Women and people from other marginalized groups continue to face discrimination in STEM fields, which imposes extraordinary challenges for their access to education and healthcare. My research program is focused on finding solutions to the issues surrounding (in)equity in STEM, particularly in the biomedical research space, with the goal of improving the lives of women and people from other marginalized communities. We are achieving this goal by 1) addressing research questions that are of fundamental importance to women’s health and 2) by improving the working environment for people from marginalized communities in STEM fields through research and advocacy. Our women’s health research program uses an interdisciplinary approach, comprising molecular biology, biochemistry, chemical biology, and cell biology, to understand how glycans are different in male and female humans, how these differences contribute to health and disease, and how these differences can be leveraged for improvement of women’s health through improved diagnostics and novel therapeutic approaches. Our strategies for improving the working environment for people from marginalized communities in STEM are comprised of developing and evaluating tools that help students, staff, and faculty to be engage with equity, diversity, and inclusion (EDI) literature in order to be better citizens and allies. Our partners include people from academia, government, industry, and not-for-profit organizations, including scientists, social scientists, teachers, clinicians, and students.
New tools to study glycans:
The pivotal importance of glycans to the function of biological systems has long been overlooked, in large part due to their complexity and a dearth of analytical tools with which to study them. Developing tools that we and others can use to understand the biological role of glycans will substantially advance our understanding of health and disease. We developed methodology to quantify glycans and glycoproteins in complex mixtures, to identify novel glycoproteins, to investigate the role of glycans in interactions between cells, and to temporally inhibit formation of glycans. We have ongoing projects working on method development to adapt our technology for use with additional glycans, as well as to isolate glycans of interest, identify glycan receptors, and characterize glycosylation on a single cell level.
Glyco-immunology in healthy adults:
We focus primarily on the glycan polysialic acid (polySia), which is a long polymer with highly restricted expression in adult humans. It has been found on less than a dozen proteins and is limited to the nervous, immune, and reproductive systems. The presence of polySia imparts profound consequences on the proteins and cells on which it is found, particularly with regards to cell migration and attenuation of the immune response. We discovered sex differences in the concentration of polySia in healthy human serum, with healthy 20 year old males having higher levels than females. We are working on elucidating the mechanism, by investigating sex differences in levels of polySia on PBMCs. We also discovered novel polysialylated proteins in T cells which are differentially regulated with T cell activation, some of which can be secreted as part of extracellular vesicles. We have projects investigating the role of polySia in T cell migration and activation, as well as characterizing polysialylated extracellular vesicles.
Dysregulation of glycans in disease:
Dysregulation of glycans is a hallmark of a number of chronic diseases, including cancer. PolySia has long been known to be overexpressed in numerous cancer types and strongly correlates with metastatis and poor patient prognosis. We hypothesize that polySia expressed by cancer cells is acting like an immune checkpoint and have projects investigating the role of polySia in interactions between transformed cells and the immune system. Similarly, we discovered that polySia is strongly dysregulated in patients with scleroderma, a rare autoimmune disease that differentially affects men and women. We are developing a polySia-based liquid biopsy that can prognosticate women patients and are trying to understand more about how polySia contributes to pathogenesis of scleroderma.
We also have projects focused on pregnancy and reproduction, mainly as collaborations. One involves the development of a liquid biopsy for placental malaria, a disease that leads to poor outcomes for mother and infant in developing nations. Another involves developing a vaccine targetting intracellular pathogens in pregnant pigs.
EDI solutions:
The literature on EDI in STEM is full of articles describing the myriad effects of bias and discrimination. However, there are relatively few studies that describe effective solutions, which prompted us to start doing research in this area. The project we are currently working on addresses EDI issues in the undergraduate student population by introducing educational materials into first year biology and engineering labs.
WillisGlycobiologyLab 