of research? What drew you to HIV as a disease? 

Dr. Luis Montaner: The realization that our scientific effort has not yet conquered a chronic viral infection at the time that I started HIV infection because we now have, for example, a cure for hepatitis C, but at most chronic infections remained uncured and the burden, the societal burden, the need for intervention globally in the context of the HIV pandemic when I started my career, was one of the leading public health emergencies of the time. And as I became more engaged in the research, then I obviously became more empowered to contribute. So as time has moved forward, I've been fortunate enough to be able to lead the effort on a global scale, but it really started from a very sort of initial desire to contribute to this problem because I was in veterinary school when I started and my vision was to become a veterinary pathologist and maybe sit at the microscope and contribute to diagnosis of research animals engaged in research. And I've come a long way from that vision to what I'm doing now. 

Dr. Maureen Murphy: So going back to that time, in 1995, that was the year you earned your degree from Oxford and you joined the Wistar Institute. What drew you to Wistar? What made it unique that made you want to come here? 

Dr. Luis Montaner: The unique aspects that made me want to come here is one, the boldness by which Wistar recruited talent. I was actually just finishing my Ph.D. and they basically recruited me to start a lab at 27. And the second reason was that the scientific talent that was here created a really secure environment for which I could grow. So when you put those two together, the vote of confidence for independence and the mentorship and oversight of trusted colleagues that would actually help the scientific process move forward, was a combination that you didn't find anywhere else. 

Dr. Maureen Murphy: Something that most people probably don't know about science is that a lot of scientists don't stay in one place for very long. They move to another university to obtain either recruitment funds or maybe a leadership position. But you've stayed at Wistar for how long? 

Dr. Luis Montaner: I think I'm going on to 27 years. 

Dr. Maureen Murphy: 27 years. Alright. So back to the Delaney grant, which was a huge effort that must've taken six months? 12 months to put the grant together? 

Dr. Luis Montaner: It was an initiative that brings together multiple teams as we talked about globally. So sort of coordinating how all the leading labs would work together I think was one of the arts of getting these awards and keeping it and renewed, which we did. It's almost like a positive feedback when you make it work and people get comfortable that they can contribute and they acknowledge and they see the productivity of the team, then it becomes even a larger coalition to the point that when we actually renewed the second time, part of our problem was that even though we had 85 to 90 investigators, we could actually only support 21 with independent funds. But the beauty has been that as we renewed twice, we basically were able to select the leading science out of the 85 and we still have over 85 to 100 people being part of this coalition. So it still has maintained a collaborative nature. Whether you're supported by this effort directly or not, you're going to be part of the dialogue, and this is one of the things that the program provides globally. 

Dr. Maureen Murphy: That's powerful, that people play a role even though they're not necessarily getting monetary support.

Dr. Luis Montaner: But they're part of the dialogue and they're part of the science and they actually come in to collaborate with existing groups or within the groups as a whole. And it doesn't really matter whether you're supported. What it matters is are we actually working together or not? 

Dr. Maureen Murphy: So when you found out you were awarded the Delaney grant, what did you do to celebrate?

Dr. Luis Montaner: In science, we don't really celebrate a lot because it's almost like a horse on a race where all of a sudden you prep to go and you've identified all the things that you want to do, and all of a sudden somebody says, "Go!" So the first thing that you think about is, "Oh my God, we're going to do this." So you start calling everyone and say we're going to do this, and we start working. So yeah, so oddly enough, it's not about kind of celebrating, it's almost about going, "We finally get to do what we envisioned we wanted to do," and to get that excitement of actually starting to work is actually the celebration.

Dr. Maureen Murphy: So the reward is actually the work. Do you think scientists are in general not very good at celebrating their wins?

Dr. Luis Montaner: I mean, we do celebrate. No, we celebrate our wins when we publish our findings. We celebrate our wins when we report at conferences because we kind of gather and we acknowledge what we've been able to do. We have yearly meetings of the program where we celebrate what we've been able to do. So I guess it depends what you define as celebration for, at least what I've experienced is, we celebrate when we come together and review our progress. And that time to just step out of the lab, commune with your colleagues and reflect on what we've been able to accomplish - that's as close as a celebration as we get.

Dr. Maureen Murphy: What are some areas of research that you're pursuing now for the BEAT-HIV endeavor that you're particularly excited about? 

Dr. Luis Montaner: I am still very excited about the potential of the immune system to conquer HIV. I'm still excited about the prospect that we could manipulate our systems to cleanse and get rid of the virus once and for all. 

Dr. Maureen Murphy: Sort of tackling the reservoir that's in the T-cell still. 

Dr. Luis Montaner: Correct. And the approach that I'm still very enthusiastic about is your immune system is divided into two camps: into the camp that you can train and the camp that you're born with. And the one that you're born with is to some extent less specific, but at the same time more robust in numbers because it's all available at once, if you like. HIV virus has learned how to evade the immune system that we can train. That's part of the reason why the immune system can never catch up with the virus, but it hasn't completely been able to get rid of how the components of what we refer to as innate immune system, or what you're born with, how that deals with infection. So we're really focused on how to empower this side of the immune system we're born with to actually deal with the virus in a manner that the virus cannot escape from it. By using some of the killer pathways that part of the immune system uses, that the virus cannot escape from, can we empower that so that it could become a strategy by which the virus cannot escape from? So that whole approach, I think still remains untapped. And we have several strategies that are underway that are looking to test them. 

Dr. Maureen Murphy: So who are we pinning our hopes on? Natural killer cells? Macrophages? Dendritic cells? Which? 

Dr. Luis Montaner: Oh, now you're getting technical. Okay. So in the context of the innate immune system, as you said, you have multiple players, and among them you have the natural killer cells, which are the ones that we're particularly excited about because obviously they kill. You have macrophages and you have other cells of the innate immune system. Now, let's talk about natural killer cells. In the context of a natural killer cell, this is a cell that surveys your body, that has a greater frequency in the blood than the T-cells for any particular pathogen. And that has an ability to kill upon demand if the signals from the other cells are disturbed and actually protects us against cancer as well as it surveys against infectious diseases. So part of what we're trying to do is in the context of detecting an HIV infected cell, we have learned that there are individuals that carry antibodies that can detect infected cells across multiple individuals.

That's quite unique. They call these "broadly neutralizing antibodies." But the benefit of the natural killer cell is that it can actually use an antibody to kill a cell. So it can actually load the antibody onto itself as a homing mechanism to go in and kill the other cell. So now let's look at the frequency of the NK, empowering it with the tools to detect an infected cell through a mechanism that we already know the virus hasn't been able to escape from. Can that cell find and clear the virus infection? So that's currently where we're headed. 

Dr. Maureen Murphy: Amazing. We're going to go a little less scientific now and ask you about the best advice you were ever given. 

Dr. Luis Montaner: The best advice that I was ever given. Well, there's a lot of people that have been on my path that have been really instrumental and supported my entire professional education and career. So there's a lot of people to be thankful for. But if I had to choose one sentiment, I guess, I think it's perseverance and vision, meaning that trust your vision and persevere. Because there's been times that had I listened to the feedback that someone else was giving me about their vision, I would not be where I am today. And so staying true to your vision and trusting that that's the right way forward is I think the best advice I was given. 

Dr. Maureen Murphy: And multiple people gave you that advice or... 

Dr. Luis Montaner: In different ways? Yes, different ways because in scientific career, one of the things that is part of it is failure. And the other part is trying to break down processes that are really beyond our ability to comprehend, like the immune system, the persistence of a virus in a body that encompasses multiple compartments and multiple age and different conditions that the individual may have pediatric or adult or you name it. Our complexity is infinite. And so the ambition to try to understand that requires some degree of perseverance that you can find a question that you can contribute, but also humility that you are basically only trying to tap into a much bigger question that you're not going to be able to understand. So that means that you could be wrong at times or that your vision is not shared by your colleagues, and your proposals are not going to get funded right away. So you have to continually have a clear idea of where your vision is and persevere through what is really a back and forth, not only with your colleagues, but with the scientific question that you're actually going after. Because there's many experiments that have beautiful hypotheses, and you think that they're going to work and you do them and you get the opposite result, and then all of a sudden you go, wait a minute, I was wrong. I need to rethink this. So stay true to your vision, persevere...

Dr. Maureen Murphy: Admit you're wrong. Don't stop learning... 

Dr. Luis Montaner: Don't stop learning. All of those things are part of the equation. 

Dr. Maureen Murphy: Yeah, all good advice. Do you have a favorite motivational quote? 

Dr. Luis Montaner: Yeah, I mean, I grew up in a Christian tradition, so one sort of story that has always sort of resonated with me is in the Jesus story, the parable of the talents. It's a story where this merchant gives people different amounts of money, and some people decided to bury it, some people decided to invest it, and this merchant comes back to recount all these people that he gave the money to and say, well, what did you do with it? And obviously the message of the story is that if you're given gifts, you need to invest them for the benefit of moving those gifts forward. And I think that that has always resonated with me about we're all given gifts, but they're just as good as if we use them. 

Dr. Maureen Murphy: What advice would you give either a young scientist starting out now or even yourself 30 years ago, 27 years ago? What advice would you give yourself? 

Dr. Luis Montaner: Don't be afraid to ask big questions. Just because you think somebody else has figured it out, more times than not, it hasn't been figured out. Sometimes I remember thinking, "Surely this has been done," so I just have to find it because it's pretty obvious that this should be addressed. And more times than not, it either wasn't addressed or it was addressed in a manner that is not as well developed as it could be now. I mean, there's been many times when I remember in vet school when I would ask a question and the teacher would say, that's a wonderful question. If I knew the answer to that question, I would get the Nobel Prize. And so just hold on tight and go after that question yourself because we don't know the answer. Interestingly, today, our understanding has advanced, but our ability to learn has advanced even more. So the things that we still don't know and we could learn, I think are still leading the way forward. 

Dr. Maureen Murphy: So your research really spans multiple areas, immunology, virology, public health, and even as you said, some relevance to cancer where the areas sort of blend. Is being at a place like Wistar, where we specialize in immunology, virology, and cancer, does that make your research stronger? 

Dr. Luis Montaner: Oh, absolutely. That's why I'm here, because Wistar really is one of the best places that I've known where you can develop a research career and an impactful career because the ability to build coalitions that span global reach, the ability to have a supportive environment that acknowledges the importance of community and the importance of communicating our science and the investment that Wistar makes in each one of our laboratories to make sure that innovation remains a critical component of the future. And the attention of all the faculty that work together, almost like a cooperative, not as independent units, but as one integral group that knows that everyone's success is the success of us all, and that intent to invest in others, innovate and advance the science with a community perspective and an impactful message, not only to the community, but to our scientific colleagues, is something that Wistar excels in.

And I've been all over the world, and I can tell you that there's no place like Wistar. Wistar remains one of the best and most focused, impactful research centers globally, and I think that our trajectory and our ability to contribute reflects that. And our colleagues acknowledge that. That's why they come with coalition. I mean, there's many times that I've described Wistar and I say, well, we stars both a think tank of science, but also a command center for scientists globally. And it's that balance between being able to generate our own science but lead others in coalition science is a balance for which Wistar is basically an outstanding place for.

Dr. Maureen Murphy: I completely agree. I mean, I've been here for 12 years and I've always felt that what I love most about it is whatever success a scientist or group of scientists have, every single person here feels that they were a part of that success. They feel that they contributed - appropriately so - because they did. And that's what I love about this place. We're all working together. 

Dr. Luis Montaner: I've been at Wistar 27 years, but I still think I got here yesterday in that the excitement of starting at Wistar and being here, it's as if I've been here only one day. 

Dr. Maureen Murphy: Well, I wish you the best. Very important work. You're obviously a leader in this area, and you've galvanized other leaders to work together, which is a huge strength. So I appreciate your time. 

Dr. Luis Montaner: Thank you. 

Dr. Maureen Murphy: That was my interview with Dr. Luis Montaner, the Herbert Kean Family Professor and the Vice President of Scientific Operations at the Wistar Institute. Thanks for listening to the very first episode of Wistar Science Up Close. 

This show is produced by the Wistar Institute in partnership with Rowhome Productions. Our executive producer is Michele Schiavoni. Rowhome's executive producers are Alex Lewis and John Myers. This episode features music from Blue Dot Sessions. For more information about the Wistar Institute, visit wistar.org and make sure to subscribe to Wistar Science Up Close on Apple Podcasts, Spotify, or wherever you listen to podcasts. I'm Dr. Maureen Murphy and I thank you for tuning in.