Dr. Dori Germolec — Environmental Chemicals Versus the Immune System

Friday, June 28, 2019

Dr. Dori Germolec is a biologist studying how the chemicals in our environment affect the immune system, including toxic or carcinogenic effects of molds and dietary supplements. From bisphenols and flame retardants to arsenic in the drinking water and polycyclic aromatic hydrocarbons, we are all exposed to a mixture of different compounds on a daily basis. Dr. Germolec’s research as part of the National Toxicology Program informs agencies like the EPA and FDA about the potential hazards of environmental toxins so that chemicals and substances can be properly regulated to keep people safe and healthy, both at home and in the workplace.

Dori Germolec, Ph.D., leads the Systems Toxicology Group of the NIH's National Institute of Environmental Health Sciences (NIEHS) National Toxicology Program (NTP).

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Transcript

>> Have you read any good books lately?

>> I'm really interested in science books that kind of have an evolutionary perspective to them.  So, right now, I'm reading David Reich's "Who We Are and How We Got Here," which is about sort of the genetic basis for who we are as different populations and kind of helps explain different population migrations.  With an idea of using the genome to identify where genetics may influence the burden of disease and how we can develop better therapies.

>> Sounds very interesting.

>> It is.

>> So, you do systems toxicology research.  And so one thing I'm wondering, is there fungus among us?

>> There is.  So my focus of research is looking at the effects of things on the immune system, and one of those things that we look at are molds and fungi.  I have a collaborative interaction project with NIOSH.  And I'm working with Dr. Don Beezhold and Dr. Brett Green.

>> What is NIOSH?

>> NIOSH is the National Institutes of Occupational Safety and Health.  And they have designed a very special exposure system there that allows us to look at the effects of fungi in animal studies. 

>> So what is that exposure system that they've designed?

>> It's called an acoustical generating system.  If you've ever looked inside a stereo speaker and you see the rubber panel that's inside the stereo speaker, it vibrates, and that's how you get the sound.  And the acoustical generating system is kind of based on the same principle.  So the mold is grown on rice and it's placed on the vibrating disk that looks like the inside of the stereo speaker, and when it vibrates it aerosolizes the mold into the air.  And it's highly controlled.  And we can use that to generate an exposure system that we use to study the health effects of different fungi.

>> Okay.  So NIOSH, where are they located?

>> They're in Morgantown, West Virginia.

>> Okay.  And so you collaborate with them.  How does that work?

>> Well, so the NTP is an inter-agency group -- interagency program.  And so there are many other federal agencies, including NIEHS, that are partners in the NTP and NIOSH is one of those agencies.  And so we collaborate.  We design the studies together.  We fund the studies together.  And the studies are actually conducted at NIOSH because they have very specific expertise in this area.

>> And so what is the role of the National Toxicology Program for the typical American?

>> The National Toxicology Program is designed to protect the public health.  The NTP's mission is to ensure that things that are in the environment are safe and that people aren't exposed to levels of things that would cause them disease.  So we're looking for things that potentially could cause cancer or cause reproductive and developmental effects, potentially leading to birth defects in children, for example.  We look at things that affect the immune system.  Because if something affects the immune system, it will impact your ability to fight disease or resist cancers that naturally arise in your body.  So we look at a wide variety of things and the idea is to protect public health.

>> You personally, are you focused on looking at like consumer products or things in the workplace or in people's homes or are all of the above or something else?

>> Not very focused on consumer products.  It's mostly chemicals in the environment, sometimes it's things that are in the workplace.  Again, we often partner with NIOSH, and NIOSH will do health assessments or exposure assessments in the workplace.  And we will conduct research studies that might help to explain what the risks are of chemicals in the workplace.  Or might help predict potential health effects following chemical exposure in the workplace.  So there is consumer exposure sometimes on the end to those products as well.

>> Could you maybe talk about a little bit how you found your way to the National Institutes of Health?

>> So I started out at the NIEHS actually as a research technician.  I really liked what I was doing and so I went back to school and got my PhD and then had an investigator-initiated research laboratory here, studying the immune system for some number of years.  And I was also doing work with the NTP at that time.  I transitioned to the NTP full-time in 2006 I think it was, -- because I wanted to learn about other aspects of toxicology that I was less familiar with, I specialize in the immune system but I really wanted to get some involvement in looking at things like carcinogenesis and reproductive and developmental toxicology, toxicity in the lung and other things.  So transitioning to the NTP full-time allowed me to get exposed to some other things.  It also was a time when I had a young child, and so it allowed me to achieve some work-life balance.  I had been kind of doing two jobs before that. 

>> Obviously there's a lot of different types of toxins that people could be exposed to -- through the air or through their skin or by eating them I suppose, and probably some others I'm not thinking of.  Is there a typical process that might follow when you're exposed to a toxin, sort of a generalized process that you could describe?  Or is it very particular to which toxin it would be?

>> I think the process that people might be the most familiar with is allergy or contact allergy.  So there are chemicals that induce contact sensitization or dermal allergy.  And people get respiratory allergy obviously when they inhale pollen and things like that.  Chemicals can induce hypersensitivity responses similar to that.  I think that that process is probably what most people would be familiar with.  And that's when the immune system is sort of inappropriately stimulated for whatever reason.  In individuals that are sensitive to allergens, you have an exaggerated or inappropriate immune response.  And in individuals who get sensitized to chemicals, you can have that same sort of inappropriate immune response. 

>> What are some of the toxins that you focus on in your research?

>> So one of the more exciting projects that we're working on right now is a project looking at mixtures of polyhalogenated aromatic hydrocarbons, which are things like diesel exhaust, carbon fumes, pollutants in the air.  And the idea is that we are all exposed to mixtures.  We're never really exposed to one single thing.  And these poly aromatic hydrocarbon mixtures, people, you know, see in air pollution all the time.  And when there's a spill or some kind of accidental exposure, we'd like to be able to predict what kinds of health responses or problems people might have after exposure to these mixtures.  And we can't look at everything in the mixture.  So with this project that I've been working on in collaboration with Dr. Cynthia Rider in the NTP, we're looking at the different types of responses that we see following exposure to these compounds and then using that data to try and predict what might happen with a mixture.  The immune system is particularly sensitive to these compounds.  And we've looked at the effects on the immune system for a number of these compounds now, and we have a really good idea of what the responses look like.  And now we're getting ready to test some real-world mixtures.  So things like diesel exhaust, where we can put it in and see if, based on what the makeup is of the mixture, whether we can predict what the health effect would be.

>> And so what all's in those mixtures?  Diesel exhaust — is it mixed with something else, or the exhaust itself is the mixture?

>> The mixtures will be different polycyclic aromatic hydrocarbon chemicals.  So there are things like -- in our mixture, there will be things like benzopyrene and phenanthrene, a lot of complex chemical names, which maybe people would not be so familiar with.  Some of them are compounds that we know cause cancer in rodents.  And some of the compounds -- they have a wide spectrum of effects.  And so the idea would be to, if we have a mixture that we can define, then the idea would be to use the effects that we know from the individual chemicals to predict what would happen after exposure to a mixture.

>> Polycyclic aromatic hydrocarbons.  Are there other examples of where these — would you call them PAHs?

>> Yes.  Or we call them PAC MAPS.  So it's poly aromatic hydrocarbon mixtures.  So it's a handy acronym.

>> Are there other examples of PAC MAPS that you haven't really talked about yet?

>> So coal tar is another good example.  It's a driveway sealant.  You can go down to your local hardware store and buy it to seal up cracks in your driveway.  So that's a way that consumers can get exposed to those sorts of things.  And obviously there's occupational exposure to those kinds of things as well.

>> When someone's exposed to one of these mixtures as a bunch of chemicals that they would breathe in I assume is the primary exposure, possibly on their skin too, or irritate their lungs and eyes, maybe.  What are the effects of that?  What happens when they're exposed to these mixtures?

>> So it depends on the chemical.  As you mentioned actually, they can irritate the eyes.  They can irritate the skin.  I think what we're most worried about is the perhaps potential disease consequences if people are exposed to high levels of chemicals.  And obviously that depends on the chemical and how much they're exposed to.  And so for a lot of these things we really don't know what will happen long term.  And that's what the NTP does.  We try and study the effects of what might happen following long-term exposure.  And we do studies using cells in vitro and using different molecular-based models.  And we're trying to predict what will happen based on sort of in vivo to in vitro extrapolation and then extrapolating other studies to what might potentially happen for exposed humans.  What we're most concerned about is when people are accidentally exposed to things.  So think about, for example, things like the Gulf oil spill, where there were people that, you know, first of all they were exposed during the spill.  Then there were people that went out and remediated, cleaned up, and obviously they're wearing protective equipment.  But still, we want to be able to predict potential health effects.  Things like accidental exposures during the World Trade Center bombing.  So what can we -- what can we tell people about potential health effects?  What can we tell physicians about what to look for?

>> Did you do any work or research related to either of those two disasters?  I actually worked on, as a reporter, on the Gulf oil spill.  I spent the whole summer writing stories about that.  It was very interesting, obviously very tragic.  So the workers cleaning up wore protective equipment, as you mentioned, but they probably still were not fully protected, I imagine.

>> So I didn't do any work with Gulf oil spill.  But the mixtures project that we're working on is actually a direct measure to sort of respond to that and try and better predict when we have some sort of accidental exposures what kinds of things we can do to predict potential health effects.  I did have an opportunity to do some work with World Trade Center dust.  And we looked at the effects on the immune system following exposures.  But what we saw was very equivocal and we didn't -- we didn't get a clear pattern of what the potential health effects might be.  And other people published on that.  So we didn't -- we didn't study it extensively in our lab.

>> You also do work with herbal products and dietary supplements?

>> I do.  So my very first project in the NTP was looking at resveratrol, which is the compound, if people are familiar with it -- it's a compound in red wine that is a compound that has the purported health benefits.  And the NTP was looking at whether significant exposure to resveratrol would have potentially adverse health effects.  So resveratrol, because it was identified as the compound in red wine, it was a dietary supplement.  And we wanted to ensure that people that were taking it as a dietary supplement wouldn't have adverse effects.  And those studies actually were really interesting because everyone else at NIH was studying resveratrol for its efficacy, and we were studying it for its toxicity.  Those studies are getting ready to be published in a report form within the next year or so.

>> So that was one of the earlier studies in your career that you were working on?

>> Yes.  In my laboratory, when I had a research laboratory, my work focused on arsenic and the mechanisms of arsenic-induced skin cancer.

>> How do people get exposed to arsenic typically?

>> Typically via the drinking water.  It's not a huge problem in the United States, but there are many countries where arsenic heavily contaminates the drinking water in wells, particularly India, Pakistan, some countries -- other countries in Southeast Asia.  There are point sources in the US.  There have been, you know, occasional findings.  But since most people are not necessarily on well water, particularly in large urban areas, it's not as big an issue.  And there are a wide variety of cancers associated with exposure to arsenic in the drinking water.  And we were looking at skin cancer and the impact of growth factors and how that modulates skin cancer.

>> Growth factors that were different in people's bodies or giving people growth factors?

>> Arsenic induces the production of growth factors.  That it induces abnormal production of certain growth factors in particular cells in the skin.  And so we believed and we published that it was the overproduction of certain growth factors that might contribute to the increased incidence of skin cancer in people that were exposed to arsenic in the drinking water.

>> So you work on perfluoroalkyl substances.  What is that?

>> Per and polyfluoroalkyl substances, we can abbreviate to PFAS because it's a lot easier to say, if that's all right.

>> Yes.

>> And these are substances that are produced for their water-resistance properties mostly.  So you would know that they were in some of the products that are used to waterproof your carpet or waterproof fabrics.  They're also used in food packaging.  So when you get a takeout container that has come of that thin coating of wax or waxy like material in it, the inside of those kinds of cartons that you get, for example, Chinese food in.  Usually they contain some level.  And the levels of those substances are regulated in food packaging.  So that's one place you can find them.  Another place that is common is firefighting foams.  So they're used in the military.  They're used in airports to put out fires associated with blacktop and things like that.  So they have become a problem because there has been leakage into the drinking water from a variety of sources.  Here in North Carolina, it's a very public issue right now because it was found that the compound GenX -- which is a perfluoroalkyl substance -- was found in the drinking water, was found to be leaked into the Cape Fear River and was found in a number of wells around a particular chemical plant near the coast of North Carolina, so near Wilmington, North Carolina.  So there's been a lot of interest locally in that as well.  And then there have been quite a number of areas in the US now that have been found to have higher levels of PFAS in their drinking water, potentially because of leaching from other chemical plants.  So there was a very famous chemical spill in West Virginia some number of years ago and there was quite a lot of human exposure as well as environmental exposure.  So PFAS have been in the news and they've been sort of a public concern for a long time and they're kind of rising to the top again with some frequent exposures.  And we're coming to realize just how many of these compounds there are.  I think the last count from EPA was that there were more than 5000 of these compounds.  The long ones can be very environmentally persistent.  So it's a continuing public health problem.

>> And by long ones, you mean long in time or long in like the compound structure?

>> Long in the compound structure.  So there are short-chain and there are longer-chain.  And so the concern is about some of the -- we don't know the health effects of the newer shorter-chain ones.  So the NTP has been studying that.  And there are some public health concerns about the longer ones.  There have been a number of published studies indicating, for example, long-term immune effects from exposure to these compounds.

>> Is it logical to say that a shorter compound would be more reactive and potentially process faster but maybe more readily cause damage to people?  Versus the longer one, you said, persists longer over time and would be maybe lower-level effects but for longer?

>> So we don't know a lot about the health effects of some of the newer PFAS.  What we do know is that the shorter-chain compounds have shorter time in people's bodies, shorter time in the environment.  And so the belief would be that they would have less health impact than the longer-chain compounds.  But again, we don't really know the answer to that.  And some of the data that's emerging at this point suggests that maybe that's not the case and that there are still potential health effects from these shorter-lived compounds.

>> You mentioned that there were some big spills in the news from chemical plants where these PFAS substances got into the water and that's how some people are getting exposed, but there is also exposure through consumer products.  Are you studying both of those or one of those?

>> So we don't study the individual sources per se, we study the chemicals.  So we're not looking at -- or we're not extracting things from food packaging and looking at what's in food packaging and then testing that.

>> Got 'ya.

>> We're looking at purified compounds.  And so some of the -- for example, looking at GenX, that was a compound that was discharged into the river rather than an actual accidental spill.  So we're looking at individual chemicals versus things that are in specific products or environmental mixtures.

>> So out of those 5000 PFAS, how many have you looked at so far?

>> So right now we're in the process of doing some in vitro studies looking at about 20.  And the plan is to look at perhaps another 75.  And what we're trying to do is to do a number of short-term in vitro studies to screen and prioritize which of these compounds might be the most biologically active.  The idea being to identify those compounds which we might want to have a closer look at later.  So obviously we can't look at the entire world of those chemicals, but we can do short-term studies and in vitro studies that will allow us to prioritize those compounds that we really need to take a closer look at.

>> And you probably pick them sort of also based on how common they are in the environment?

>> So there's good evidence from the NHANES study.  We have some good information about what people are exposed to.  Because in these large population-based surveys, they will quantitate the levels of different PFAS in people.  So we have an idea for some of them.  For others, we're looking at ones that are commonly found in the environment and also ones  that have been nominated to us by agency partners. 

>> And so in the US, is your group one of the primary people doing this, or is NTP the primary agency doing research on PFAS, or are there lots of places around the world where these types of studies are happening?

>> I think there are lots of places where these types of studies are happening.  There's quite a few universities that are doing PFAS research.  I know that East Carolina University here in North Carolina and North Carolina State University have big efforts because of the GenX leakage into the Cape Fear River.  But there are a number of federal agencies and NTP partners that are studying PFAS as well.  We're collaborating quite a lot with the EPA.  And I know the Department of Defense has a lot of interest in PFAS as well.  PFAS are found in some of the firefighting foams that are used on military bases.  And there have been concerns about potential contamination from the use of those firefighting foams.  So I think the military has an interest in getting a handle on what the potential health effects could be.  I particularly think PFAS are important because they have lots effects on the immune system.  And so I think that they have the potential to impact human health. 

>> And it's probably more of a concern when it's chronic exposure versus acute?  I mean, I guess that's obvious but?

>> One of the things we don't really understand about these compounds is what happens with chronic low-level exposure.  And I think those are the kinds of things that we're most concerned about.  Those are the kinds of things that we don't monitor very well. 

>> The low-level exposures would be a very interesting place to look at the effects of that?

>> Yeah.  I mean, I think that we're all exposed to chemicals in our environment.  And because we're exposed to a soup of things, and sometimes we're exposed to more of the soup than we probably should be, the idea is just to study the impact of, again, inadvertent, chronic, low-level exposures to things in the environment that really have the potential to impact health.

>> Yeah.  Because you can't really remove all the bad stuff, but there's a few big bad things that would probably be good to take care of.

>> Well, you can't remove the bad stuff, but what you can do is make sure that we're not exposed to high levels of the bad stuff at any one time.  So I think it's managing the levels of exposure.

>> There was an interesting news article recently, I think some guy in California at the University -- I don't know if it was Stanford, I'm not sure -- but he put a thing on his arm and a bunch of other people's arms to capture everything they were exposed to over a day or a year.  They did different time periods.  I was just curious, did you see this story or hear about it?

>> I did not.

>> Yeah, it was just very interesting because he had -- they could identify all the things that different people were exposed to.  And it was very different for each individual even if they lived in the same city.

>> They do similar sorts of things with workers, right?  They'll put a badge on and, you know, look at what levels of particular chemicals they're exposed to.  It's actually pretty interesting to follow where, depending on where they go in the plant, how much they're exposed to and what they're exposed to.

>> Yeah.  It would be nice if one of those smart watches or something would integrate this.

>> That's a new patent, right?  New technology.  That would be really good.  I think what it would serve to do probably is scare people.  And I don't think that, you know, I don't think people need to be scared every day.  I think that it's just when you have a sort of accidental overexposure.

>> Sure okay, that makes a lot of sense.  And so bisphenols.  What are bisphenols?  How do you say bisphenols?

>> I say bisphenols.  I think most people say it that way.  So bisphenols are, you know, compounds that are in plastics.  And there was a lot of public concern about the potential health effects of bisphenol A.  I think there's been a lot of conflicting evidence about the potential health effects of bisphenols.  There has been some work published that they affect the immune system and some work published that says they don't affect the immune system.  So I think, like other scientific evidence, sometimes there is conflicting things.  And I think the jury's still out about that.  The NTP just recently published the Clarity Studies, and I think that goes a long way to address some of the concerns that the public has had about bisphenols.

>> What do they say?  Should we be afraid of canned food?

>> I don't think we should be afraid of canned food.

>> Okay, good. 

>> I'm not an expert on bisphenols and I'm not -- I didn't participate in the Clarity Studies, so I probably don't feel really comfortable talking about the results.

>> Sure, that's fair.  And then do you do studies on flame retardant chemicals?

>> So I do do some studies on flame retardant chemicals.  They're mostly in the initial stages.  So we're looking at the potential effects of flame retardants on the developing immune system.  So we have done some studies.  Right now we have an ongoing study that we're hoping to report out in the next few months.  So I don't have a lot of data to talk about there.  But we're looking at -- we're looking at the developing immune system appears to be more sensitive.  And we're looking at potential effects following developmental or in utero exposures to different flame retardants.

>> What ages would you classify as the developing immune system for people?

>> So we're looking at -- so the developing immune system -- in people, the immune system continues to develop after birth.  And so neonates don't have a full complement of immunity and they get a lot of their immunoglobulin, for example, from nursing.  And so they're not immunocompetent really until sort of age two. 

>> And so that's what your studies are focusing on?  And after age two, it's more…

>> We're doing studies in laboratory animals.  And actually laboratory rodents are a little bit more immune mature when they're younger than humans.  Their immune system development is -- obviously because of their shorter life, they're.

>> Smaller?

>> Yeah.  Well, yeah, they're smaller and their immune systems develop a little bit more quickly.  So we're looking at laboratory rodents that have been exposed while they're in utero, so prior to birth.  And then exposure continues, just like it would in a human infant who's born and is exposed to different things through, for example, the linens in their crib or the furniture in their.

>> Do they put flame retardants in linens and sheets still, furniture?

>> They put flame retardants in furniture still.  It's regulated more or less depending on where you are.  I think California has more strict regulations about the content of flame retardant in materials.  But it's in furniture and it's in clothing.

>> Does that generate an immune reaction or DNA damage?

>> Not at the levels in those products.  Or we would argue not at the levels in those products.  So the idea is all about setting levels that are safe.  And NTP is not a regulatory agency, so we don't set those levels.  We just provide information for the regulatory agencies about, you know, what levels we think could potentially have health effects or where we can clearly demonstrate that it doesn't appear that there are health effects.

>> So you've mentioned that you're doing these studies.  You also mentioned that you don't have a lab.  And I know you're a group leader.  So I'm just curious what that looks like.  What does your team look like and how do you do these studies without a lab?  Are you collaborating with other people to make these studies happen?

>> So the NTP as a whole has some laboratories.  But in the toxicology branch where I work, most of the studies that we do are done through contract research laboratories.  So the NTP will take in a nomination, they'll design a research program to study the potential health effects, and then they will partner with a contract research laboratory.  I said partner but we actually pay them to conduct the studies.  And so we pay those laboratories to conduct research studies for us, and then they report those studies back to the NTP.  And any given study will involve many, many pieces.  So we do a very complex chemical characterization when we do a study.  So we have a separate chemistry lab that looks at those things.  Then we'll have a group that actually conducts the research.  We might have an immunology piece or a different piece, and then all those different pieces come together to make what ultimately constitutes an NTP report.  So that's how those things are conducted and reported.

>> Okay.  And so the NTP I believe it is intramural and extramural or certain components of it are?

>> Yes.  So there's the NTP, big NTP, is actually kind of an umbrella for a number of different agencies that participate in the National Toxicology Program.  There's a division of the National Toxicology Program that's housed at the NIEHS, which is an intramural research program.  And we have research laboratories and then we have staff scientists that do and design contract-based research. 

>> And the EPA is right next door.  Why did they call this area the Research Triangle Park?

>> So the EPA is across the pond, which is nice because we can walk over there and collaborate with our colleagues over there or take a bus around.  And the reason they call this Research Triangle Park is because more than 30 years ago now, they decided to have an area which would be in North Carolina which would have a very high science and technology focus.  And they gave I guess tax incentives, I don't really know what the history of the park is.  But the idea was to create an environment where innovation and science and technology could flourish.  And so the park was born and it attracted both government agencies and quite a lot of corporations as well.  And it's grown and expanded greatly just in the time.

>> What are some of your favorite parts of the campus down here at NIEHS?

>> It's beautiful all the time.  So it's nice to just sit and look at the pond and watch the leaves change.  It's lovely to watch things bloom in the spring.  I guess spring is my favorite time here because the flowers are so beautiful.  It's nice to be on a campus where it's so green.

>> Yeah.  I remember last time I was down here, seeing a bunch of animals.  And I walked around the lake.  You've got a trail around Discovery Lake.

>> Yes.

>> Is that the pond you're referring to?

>> That is the pond, yes, Discovery Lake, sorry.  Yeah, there's a nice trail that goes around it and we can walk over to EPA or just have a nice walk in the afternoon.

>> So going back to fungi.  What types of fungus do you work on?  You might have already talked a little bit about this with the speaker acoustic study.  What are the common fungi that people are commonly exposed to?

>> So I think the one that people are probably most familiar with is Stachybotrys, which is the black mold that you see in your bathroom.  And so everybody gets very nervous about that.  Molds are and fungi are everywhere.  I always kind of smile a little bit when I see that someone has a report that says they found mold in their crawlspace.  Mold, yes, mold is everywhere.  You know, we see it, we breathe it.  Again, it's when you're exposed to a lot, an excessive amount, that it's a problem.  So when a building is water damaged or there's a lot of humidity.  So Stachybotrys is what people see in humid indoor environments like your bathroom. 

>> Yeah.  I've seen a lot.  It likes to -- does it eat soap?  It always seems to grow by where the soap dish is.

>> Yeah.  It doesn't eat soap, but it loves humidity and, you know, it will -- it likes the compounds that are used to caulk.  It'll grow in the caulking and things like that.  And they'll take advantage of anything with sugar and protein in it that they can grow on.  So, you know, molds are pretty much everywhere.  And the other molds that we've studied are we're looking at Aspergillus fumigatus, which is another mold.  And those studies are probably the farthest along of the studies that we've done.  And what we're really looking for in these mold studies is whether there are effects sort of outside of the lung.  We know that, you know, people have things like runny noses, watery eyes when they're exposed to molds.  And molds generate a lot of different things that are irritating and potential allergens.  And the idea is to really find out if there's long-term health consequences to exposure to molds outside of the lung.

>> Like on the skin or you're talking about after the lungs kind of process it?

>> Yeah, after the lungs kind of process it.  More burden of disease.  You know, does long-term, low-level exposure to molds cause changes in the brain so that, you know, there's changes in cognitive function?  Or does it get to the liver or other organs and, you know, potentially cause cancer or disease in other tissues?  So that's really what we've been focusing on in our mold studies are the idea of looking at whether there's exposures outside -- or health effects outside the lung that we should be concerned about.

>> Where is Aspergillus fumigatus -- where do people encounter that?

>> Oh, it's in the air kind of everywhere.  But again, it's one that in heavily damaged, water damaged buildings, in very, very moldy environments that it would be more likely to be present than other molds.

>> And so you're studying that one in particular to see how it affects cells?  Or you mentioned if these things affect other organ systems like the brain.  Are you looking at that right now?

>> So the studies that we've conducted have all been in laboratory rodents.  So, you know, we've done a number of studies looking at the effects on the respiratory system, the lungs, and the nose, and we've also looked to see if there are effects outside of the lung.  But again, all in rodents at this point.

>> Have you found anything that you can talk about?

>> I will say that most of what we found is concentrated in the lung.  And that we see responses that looks similar to allergy, but the timing is slightly different.  And I think that's all I'll say until the data is a little more firm and published.  I guess one other thing I can say that we found is it that in laboratory rodents at least, we found that it's important -- or we noted that the spores germinate in the lung.

>> That doesn't sound good.

>> Well, it's not all that surprising.  It's a moist and humid environment.  And we've found that the germination of the spores in the lung actually seems to be an important component in the response.  So if we use -- we can use heat-killed spores and we see a different response.  So we know that it's the germination of the spores in the lung that's leading to the response that we see.

>> If you see a little black mold in your shower, would that concern you?

>> No.

>> No?

>> I'm sure there is black mold in my shower.  Again, what we're talking about is when there's a really heavy exposure.  So people remediating homes that have been damaged by hurricanes.  People that are chronically going to work in very heavily contaminated environments.  So the levels of mold spores that people are normally exposed to is relatively low.  It's when you get excessive growth and you are exposed to really high levels, then I think it's, you know, sometimes there's cause for concern.  In a water-damaged home, you will have entire walls.  And it's not only the outside of the wall, it's often the inside of the wall.  And so it's the damage that you can't see.  And again, it's when you have excessive growth, not just a little bit in your shower.  I can't stress that enough.

>> Okay, yeah, that's good to know.  And yeah, so the issue with the molds is that they sort of -- is it that they germinate and release spores into the air that people are breathing?

>> So that's part of it, yes.  Mold has a lot of different aspects to its life cycle.  So there are little fragments of molds that get released into the air that are the actual organism itself.  There are spores that get released into the air that are the way that mold reproduces.  So there are lots of different little pieces of mold.  There are proteases that the mold produces that people can be allergic to.  So there are lots of different aspects of molds that can potentially cause a reaction.  One of the very unique things about the studies that we're doing is that we're kind of doing a whole exposure rather than just isolated components.  And so that's one of the powers of the study that we're doing or one of the very positive aspects.

>> For mold to affect places outside of the lungs, is the mold actually traveling through the body, or is it causing some sort of cascade of effects like inflammation or something that would affect the brain?

>> That's one of the things that we're looking for.  So one of the things we specifically look for is when you're exposed to mold through the air, whether the mold gets outside of the lung, is it carried to other places to potentially cause effects there?  We don't have evidence that that's the case.  The second thing would be is, does the mold get in there and produce stuff that goes other places to cause health effects?  And so we're looking at that.  And again, as you said, the molds potentially cause inflammation in the lung, and does that inflammation change things in other places that could cause potential health effects?  So those are really the three things that we're looking at in these studies.

>> Okay.  So yeah, one thing that a lot of people are also afraid of is mycotoxins in their food.  Do look at anything like that, mold in food?

>> So we've looked at -- the NTP has historically looked at some mycotoxins in food.  They've looked at some of the very sort of prototypical mycotoxins, and several of them cause liver cancer.  But they're highly regulated in food content.  So it's unlikely that unless something, you know, there was an accidental contamination, people wouldn't be exposed to high levels of mycotoxins in their food.  Mold is hard.  The people that that are exposed to molds and experience health effects are -- it's very difficult for them.  And they have sometimes headaches and, you know, very chronic symptoms and it's really a concern for them.  But the difficult part is really specifically associating what the exposure is with the symptoms that they have.

>> Yeah.  Are there any particular tools or resources you have here at the NIEHS that really help with your research that maybe drew you to stay here, or you might find difficult to do what you're doing somewhere else?

>> I think one of the really unique things about NIEHS is maybe the presence of the two intramural programs here.  So that it's a really collaborative and collegial research interaction.  And so we have the opportunity to work with our colleagues in DIR that are looking at mechanistic science.  And we have the opportunity to collaborate with them.  So sometimes when the NTP will ask yes or no is there a health effect, we have the potential to collaborate with our DIR colleagues to ask why.  And so that's a very positive and fruitful interaction I think that makes the NTP unique.

>> Very cool.  What's the most interesting or satisfying aspect of your career so far?

>> I like knowing that I have an impact on public health.  For me, I think knowing whether things affect the immune system in the big picture really has the potential to impact the global burden of disease in public health.  So if we are even modestly immunosuppressed from some exposure to a chemical or a drug, if you think about it on an individual level, maybe you get one more cold a year.  And that's not such a big deal.  But if you think about it on a population level, just in terms of increased doctors' visits or workdays missed, there's an economic cost to changes in how we fight disease that can be very important.  And so I think for me, the public health aspect is the most satisfying in trying to identify those things that might have the potential to impact how we resist disease.

>> Are there any things in the scientific world, any new developments or new tools or anything that you're looking to -- or that you're excited to maybe dig in to or take advantage of?

>> I think there are a lot of really novel in vitro models that we can take advantage of to reduce the levels of animal testing.  So things like organs on a chip.  And, you know, changes in the ability to predict what an in vivo response is from things like organs on a chip where you have many cell types that you can look at.  The immune system is very complex and there's a lot of different cell types involved.  And so to be able to have in vitro systems that mimic different aspects of what happens inside the body are exciting and will be good tools for us to use in the future.

>> In the immune system, which are the cells that you are most often looking at as you're studying these things?

>> We try and look at there's kind of three aspects of immune responses that we really focus on.  We focus on innate immunity, which is kind of your first response.  Think of the first responders, they're very nonspecific.  They're just kind of -- they respond immediately to danger signals, get there, and do what they can to clean things up.  And then we look at antibody-mediated responses and then T-cell mediated responses.  And both of these are kind of learned responses.  So there the second-line responses and they evolve and learn based on what your body sees and they get more exquisitely specific.  And so we look at all three aspects.  We're really trying in our program to kind of do a broad screen rather than a narrow focus.  So that we have an idea of whether any aspect of the immune system is compromised.  So for PCBs, we have really good studies of health effects in human populations that have been exposed to higher levels of PCBs, as well as good animal studies, as well as good in vitro studies.  And what we've been able to do is use that data to do some burden of disease and economic cost modeling, where -- because we know what the potential health effects are in humans.  And we know what exposure levels have been in human populations.  We can get an idea of what sort of chronic low-level exposure to PCBs and their effects on the immune system cost.  Things like, you know, missed workdays, increased doctors' visits, caring for your child who may get more than their normal share of ear infections because they carry an increased body burden of these kinds of substances. 

>> And the different genetic profiles for each person, the substances will affect them differently?  Which kind of complicates the whole picture, I imagine.

>> It does.  If you think about just allergy, for example.  Some people are predisposed to allergy.  Their parents had them.  And some people are -- you know, there's a genetic component to autoimmune disease.  And so when you think about it, if you have some genetic predisposition to things, and chemical exposures on top of that may change that.  So for example, for autoimmune disease, we don't often think that chemical exposures cause autoimmune disease.  In some cases they do.  But really what we often study is how they exacerbate sort of that, you know, pre-existing genetic component.

>> Very cool.  Well, yeah, all of your research sounds super interesting and affects pretty much everybody with these chemicals and toxins and natural things like fungi, pretty much everywhere.

>> Yeah.

>> So thank you very much for looking at them and how they affect us.  And good luck figuring it all out.

>> Thank you.