Personalized medicine and human skin diseases
We solve medical mysteries. Some individual patients have skin conditions that are unrecognizable or resistant to treatment. Since skin is on the outside, we collect their diseased skin and use genomics to unravel the molecular mechanism. This work has literally changed the lives of some patients and has led to new ways to diagnose and treat different diseases.
We had one patient with acute febrile neutrophilic dermatosis (Sweet syndrome), a potentially fatal multiorgan inflammatory disease. She was refractory to conventional treatments and was hospitalized 4 times in 6- months. Using whole genome sequencing and transcriptomic profiling, we identified a PIK3R1 gain-of-function mutation in her neutrophils that increased their ability to migrate towards a cytokine signal, IL-1β. Targeted treatment with an IL-1 antagonist resulted in complete disease remission for the patient, and she is now living a normal life. This rational and personalized approach identified a new targeted treatment and improved our understanding of disease mechanisms.
We figure out how diseases work. We study larger groups of patients with the same disease to better understand disease pathology. Sarcoidosis is a disease characterized by granulomas, clumps of immune cells, that may form in any organ. Patients experience severe fatigue and difficulty breathing. Clinicians call sarcoidosis the “the great mimicker”, because the disease does not present in any specific pattern, and there are no confirmatory diagnostic tests. Treatment is inevitably delayed, because clinicians need to rule out all other potential causes. This is frustrating for everyone.
While lung is most common organ involved, skin is second. We performed single-cell genomics on skin and blood from 30 patients with skin sarcoidosis or non-sarcoidosis skin granulomas. Our analysis revealed a new type of immune cell, innate lymphoid cell, that was present specifically in sarcoidosis samples.
Excitingly, these cells were also enriched in the blood of sarcoidosis patients and changed with treatment status. We hope that innate lymphoid cells may serve as a diagnostic test for sarcoidosis diagnosis and disease activity. This will speed up the care and treatment of these patients. We also study how innate lymphoid cells contribute to granuloma formation in an effort to identify new targeted treatments for sarcoidosis.
We are continually applying these methods to other diseases and welcome new collaborations.
How to heal skin without a scar