How do chemical exposures trigger autoimmune diseases?

$1,558
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  • $1,558
    pledged
  • 52%
    funded
  • 19
    days left

About This Project

The cause of onset of autoimmune disease is poorly understood, but may be linked to exposure to certain chemicals. We plan to study the response of melanocytes to monobenzone and thyrocytes' response to PBDE and BPA to determine how they lead to autoimmune diseases like vitiligo and Hashimoto's thyroiditis. To do this, we will look at the antigens (molecules presented to immune cells) on the cells' surfaces using mass spectrometry.

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What is the context of this research?

Many scientists believe a combination of genes and environmental factors, like chemical exposure, causes autoimmunity. However, little is known about how chemical triggers work. Research suggests monobenzone binds to a protein in skin pigment cells, and that this activates immune cells which attack and cause vitiligo, a condition in which skin loses its color in patches (van den Boorn et. al, 2011). There is also evidence that chemical-protein interactions cause thyroid autoimmunity, as antibodies against thyroid protein are found in patients exposed to PDBEs (Pearce & Braverman, 2009). By studying chemical-induced autoimmunity in vitiligo and Hashimoto's thyroidits, we hope to find and characterize changed proteins whose role in these disorders is not yet understood.

What is the significance of this project?

Vitiligo and Hashimoto's thyroiditis seem to be linked - those with one disease are at higher risk of getting the other (Cunliffe et al, 1968). Further, the immune system responds to similar cellular components, or antigens, as well as cellular stress signals in both Hashimoto's thyroiditis and vitiligo (Gong et al., 2016).

Finding the proteins that are changed by these chemicals and activate the immune system in these diseases would make it easier to develop better treatments.


What are the goals of the project?

We would like to study the proteins in cells exposed to the chemicals in question using mass spectroscopy, to see if there are any differences that could cause an autoimmune reaction. We will test two concentrations of chemicals in each experiment. Cells will be exposed to the chemicals overnight before being prepared for mass spectrometry. Any possible neoantigens (changed proteins that can activate the immune system) that are identified only in cells exposed to the chemicals would be tested by exposing immune cells to them. If the cells respond and try to destroy these proteins, this would suggest that they are indeed neoantigens and may help cause autoimmune disease.

Budget

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We have applied for private research grants, but need more preliminary data to get our project off the ground. Performing mass spectrometry analysis of proteins in cells after chemical treatments will allow us to identify changes in the proteins/cells that activate the immune system. We can then study the ability of these altered proteins to trigger autoimmune diseases. Further, we plan to test whether or not these altered proteins could be used for cancer immunotherapies.

We will be using the UMass Mass Spec Core Facility to test our samples. $3000 will cover the cost of running a minimum of 5 samples ($500/sample) plus using disposable reagents/buffers ($500). The associated analysis fees is included in the sample fee.

For every $500 we raise beyond the initial goal we will be able to add an additional sample.

Endorsed by

I am really excited about this project. It may provide insight into how autoimmunity begins, which will lead to preventative and treatment strategies for patients.

Flag iconProject Timeline

We currently have melanocyte cell lines growing in our lab, and we already have the chemicals we wish to test. We plan to obtain thyroid cell lines in the next 2 months. Performing the mass spectrometry and analysis should take about 1 month. Therefore, we hope to acquire all of the data from this Experiment by spring 2018, and we plan to perform further studies through 2018 and beyond.

Jan 15, 2018

Test Monobenzone on Melanocytes

Jan 24, 2018

Project Launched

Feb 15, 2018

Test BPA on Thyrocytes

Apr 15, 2018

Complete Mass Spec Analysis on all cells/chemicals

Meet the Team

Senegal Carty
Senegal Carty
Graduate Student

Affiliates

Clark University, Gustaf H. Carlson School of Chemistry and Biochemistry
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Jillian Richmond
Jillian Richmond
Instructor

Affiliates

University of Massachusetts Medical School
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Senegal Carty

I recently graduated from Clark University with a Bachelor's degree in Biochemistry and Molecular Biology, and am currently pursuing a Master's degree in the same field through Clark University's Accelerated Degree program.

My current project is a collaboration between the Lazo Lab at Clark and the Harris Lab at UMass Medical School's Vitiligo Research Center, with the aim of elucidating the links between reactive oxygen species, tyrosinase misfolding and decreased melanocyte viability in vitiligo.

Jillian Richmond

Jillian Richmond, PhD is an Instructor in the Department of Dermatology at the University of Massachusetts Medical School. Dr. Richmond earned her undergraduate degree in Molecular and Cellular Biology from the Johns Hopkins University, and her doctoral degree in Pathology and Immunology from Boston University School of Medicine. She performed a postdoctoral fellowship in chemokine biology at Massachusetts General Hospital before moving to the Harris Lab at the University of Massachusetts Medical School to study chemokines in vitiligo. Her postdoctoral work examined which cells in the skin produce chemokines to drive vitiligo pathogenesis, as well as how subsets of autoreactive memory T cells follow these signals, kill their target cells, and survive in the skin.

Additional Information

More technical info:

Chemicals such as PDBEs in the environment can induce autoimmune responses in the thyroid (Pearce and Braverman, 2009) while monobenzone causes vitiligo-like skin depigmentation (Taïeb and Picardo, 2009).


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  • 52%Funded
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