Ian Mills, COL ’24, Hershey, PA
This summer I had the opportunity to conduct research in Werth Lab on extracellular vesicles(EVs) and their effect on the immune system. Werth lab primarily focuses on research relevant to the treatment of cutaneous diseases with the most common disease being cutaneous lupus. My mentor, Ming-Lin and I hypothesized that EVs play an important role in cutaneous lupus, and we are looking for ways to treat this disease and mitigate symptoms. Our research project focuses on the use of two inhibitors to decrease activation of the STING pathway in the macrophages found in the skin.
The inhibitors used are both commercially available and can prevent the activation of the STING pathway. Without STING, macrophages are unable to trigger an inflammatory response in the affected area. We hypothesize that these “STING antagonists” can be used as treatment for patients with cutaneous lupus to decrease symptoms after sun expose. This idea stems from the fact that, when keratinocytes are exposed to UV radiation, they become damaged and some die, resulting in EVs being found in the affected area. Normally, the EVs are not a problem as people’s bodies are able to eliminate these autoantigens without a large immune response. Contrary to this, patients with cutaneous lupus have a lower threshold for the autoantigens and their immune systems are more reactive to these EVs.
Over the course of this summer, we were able to culture several plates of macrophages from fresh PBMCs multiple times treat them with EVs found in the blood plasma of cutaneous lupus patients. In the future, we intend to irradiate immortalized keratinocytes, and treat the macrophages those EVs, to simulate the sun exposure. Over the Couse of this academic year, we will be working on the analysis of our experiments using FLOW Cytometry as well as ELISA to detect cytokine concentration using that as an indicator for STING activation. Hopefully, we can observe decreased STING activation from the use of these inhibitors. With this being my first wet-lab experience, the Career Services Summer funding grant allowed me to develop important skills in cell culture, immunology, and dermatology.
In the future, I intend to continue research related to immunology/dermatology with the hopes of attending medical school and dual specializing in internal medicine and dermatology. I anticipate working on several projects related to extracellular vesicles as I hypothesize they have a larger effect on the immune system than previously thought.
This is part of a series of posts by recipients of the 2022 Career Services Summer Funding Grant. We’ve asked funding recipients to reflect on their summer experiences and talk about the industries in which they spent their summer. You can read the entire series here.
