The following has been edited for brevity and clarity. It is excerpted from a recent conversation with Dr. Bill Funk, assistant professor in Preventive Medicine - Cancer Epidemiology and Prevention, at the Feinberg School of Medicine. Dr. Funk researches environmental risk factors associated with chronic diseases, cancers, and complex disorders.
Where are you from and when did you join faculty at NU?
I’m originally from California. I did my graduate work at UNC Chapel Hill in environmental science and engineering, and before that my background was in chemistry. Going into environmental science and engineering, there was more of an applied approach to chemistry. It was still mostly laboratory-based work, but with more a focus on human health.
I joined the faculty at Northwestern 5 years ago, and I started as research faculty in anthropology. And what drew me there was Thomas McDade, the director of the Laboratory for Human Biology Research. He’s really been a pioneer in finger-prick blood spot analysis. His approach has been to look at human biology with blood spots. They offer this nice resource for obtaining blood samples in community-based research. My work prior to that was working with blood spots, but more on the environmental side, looking at biomarkers of exposure to pollutants in the environment, and so I had a lot of interest in seeing some of what Thom was doing.
I joined the faculty in preventive medicine two years ago, and that’s when I started my lab here, which is located in the Cancer Center. It’s a mass spectrometry-based lab. My work is focused in two areas: one is being able to get blood samples and doing community based research. But then, also doing some more exploratory stuff, trying to figure out some of the risk factors for chronic disease and cancers that have environmental links that we haven’t discovered yet.
You said you’re from California, and you moved to the Chicago area five years ago when you joined Northwestern. So what’s your favorite thing about living here? I assume it’s not the weather.
Actually, I’ll probably sound like a crazy person, but it is the weather. I grew up in San Diego and we didn’t have seasons, so it’s actually kind of fun to have snow during Christmas. Fall and Spring are great.
Tell me about your research.
One of the things we focus on is called adductomics. It’s a global approach, where you’re not just looking for single biomarkers, but you’re doing profiling to try to measure everything you can. An adduct is an addition product of protein. A lot of these chemicals that are in the body that are harmful are very reactive; and because they’re reactive, which makes them dangerous, they’re very short-lived in the body. So they’re hard to measure directly in the blood.
So we extract abundant blood proteins, for instance, albumin is the most abundant protein in serum, and it has this hotspot on it. It’s this really reactive spot, and it acts as a sink to pull out these harmful chemicals from the blood. Because of that, it makes it a really nice location for biomarker discovery, to look at what’s bound there. The types of molecules that bind here are things like tobacco smoke, pollution, even oxidative stress and inflammation; they all produce small reactive molecules that bind to this spot.
We extract these proteins and do a case-control approach. For example, we’re submitting a grant looking at congenital heart defects. So we have dried blood spots from newborns that are born with heart defects, and control infants that are not. We look at their blood spots and we profile them to come up with these adduct maps, and you can compare the two to look for new risk factors that might be causing the defect. Using mass spectrometry we map all the different adducts that are on the spot.
So this process tells you what contaminants are in the blood, but does it tell you the level, as well?
Absolutely. We can quantify the intensity of how much is in there. And that’s one of the key things - to compare the intensities of each of these adducts that we pick up on. We have instrumentation in my lab to do this, but we’re also collaborating with the Proteomic Center of Excellence, Neil Kelleher’s group up in Evanston. They have lots of high-resolution mass spectrometry there that we’re using.
So do you already have the blood spots for the newborns in this study?
My collaborators at UNC Chapel Hill have them. Newborn screening programs in the U.S. collect blood spots in all newborns. A day or two after birth they’ll do a heel prick and they’ll spot up five drops of blood on filter paper. They use it for metabolic testing, but a lot of states will take leftover spots, typically there are two or three leftover, and they’ll store them. A lot of states are now letting researchers access these samples for other research, and so that’s what we’re doing here.
This approach is really general though. Because it picks up on all biomarkers in the blood, not just pollutants, we think this approach is very promising for cancer detection, as well.
More broadly, what drew you to public health and environmental health?
Blood spots are a tool for getting the answers we need to the big questions. But the big questions are what really drew me to this. There’s a lot of evidence coming out now that a lot of chronic diseases and cancers are attributed to environmental factors. There’s a paper in Science by Steve Rappaport that came out a couple years back that said 70% - 90% of diseases and cancers are due to environmental factors. And by environment, more broadly, we’re saying things that are not strictly genetic. So we could be saying gene-environment interactions, as well, but there’s this huge environmental component, which is largely unknown.
This concept is being referred to as the “exposome," as a compliment to the genome. There have been two National Academy of Science meetings that were held to look at this new approach to looking at environmental contributions to disease etiology. So when you’re looking at that, the two big questions are: what are these risk factors that we don’t know, so you need to have these discovery type approaches like adductomics; then also the logistics – how do you do this in population-based research? Blood spots are a really great tool for that.
Tell me about the finger prick test you developed that you hope to pilot in the town of DePue, which is a superfund site contaminated with heavy metals, such as zinc and arsenic.
There are some things we know we want to look for. DePue is very contaminated with heavy metals. In collaboration with the EPA I started, many years back, developing a method for looking at heavy metals in dried blood spots. We ended up validating that here at Northwestern with a grant that we got through the National Children’s Study. This was to come up with a better way to, in prospective studies - when the blood hasn’t been collected already, to pre-treat the paper to remove contamination so you can get a more precise measurement of these metals just using a finger prick.
The superfund program looks at the most contaminated places in the United States, and for the state of Illinois, DePue is really the most polluted site. It’s a big concern. So this was a focus of our superfund grant that we put in, which unfortunately didn’t get funded. When it didn’t get funded, I started thinking, this is such important work, if I could at least pull out the piece that we wanted to do originally and resubmit it as an independent grant, that was something I was very interested in doing. So that’s what this study is.
So how will the study happen? How many people do you hope to get?
We’re looking for about 300 people. It’s a small town, so that’s a good portion of the town. And we’ve just had tremendous support. The mayor has been great in helping us out with this. We sent out a mailer with the water bill to introduce the study and got a nice response back from that. So, if this was to be funded, what we’re really looking at is the exposure assessment. But even beyond that, we’re taking a broader picture across the whole continuum of exposure: internal dose, how much of the chemicals get inside you; biological response, so once it gets inside you, your body starts to respond to it. There are markers we can pick up on like inflammation. Then the long-term health effect we’re interested in is reproductive health. We know that things like zinc affect reproductive health, and that’s one of the metals we’d be measuring. Using the dried blood spot method we’d be able to actually collect the blood spot samples in the town, in their homes using a simple finger prick.
My understanding is there haven’t been many public health studies in DePue even though it’s been a superfund site for decades?
It’s been very limited. Just like in all children, they’ve measured lead, and it has been shown to be elevated. But in Chicago it’s elevated in a lot of people. I think it’s more important to go in and look at a bigger profile of what these metals look like. One of the big challenges to doing that is the need for venous blood samples, and for people to go to a clinic. So I think the new technology of being able to go into the home, prick a finger, and take the blood sample back to the lab with you really opens up the possibility to get some of this important work done.
What do you hope this study accomplishes?
My hope would be to uncover how much of a problem this is. What are the current exposures? What are the current health effects? And hopefully be able to influence policy that can start to change this, and influence remediation. But what’s also exciting is the huge amount of other people interested in working on this. If we can get this started with one piece of the project, then hopefully we can bring in follow-up studies in some of the important research that was planned with water remediation, soil analysis, and looking at zinc and reproductive health.