Faculty Profile: Christian Stehlik, PhD, John P. Gallagher Research Professor of Rheumatology
Christian Stehlik, PhD, John P. Gallagher Research Professor of Rheumatology, and his team recently discovered a new gene and defined its role in the body’s inflammatory response against infection. His study, published in Nature Immunology, found the protein POP3, interferes with the function of special sensors that detect viruses and trigger defensive inflammatory responses.
These findings may provide new therapeutic targets against inflammatory responses produced from viruses like HIV or in autoimmune diseases.
What are your research interests?
My research interest is innate immunity, and our research centers on the host response during inflammatory and autoimmune disease. In particular, our research focuses on the function of cytosolic pattern recognition receptors in macrophages. We work to unravel the molecular mechanism by which these receptors promote inflammation. A main emphasis is on the mechanisms that negatively regulate and mediate the resolution of these responses, as this understanding may allow us to inhibit excessive activity linked to disease. We use biochemical and cell biological approaches to investigate human and mouse cells and utilize mouse genetics and mouse disease models for these studies. Some of the disease models we utilize to dissect these pathways include gout, rheumatoid arthritis, systemic lupus erythematosus, Cryopyrinopathies, and sepsis.
What is the ultimate goal of your research?
Our goal is to define the molecular mechanism by which cytosolic pattern recognition receptors are activated, their downstream signaling properties, and their regulation. Hereditary mutations and other defects in these pathways cause excessive and uncontrolled production of downstream effectors, such as pro-inflammatory cytokines and type I interferons, which contribute to, but can also directly cause inflammatory and autoimmune diseases. Besides defining the function of these pathways, we attempt to modulate pathway activity, such as delivery of antagonists and inhibitors into macrophages, to blunt excessive pathway activity and investigate the impact on disease severity in mice. Ultimately, these studies may open novel avenues for developing improved therapies to dampen these responses to benefit patients.
What types of collaborations are you engaged in across campus?
The environment at Feinberg enables us to benefit from several collaborations, in particular with labs in the Department of Medicine on inflammatory and autoimmune disease. Studies with Harris Perlman, PhD, and Richard Pope, MD, already have resulted in several publications and National Institutes of Health grants. We also collaborate with faculty from the Department of Microbiology-Immunology on microbial and viral activation of the signaling pathways we study, including Eva Gottwein, PhD, Alan Hauser, MD, PhD, Karla Fullner-Satchell, PhD, and Nicholas Cianciotto, PhD. We also collaborate with several labs outside Northwestern on various disease models, including Yon Rojanasakul, PhD, at West Virginia University, Harold Hofmann, MD, at University of California-San Diego, Virginia Pascual, MD, at Baylor Health Care System, Divaker Choubey, PhD, at the University of Cincinnati, David Greaves, PhD, at the University of Oxford, and John Reed, MD, PhD, Roche Pharma Research and Early Development.
How is your research funded?
My laboratory is funded by two National Institutes of Health (NIH) R01 grants, an NIH postdoctoral training grant, a grant from the American Heart Association, and the John P. Gallagher Research Professorship.
Who makes up your research team and what role does each individual play in your research?
I am lucky to work with a great research team on a daily basis, comprised of scientists at all levels, who are really key to translate our research ideas into results. My laboratory consists of two research assistant professors, Andrea Dorfleutner, PhD, and Sonal Khare, PhD; two postdoctoral researchers, Lucia de Almeida, PhD, and Rojo Ratsimandresy, PhD; three DGP graduate students, Alexander Radian, Anu Gangopadhyay and Lan Chu; and a research technologist, Melissa Wallin. Each member has his or her own project, but all also collaborate with each other to produce results more efficiently. This is helpful, since all lab members study related signaling pathways and encounter similar difficulties.
Who inspires you?
My biggest inspiration comes from my dad, who is a biochemist and until his retirement, directed a research institute in Austria. When I was little, he sometimes took me with him to work. I was fascinated by the exciting things that I saw happening there and by all the fancy equipment present in a laboratory. These were lasting impressions and I knew from early on that I wanted to one day work in such a laboratory.