Transcript:
Chuck Cohen: Welcome, everyone. I’m Chuck Cohen, managing director of Benco Dental, and I’m here today with a truly awesome individual with a very interesting story, Dr. Blake Warner.
Dr. Warner is the assistant clinical investigator for the Salivary Disorders Unit at the Epithelial and Salivary Gland Biology and Dysfunction at the NIH. I’m sure I somehow botched that title, but I am fascinated by dental researchers, and Dr. Warner is going to tell us a little bit about how he got to be one of the few, in my experience, really full-time or almost full-time dental researchers in America.
He is a full-time dentist and researcher at the National Institutes of Health, the NIDCR, which is where most of the dental research in America happens. So welcome, Dr. Blake Warner. Thank you for being with us today.
Dr. Blake Warner: Thanks, Chuck. You can call me Blake, and thank you for that warm introduction. Yes. I am basically a full-time clinical and translational dental researcher at the National Institute of Dental and Craniofacial Research, and I sort of came to this way sort of circuitously like many scientists do.
It wasn’t originally my plan to become a dentist-scientist. I started out thinking I want to be a geneticist, and I didn’t know what that meant, and I went to college, and I took genetics, and I loved it. But then something didn’t click, and so I decided to do organic chemistry research.
That was my first real research experience, and that didn’t click either. There was something missing. I had some other experiences, and I taught water fitness classes, and I learned that I really like to talk to the public.
I like to engage with patients, maybe even. That’s when it got the gears rolling that I should consider going to dental school because my dad’s a dentist, and I knew that. But when I was a kid, I always said, I’m not going to be a dentist. I don’t want to do that.
But then I became a research assistant myself, and I studied cancer, and I did molecular biology and tried to understand the molecular basis of tumors. But still, something was missing.
I was always working alone. I was in the basement. I was working with my animals, and I miss some sort of spark. It wasn’t there, and so I decided to do a master’s in public health.
That’s where I started doing oral biology and cancer chemoprevention, where I was trying to prevent oral cancer, and that snowballed, in a way, into going to dental school and applying for a Ph.D. and then being fully in dental school and fully in the Ph.D. at the same time, and I was a little wild.
I did both of those basically in a 5-year period, DDS Ph.D. I hit it really hard. I was lucky because my girlfriend at the time, now my wife, was also in grad school at another university, and so I could devote basically a hundred and fifty percent to research.
When I ended, I knew I wanted a clinical specialty that would sort of work well with my desire to do research, and for me, that was pathology. I could use the microscope. I could look in the mouth of patients, I could do clinical pathology, and for me, that was the intersection.
Oral pathology plus microscopes equal: I can find new things. So in the process of residency, I found that some of the patients who struggled the most were those patients who had dry mouth conditions, either from external beam radiation due to head-neck cancer or possibly autoimmune diseases like, Sjogren’s Syndrome.
In doing a little research, I found a clinical trial at the National Institute of Dental Craniofacial Research, which was led by my now mentor, Jay Carini. He was doing gene therapy to correct the saliva dysfunction or salivary dysfunction or lack of saliva in the mouth due to external beam radiation. By putting this small gene just in the salivary glands, he could correct the water movement or the salivation in pigs and mice and monkeys, and now, we’re going to do it on humans.
I got to actually do the gene therapy administration into the parotid glands of about 12 patients at NIDCR. So the first year I got there, Jay asked me, can you do this? I said, yes, I can. I can do this. I had done imaging in the salivary glands before, and it’s basically the same process, and we went.
So for me, doing gene therapy and things that I thought were only possible in sci-fi movies, I was doing it on humans. Then, I was sold. I was like, this is going to be my career, and if I could run a lab, and I could have a clinical research program and work in the clinic every day and basically do both, I was going to be a happy man. That’s what I’ve been pursuing ever since.
Chuck Cohen: That is very awesome. So let’s describe, first of all, the first research project you worked on about gene therapy for salivary disorders.
First of all, for those who don’t know, not being able to produce saliva is a horrible situation to be in. It’s just a horrible side effect of some awful cancers. So being able to fix that is very, very important.
Did you actually come up with a therapy that fixes that?
Dr. Blake Warner: We’re not there yet. We’re in a safety study, and we’re almost done with that safety. So I can say that the animal models are very, very promising.
Chuck Cohen Wow.
Dr. Blake Warner: And not only are they very promising, but they do seem to be relatively safe. The beauty of this type of approach is that once you correct the deficit, it seems to be a treatment that will last for a very long time.
I want to say almost a lifetime potentially because it does last the life of the mice, and for the pigs, it lasts for years. So for humans, you know, we need to let that trial progress a couple more years, and we can tell you how that works.
But all in all, I’m very excited about it. I think it’s going to be a way that we treat many other conditions, not just salivary dysfunction. But if you could co-opt the salivary glands to do other things, possibly act like an endocrine organ, now the sky’s the limit in how you can sort of reprogram an already very functional gland to do just a little bit more and maybe correct a systemic disease, something like a hormone deficiency. That’s kind of where the promise of this type of therapy lies, and that’s all the research of my mentor, Jay Carini.
For me, I wanted to create a clinical program of my own that was very complementary to this already established clinical trial, and so, together, we can really address some unmet medical needs. That’s kind of like my interest, being able to integrate dentistry with medicine and sort of being on the front lines and saying, you know, dry mouth is a real problem, and this is a complication of either radiation therapy or oncologic therapy or some sort of systemic autoimmune disease, and we need to pay attention to it.
Medical insurance, by and large, doesn’t reimburse patients if they lose their teeth. They don’t reimburse for placing implants. Now, if you were to lose a limb in an accident or an infection, you could have a prosthesis made. That’s not true for dentistry, and I feel like there’s a lot of room, there’s a lot of distance to sort of improve that relationship between medicine and dentistry.
Being able to salivate, being able to chew your food, having a high quality of life is really important. So my research might be a very small portion of that, but that’s sort of how I wanted to blossom into a greater acknowledgment of the role of the oral cavity in systemic health.
Chuck Cohen: That is totally cool. Of the projects you’re working on today, from a research basis, what are the one or two that have you the most excited about?
Dr. Blake Warner: I already told you about the radiation-induced xerostomia. The next project, I’m going to end on a capstone project that happens pandemic-specific. The next project is trying to better treat Sjogren’s Syndrome.
Right now there are no drugs to treat children that are very effective. The ones that we do have are like hydroxychloroquine, which you heard about in the news about this possible COVID therapy.
It wasn’t proven to be very effective, but it’s very effective at treating some of the systemic symptoms of Sjogren’s Syndrome. It has no impact on patients’ salivation.
The main clinical complaints of Sjogren’s are dry eyes and dry mouth, and it has no benefit for either of those organ systems. Dry eyes, it’s treatable. You hear of patients having Xiidra or other drugs to treat their dry eyes.
Actually, I can show you in my data, I have longitudinal data, that the patients that go on some of those medications, their eye function gets better, but their oral function continues to decline. I think that’s, again, one of these unmet medical needs.
We need therapies that target pathogenic inflammation in Sjogren’s Syndrome, and I think we have a drug that we could repurpose from other indications. We have a clinical trial starting where we’re using Pfizer or the drug Tofacitinib, which is marketed under Xeljanz, and we’re testing its safety in patients with Sjogren’s Syndrome.
So I’m very excited about that because we’re going to look at the actual tissue with some really new technology called single-cell RNA sequencing. Basically, we look at all the genes that are on and off in every single cell in a biopsy, and we do that before they get drugs, and they get it after they get drugs.
We can see the individual cell types that respond to that medication in the target tissue of this autoimmune disease. That’s going to be revolutionary, being able to say this is the cell that I thought would respond, and in fact, it did respond, and the patient has better saliva flow because of it. Having that granular of detail is really critical.
Chuck Cohen: That’s awesome.
Dr. Blake Warner: The second story is very pandemic-specific. My wife is an epidemiologist, and she works in critical care medicine at NIH, and her background is infectious disease epidemiology.
When we started to get these reports from Wuhan, China that there was an emerging severe acute respiratory syndrome-type disease that likely was a coronavirus, NIH mobilized, everyone mobilized, anybody who could do coronavirus work from big data analysis all the way down to molecular biology, we were doing it.
So she kind of said this is going to be big, and that night, I talked to my mentor, and he said, you know, it’s possible viruses sometimes have tropism or they can grow really well in salivary glands. I said, yeah, you know, this could be big.
Let’s look at our single-cell RNA sequencing data that we already had, and sure enough, we saw the target, which is called ACE2. You hear about ACE2 on the news all the time and a couple of the other proteases, very specific proteins that help that virus gain entry into the cells.
They were present in the ducts and acini of the salivary glands. So, we very rapidly decided to do two things. One, we wanted to get access to tissues from patients who were infected, and we wanted to start a clinical trial or a trial to compare saliva to nasal pharyngeal testing.
This was actually mid-March. By late March/early April, we had initiated the trial. Basically, about two weeks into this, that’s when Yale and the group from Anne Wyllie actually came up with SalivaDirect. So we were beaten to the punch, but that’s okay.
Chuck Cohen: That happens.
Dr. Blake Warner: It happens when you’re working on something exciting.
Chuck Cohen: Absolutely. Good for you.
Dr. Blake Warner: So we pivoted a little bit. We kept collecting data. We kept collecting NP swab, saliva, and we were fortunate to have a connection to a group of pathologists that were receiving unfortunate COVID-19 autopsies.
The death toll in the United States is astronomical. But there is an opportunity to learn something, to understand the biology, to understand the immune consequence of SARS-CoV-2 infection. That’s just what we did in the salivary glands.
We collected those glands from the autopsies, and we did a number of studies on them so that we could better refine the involvement of the oral cavity, something that every dentist is really interested in in SARS-CoV-2. So, we did.
We established that saliva contains the SARS-CoV-2 virus. We did some tests to show the efficacy of mask-wearing, just regular procedures to prevent the expulsion of salivary droplets.
Very logical data, but no one had done this yet, and we did this all through basically a car line testing facility. So I was doing dentistry in the car window. So of all the exciting things we were doing, I was like reaching into car windows…
Chuck Cohen: Like a suit on? Like a whole hazmat suit and the whole thing?
Dr. Blake Warner: There weren’t enough of those suits to go around. So, we were doing N95 and a face shield. Because they were spitting into a cup in a car, there weren’t a lot of aerosols, and I can attest to this. I never got COVID.
I tested myself in my lab for the antibodies. I was negative right up until I got the vaccine. I got my first dose about 28 days ago or 29 days ago. I got my second dose yesterday, so I’m a little fatigued.
Chuck Cohen: How exciting it was to see an intersection between dentistry and research and COVID-19? I just think it’s so exciting to be at the cutting edge of something that’s so, unfortunately, a big deal in the United States right now and around the world.
Dr. Blake Warner: Yeah, it is. It was really unfortunate, and I was very lucky. I’m very privileged to work with a good team, a good team that not only was excited to do the work during the pandemic but also willing to come in with all the unknowns.
I couldn’t have done it without them. It’s one thing for me. The [00:15:16]PI [0.0s] works long hours. It’s a totally different ballgame for your employees to be putting 12-hour shifts entirely through the pandemic, dealing with kids at home, and the whole bit.
But in the end, we have a paper submitted now, and it’s available to read and review. We think it does highlight some important facts about the salivary glands and the oral cavity’s role in COVID-19, but I think that dentists overall can use this information to protect themselves.
They can use this information to protect their employees and to sort of understand how it is we do our jobs safely. I think in general, if you look at the population of dentists, we’ve done a pretty good job of not having a lot of outbreaks in the dental office…
Chuck Cohen: Absolutely true.
Dr. Blake Warner: …which I think is a testament to PPE. Right? The importance of having access to good PPE and that PPE works. I think it also is a testament to, you know, this hygiene aspect, which to us dentists, actually, is not any surprise.
Dentists do a good job because I think for the rest of the medical community, it’s a big unknown. I think you go in, you use these instruments that make aerosols, and your face gets splashed. To understand that, that’s very different.
We use high-speed suction and all of these things to try to protect you. I think it kind of puts our profession in the spotlight a little bit. But in the same regard, we did a really good job of saying, we are trying to keep you safe.
Chuck Cohen: No doubt. And our profession’s dedication to the universal protocols was very helpful here because all we really did was add airborne pathogens to what we were already doing about blood-borne pathogens.
The process is virtually the same. Some of the equipment may be different. I agree with you a hundred percent. Dentistry has really been a superstar among some of the health care professions and some of the segments. So that’s great.
Question: how many doctors or how many dentists are doing research on a semi full-time basis at NIH with you? I mean, are there 10? Are there a hundred?
Dr. Blake Warner: I would say there’s probably on the order of 10 to 12. The people who are kind of like me, where they are a dentist-scientist that lead a clinical program and a research program, there are probably 8.
Then we have fellows that train in our program, kind of like me, I advanced from the fellowship. We have another 10 fellowship that also do varying amounts of clinical and basic science research.
I knew early on when I got there that I wanted to do both like 50-50. But that ratio changes for each individual fellow.
Chuck Cohen: So, if you are speaking to a young dentist, maybe a young dental student these days, what would you say to them about why they might consider a career or supplementing some of their career in dental research?
Dr. Blake Warner: Sure. I mean, I think there are basically three reasons why dental research is critical. The first is, in order to maintain the relevance of our profession, the generation of new knowledge, and new knowledge includes synthesizing other published works in a digestible format.
That’s kind of like what you do in dental school. You read papers, you try to understand them. But then the next level up is basic science. Trying to understand some phenomenon that’s related to oral health.
If that level kind of excites you a little bit, I always tell people when that’s when you consider maybe spending a summer doing research or spending a year out of dental school and doing research.
There are programs that will pay you to do research, even at NIH, to take a year off from dental school or medical school, for that matter, and come and hang out in the lab and learn some new techniques.
I think it’s for those students that do that level of research that if they get the bug and that is “I’m excited about my negative results as much as I am about my positive results, and I could possibly see myself working in like an academic institution or even a company that does dental research,” there’s a couple out there, Procter & Gamble comes to mind, then there are opportunities for you to basically be a lifelong learner.
You can always learn through CE, but generating the data and going out there and communicating your findings with other dentists, I think it takes a little bit of a spark. I say this a lot, but, you know, it’s like a light bulb going off in your head.
Then something happens and you’re like, “I’m going to devote my career to this.” I would say that it comes with a different set. Your life is a lot different in a way.
I think private practice has different types of stressors than research. I think you don’t have as much of the worrying about the business and worrying about the staff, and where the next group of new patients is going to come from.
But you do worry about other things like: where’s the funding coming from? Are we going to shut down again? How do I plan for two years from now? Because the hiring process takes a while.
Are my experiments going to come out? Am I going to have a good result? I would say, you have to be strong; you have to be committed because it’s mostly going to be not positive results.
You’re not going to be having it right all the time. If everything goes right all the time, there’s something not going right.
Chuck Cohen: That’s a very good point. You need negative results as well as positive results.
Dr. Blake Warner: You need them both. Right. You need some experiments to fail to remind yourself that everyone makes mistakes, but you need to take good notes. You note where your mistakes happen so you don’t have to make it the next time.
Chuck Cohen: Well, Dr. Warner Blake, thank you very much for spending some time with us today. I found it truly inspirational.
On behalf of the rest of the dental profession, thank you very much for spending your career doing dental research at NIH. I don’t think that what you do gets nearly enough publicity or play.
What you do is hugely important, and we very much appreciate it. So, thank you very much.
Dr. Blake Warner: Thank you, Chuck. Thank you for that warm sign of appreciation. I do appreciate it. I have a blast. Thank you to all taxpayers out there. I do use your money diligently, and I do try to create new knowledge.
I know it’s hard to kind of understand some of the data or maybe how it all works, but I promise you that I’m committed to the public in that way, and that I will use your money well, and I will change people’s lives. That’s my interest.
Chuck Cohen Thank you for doing that. It’s nice to meet you today.
Dr. Blake Warner Nice to meet you. Have a great day.
Chuck Cohen You, too.
