SPOTLIGHT on Liang Shan
The Midwest D-CFAR community is full of brilliant and inspiring people, and we want to introduce them to the world! For our September 2024 spotlight, we are featuring Liang Shan, associate professor in medicine and of pathology and immunology at WashU, and co-director of our Advanced Technology Core. Many thanks to Dr. Shan for taking the time to speak with us!
Dr. Liang Shan
Q: Could you briefly describe your career journey and research interests?
Dr. Shan: Ever since I was a little kid, I have been very interested in persistent viral infections such as HIV and hepatitis viruses. I started my PhD in Robert Siliciano’s lab at Johns Hopkins University, where we worked on HIV latency and viral persistence. Although the lab was focused on very fundamental virology questions, I was one of a few people who became interested in immune topics, particularly understanding the role of T-cells in clearing residual virus in people living with HIV (PLHIV). For example, I did several experiments utilizing tissue samples to understand how we can boost the T-cell response.
By the time I graduated, it was clear to me that a major limitation in HIV research is the lack of convenient and cost-effective animal models to study the virus. I decided to join Richard Flavell’s lab at Yale University for this reason. His lab utilizes novel and robust humanized mouse models, which allow us to study human immune responses to HIV within a controlled environment. When I came to WashU in 2017, I put these two pieces together; eventually, I was able to access both in-vitro and animal models to study immune responses to HIV.
Q: What projects do you currently have ongoing?
Dr. Shan: I am particularly interested in identifying unknown immune mechanisms to clear HIV virus. So far, the human immune system fails to do this job. As we all know, for PLHIV on antiretroviral therapy (ART), that virus becomes a life-long infection. Nobody has been cured of HIV, except for select cases involving bone marrow transplantation. However, this approach is not widely accessible. Some of the key questions I am asking are: how can we boost immune responses to have a generalizable approach to clear residual virus? Are there immune mechanisms we haven’t fully tapped into yet?
One promising area coming out of our lab is an innate immune mechanism called the CARD8 inflammasome. This inflammasome can recognize a viral protein called protease, which is the enzyme that activates the CARD8 inflammasome to kill cells infected with HIV. We’re exploring how this novel innate immunity works and how we can move this discovery into clinical studies. In fact, Dr. Priya Pal, Dr. Rachel Presti, and I recently worked with our Infectious Diseases Clinical Research Unit to recruit participants for a clinical trial. Our goal is to evaluate how drugs can target CARD8 inflammasome in people living with HIV, and whether this has any impact on viral persistence. I think this is a good example of how you can make bench basic discoveries and then translate them into clinical applications.
We’re also investigating a number of other mechanisms, including NK cells, antibodies, T-cell response, and macrophage response to HIV. Ultimately, we’re looking at different immune responses and pathways to improve viral control and, hopefully, achieve better clearance of persistent infections.
Q: Could you talk briefly about the initiatives that the Advanced Technology Core (ATC) has coming up?
Dr. Shan: The primary goal of the ATC is to develop and support basic and translational HIV research to boost the local research community. There are three communities we are working to recruit, retain, or support. We want to recruit junior investigators from outside institutions, as well as senior investigators who are new to HIV research. We are also working to retain our own investigators to prevent them from leaving HIV research.
A key challenge is that we don’t have enough local resources or specialized training to support these researchers in HIV-specific work. To address this, the ATC offers a range of services. Junior investigators can book consultations with the ATC to receive guidance on how to refine their projects and align them with HIV research priorities. Working with HIV requires specialized resources and materials, and this can be a major hurdle to HIV research. Fortunately, our Virology Research Unit (VRU) is equipped to produce viral stocks, process infectious tissue cultures, and process samples from people living with HIV. Finally, we also offer training to investigators on using state-of-the-art technologies, such as single cell sequencing and high-resolution imaging platforms. Through our partnerships with the Institute of Clinical and Translational Sciences (ICTS) cores, we can provide this training specifically for HIV research purposes. We’re also excited to offer funding opportunities like the D-CFAR Enhancement Fund and the ATC Scholar Award.
Q: You certainly have a lot going on with your work! What do you do in your free time?
Dr. Shan: I’m a soccer fan! I started playing when I was eight or nine years old, and I also enjoy watching professional soccer. I’m a big Manchester United fan. During my time at Johns Hopkins, I picked up a love for American football as well. Now, I’m also a Baltimore Ravens fan. Aside from soccer and football, I have also recently started playing tennis with my daughters.
Dr. Shan (far right, back row) with his lab group on an outing to Top Golf.
Written by Kate Gershwin.