29 years ago, Dr. Luis Montaner started an HIV cure research program at The Wistar Institute. Today, he is the newly minted founding director of Wistar’s HIV Cure and Viral Diseases Center. His innovative work spans the globe, across research groups in Philadelphia and throughout the U.S., to South Africa, Vietnam, and beyond. His collaborators include top advocacy groups & activists, community members, pharmaceutical & biotech industry leaders; academic scientists; and government officials all united toward the goal of a cure to HIV.

Tell us about your research and the need for a center for HIV cure research.

Our HIV cure research focuses on the fundamental biomedical science & mechanics of HIV and understanding the context of this disease in relation to our greater society. I want to know: How can we manipulate the immune system to rid the body of HIV? But also, how do we develop scientific answers that can also help address the health care barriers & stigma of living with this incurable disease? Curing HIV will result in a great many benefits to the individual but also to the greater society.

The new HIV Cure and Viral Diseases Center is a natural extension of the momentum building now to find a cure for HIV. Wistar’s $24 million investment in the Center comes at a time of increased global enthusiasm to develop an HIV cure — so, this Center is the right investment at the right time.

Where is HIV research today?

Right now, we can manage the virus with antiretroviral drugs, also referred to as “ART,” or antiretroviral therapy. But to achieve an HIV cure, we want to eradicate and remove HIV from the body. When we talk about an HIV cure, we talk about living without antiretrovirals. These drugs have saved lives, but they are taken throughout one’s lifetime and treatments come with the risk of complications upon long-term use.

Why a cure?

We want to develop an HIV cure strategy that works and then make sure it is accessible around the world, because the value of an HIV cure extends beyond HIV itself. HIV is a challenge because of its capacity to mutate — the immune system starts to catch on to the threat, but then the virus changes itself to evade our natural defenses, ensuring its persistence. In addition, once a patient starts ART, the virus can persist without replication by hiding in immune cells over time — ready to come out again and flare up if ART stops.

Accessibility to drugs and therapies is also a big problem. A lifelong drug regimen costs money, living with HIV can also raise stigma and discrimination, and we’ve seen that access to therapy can be worse in developing countries — where most HIV cases in the world happen. Health disparities and access to care & therapies are critical components we would still need to address in our health systems in the United States and globally once we find a strategy to cure HIV.

It is also important to stress that HIV research benefits our understanding of other diseases and vice versa. Hepatitis C treatment and eradication, as well as the RNA COVID vaccine, were greatly aided by the work done in HIV research on protease inhibitors and HIV vaccines, respectively. CAR T-cell therapy for cancers, which is available to patients today, was also greatly accelerated by the preclinical work on using CAR T-cells against HIV. And in turn, Wistar’s research on Epstein-Barr virus and other diseases has helped us to advance our HIV cure research. Anything that we can discover that would cure HIV will carry important lessons for all viral research.

How does the new HIV Cure and Viral Diseases Center distinguish itself in this area?

The HIV Cure and Viral Diseases Center supercharges our research efforts to get an HIV cure to persons living with HIV as we advocate strongly for awareness and change. Our network has a record of success sharing information with groups that otherwise may not have access. We provide seminars to persons living with HIV within our community, and we have community advisory boards that bring feedback from the community into research and clinical processes. We want to end stigma and discrimination with an HIV cure so that persons living with HIV can be permanently free of the virus.

To find a cure you need science — but you also need commitment and investment. The new Center now gathers all three under one roof with a common mission: realizing an HIV cure within our lifetime.

Dr. Gauri Mirji, Ph.D., is a research fellow in Wistar’s Molecular and Cellular Oncogenesis Program of the Ellen and Ronald Caplan Cancer Center.

“When we walk together, exchanging our ideas and our knowledge, we can start to find better solutions.”

How did you become a scientist?

When I was a kid, I was very curious, always asking the question “why.” I think that’s where the roots lie for me to become a scientist. At the same time, I didn’t want to become a doctor or engineer, which is the default path in many Indian households. I wanted to do something different. I pursued biotechnology for my Bachelor’s and Master’s, and then I thought about going deeper into the actual research questions. I also wanted to do something for society. What could be better than finding answers to the biggest health challenges facing people today? This is how I decided to get into basic research and to be a scientist.

What drew you to immunology?

I had very good teachers who sparked my curiosity about this field. Immunology is the study of our body’s defense system. It’s one of the most important functions of your body, protecting you from the environment and from pathogens. It’s also highly complicated to understand. We still don’t really know exactly how these immune cells interact with each other, and how they keep us healthy and protected from different diseases. There are so many questions that are still unanswered in the field, and that’s fascinating to me.

Did you have any mentors or role models who inspired you in pursuing a career in science?

My Ph.D. mentor is a big role model for me, because she was an early female in the field. There weren’t many female immunologists back in my country at that time, she worked very hard and put a lot of dedication to be what she is today. She started from scratch, and then she started her own lab. Eventually she climbed up to the topmost position and became director of the institute where she worked. That is really inspiring to me.

What brought you to Wistar?

Before coming to Wistar, I didn’t know much about it. When I was applying for postdoc positions I was going through the profiles of different scientists at the Institute, and I was really attracted to the way research is done here. The level of research here is really top notch, and the scientists are amazing. It’s really a world-class institute. At the same time, I was attracted to Philadelphia. It has a lot of history, which I like, and it’s also the city where the first female Indian doctor, Anandi Gopal Joshi, got her medical degree. As an Indian, I have a special place in my heart for this city.

What is a typical work day like for you?

I often plan my week or a day ahead of time. We mostly do in vivo tumor studies in mouse models. I also perform a wide range of in vitro assays on macrophages isolated from mouse bone marrows. One of the major techniques that we do in the lab is flow cytometry, which gives us a huge amount of data. So, I spend a lot of time doing data analysis, preparing presentations and again planning my next set of experiments.

What do you find most rewarding about your work?

Our focus is pancreatic cancer. The thing that is most rewarding is the possibility of finding — I won’t say a cure — but something that has the potential to be a cure for these patients. We are studying gut microbial metabolites and diet, looking at different aspects of these factors and how they impact cancer progression. If we can modulate the diet or the gut microbiome, can we affect the cancer or even push it back? Finding even one particular metabolite or one particular drug that we can use against it would be a game changer.

What are some of the scientific questions that inspire you most as a researcher?

Therapy response is the major challenge in the pancreatic cancer field. How to break the resistance of this cancer, how to make the tumor microenvironment more immunogenic, and how to make patients respond better to therapy so that we can improve survival. These are the most challenging questions, and we are working on solving them right now.

What do you enjoy most about working at Wistar?

The work environment here is awesome. The people here are very helpful and easy to connect with, and it’s highly collaborative. Another thing I like is the diversity. This is my first experience working abroad from India, so I have never been in a workplace which is so diverse. It’s exciting, personally. There are people from more than 20 different countries, chatting with each other, sharing their ideas, and collaborating with each other. It’s scientifically very strong.

What does diversity, equity and inclusion mean to you, and why do you think it’s important in science?

Every individual is unique and there is beauty in this diversity. Every human society has their own values and traditions, and we have to respect all of them. The challenges faced by human beings are seen everywhere. When we walk together, exchanging our ideas and our knowledge, we can start to find better solutions. So I consider diversity, equity and inclusion as an integral part of research.

Do you have any hobbies or passions outside of work?

My favorite hobby is photography. I love to click nature, landscapes, and animals. I really enjoy taking photos. I also spend time reading philosophical and spiritual books. I follow Rumi, Eckhart Tolle, and Sirshree, an Indian spiritual teacher. Reading or listening to these philosophical books really motivates me and keeps me grounded.

More than 200 attendees joined in-person and virtually from around the world to hear from 2023 Nobel Laureate Drew Weissman, M.D., Ph.D. — Wistar’s 2024 Jonathan Lax Memorial Awardee, Roberts Family Professor in Vaccine Research, Director of Vaccine Research, and Director of the Institute for RNA Innovation at the University of Pennsylvania. As the recipient of the 28th annual Jonathan Lax Memorial Award, Dr. Weissman was honored for his contributions to HIV research, which he presented in this year’s lecture, “Development of novel therapies based on RNA: from COVID vaccines to anti-HIV strategies.”

Before the award ceremony began, Wistar president and CEO Dario Altieri, M.D., addressed the audience with a special announcement: Wistar’s $24 million investment in the HIV Cure and Viral Diseases Center was to be led by founding director and executive vice president Luis Montaner, D.V.M., D.Phil. Speaking to the importance of the moment for HIV research, Dr. Altieri emphasized the need to build on the progress made so far:

“Wistar’s HIV program has grown dramatically throughout its twenty-five-year duration, with members and participating institutions spanning the world. So the question for us is, how do we build on this legacy of accomplishments? I am absolutely ecstatic to be able to announce today—fittingly at the Jonathan Lax Memorial Lecture—the creation and launch of the new HIV Cure and Viral Diseases Center. We look forward to the leadership of Dr. Luis Montaner in bringing the new HIV Cure and Viral Diseases Center to new heights of collaboration, impact, and innovation.”

Following Dr. Altieri’s historic announcement, longtime CEO of Philadelphia FIGHT Jane Shull introduced the Jonathan Lax Lecture through a history of the people & activism behind today’s advances in HIV medicines. In speaking on the need for continued investment in science, Ms. Shull meditated on the nature of hope and what it meant to people like Jonathan Lax in the days before effective HIV treatments, let alone a cure.

She quoted former president of the Czech Republic, Vaclav Havel: “Hope is an orientation of the spirit, an orientation of the heart. It transcends the world that is immediately experienced and is anchored somewhere beyond its horizons.”

After receiving the Jonathan Lax Memorial Award, Dr. Weissman’s lecture highlighted the long journey of RNA from its discovery in the 60s to its role in mitigating the worldwide COVID-19 pandemic. The technology took years of refinement, Dr. Weissman said, but is now poised to transform several fields in human health — including, prominently, HIV cure research.

One key advantage of modern RNA approaches that use lipid nanoparticle (LNP) delivery is their comparative affordability as a scalable therapeutic. For example, the Weissman lab is developing strategies that use RNA as an alternative method for programming anti-HIV CAR T cells, which are a critical component of HIV cure strategies at Wistar and through the BEAT-HIV Collaboratory.

RNA-based approaches to CAR T cell therapy offer the potential to bypass the current ex vivo cell engineering process that can cause toxicity in patients — and at significant lower cost per-patient when compared to current approaches. As Dr. Weissman said, pointing to global population and resource-distribution maps, “Diseases are where the people are — but the people are not necessarily where the money is. So getting treatments everywhere around the world where they’re needed means finding treatments that are workable at scale.” At the conclusion of his talk, Dr. Weissman received a rousing standing ovation.