Being involved in the Cytokine Society has been immensely beneficial to my career. It has provided a valuable platform for connecting with fellow researchers with diverse skills and expertise, fostering interdisciplinary collaborative relationships, and developing innovative ideas to advance the field. The Society is crucial for bridging the gap between basic, fundamental research and translational applications for therapeutic approaches to maximize our impact.
Please tell us your name, degree, where you currently work, and position.
Thirumala-Devi Kanneganti, Ph.D., St. Jude Children’s Research Hospital
Member and Vice Chair in the Department of Immunology
Rose Marie Thomas Endowed Chair
Director of the Center of Excellence for Innate Immunity and Inflammation
Where did you do your training?
I obtained my PhD from Osmania University in Hyderabad, India, in 2001. I completed my thesis work at the International Crop Research Institute (ICRISAT) and in Dr. Mike Mayo’s lab at the Scottish Crop Research Institute (SCRI) in Scotland. Dr. Mayo was an excellent wealth of knowledge on viruses, as he served on the International Committee on Taxonomy of Viruses for almost two decades. From there, I went on to do postdoctoral fellowships at University of Wisconsin, The Ohio State University, and University of Michigan. During that time, I made the transition from studying fungal genetics and plant innate immunity to studying mammalian innate immunity. Plants are equipped with innate immune sensors called NLRs that induce cell death to defend against infection. Mammalian NLRs were discovered based on their structural similarity to plant NLRs; when they were first beginning to be characterized, I saw an exciting opportunity to apply the knowledge I had gained over a decade studying plant innate immunity and cell death to mammalian NLRs.
Briefly, what is your research about?
My research group is interested in understanding how the innate immune system recognizes and responds to pathogens and how genetic mutations in innate immunity affect the development of infectious, inflammatory, and autoimmune diseases and cancers. My group has been in the inflammasome field from its early days; inflammasomes are multi-protein complexes that assemble in response to sensor detection of PAMPs/DAMPs. We have elucidated the function of several innate sensors and inflammasomes to establish their relevance in infection, inflammatory diseases, cancers, and beyond. The more immersed we become in the field, the more we perceive cellular perturbation as a multifaceted, dynamic process that does not rely on a single sensor-PAMP/DAMP interaction. Understanding the synergistic interactions of the numerous innate immune sensors that detect live pathogens, cancerous cells, or other cellular threats is our current interest and priority.
My research group has also been addressing several fundamental questions related to innate immune sensor-induced programmed cell death pathways. Our current studies are further defining the regulatory mechanisms of PANoptosis, a unique innate immune inflammatory cell death pathway driven by caspases and RIPKs and regulated by PANoptosome complexes. Additionally, we are identifying the molecular mechanisms driving the formation of PANoptosomes and translating the relevance of these complexes and pathways in health and disease to develop therapeutic targeting strategies.
Overall, the conceptual advancements and frameworks developed in these studies have enabled us to make significant contributions to the emerging research frontier of innate immune cell death, shedding light on its implications across various physiological and pathological contexts. Our overarching objective is to bridge the gap between traditionally siloed research areas of pathogens (microbiology), innate immunity, and cell death. Through our work, we have made significant contributions to understanding innate immune-mediated cell death from a holistic viewpoint, aiming to inform strategies for the development of novel therapeutics. These strategies targeting innate immune cell death hold promise for treating infections, inflammatory conditions, and cancers through innovative immunotherapies.
Tell us your thoughts about ICIS: how has being involved in the Cytokine Society help your career?
Being involved in the Cytokine Society has been immensely beneficial to my career. It has provided a valuable platform for connecting with fellow researchers who share similar interests, fostering collaborative relationships that have enriched my research projects and led to the development of innovative ideas to advance the field. The diversity of skills and expertise among members has also opened doors to interdisciplinary collaborations, crucial for bridging the gap between basic, fundamental research and translational applications for therapeutic approaches. Additionally, participating in annual meetings has offered a platform to share our work and expand our professional network. These engagements, along with my other memberships within ICIS, have allowed me to contribute to the society’s initiatives and further strengthen my connections within the community. Additionally, receiving recognition through awards programs sponsored by ICIS, such as the Seymour & Vivian Milstein Award in 2018, has helped advance our research profile, provided valuable support, and opened doors to new opportunities throughout my career journey.
What do you like to do when not in the lab?
Outside the lab, I enjoy spending time with my family, gardening, and watching mystery shows.
What is the best life/career advice you’ve ever received?
No one knows everything, and that’s ok. Always continue learning and advancing your knowledge in your research area. This will allow you to develop informed questions and hypotheses to test. Be passionate and persevere!
Pay attention to the details and cultivate skills to make comprehensive observations. Many important breakthroughs came from scientists making careful observations, which goes beyond simply looking and collecting data. Careful observation requires rigorous questioning and re-questioning at every step of a project and in each experiment to fully consider all aspects of the observed activity, forming the fundamental basis for discovery.
What is your favorite cytokine?
The IL-1 family. This versatile group of cytokines has diverse functions in health and disease, and we are only beginning to understand their many roles. The clinical progress in targeting this family has also been very exciting, with treatments like anakinra and canakinumab having strong therapeutic effects across the disease spectrum, from inflammation to cancers. My group continues working to understand the unique functions of the IL-1 family members, as well as studying TNF and IFN, to elucidate their complex regulatory processes.