Collin Kieffer, PhD

Collin Kieffer, Ph.D., is an assistant professor of microbiology in the School of Molecular & Cellular Biology and has an affiliate appointment in the Carl R. Woese Institute for Genomic Biology. Before joining the faculty at Illinois, he completed a doctorate in biochemistry at the University of Utah and a post-doc in biology and biological engineering at Caltech. Research in the Kieffer Lab is focused on mechanisms of HIV pathogenesis in animal models and human patient samples, and the development and application of multiscale tissue imaging methods.

What is your research in microbial systems about?
The overarching research theme in my lab focuses on understanding the complex interplay that occurs between pathogens and the immune system during infection within the body. We primarily study the Human Immunodeficiency Virus (HIV) because it specifically targets immune cells and rapidly disseminates throughout the body to establish an incurable chronic infection that destroys immune function and ultimately leads to the development of Acquired Immune Deficiency Syndrome (AIDS). We are interested in why interactions between the virus and the immune system vary between tissues and individuals, and how these differences impact disease. For example, how does the composition of local cell populations, immune signaling, and tissue architecture impact disease course and response to treatment? Taking a more holistic, systems-based approach towards virus pathogenesis allows us to integrate our reductionist understanding of the virus in culture and translate that information to the context of the disease heterogeneity that occurs within the human body.

How are you conducting your research?
My lab utilizes advanced tissue imaging techniques to spatially resolve and quantify aspects of virus pathogenesis at multiple levels of volume and resolution. For larger volume imaging with single-cell resolution, we combine tissue clearing with light sheet fluorescence microscopy (LSFM). Cleared tissues are see-through and can be labeled with fluorescent probes for HIV-infected cells, specific immune cell populations, and immune signaling molecules. LSFM of labeled tissues reveals the spatial distribution of individual HIV-infected cells and target cells in a quantifiable way within volumes (mm3-cm3) of intact tissue containing tens of thousands to millions of cells. For smaller volume imaging with single-virus resolution, we use electron tomography and serial blockface electron microscopy to generate higher resolution 3D information and reveal ultrastructural details of individual HIV-infected cells and viruses within tissues. This multi-scale imaging approach reveals biological mechanisms of HIV pathogenesis, allowing us to correlate global pathology with structural details that help HIV avoid cure strategies. 

How does being a part of the Illinois community support and enhance your research?
The highly collaborative environment here at Illinois has allowed me to rapidly establish projects with other labs, encompassing other new faculty members all the way to long-term faculty with large, established labs. These opportunities allow me to generate important new insights for well-developed biological research programs, while I simultaneously build the foundation for the research focus of my lab. I have also benefitted from being affiliated with the Infection Genomics for One Health (IGOH) theme at the Carl R. Woese Institute for Genomic Biology. This opportunity has provided me with many additional resources and core facilities for my research, including microscopy expertise, data processing workstations, and access to high-end instrumentation critical for my group’s work.

How will your research or work improve society or reach people?
HIV, the causative agent of AIDS, was discovered nearly 40 years ago and remains a global health concern with an estimated 37 million individuals currently infected worldwide. Despite intensive efforts, there is currently no cure for HIV and although antiretroviral therapy allows infected individuals to lead normal lives, the presence of a reservoir of latently infected cells that allow virus rebound upon cessation of treatment requires infected individuals to remain on treatment indefinitely. My lab focuses on understanding relevant modes of virus dissemination, investigating the latent virus reservoir, and characterizing the effectiveness of anti-HIV therapies. My hope is that our findings will help guide the field to more effectively evaluate new HIV cure strategies. Additionally, the approaches we use are broadly applicable to other important diseases, including staph infections, COVID-19, and cancer.

Do you have a personal story or path to share that led to your interest in this area of study?
My favorite thing about research is that you never know where the science is going to take you. I majored in Bacteriology at the University of Wisconsin-Madison and was fully prepared to go to medical school after completing my undergraduate degree. However, during my junior year, I took courses on host-pathogen interactions and medical microbiology and never really stopped studying those topics. I was blown away by the complexity of the ongoing biological arms race that occurs between the immune system and pathogens. This led me to the University of Utah and the lab of Wes Sundquist for my Ph.D., where I studied how HIV hijacks the host-cell machinery to drive virus release from infected cells. This was during the time where host-cell restriction factors, part of the innate immune system, were rapidly being discovered as keys to limiting virus infection. Essentially, the virus commandeers the host to produce more of itself, the host evolves mechanisms to limit virus release, and the virus evolves ways to counteract mechanisms of restriction. During my Ph.D., I learned that if you dig deeper or look at a biological process in a unique way, you can find something that no one has seen before. This led me to my post-doc in the lab of Pamela Bjorkman at Caltech where I studied advanced imaging modalities like electron tomography and light sheet fluorescence microscopy and incorporated them into my analyses of HIV-infected tissues. We began seeing things that no one had seen before in tissues and sometimes contradicted what researches previously saw in the test tube for the past 20 years. This work has catapulted me to my current position at Illinois in the Department of Microbiology, where I am continuing a portion of my post-doc work and also delving into uncharted territory with alternative approaches to image new tissues and pathogens. You never know where the science is going to take you.