J. Michelle Kahlenberg, M.D., Ph.D.
Associate Professor of Internal Medicine, Division of Rheumatology
Dr. Kahlenberg is a physician scientist and Assistant 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. She has been named an ACR Distinguished Fellow and an Eng Tan Scholar and a Vic and Kelly Braden Memorial Fellow for the Arthritis National Research Foundation. She was awarded an ASCI Young Physician Scientist award in 2015 and was recently awarded the Edmund L. Dubois Memorial Lectureship in systemic lupus at the 2017 ACR National Meeting.
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. Our collaborative work with Dr. Gudjonsson recently published in Nature Immunology (PMID: 27992404) utilizes our cutaneous lupus data to understand a novel mechanisms 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 role of two novel transcription factors: BATF2 and PITX1 in regulation of interferon responses. Other projects, including the impact of ultraviolet light on lupus activity will also be available.