Dr. J. Michelle Kahlenberg MD, PhD is the Giles G. Boles MD and Dorothy Mulkey MD Research Professor of Rheumatology and Associate Professor of Internal Medicine at the University of Michigan. She completed her undergraduate degree at Denison University, her MD, PhD, and Internal Medicine training at Case Western Reserve University and, her fellowship in Rheumatology at the University of Michigan. She has been running her own laboratory and has been an active member of the Immunology Training Program since 2013. Her clinical work is centered on the care of complicated lupus patients, including those with refractory skin disease. Her R01-funded research laboratory combines translational approaches using patient samples and murine models to uncover the mechanisms that drive lupus and lupus flares. In particular, she is focused on unraveling the pathogenic mechanisms in cutaneous lupus, the factors that drive photosensitivity, and how skin inflammation can influence systemic lupus activity. Her work has received institutional accolades and national recognition from the Arthritis National Research Foundation, The Rheumatology Research Foundation, American Society for Clinical Investigation and the Lupus Foundation of America. In addition, she was recently awarded a PECASE from the U.S. government. In her spare time, she enjoys organic gardening, working on the family farm “EMMA Acres” run by her husband, Mark, and spending time with her husband and children.
My lab has demonstrated that epidermal injury can stimulate nephritis flares in lupus-prone mice, and we have investigated the role of S. aureus peptides in inflammasome activation in keratinocytes. Importantly, we have obtained collections of primary control and lupus keratinocytes and have used these for innovative studies to identify how lupus keratinocytes respond abnormally to environmental stimuli in terms of triggering inflammatory responses. We have identified lupus skin as an important contributor to the interferon response through its production of IFN-κ. Our recent publications in the Journal of Investigative Dermatology (PMID: 27646883) and Annals of Rheumatic Diseases (epub) demonstrate that this cytokine is responsible for driving enhanced inflammatory and photosensitive responses to UV light in SLE keratinocytes. In murine lupus, IFNs are required for suppression of Tregs (PMID:31248690). Recent work from my group demonstrates an essential role for type I IFNs in driving hyper-reactive Inflammasome responses in SLE patients (PMID: 28564495) but that IFNs may not be required for TLR7-driving nephritis (PMID: 29884703). My ongoing R01-funded work is exploring the regulation of IFN-κ and how it primes for pathogenic interferon responses in keratinocytes and enhances development of systemic autoimmunity. Importantly, we have now identified a role for IFNκ in driving abnormal systemic immune responses to UVB in SLE-prone mice. We are now applying these questions to lupus patients with in vivo phototesting experiments coupled with single-cell RNA sequencing and other omics modalities. Our recent publication in Science Translational Medicine (PMID: 35476593) identifies that non-lesional skin of lupus patients is exposed to high interferon and inflammatory cytokine environments, even in the absence of rash, and educates myeloid cells to become pro-inflammatory. We are pushing the science of lupus and autoimmune-related skin diseases forward to identify novel and better therapies for patients.
Research Opportunities for Rotating Students
Open projects include investigation of the regulation of IFNK production in humans and mice. Other projects, including the impact of ultraviolet light on lupus activity will also be available.