NPF-Funded Research

Project Summary:

Psoriatic inflammation worsens when people are exposed to air pollution, but the reasons for this are not well understood. The skin’s protective barrier works closely with helpful skin bacteria to maintain skin health. Air pollutants called polycyclic aromatic hydrocarbons can penetrate the skin and disrupt this balance, leading to inflammation. Our research focuses on a key skin sensor, the aryl hydrocarbon receptor, which responds to both pollution and beneficial molecules made by skin bacteria. We will study how pollution disrupts this protective signaling and test whether bacteria-derived molecules can reduce psoriasis-like inflammation. This work may lead to new ways to prevent pollution-triggered psoriasis flares.

How will your project help improve the lives of the 125 million affected by psoriatic disease?

This project aims to improve the lives of the more than 125 million people affected by psoriatic disease by addressing a major and poorly understood challenge: why environmental exposures can trigger or worsen psoriasis. Patients frequently report flares associated with factors such as air pollution, yet we still lack a clear biological explanation for how these exposures affect the skin. Our work will define how common air pollutants disrupt interactions among the skin microbiome, epidermal barrier, and AHR signaling pathways that normally help maintain skin health.

Importantly, this project goes beyond identifying mechanisms. We will also test whether protective metabolites naturally produced by skin microbes can restore barrier function and reduce pollutant-amplified inflammation. In the long term, these studies could help identify individuals who are especially vulnerable to environmentally triggered flares and lay the foundation for new microbiome-informed strategies to prevent or lessen disease exacerbations. By connecting environmental exposure with actionable biological pathways, this work has the potential to improve disease management, reduce the burden of unpredictable flares, and ultimately support more personalized approaches to psoriasis care.

Why is psoriatic disease research important to you, personally? What role will this award play in your research efforts or career development?

Psoriatic disease research is important to me because my scientific career has centered on understanding how the skin barrier maintains health and what causes that protection to fail. The skin is our most immediate interface with the environment, yet environmental contributions to inflammatory skin disease remain remarkably understudied compared with genetic and immune mechanisms. This gap is especially important when thinking about health disparities: exposures to air pollution and other environmental stressors are not experienced equally, and understanding how those exposures affect barrier health may ultimately help us understand why disease burden and triggers differ across individuals and communities.

For people living with psoriasis, flares are not simply changes in a laboratory measure of inflammation. They can be painful, visible, difficult to predict, and profoundly disruptive to daily life and quality of life. Patients frequently report environmental triggers, including air pollution, yet we still do not understand the biological mechanisms connecting these exposures to worsening disease. That disconnect is particularly compelling to me. My laboratory has shown that resident skin microbes actively support epidermal barrier function and repair, giving us an opportunity to ask whether environmental exposures disrupt these protective relationships and thereby contribute to psoriasis exacerbation.

The NPF award will allow me to establish this question as a distinct direction within my independent research program. It provides the support to build experimental models that connect environmental exposure, the skin microbiome, and barrier inflammation, while also testing whether naturally occurring microbial metabolites can protect against environmentally amplified disease. Just as importantly, it will generate the foundational data needed to develop a longer-term research program focused on identifying modifiable environmental contributors to psoriatic disease and, ultimately, strategies that could make flares more predictable, preventable, and less disruptive to patients’ lives.

Researcher Profile:

Aayushi Uberoi, Ph.D., is an Assistant Professor in the Department of Pathology & Immunology at Washington University School of Medicine in St. Louis, with a secondary appointment in Dermatology. Her research program investigates how the skin microbiome, epithelial barrier, and environmental exposures interact to regulate skin health and inflammatory disease.

Dr. Uberoi’s work has established that resident skin microbes actively contribute to epidermal differentiation, barrier function, and tissue repair. Her research has been supported by the NIH/NIAMS K99/R00 Pathway to Independence Award, which supported her transition to an independent faculty position, as well as the Society for Investigative Dermatology (SID) Innovator Award. Her laboratory now combines gnotobiotic models, microbial ecology, multi-omics, and epithelial biology to define how microbial and environmental signals shape skin barrier function.

Her long-term goal is to uncover mechanisms through which the microbiome and environment influence inflammatory skin disease and to translate these insights into new approaches for preventing and treating conditions such as psoriasis.