Dr. Kahlenberg is a physician scientist and Associate Professor at the University of Michigan. She completed her MD, PhD, and Internal Medicine training at Case Western Reserve University and completed her fellowship in Rheumatology at the University of Michigan. 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 flares. In particular, she is focused on unraveling the pathogenic mechanisms in cutaneous lupus and how skin inflammation can influence systemic lupus activity. Recent awards include an ASCI Young Physician Scientist award in 2015, the 2018 Jerome W Conn Award for Excellence in Research, the 2018 Mary Betty Stevens Award from the Lupus Foundation of America, and a 2019 Presidential Early Career Award for Scientists and Engineers (PECASE) by the POTUS. She also holds the Giles G. Bole MD and Doroth Mulkey MD Research Professorship in Rheumatology.
We have a particular interest in lupus skin disease and the role of interferon signaling in its development. 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). Our collaborative work with Dr. Gudjonsson recently published in Nature Immunology (PMID: 27992404) and JCI insight (PMID: 30996136) utilizes our cutaneous lupus data to understand a novel mechanism for the female predisposition to autoimmunity. 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 also examining the effects of cutaneous type I IFNs on colonization by S. aureus. 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.