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Pursuit of Discovery featuring Dr. Jared Brown

Pursuit of Discovery
 
 
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Podcast Transcript



Introduction (Dr. Peden Talking)



Welcome to Pursuit of Discovery, East Carolina University’s podcast about innovative research happening right here on campus. I’m Dr. James G Peden, Director of Medicine and Psychiatry. Join us today as we explore research in the Division of Health Sciences; where doctors, researchers, and scientists are making an impact on a global level.

Nanotechnology, the study of manipulating matter on an atomic and molecular scale, is a field that has been steadily growing in the last 10-20 years. Nanomaterials used for drug delivery are a major concern. Researchers know what happens to a drug when it is put into the body; it is metabolized and excreted. But they are not certain what happens to nanomaterials when they are put into the body. Do they stay in the body and can they potentially cause toxic effects such as cancer?

Dr. Jared Brown, assistant professor in the Department of Pharmacology and Toxicology, and the researchers in his lab here at East Carolina University have been researching nanomaterials, especially in understanding what impact inhaling nanoparticles may have on human health. Dr. Brown first became interested in nanotechnology when he was in graduate school at the University of Montana, where there were environmental exposure concerns from different mining operations and asbestos exposure.



Dr. Brown talking

I was at the University of Montana where we have a lot of environmental exposure concerns from mining operations and from asbestos exposure. In Montana, one of the areas that produced probably about two-thirds of the world’s asbestos is there in northwest Montana. There was a lot of research when I was in graduate school looking at environmental exposure and how the asbestos impact human health. My interests started there because you could see those impacts on human health in that region of the country. That continued on from graduate school and looking at particle exposures. In this case silica particles and how they might lead to autoimmune disease. So, there is a strong link between silica exposure and development of certain autoimmune diseases. Then, I progressed into mast cells in my post-doctoral training at the NIH in Bethesda, Maryland. I worked in the mast cell biology section there.



Dr. Peden Talking

Dr. Brown’s recent research suggests that the activation of mast cells is an important step in the initiation and progression of pulmonary inflammation, fibrosis, and cardiovascular injury following exposure to nanoparticles. He has discovered that understanding mast cells is vital to comprehending the full impact of nanomaterials.



Dr. Brown talking



Mast cells are our favorite cell type, and they are the cells that are involved in allergic responses. They are the ones that cause all of your seasonal allergy problems. So, if you are allergic to any sort of grass pollens or any sort of pine pollens, pet dander, things like that cause your itchy eyes and runny nose. And things that cause skin irritation as well. Certain cosmetics will cause eczema in the skin and rashes. So, the mast cells mediate a lot of those effects. So, what happens is, the body will get exposed to pollen, for example, and then it will bind to the mast cell and the mast cell will cause degranulation and release things like histamine. So, we have histamine receptor blockers, drugs that we take to try and alleviate allergic symptoms and so forth. So, it’s the mast cell that mediates a lot of those effects. We are studying a little bit different of a context in that it’s also an immune cell. So it does have the purpose of causing problems and causing allergic responses. It’s also involved in fighting bacteria and viruses. And it’s involved in wound healing. It’s involved in different autoimmune diseases, and things like pulmonary fibrosis and different diseases that might occur. So, it’s an immune cell that causes a lot of different problems but also has some good functions as well as far as fighting infection.

Well, mast cells are also located in areas where we are exposed to environmental pollutants. So, they are found in a lot of mucosal tissue, so the lung, the skin, and GI tract. So, those are all places where you are going to be exposed, whether you are ingesting something or it gets on your skin or you inhale it in. The mast cells are one of the first immune cells that might encounter any sort of pollutant like that. So, then for my interests, I asked whether mast cells might be involved in responses to different particle exposures. Then, from there, it went to asking the question about nanomaterials because there is this big open-ended question out there as we develop more and more nanomaterials. How could they impact human health? So, I asked the question what about mast cells? Could they potentially be impacted by nanomaterials? In several ways too. One, could nanomaterials exacerbate mast cell activation? So, could it exacerbate allergic symptoms? If someone already has asthma, for example, mast cells play a significant role in asthma, or an allergic disease, if they were exposed to nanomaterials, could that exacerbate the disease process and make an asthmatic response worse? And also look at mast cells as a cell that would interact with nanomaterials whether it’s giving an IV or a lot of them are being used in cosmetics as well. So, if you put that on your skin, could that exacerbate an allergic response on the skin and activate mast cells by different nanomaterials. Sunscreen is a classic example of that. Sunscreen uses titanium dioxide nanomaterials already. So, if you put that on the skin, could that potentially activate mast cells and exacerbate allergic responses?



Dr. Peden Talking



For the next step in his research, Brown is looking at how to design nanomaterials to make them less hazardous. If he can understand what properties make the nanomaterials toxic, he can modify those properties to make them safe.


Dr. Brown talking



We are working with a group of chemists right now. We are coding materials of different polymers. The idea is that we can take that polymer and encapsulate a drug inside that polymer. As the polymer slowly degrades over time, that drug is released into the body. That is our next step—to see how these drugs can be engineered to be safe and also where we can encapsulate a drug within these different nanomaterials and provide a more ethicatious drug delivery.


Dr. Peden Talking



Brown has received an impressive amount of grant funding for his research. In fact, he has over $3 million in grants in the lab right now. The three grants are from the North Carolina Biotechnology Center, the ONES award given by the National Institute of Environmental Health Sciences, and a U19 grant from the National Institutes of Health.



Dr. Brown talking



We have over $3 million in grants in the lab right now. I think that has come from the interest in how nanomaterials might impact human health. There is a legitimate concern out there from the public to different government agencies about how these materials might impact human health.

The first grant we received was from North Carolina Biotechnology Center. This grant was aimed at looking at mast cells as a model to investigate nanomaterial toxicity. So, as I mentioned before, as a mast cell is activated, it can cause all of these different symptoms and problems. So, the idea was if we can expose mast cells in a cell cultural system to nanomaterials and if it activates them, these materials might become a problem. So, it is a screening process to look at these materials and whether they are toxic or not.

The second grant we received was the ONES award- Outstanding New Environmental Scientist Award by the National Institute of Environmental Health Sciences. This was a $2.2 million award. Looking at how mast cells might influence toxins in nanomaterials. So, it’s looking more at mechanisms. So, if you are exposed to nanomaterials, whether through IV through drug delivery or inhalation like an occupational setting. Do these materials activate mast cells and if they do activate them, what problems might they cause? Do they cause changes to the asthmatic symptoms or do they cause pulmonary fibrosis or cardiovascular complications? So, you find a lot of mast cells on the heart. So, we have some data that shows if we expose animals to nanomaterials, we can exacerbate a heart attack in these animals. These materials actually have the potential to cause cardiovascular complications as well.

The third grant was a U19 grant from the NIH. A five-year, multi-project grant that is across institutes. So, it’s a center grant. It consists of ECU, the Hamner Institutes in RTP, and Research Triangle Institute in RTP. This is a three-part grant where we have three projects. The first project is the one that is here at my lab, so it is looking all in-vitro, so all cell toxicity. We are going to expose different cell types. We are looking at cells from lung, heart, and reproductive tract and look at how the nanomaterials might affect the toxicity of the cell types. The second project is looking in animals. This group of people will expose animals to nanomaterials and look at effects on the lung, heart, and reproductive tract. The third project is all computer modeling. The computer models will take project one- the cell part- and project 2 the animal part- and combine them together and try to create a computer model and predict how nanomaterials might impact human health based on what we find in cells and animals. If we figure out certain materials are taken up by certain cell types and these cell types are impacted in the animal, they also might impact human health as well. So, if you have the cells in the heart that are damaged by nanomaterials, we also find that we have cardiovascular complications in the animal and the computer model will take that data and predict- yeah in humans we might also at certain levels of exposure expect to see cardiovascular complications.



Dr. Peden Talking



One of Brown’s grants, the U19 grant from the National Institutes of Health is a five-year, multi-project grant across institutes. ECU, the Hamner Institutes for Health Sciences, and the Research Triangle Institute are participating in this three-part grant. According to Brown, it is important to collaborate with other researchers.



Dr. Brown talking



We all have different expertise. For example, I bring the mast cells and Immunolgy. I look at how effects of how these nanomaterials interact with the immune system. A collaborator, Dr. Chris Wingard, whose lab is right next door to mine, works on cardiovascular biology. So, he can look at how these materials impact the heart and together we can look and say, “OK. Mast cells are activated in the heart and that leads to cardiovascular complications.” The two of us together can make a lot better story and impact on how these materials might impact human health. Then we also work with a lot of chemists and biophysicists because we are neither one of those and it’s hard for us to understand how to generate these materials, how to characterize them, and how to understand their physical chemical properties. That makes a big impact on how these materials are going to interact with cells and organs. If you change any property of these materials, it’s going to bind to different receptors or pick up on different cell types or impact different organs. So, by having these biophysicists, we can start to look at these molecular interactions and how these materials might react with a cell membrane for example, which is beyond our capability in our lab. So, by interacting with these groups of people, we can really understand a complete picture from the very small interactions up to the physiological responses we might see in an animal model or a human.



Dr. Peden Talking



Brown has two graduate students and a post-doctoral fellow helping him out in the lab. The oldest graduate student is concentrating her research on learning what the mast cells produce in response to the nanomaterials that might impact physiological function. The other grad student is from Saudi Arabia and he is researching mast cells and how they might influence fibrosis or scar formation in response to nanomaterials. The post-doctoral fellow is from China originally, but she graduated here at ECU from the department of physiology. She is looking at how nanomaterials might impact pulmonary functions. According to Brown, it is important to have graduate students working on research.



Dr. Brown talking



It’s a great educational opportunity for grad students. They are learning cutting-edge technology and techniques. I hope it will set them up really nice for going to a post-doc somewhere and doing research there or maybe going into industry or academics, and a successful career.



Dr. Peden Talking



The research in nanomaterials Brown is doing at ECU is not only important to the university, but to the whole world. Understanding how the materials actually impact human health is a concern that everyone shares.



Dr. Brown talking



I think that our research on nanomaterials is going to impact nationwide, and worldwide. Understanding how these materials can cause human health problems is a big concern. North Carolina specifically is probably one of the top leading states in nanotechnology, outside of California and Massachusetts. North Carolina has a strong biotechnology center within the state and a lot of that is driven by nanotechnology. It will impact the economy through that. A lot of our studies looking at health effects due to airborne particulate matter or air pollution particles has a big impact on eastern North Carolina because exposure to these particles has been linked to cardiovascular diseases, diabetes, obesity, asthma, which are all major problems in eastern N.C. As you go east of I-95, it seems that there is an increase in these diseases. There is also a change in the type of air pollution that occurs here. A lot of this is due to farming in the area. So, our research has a big impact in understanding how the air quality is going to impact these different diseases, such as diabetes, obesity, and cardiovascular diseases.


Dr. Peden Talking



We all look forward to the findings of Dr. Brown and his lab as they dive deeper into understanding the world at a molecular level.

This has been a production of East Carolina University. To hear more, please visit www.ecu.edu/pursuitofdiscovery.