New York Public Health Now

s3e06 Battling Emerging Threats: The Vital Role of Microbiology Research, a Conversation with Wadsworth's Dr. Nicholas Mantis

• New York State Deparment of Health (NYSDOH) • Season 3 • Episode 6

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In this episode, Commissioner Dr. Jim McDonald and Executive Deputy Director Johanne Morne sit down with Dr. Nick Mantis, a Research Scientist and Principal Investigator at the New York State Department of Health's Wadsworth Center, to explore the vital role of microbiology research in improving public health outcomes. Discover how Dr. Mantis and his team's discoveries are paving the way for more effective vaccines, diagnostics, and treatments for a wide range of infectious diseases.

From investigating the immune response to Lyme disease to tackling the rise of drug-resistant fungal infections, this episode delves into the critical work that is shaping the future of public health.

Find out more about the work being done at the Mantis Laboratory: https://www.wadsworth.org/research/laboratories/mantis

If you have an idea for topics we should discuss, please let us know: PublicHealthNowPodcast@health.ny.gov

Jim McDonald:

Hey, welcome back to New York Public Health Now. This is where we talk about the why, so you could decide what to do. Hello, once again, from the 14th floor here at Corning Tower in downtown Albany, overlooking the Empire State Plaza and what is, quite frankly, an exceptionally clear day where I can see the Adirondacks to my right, the Heldlebergs to my left, gorgeous day in downtown Albany. Hello, I'm Dr. Jim McDonald, Commissioner of the New York State Department of Health, and alongside is my co-host, as always, Johanne Morne. Johanne, how are you today?

Johanne Morne:

I'm doing great, and I'm glad to enjoy this beautiful view with you.

Jim McDonald:

It is awesome, isn't it? Today, I'm very excited about our episode. We have a lot of brilliant minds at the New York State Department of Health Wadsworth Laboratories, but our own Dr. Nick Mantis is joining us today. Dr. Mantis is a renowned Research Scientist and Principal Investigator here with us. He's investigating how pathogens, things like bacteria, viruses and fungi, interact with their hosts. So great to have Dr. Mantis with us. It's not just Dr. Mantis. He has a whole laboratory. It's the Mantis Laboratory. He collaborates with academic institutions and pharmaceutical partners to create vaccines, specialized antibodies for human use, and their current project targets a range of health concerns, including COVID-19, Lyme disease, pertussis, also known as whooping cough, tetanus, salmonella, cholera and even ricin poisoning. So Dr. Mantis, really, really impressive work you're doing over here at Wadsworth. Really appreciate you spending time with us today and joining us. Welcome to the conversation.

Nicholas Mantis:

Thank you. Thank you for having me and for giving me the opportunity to share my research with you.

Jim McDonald:

That's wonderful, and I you're just one of many researchers we have here at the New York State Department of Health and again, humbled to lead such an impressive agency with so many brilliant minds here. But I'm really looking forward to hearing more about that work. But first, let's start by having you tell us just a little bit about yourself and your background, about what I just spoke to in your introduction.

Nicholas Mantis:

So as you noted, I'm a Research Scientist and Principal Investigator in the Division of Infectious Diseases here at the Wadsworth Center. I received my PhD in microbiology from Cornell University, studying the molecular interactions between plants and disease causing microbes. After I completed my degree, I spent two years as a Fulbright scholar at the Pasteur Institute in Paris, where I studied infectious diseases of the human gastrointestinal tract. I then returned to the United States and assumed a fellowship at Children's Hospital Boston and Harvard Medical School, studying the immune system, particularly the immune system in mucosal tissues such as the gut. I joined the Wadswroth Center in 2004.

Johanne Morne:

Wow. So Dr. Mantis, you've certainly done a lot, and you've been in many, many spaces. Can you explain to our listeners what does it mean to be a Principal Investigator, and basically, what are the responsibilities and the importance of having that role?

Nicholas Mantis:

Well, from the standpoint of a funding agency like the National Institutes of Health, a Principal Investigator often referred to as a PI, is the person in charge of a scientific research grant or clinical trial. But in reality, a PI is a lot more complicated than that, because running a research lab is very much like running a small business. So basically, on a daily basis, you deal with an alphabet soup of activities with the most important letters, if you will, being a, e, i, o, u and y. And if you'll indulge me, let me just give you a little background of what that means. So "A" for administration and of research awards and overseeing staff and funding. "E" for experimentation, when you submit a grant proposal, you outline specific experiments, and you have to undertake those when awarded. "I" for investigation, because once you've done an experiment, there's always the what's next, and that's the investigation. "O" is for observation, because science isn't always so much about their eureka moments. It's actually about, hmm, that's interesting. What's going on here? "U" for United, because it's really a team effort, as you mentioned earlier. It's a whole staff and a whole research lab that makes things happen. And then "Y" is not so much the letter "Y", but"why" as in, W-H-Y, because really at the core of being a principal investigator is being able to always ask the question, why, you know, why does this happen? Why does COVID spread so easily? Why don't antibodies protect against this disease? Why do some people get more severe disease than others?

Jim McDonald:

Yeah, that's really fascinating. And I, I love the analogy you made that running a research lab is a little bit like running a small business, because you have a staff down there. I mean, you really do have quite a team down there. And you know, you rely on external funding, which I understand, you recently received a significant grant from the National Institute of Allergy and Immunology and Infectious Diseases. Why don't you just tell us a little more about that grant in particular.

Nicholas Mantis:

Perhaps I can give you a little background. So as you know, and I'm sure most of your listeners know, Lyme disease is a tick borne infection caused by a corkscrew shaped bacterium known as Borrelia burgdorferi. And for today, I'll just refer to it as Borrelia. Borrelia's primary vector is the black legged or also known as the deer tick, and during the course of a tick taking a blood meal, the bacterium is deposited in your skin where it can replicate and then spread through the bloodstream to distant tissues, eventually causing disease symptoms associated with Lyme disease. So when Borrelia replicates in skin tissue, it actually sets off the equivalent of an immunological fire alarm with an array of different cell types, and you could refer to these as first responders, are called to the scene within a matter of hours, and then within days, humans produce swarms of antibodies directed against the invader. In fact, the current Lyme disease diagnostic tests are based on the appearance of these Borrelia specific antibodies in blood. But antibodies do more than just alert you to an infection. Their goal is to coat the surface of the invading bacteria a phenomenon known as opsonization, and then render them non infectious. So what does this have to do with my research? Well, the goal of my research program at the Wadsworth Center is to really understand the molecular details of the human antibody response to Borrelia. Specifically, there's evidence that certain antibodies are better than others at clearing Borrelia infections and preventing Lyme disease. Indeed, why do some individuals clear an infection without any symptoms? This would be subclinical, while others develop disease symptoms that can progress and persist for weeks or even months. We postulate that antibodies play a pivotal role in these different outcomes.

Johanne Morne:

Wow, so that's really exciting. Congratulations to you for the tremendous work that's being done. Can you talk just a little bit more specifically what a Lyme disease vaccine would look like, and then how would it work?

Nicholas Mantis:

So they're actually both Pfizer and Moderna have candidate Lyme disease vaccines that are there in clinical trials. Their vaccines are based on the same Borrelia protein known as outer surface protein A or OSP-A. Pfizer has a protein vaccine, and Moderna has an mRNA vaccine. So in both cases, the vaccines are designed to stop the ability of Borrelia to be transmitted to humans in the first place. And if you want to dig a little deeper, during the course of a blood meal, the tick ingests antibodies that are present in the blood, that are elicited following vaccination. The antibodies go to the blood. In the blood interact with Borrelia in the tick's stomach or mid gut. So go figure. We don't know exactly how these antibodies work, but they prevent Borrelia from exiting the tick and entering your skin. And sort of the molecular interactions that prevent this transmission are something we are investigating. But to your question, sort of more broadly, a Lyme disease vaccine will really only work against Borrelia. And I should just point out that there are other there are several other tick borne diseases that New Yorkers should be aware of. These include Anaplasmosis, Babesiosis, Powassan, Ehrlichiosis, that are caused by viruses, bacteria and parasites, all carried by black legged ticks. They also have the potential to cause serious diseases on their own and even potentially work together and cause what are known as co-infections.

Johanne Morne:

So the way you describe it, Dr. Mantis, it is almost like it creates a barrier so that the infection can't go from the tick to the person.

Nicholas Mantis:

Correct. It serves as a block. And the spirochetes aren't necessarily killed. The bacteria aren't necessarily killed in the tick. They just can't get out of the tick and into the body.

Jim McDonald:

Yeah, so that's fascinating to me, because when you think about when we get a tick bite, it's happened to everybody you know, and you talk about the tick taking a blood meal, which quite frankly, isn't a refreshing thought for me to think about, but really the tick is actually taking blood from me, but actually the bacteria jump into my body at that time. And so when you talk about a vaccine, in this case, it would actually prevent the bacteria inside the tick from jumping into my body, if you will, or sliding in during that liquid meal, if you will. Is that right?

Nicholas Mantis:

That's exactly right. And actually, in the case of Borrelia, and people say, you know, the bacteria are dormant, typically in the tick, until the tick starts a blood meal. At that point, the bacteria awake, they start to proliferate, and it takes them a day or two to make it to the skin. So if that's why this issue of removing a tick very quickly, after you identified it, really is a good practice, because it will shorten or reduce your probability of getting Lyme.

Jim McDonald:

So I really didn't know that. And I think that's wonderful, because, you know, as a treating physician like I've seen so many people who had tick bites, right? But we've often told people like, you know, how long was the tick on there for? Which, by the way, quite frankly, not everybody knows, because if, you know, if you think about it, once a tick gets on you, you try to get rid of it. You don't let it sit there. But sometimes people know because they said, Well, you know, I was inside all day on Monday, and I went out on Tuesday, I saw the tick on Wednesday. So it might have been there too long, but what you just explained was the Borrelia bacteria that live inside that, you know, cause Lyme are actually just dormant, resting, and then once there's that blood meal, they wake up, they come inside, and then they start replicating inside of the person it fed on. That's fascinating.

Johanne Morne:

You talked about different vaccines earlier. Do you anticipate that we'll ever get to a space where there's a single vaccine that can protect against all of the tick borne diseases?

Nicholas Mantis:

Yes, perhaps, for example, a team at Yale University are leading efforts to develop a vaccine that actually prompts a quick response in the skin to components of tick saliva, thereby limiting the amount of the time the ticks will feed upon you as the host. So that's one thing. The other is there are efforts to develop oral acaricides, these are insecticides that work against ticks. Currently, they're used in veterinary medicine, but being adopted for humans, and the idea is to kill the ticks immediately upon attachment to a human. And there are ongoing trials right now to assess the safety and tolerability of such drugs.

Jim McDonald:

So, in other words, there is work going on

Nicholas Mantis:

Well, we have numerous ongoing projects, I developing medications that if I got in, you know, infected with guess. One in particular that of interest for today is a new a tick bite I could take that would prevent me from getting Lyme disease or out of their tick born diseases, right? You call them acaricides, but I think that's really the way we look at that, right, correct? I mean, it's really exciting, and, you know, so and by the way, just to remind folks, we're talking to Dr. Nick Mantis, a research scientist and Principal Investigator here at the New York State Department of Health Wadsworth Laboratories. And Dr. Mantis, I'm curious, what are the research projects are you in your lab working on right now? collaboration with a colleague at the Wadsworth center to study an emerging fungal pathogen known as Candida Auris. It is a fungal infection that can cause severe illness and spreads rapidly among patients in healthcare facilities and nursing homes. It generally targets immunocompromised individuals. The problem is that it can persist in the environment and on the patient's skin for prolonged periods of time. Moreover, isolates have been identified that are highly drug resistant, therefore, of grave concern to hospitals and nursing homes. Our project is to investigate the role of antibodies in preventing these types of infections.

Jim McDonald:

Candida Auris is something I do worry about. It's not an easily treatable disease, it's a fungal disease, and you know, it's a problem in New York, you know, it's one of those things where, you know, again, that's a really, really relevant project that you're working on here. And you talked a little bit about whooping cough earlier that you're working on, you know, pertussis, which is a terrible disease. You know, it's funny, whooping cough used to be called the 100 day cough, not mysteriously, but because people would cough for 100 days. And I've actually seen adults break ribs from coughing so hard from pertussis is a terrible disease. Any inroads about maybe where you see us going with pertussis? Any any ideas about where we're headed with Pertussis vaccine? Are you guys working on that too?

Nicholas Mantis:

We've principally been working on pertussis in the context of what are known as combination vaccines. So particularly in the developing world, pertussis is combined with three or sometimes up to six other vaccines together to give to children as part of their normal vaccine regimen. The problem is, making those combination vaccines can cause certain efficacies of one component to decline. And so what we've been trying to study is, you know, the combinations. How do you optimize a combination of many different vaccines, up to six or even seven, that could be retained full potency across the board and be given globally.

Jim McDonald:

Yeah, that's fascinating. Just so you know, I am old, and I started pediatrics when it wasn't six different vaccines, it was just whole cell, diphtheria, pertussis, tetanus vaccine. Then we went to acellular then they added polio, then they added Haemophilus Influenzae type b, and you see where this went. But I really think one of the things I've learned as a pediatrician is having done a survey of toddlers or infants, but none of them like shots. And so universally, they have spoken to me saying, less shots, happier, happier baby, which is something I like, happy babies and happy toddlers. One of the things I want to get to Dr. Mantis is I like to ask everybody a little bit about inspiration and motivation, because I think that's what drives people. And you know, one of the things I'm just curious about is what inspired you to become a research scientist in the first place? Because I gotta tell you, most kids growing up don't know a research scientist even exists. But here you are.

Nicholas Mantis:

Actually my original career goal was to go into the world of biotechnology, as I was inspired by the power of recombinant DNA technologies to harness bacteria like E. coli to produce drugs like insulin. Therefore, as an undergraduate, I chose my major to major in microbiology and minor in business. Well, as it turns out, my introductory course in microbiology opened my eyes to the fascinating world of microbes and their interactions with a variety of hosts. So basically, my original career goal, to go into business got sidetracked in order to pursue life in the laboratory.

Jim McDonald:

Yeah, but it's interesting that minor in business probably helps you run a very effective laboratory, because it really is a small business. I mean, you're amazing how many grants you acquire and how many people you employ, just because you're so talented at acquiring grants, which, you know, we appreciate that at the New York State Department Health, and I know that people work for you really appreciate that as well. So, you know, just to pick up on that a little bit, what is it that still inspires you and keeps you motivated in this work today? You've done a lot in your career, but you're still doing this. So what inspires you?

Nicholas Mantis:

You know, I'm really just fascinated by the interplay between microbial invaders and the human immune system. You know what factors determine the outcome of an infection, and how do we use this information to develop more effective vaccines and therapeutics against emerging infectious diseases like Lyme disease?

Johanne Morne:

What a wonderful perspective. And you know, let's look to the future. Are you generally optimistic about the direction of science and the potential to address the challenges that we face?

Nicholas Mantis:

So, I'll say, of course, we are, I am. We are definitely entering a new age of biomedical science with the advent of genomics, genomic edit, genome editing tools, artificial intelligence and mRNA delivery and other areas of molecular biology. In fact, I think that a world of personalized medicine is just around the corner. However, with these advances comes a guarded optimism, because sometimes good science can be co-opted for malicious intents. So it is critical that appropriate regulations and oversight at the local, state and federal agency be in place.

Johanne Morne:

Thanks so much for that response, and absolutely, I'm glad to see that we anticipate even more for the future, but we're also very aware of the things that we need to do in order for us to advance. So Dr. Mantis, I just I have to say, thank you so much for taking the time to join us today, as well as for sharing your insights. I'm sure that listeners have gained a much deeper appreciation for the important work that both yourself and your team continue to do.

Jim McDonald:

Yeah, I echo Johanne's sentiment. You know, the work you and your laboratory team are doing is truly inspiring. And, you know, I'm so thankful for your dedication to advancing our understanding of infectious diseases. And I love how you you just talked about that earlier. You know, I think about where we are in the history of us. Just when I look at science, there's so much we have in front of us, but when I think about some of the gifts we have, whole genomic sequencing, genomic editing tools, artificial intelligence, messenger RNA delivery; All these other areas of molecular biology, it is a great time to be in science. I never saw this coming when I was doing my biology degree at Siena College in Loudonville, New York, and it's amazing right now to be connected to science. It's just so downright inspiring.

Nicholas Mantis:

From the laboratory to the level of public health for sure. So thank you for having me, and if you'd allow me to just like to acknowledge the many people in my lab that really make things happen on a daily basis, students, technicians, postdocs, research scientists and all our staff at the Wadsworth Center who make science possible.

Johanne Morne:

Absolutely and for our listeners, if you'd like to learn more about the work of Dr. Mantis and the New York State Department of Health, please be sure to visit our website at health.ny.gov and the Mantis Laboratory page on the Wadsworth website wadsworth.org. We've included a link to the Mantis Lab page in the show notes for this episode.

Jim McDonald:

Hope you enjoyed our conversation with Dr. Nick Mantis. I sure did. I hope you're also looking forward to our next episode. I'm excited about we're going to be talking to none other than Dr. Ashish Jha, Dean of the Brown School of Public Health, White House COVID Director, one of the nation's doctors. I'm looking forward to hearing what he has to say. A lot going on in the country right now, and Dr. Jha has some thoughts to share, I am sure. As always, if there's a topic you'd like to hear more about, reach out by email at PublicHealthNowPodcast@health.ny.gov

Johanne Morne:

And to find our latest episodes on Apple podcast, overcast, Spotify, YouTube and Google Podcasts, just search for New York Public Health Now or "NYSDOH" to subscribe and be notified when we release new episodes every other week.

Jim McDonald:

And if you're enjoying the show, please leave us a review. For New York Public Health now, I'm Dr. Jim McDonald.

Johanne Morne:

I'm Johanne Morne.

Nicholas Mantis:

And I'm Nicholas Mantis.

Jim McDonald:

Thank you for listening.

Monica Pomeroy:

New York Public Health now is a production of New York State Department of Health's Public Affairs Group. Michael Wren is the executive producer and engineer, with additional production support provided by Sarah Snyder, Genine Babakian, Barbara, Stubblebine, Alicia Biggs, Monica Pomeroy and Kyle Kotary. Copyright 2024 All rights reserved. We welcome your feedback. Please email us at public HealthNowPodcast@health.ny.gov

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Dr. James McDonald

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