Sullivan roadmaps her way to revealing chronic disease risk of trace and toxic metals
It’s not always that a budding research career and the skills required to pursue it align well with emerging technologies, public health needs, and funding opportunities. In the case of LMP assistant professor Shannon Sullivan, they do.
Sullivan’s educational roadmap from chemistry to epidemiology to genetics makes her exceptionally qualified to explore how trace and toxic metals, ubiquitous in the environment, affect the human body from fetal development through adulthood. She has her eye on unearthing genetic biomarkers for metal exposure that can reveal risk well before disease sets in.
Sullivan joined LMP in 2023. She works in LMP’s Advanced Research and Diagnostics Laboratory (ARDL). In 2024 she was named a Building Interdisciplinary Research Careers in Women's Health (BIRCWH) Scholar. A National Institutes of Health training grant program created by the Office of Research on Women’s Health (ORWH), BIRCWH “fosters mentored research career development of junior faculty of any gender who are engaged in interdisciplinary women’s health or sex differences research.” The program awards $30,000 per year in research support and 75 percent salary support for three years. Her research project is “Sex disparities in metal exposure, chronic kidney disease, and potential molecular pathways.” She aims to determine sex differences in metal concentrations and whether female susceptibility to chronic kidney disease can be attributed to these exposures. She also aims to identify biological pathways and biomarkers that may underly sex differences in metal-related exposure responses, including biological aging.
Sullivan’s mentors for her BIRCWH research are LMP professor and ARDL director Bharat Thyagarajan, a biomarker authority; LMP professor Amy Karger, a kidney disease expert; and the University of Michigan’s Jessica Faul, a co-investigator with Thyagarajan in the Health and Retirement Study (HRS), a longitudinal study that involves collecting survey data and blood for analysis from of more than 37,000 Americans age 50+ to support research and inform policymakers. University biostatistician Weihua Guan is mentoring Sullivan in her goal to develop statistical and analytical methods for genetic data.
As part of the HRS study, Sullivan has also analyzed sex differences in immune cells and kidney function. The rising profile of these differences in human health owes much to new tools and new methods such as the ones Sullivan employs. She was one of four BIRCWH Scholars from 19 active BIRCWH programs selected to give an NIH BIRCWH Annual Meeting podium presentation.
A focus on metals
A Georgia native, Sullivan earned an MS degree in organic chemistry from Georgia State University followed by an MPH degree in environmental health and then a PhD in occupational and environmental epidemiology, both from the University of Minnesota. In between her master's degrees, she was a research and development scientist at the Centers for Disease Control and Prevention (CDC) in Atlanta.
“I’ve worked in metals for a long time,” Sullivan said in an interview.” “My background is in chemistry. After completing my first graduate degree (organic chemistry), I spent six years in a CDC laboratory developing methods to measure biomarkers of metal exposure for the National Health and Nutrition Examination Survey (NHANES) and the Population Assessment of Tobacco and Health (PATH) Study. That work introduced me to the world of public health and epidemiology, and I really fell in love with understanding how metal exposures relate to disease and ultimately how can we identify and prevent those exposures. That’s how my research program has evolved.”
Trace and toxic metals are naturally occurring and commonplace in the environment. They come from below and above, surfacing over time from the Earth’s crust and bedrock through soils into the water table, and descending from clouds after being put there by industrial emissions. Metals can be present in the air we breathe, the water we drink, the plants we grow and the food we eat, in industrial products, and in some common objects that surround us. Certain metals in proper amounts – iron, copper, zinc – are essential for our bodies to function normally. Others – arsenic, cadmium, lead, and nickel -- are non-essential and can be toxic, leading to heart, liver, and kidney diseases, dementias, aberrations in neural development, and cancer. Toxic metals induce oxidative stress and chronic inflammation, leading to tissue damage and disease.
Metals accumulate in the body and are eliminated through urine. Sullivan’s PhD dissertation, titled “Urinary cadmium and lung cancer risk in smokers from the Multiethnic Cohort Study” examined how a combination of factors, including social determinants, occupation, genetics, and environmental risk factors, collectively contribute to racial and ethnic disparities in lung cancer risk. The Multiethnic Cohort Study (MEC) involves investigators from the University of Hawaii, the University of Southern California, and the University of Minnesota. Sullivan is a co-investigator in LMP professor Stephen Hecht’s program project grant “Mechanisms of ethnic/racial difference in lung cancer due to cigarette smoking” of which the study of urinary biomarkers is a component.
The tools of genetics, such as RNA sequencing and epigenetics – the way cells control gene activity through certain DNA modifications without changing the DNA sequence – can yield insights into how toxic metals cause disease. In November, Sullivan was awarded a $25,000 grant from the National Institute on Aging (NIA) Biomarker Network for “Developing epigenetic signatures of metals exposure for use in aging cohorts.” Her research program seeks to understand the interplay between environmental risk factors, namely trace and toxic metal biomarkers and tobacco exposure, and genomics/epigenetics in carcinogenesis. The grant will support a data analyst in Sullivan’s plan to broaden the scope of her research into the development of DNA methylation–based (epigenetic) signatures of exposure to arsenic, cadmium, and lead, enabling further research into the health effects of metal exposures in aging populations.
Sullivan and LMP assistant professor Stefani Thomas won a $50,000 “Great Ideas Award” for 2025. The competition is funded annually by LMP’s Molecular Pathology and Genomics Division. Their project is: “Development and validation of ICP-MS methods to quantify metals in tumor tissues.” ICP-MS is a highly sensitive mass spectrometry method capable of detecting elements at parts-per-trillion (ppt) levels. Their goal is to develop, optimize, and validate ICP-MS methods to quantify multiple metals in tumor tissues. They aim to establish an analytical platform that will enable future research on metal mixtures and tumor biology in colorectal cancer (CRC) and other environmentally related cancers. Last summer, the Masonic Cancer Center awarded Sullivan and LMP associate professor Anna Prizment a grant to study trace and toxic metals in relation to CRC risk using the Multi-Ethnic Study of Atherosclerosis (MESA) cohort.
The way forward
Sullivan’s BIRCWH training grant award supports stops on her career roadmap journey. She completed a Columbia University “Epigenetics Boot Camp” and a summer course “Epigenetics and Gene Regulation” at the Georgia Institute of Technology.
Sullivan’s award as a BIRCWH scholar award supports not only her research but also her further education and professional development as a junior faculty member, which serves as a foundation for pursing National Institutes of Health (NIH) funding. “It’s providing me an opportunity for training about how I can become an effective PI,” Sullivan said. She completed the National Center for Faculty Development and Diversity (NCFDD) Faculty Success Program, a 12-week online course designed to “Enhance research and writing productivity while maintaining a healthy work-life balance to be a productive faculty member.”
Another program in Sullivan’s professional development pathway, closely aligned with her BIRCWH award, is an NIH online course she took focused on understanding the influences of health and gender on health and disease. In March 2024, U.S. President Joseph Biden issued an “Executive Order on Advancing Women’s Health Research and Innovation.” He wrote: “It is the policy of my Administration to advance women’s health research, close health disparities, and ensure that the gains we make in research laboratories are translated into real-world clinical benefits for women.”
Sullivan’s research interests in toxic metals and gender disparities dovetail with future funding opportunities. The NIH has pledged $200 million to launch an NIH-wide effort “to close gaps in women’s health research.” Coordinated by ORWH across NIH’s 27 institutes, the effort “will invest in research on a wide range of women’s health issues, call for new proposals to research emerging women’s health issues, and study the effect of environmental factors on women’s health.” The agency issued a new Notice of Special Interest (NOSI) to identify funding opportunities related to women’s health research across a wide range of health conditions.
A ranging landscape
As noted above, it’s not always that a budding research career and the skills required to pursue it align well with emerging technologies, public health needs, and funding opportunities. By “unlocking new dimensions of genome complexity” in detecting toxic metal signatures in DNA, Sullivan’s innovative approach opens up a potential biomarker landscape that ranges from placental tissue, where metals accumulate, through newborns to children, adolescents, adults, and indeed, to autopsy tissue and paleogenetics, the study of ancient genetic material recovered from the remains of extinct or ancient organisms.
We don’t think much about the metals we encounter and accumulate from sources below, above, and around us as we move about the Earth’s surface, but they are there and in some cases in greater amounts, depending on where you live and work. As the metals biomarker landscape in the human body is revealed, it will be reflected in populations, their “exposure and susceptibility” to toxic metals. The implications for disease prevention and public health are hard to overstate.
