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Leung Lab

Research Overview

Our group studies how injured tissues heal, and in some cases, how injured tissues regenerate without a scar. We have innovated new methods for studying wound healing and tissue regeneration in mice and humans. Based on our own findings, we are actively running clinical trials to bring these therapies to the clinic. Our group also studies inflammatory skin diseases. We are actively collecting human patient samples and performing genomics studies to understand the underlying pathophysiology of disease.

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Mammalian Tissue Regeneration

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Inflammatory Skin Diseases

We are interested in understanding how inflammatory skin diseases develop. We collect human patient samples and use them for genome-wide studies to dissect out the underlying pathophysiology. We confirm these changes using in vitro and in vivo model systems.

Recently, we had a patient with acute febrile neutrophilic dermatosis (Sweet syndrome), a potentially fatal multiorgan inflammatory disease. While corticosteroids and steroid sparing agents remain mainstays of treatment, she was refractory to these treatments and posed a clinical challenge. Using whole genome sequencing and transcriptomic profiling, we identified a PIK3R1 gain-of-function mutation that is specifically found in neutrophils. This mutation specifically increased neutrophil migration towards IL-1β. Targeted treatment with an IL-1 receptor antagonist in the refractory patient resulted in a dramatic therapeutic response and enabled tapering of corticosteroids. 


Dysregulated PI3K-AKT signaling is the first signaling pathway linked to Sweet syndrome. Our data counters the current dogma that Sweet Syndrome is simply a “reactive” process to an unknown antigen. Integration of molecular data across multiple levels identified a distinct subtype within a heterogenous disease that resulted in a successful clinical intervention enabling disease control. This rational and personalized therapy is, to our knowledge, the first example of identifying a targeted treatment for Sweet syndrome. It showed how the use of modern molecular and genetic techniques may create a personalized treatment approach in a challenging patient. We are using this approach for mechanistic interrogation of diseased skin to other skin diseases. 

Molecular Therapeutics

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