How an Environmental Toxicologist Tracks HIV's Ripple Effects on Infant Health—Through Breast Milk

As a PhD student in California, Allison Kupsco investigated how polluted waters disrupt the developmental trajectory of fish embryos. To zero in on how environmental cues affect the intricate choreography of embryonic cell signaling in vertebrates, Kupsco combined novel molecular and toxicological techniques. In 2017, she embarked on a two-year postdoctoral fellowship in molecular epidemiology at Columbia Mailman to bring those analytic methods to human health.

“Biology is so complex and layered,” says Kupsco, now an assistant professor of Environmental Health Sciences at Columbia Mailman. “Having a more nuanced picture of how toxicity occurs gives us the opportunity to understand how these chemicals cause disease and also identify targets for therapeutics and markers to identify whether, for example, a mom and her baby might be at risk for an environmental exposure.”

In July, the National Institutes of Health awarded Kupsco, as part of a multi-principal investigator team, a three-year, $2.45 million grant to investigate how HIV infection and treatment during pregnancy and breastfeeding affect the composition of human breast milk and, ultimately, the metabolic health of children. (Read more about her work on her lab page.)

“The work that I do is really about the interplay between molecular biology and public health,” says the professor, who runs an interdisciplinary lab at Columbia Mailman. In her wet lab, Kupsco’s team focuses on molecular biology; in the dry lab—equipped with powerful computers—they run bioinformatic, epidemiological, and statistical analyses. “Being able to put those two perspectives together allows us to expand beyond traditional methods to uncover insights that move the field forward,” she says. “It’s public health relevance with molecular biology underpinnings.”

A lot of your work focuses on how environmental toxins affect the epitranscriptome. What is that?

Kupsco: The epitranscriptome is an area of study we didn’t know that much about until the last ten years. When we have cells in our body working to keep us alive and do all the things our cells need to do, they need to be able to fine-tune their functions in response to environmental changes. Our cells use RNA to transcribe the proteins to regulate their survival and health. If we’re exposed to a pollutant, it can change our RNA, and thus our cellular function. I’m interested in how those changes can lead to adverse outcomes following toxic exposures.

What is your focus with the NIH-funded human milk project?

Kupsco: Milk is such an important source of nutrition that goes far beyond protein and fat. These understudied components may be impacted by the maternal environment. I’m particularly interested in extracellular vesicles, nano-sized packages that survive the infant’s digestive system to deliver their bioactive cargoes. I have two human milk projects underway—one in South Africa, and one in Zimbabwe. There are 1.2 million women globally with HIV who become pregnant each year. Human milk is essential for babies’ health, and breastfeeding is recommended globally for new parents on antiretroviral therapy. I’m working with ICAP researchers at Columbia and teams in South Africa and at Northwestern University to learn how exposure to HIV and antiretroviral treatment through breast milk affects infant development.

What else are you working on?

Kupsco: I focus on exposure during pregnancy, mostly to heavy metals. I do a lot of work in children, because they’re extremely vulnerable to these exposures. They’re at high risk because they’re still developing their defense systems. A lower exposure leads to a greater effect than it might in an adult. And a lot of my work focuses on how lead and other heavy metals—arsenic, cadmium—interact. We’re not exposed in a vacuum; it’s all together.

Does any of this relate to your early work on the embryonic development of fish in polluted waterways?

Kupsco: During my PhD, I was focusing on the interaction between human mining activity and climate change and how those may impact aquatic ecosystems. A lot of those themes I still work on, but now in humans. I’m looking at exposure through drinking water to legacy and active mining operations. One project where we’re wrapping up data analysis right now looks at metal exposures directly in the placenta in babies born in the South Bronx and northern Manhattan. We’re trying to link placental exposure levels to growth outcomes and to changes in the placenta, in both the epitranscriptome and the proteome [the entire set of proteins expressed by a genome]. Our concern is that the metals are affecting the placenta, which regulates fetal growth, nutrient exchange, and waste removal, and then, indirectly, the baby.

In addition to teaching toxicology to master’s students, you’ve also been active in curriculum development for master’s and PhD students. What’s the most important value you want to impart to trainees?

Kupsco: We always need to be the best scientists we can be and grow the best scientists we can. If we are excellent scientists fighting for the issues that we know are important, change will happen.