DNA research with a twist; empathy loss in dementia; student scientists: Upstate Medical University's HealthLink on Air for Sunday, March 26, 2023

[00:00:00] Host Amber Smith: Coming up next on Upstate's "HealthLink on Air," a show devoted to medical research. A biochemist explains how and why he's combining protein and DNA engineering.

[00:00:10] Stewart Loh, PhD: ... If you think of DNA as a blueprint, you can make machines from the blueprint, but you can actually sort of do things with the blueprint itself. ...

[00:00:16] Host Amber Smith: A neuroscientist tells why some people with dementia lose their personal warmth and social interests.

[00:00:22] Hannah Phillips, PhD: ... with frontotemporal dementia, we see these hallmark patterns that include the loss of empathy and social behaviors and eating habits early on. ...

[00:00:32] Host Amber Smith: And a molecular biologist discusses why research is an important part of medical education.

[00:00:37] Dimitra Bourboulia, PhD: ... It boosts the confidence of the student later on to come out and discuss the research they have done in a more specializing way. They know what they're talking about, and other people listen to them. ...

[00:00:49] Host Amber Smith: All of that, and a visit from The Healing Muse, coming up after the news.

This is Upstate Medical University's "HealthLink on Air," your chance to explore health, science and medicine with the experts from Central New York's only academic medical center. I'm your host, Amber Smith.

On this week's show, we'll learn what neuroscientists are learning about the loss of empathy in dementia. Then we'll hear how research during medical school can help make better physicians. But first, a biochemist shares the protein and DNA engineering he is doing, thanks to a federal grant.

From Upstate Medical University in Syracuse, New York. I'm Amber Smith. This is "HealthLink on Air."

A professor of biochemistry and molecular biology at Upstate recently received a $1.5 million grant to combine two different fields of biomedical engineering, and Dr. Stewart Loh is here to discuss his work.

Welcome to "HealthLink on Air," Dr. Loh.

[00:01:47] Stewart Loh, PhD: Thanks, Amber. Great to be here.

[00:01:49] Host Amber Smith: Now, I've seen proteins described as complex molecules that do most of the work in cells. Is that a good description?

[00:01:57] Stewart Loh, PhD: That's absolutely a good description. They do everything in the cell that you could possibly think of, that scientists can think of.

They do a lot of things that we haven't even thought of. They literally do the heavy lifting. If you're picking up your coffee cup, that's protein molecules crawling along other protein molecules. So they really do everything that you would consider responsible for life.

And they're tiny little machines. They're nanomachines that do their jobs extraordinarily well. They can do it better than we as humans can. We can do some things that proteins and enzymes do, but not nearly as well as the proteins themselves.

[00:02:33] Host Amber Smith: Your lab at Upstate for the past 20 years has been focused on engineering proteins. Can you explain what that involves?

[00:02:41] Stewart Loh, PhD: Protein engineering: It's kind of a broad term. It generally means taking a protein and changing its sequence or changing the way it's modified to improve its properties, to make it more useful, to increase its shelf life, or to make it work under more harsh conditions, or to simply make more of it so that it can be used for biomedical or other purposes.

For example, protein biologicals, drugs that are given to say, cancer patients, are typically proteins, monoclonal antibodies, for example, that can attack and treat tumors. So that's a common type of protein engineering.

The type of protein engineering we do is a little bit different. We combine two or more proteins together and try to develop ways to do that such that those two functions can be combined and integrated, so you have kind of an added benefit, something that wasn't present initially in the natural proteins.

[00:03:40] Host Amber Smith: Well, let me ask you, do enzymes play a role in this?

[00:03:44] Stewart Loh, PhD: Yes. Enzymes are, I think, some of the most interesting proteins. They are the machines that convert something to something else.

The non-enzymatic proteins can be structural, but enzymes can transform things, which is a very useful property, so we mainly work with enzymes. Those are the molecules that we work on in the NIH (National Institutes of Health) grant that you mentioned.

[00:04:06] Host Amber Smith: What do enzymes do, because I've always thought of them as breaking things down?

[00:04:10] Stewart Loh, PhD: They break things down, but they also synthesize things, and they create light, which is one of the class of enzymes that we're pursuing. They will literally just generate light out of darkness. And that is a great, very kind of neat, property, but it can be extremely useful if you convert that into a molecular switch in which it will only shine light under conditions that you specify.

As I mentioned, we fuse that to another protein, so when the other protein encounters a molecule that it recognizes, then it tells the other protein to start shining light. There's many types of enzymes, and those are just a very few examples of what enzymes are capable of doing.

[00:04:48] Host Amber Smith: The grant you were awarded will have you combine protein engineering with DNA engineering. So how will that work?

[00:04:57] Stewart Loh, PhD: Protein engineering and DNA engineering have generally been done by two separate kinds of scientific groups, and they haven't really talked to each other too much in the past, so we're trying to change that.

DNA, as you know, is kind of the blueprint for how to make proteins, so it tells the body what to make.

And DNA engineering, typically, most people would think of that as genetic engineering in which you change the DNA sequence. And the goal of that is to change the protein that is encoded by the DNA, to have that protein either present or not or whatever.

The way we approach DNA engineering is a little different. DNA is also a molecule. It's much less complex than a protein, and it can't do all these heavy lifting and other crazy things that proteins can do, for the most part. But DNA is capable of adopting kind of simple structures. It's often referred to, actually, as DNA origami (after the Japanese paper-folding art).

So, if you think of DNA as a blueprint, you can make machines from the blueprint, but you can actually sort of do things with the blueprint itself. You can fold it into these very simple structures, which nevertheless are capable of doing a few limited things. So that's how we integrate DNA engineering with protein engineering, is we develop ways to make simple structures out of DNA, and then these integrate, they will physically combine with our protein switches to get that sort of diversity of enzyme function and couple it to these very simple things that DNA can do. And if you combine those two things, then you have a truly potentially large number of amazing things that you could really do.

[00:06:31] Host Amber Smith: Can you share some examples of medically important products that have been produced through DNA or genetic engineering?

[00:06:38] Stewart Loh, PhD: Sure. The SARS-CoV-2, or the COVID, vaccine is an example of the latest generation of products or biomedical technology that's generated from DNA. These are RNA vaccines, so the vaccines contain RNA, which was made directly from DNA, and so that has really facilitated vaccine technology tremendously. So there's examples of DNA technology all around us.

There's not many examples of how protein and DNA engineering can be combined to generate something useful, but there is one that really stands out, and that's the CRISPR-Cas9 gene editing technology.

And it's hard to overestimate the importance of this single technology in biology. So I think we're already at the point where there's sort of the pre-CRISPR era and the post-CRISPR era. It's been really transformative, and that kind of revolution has been enabled by a single protein DNA molecular switch.

And that protein is the CRISPR-associated enzymes, and the DNA is a synthetic RNA molecule.

And what happens is, when that enzyme binds that RNA, then it activates that enzyme. That enzyme does one thing, and that one thing is to cut DNA, and that results in this gene editing technology.

So, what we envisioned as part of this project is, what if we could do that sort of thing to other enzymes? If this single switch can result in this sort of technology, imagine what could be done if we can activate other enzymes also with a similar event.

[00:08:21] Host Amber Smith: This is Upstate's "HealthLink on Air," with your host, Amber Smith.

I'm talking with Dr. Stewart Loh. He's a professor of biochemistry and molecular biology at Upstate, and we're talking about the grant he was awarded to combine protein engineering and DNA engineering in a unique way.

What is your goal in combining protein engineering and DNA engineering? Do you have something that you hope to create or learn?

[00:08:45] Stewart Loh, PhD: Yeah. We sort of have a grand goal, then we have practical goals. And the practical goal is, we want to be able to develop biosensors for detecting specific things in cells. For viral infections, for example, we want to be able to manipulate cells. For example, we want to be able to kill cells that have a certain type of DNA in them, like a pathogen (disease-causing micro-organism) DNA, a viral DNA, a cancer DNA.

So those are what we want. Those are the kind of the short-term goals that we think we can achieve within the time scale of this grant.

The bigger perspective is how to kind of open up the entire proteome of cells (all the cells' proteins), and not only animals, but plants, bacteria. Make those proteins controllable, and who knows what can be done after that?

We're looking at basic technology, at basic science, and we're also looking at those specific, medically related applications.

[00:09:36] Host Amber Smith: Is there a name when you combine protein and DNA engineering? Does that have a name of its own?

[00:09:42] Stewart Loh, PhD: Not really. As I mentioned, there's not too many people that are doing this, so there hasn't been kind of a nickname developed for it yet.

[00:09:51] Host Amber Smith: Well, have other scientists successfully combined protein and DNA engineering?

[00:09:57] Stewart Loh, PhD: Some, yeah. There's not a lot. I think we're one of the relatively few labs in the country that actively try to develop mechanisms for how to couple these two different technologies. Not just sort of conceptually, but physically: how to take a DNA molecule and have it interact with a protein switch and have that interaction turn the enzyme or protein on and off again. There's not too many labs doing that.

[00:10:20] Host Amber Smith: Can we fast-forward years or decades? I don't know how long this will take, but how would some of what you're doing ultimately be able to help, let's say, transplant patients?

[00:10:32] Stewart Loh, PhD: Right. We hope to have some results on that not in the 10-year time scale, but more like the several-year time scale. And what's really needed in not only transplant patients, but sort of a general medical goal, is to be able to rid the body of infected cells. And the particular target we're going for in this grant is cytomegalovirus (called CMV for short).

But you can also think of this as HIV or hepatitis or any sort of virus that persists in the body that you want to get rid of. Five years ago, I would say there's no technology for doing this, but now we're starting to see some, but it's still a huge need.

What's difficult about that, with CMV virus and others, as well, is the virus kind of goes latent in your body. And all the drugs that are being developed to treat viruses will kill actively reproducing viruses, but these generally don't. So what we hope to achieve with this grant with CMV, in transplant patients, is that many of us are infected with CMV already. We just don't know it. That's generally OK, but in the case of a transplant, then transplant patients are typically immunocompromised or given immunosuppressants, and in that case, the CMV disease flares up, and that can be a fatal thing. This is a very serious problem.

I mentioned before that we've already made a protein switch that turns on. It will generate light in response to something, and that response to something is, if that molecule senses there is CMV viral DNA present. So, we already have a sensor that's going to say we can get samples from a patient, and we hope to show this very soon, and we'll be able to say, is this person infected with CMV or not?

And we can then look at transplant tissue and say, is this infected with CMV or not? And that's important.

More important than that is, we want to be able to rid the body of these disease cells in the first place. So, we're applying our technology not only to proteins that generate light, but to proteins that will actively kill a cell if it's turned on.

So the challenge then is to make that molecule only come on when it sees CMV virus. So that's what we hope to be able to test in the coming years as this grant goes on.

[00:12:52] Host Amber Smith: So what you learn by studying cytomegalovirus, you might be able to apply to other viruses, too, in the future?

[00:13:01] Stewart Loh, PhD: Absolutely. That is a very straightforward thing because our molecules are very modular, so we just have the same protein. And I have to tell you that engineering proteins is hard. It's very difficult. It takes a long time. It takes many graduate students doing this for years to be able to get a successfully working protein switch.

The DNA part, on the other hand, is pretty easy. That can be done just by a single student on their laptop computer. You can design a DNA to do what, basically, what we want to do. So that part's easy. The whole strategy is, we already have in our hands these proteins that work as very nice switches, and then all you have to do is just plug in different DNAs that interact with different viruses, with different viral DNAs, and you have the same effect.

So I will say that it is a very straightforward thing to translate this from CMV to HIV to SARS-CoV-2.

We already have a working SARS-CoV-2 biosensor, and it is simply a matter of going through the DNA toolbox, which is a very simple thing to do, and making just different simple DNA origami-type structures, which can be done by one person on their laptop, just designing these, on their computer. And then the result that we get with SARS-CoV-2 and CMV, we think we can get that same effect for any one of a number of different viruses or bacteria or fungi or whatever pathogen is out there that you want to either detect or treat.

[00:14:31] Host Amber Smith: Well, Dr. Loh, your work sounds so exciting. I appreciate you making time to tell us about it.

[00:14:36] Stewart Loh, PhD: Thanks very much. I enjoyed it.

[00:14:38] Host Amber Smith: My guest has been Upstate professor of biochemistry and molecular biology Dr. Stewart Loh. I'm Amber Smith for Upstate's "HealthLink on Air."

Mice have empathy, which helps in the study of dementia -- next on Upstate's "HealthLink on Air."

From Upstate Medical University in Syracuse, New York, I'm Amber Smith. This is "HealthLink on Air." Some people with dementia lose their personal warmth and social interests, and they stop responding to the feelings of others. They lose their empathy. But why? I'm talking with one researcher who tackled that question. Hannah Phillips is a post-doctoral associate leading graduate students in Dr. Wei-Dong Yao's lab at Upstate. Welcome to "HealthLink on Air," Dr. Phillips.

[00:15:28] Hannah Phillips, PhD: Hi. Thank you for having me.

[00:15:30] Host Amber Smith: You and your team are studying why patients who develop dementia suffer a loss of empathy. Let me first ask you to tell us what that looks like in patients.

[00:15:41] Hannah Phillips, PhD: Empathy is the ability to share the feelings of others and to adopt, really to adopt another's sensory and emotional state. And it plays fundamental roles in one's well-being, in kinship, in our emotional and social lives. It's an important contributor to successful social interactions, enabling us not only to communicate and interact with each other in effective ways, but also to predict the actions and intentions and feelings of others.

[00:16:12] Host Amber Smith: Is there a way that it's measured so that you can say this person has this much empathy and this person has that much?

[00:16:20] Hannah Phillips, PhD: I should disclose, I'm not a clinician, I'm not a medical doctor, but based on my understanding of the literature and how it's measured in patients, basically clinicians rely on, I think in children, they rely a lot on reports of others, like caretakers, but often in adults, they administer various questionnaires that are associated with specific empathy scales, which is called "behavioral scoring," and that's how they look at empathy in patients.

[00:16:52] Host Amber Smith: Does everyone who develops dementia lose empathy?

[00:16:57] Hannah Phillips, PhD: Not necessarily. Dementia is more of an umbrella term. There's many subtypes of dementia that are defined based on the clinical features that appear first and most prominently. It depends mostly on the location of the degeneration, the region of the brain responsible for empathy. If there's specific atrophy to that region, then the patient will ultimately lose, or have a progressive loss of, empathy.

[00:17:26] Host Amber Smith: Now one of those types of dementia, the frontotemporal lobe (FTD) dementia, can you kind of describe that for us in comparison with Alzheimer's?

[00:17:35] Hannah Phillips, PhD: The most unique feature that sets the two apart is the early onset of FTD. It is considered the No. 1 cause of pre-senile dementia, so this means that it affects individuals primarily between the ages of 45 and 65, whereas Alzheimer's disease is the No. 1 cause of dementia for individuals over the age of 65. Also, as I mentioned, the areas of the brain that are affected, first and most prominently are different between different types of dementia, which gives rise to these different behavioral patterns that we see. So with Alzheimer's disease, very early on, there's a loss of memory and cognitive function. With frontotemporal dementia, we see these hallmark patterns that include the loss of empathy and social behaviors and eating habits early on. And it's more so in later disease stages that there's a loss of memory.

[00:18:35] Host Amber Smith: So the loss of empathy may be an early symptom of FTD?

[00:18:40] Hannah Phillips, PhD: Yeah, that's correct. It is considered one of the more early- to mid-stage behavioral symptoms of FTD.

[00:18:47] Host Amber Smith: Well, please tell us about your work that was published in the journal, Neuron.

[00:18:52] Hannah Phillips, PhD: OK. So we're very excited about this study that just came out. We basically, for this story we first set out to develop a mouse paradigm of empathy so that we could study it. We developed one that captures two forms of empathy -- both emotional contagion, which is a basic form of affective empathy, and distress-induced other-directed consolation, or comforting, which is an empathy-driven pro-social behavior.

It was actually initially observed in the highly social monogamous rodent species, prairie vole. And so after we had established this paradigm of empathy, we then established a mouse model deficient in empathy and observed that these aged somatic transgenic mice that are expressing a G4C2 repeat expansion in the C9orf72 gene, which is the most common gene risk of FTD. And we found that these mice, at about 12 months old, exhibited blunted emotional contagion, and they failed to console distressed conspecifics (members of the same species) by affiliative contact.

And then further, we found that this distress-induced comforting behavior specifically activated a region of the brain called the dorsal medial prefrontal cortex. And further, we found that mutant neurons in the dorsal medial prefrontal cortex fire significantly less action potentials compared to healthy control neurons from healthy control mice at the same age, indicating that there is, indeed, profound parameter neuron hypoexcitability in these aged mutant mice at a late disease stage.

And most importantly is that we showed that chemogenetically enhancing this region of the brain, the dorsal medial prefrontal cortex, by enhancing the excitability in this brain region, we could rescue empathy deficits in the mutant mice, even at advanced stages where we saw substantial cortical atrophy or neurodegeneration had occurred.

So these results were very exciting because they established cortical hypoexcitability as a new, or novel, pathophysiological basis of empathy loss in FTD, and also suggests that enhancing the activity of the frontotemporal cortex, may serve as a viable therapeutic strategy for BvFTD (behavioral variant frontotemporal dementia) for which there are currently no approved and few effective treatments.

[00:21:36] Host Amber Smith: I want to ask you a lot more about that, but let me get back to, I'm still kind of struck with these mice. So you were able to create mice that lacked empathy, essentially, compared to mice that have empathy? I guess I never even thought of mice having empathy. Did they behave differently, side by side, in cages?

[00:21:59] Hannah Phillips, PhD: Yes. Yeah, they did. And it's, empathy is a behavior that classically we think of only in humans, or historically it's considered a process experienced solely by humans.

But more recently it's becoming appreciated that many species, including rodents, display what evolutionarily conserved behavioral antecedents of empathy, or these more primitive forms of empathy, such as emotional contagion, which, in our case, we looked at the social transfer of fear or observational fear. Also consolation and social buffering of stress and even helping and sharing has been shown in rodents, and now in mice. And that's what we saw with this disease model, is that in these mice that harbor these repeat expansions, which as I mentioned is the most common gene or familial cause of FTD, side by side they show significantly less emotional contagion or this fear-related response when during the observational fear task and also empathy or comforting related behaviors. In our case, we looked at body touching and allogrooming or grooming the other mouse to comfort it.

We found significantly less of these behaviors in the mutant mouse compared to the control mouse at the same age. So it was very striking.

[00:23:30] Host Amber Smith: And did you say that the brain cells were less active in the early stages of disease?

[00:23:37] Hannah Phillips, PhD: So this is actually more of a late disease stage model, mid- to late, because these mice are 12 months old, which is equivalent to about 45 to 50 human years.

And so we consider this more mid- to late disease stage, the mouse model that we're using. And we found that the mutant neurons in the dorsal medial prefrontal cortex of these mice fire significantly less action potentials, almost half the amount of action potentials compared to controls, so they're less excitable.

[00:24:14] Host Amber Smith: This is Upstate's "HealthLink on Air" with your host Amber Smith. I'm talking with Dr. Hannah Phillips. She leads a team of graduate students in the laboratory of Dr. Wei-Dong Yao at Upstate, and their research about loss of empathy in frontotemporal lobe dementia was published recently in the journal Neuron.

So let's talk about how brain cells can be made to be more active, because that's sort of, we're on the cusp of wanting to be able to do that, right?

[00:24:43] Hannah Phillips, PhD: Yeah, yeah, definitely. So in patients, I mean, again, I'm not a clinician or a medical doctor, but based on my understanding, so there's a couple different types of approaches that can be used to manipulate brain activity that include transcranial magnetic stimulation, and then deep brain stimulation is very commonly used.

Transcranial magnetic stimulation is more of a noninvasive form of brain stimulation, whereas deep brain stimulation is an invasive procedure where they implant these electrodes into certain areas of the brain that produce electrical impulses to regulate abnormal brain activity.

This is a very exciting potential approach to be used for diseases where there's changes in activity in the brain. But, we need to work with clinicians because any of these techniques, although very powerful, can affect many brain cells. And the goal is really more to target those disease neurons specifically. And even though that's the hope and the potential at these stages, there's still a lot of work to be done to figure out how to apply this to modulate brain activity and reduce like potential side effects. But in theory, if we can increase brain activity, then we could ultimately alleviate these empathy deficits.

However, when you actually do it in patients, it's obviously much more complicated. So there's a lot of work still to be done, but it's a very exciting forefront.

[00:26:18] Host Amber Smith: Well, I understand you're starting a fellowship at Harvard University soon. Do you expect that you'll continue focusing your research on frontotemporal lobe dementia?

[00:26:27] Hannah Phillips, PhD: I won't be working on FTD here, but, I will still be studying the neural mechanisms of social behaviors and social impairments, so I'm very excited about that. And, my goal and hope one day is to have my own lab, and I would be very excited to continue researching the neural mechanisms of FTD and hopefully make significant contributions to the field and toward new and effective therapies.

[00:26:52] Host Amber Smith: Well, thank you so much for making time for this interview, Dr. Phillips.

[00:26:56] Hannah Phillips, PhD: Yeah, of course. Thank you for having me.

[00:26:58] Host Amber Smith: My guest has been Dr. Hannah Phillips, a postdoctoral associate in Dr. Wei-Dong Yao's laboratory at Upstate. I'm Amber Smith for Upstate's "HealthLink on Air."

Next on Upstate's "HealthLink on Air," students in medical school are doing meaningful research.

From Upstate Medical University in Syracuse, New York, I'm Amber Smith. This is "HealthLink on Air."

Trainees who are studying to become doctors at Upstate's Norton College of Medicine have the opportunity to do medical research as students.

Here to tell about the Office of Research for Medical Students is Dr. Dimitra Bourboulia. She's an associate professor in the department of urology and the assistant dean for undergraduate and graduate medical education. She's also the director of the Office of Research for Medical Students.

Welcome to "HealthLink on Air," Dr. Bourboulia.

[00:27:52] Dimitra Bourboulia, PhD: Thank you very much, Amber, for inviting me, and I look forward to having this discussion with you today.

[00:27:59] Host Amber Smith: Are medical students required to do research as part of their education?

[00:28:05] Dimitra Bourboulia, PhD: The quick answer is: It depends. At Upstate Medical University, we have four colleges. So, we have the College of Graduate Studies, the College of Health Professions, of Nursing and the Norton College of Medicine. We have multiple degrees that are offered from our educational programs, ranging from undergraduate bachelor's degrees to graduate, for example, master's or PhDs or doctoral degrees, of which we require students to spend significant time in research activities, so this is a requirement for graduation.

At the Norton College of Medicine, medical students can graduate with a single degree, which is an MD degree, or they might choose to graduate with a double degree, which means, for example, having an MD and a Doctor of Philosophy or doctorate or PhD, or Doctor of Medicine, an MD, with a Master's of Public Health, which is an MPH. So in some programs like these, the student is required to do research to graduate.

However, if you ask me about the MD students, students that are enrolled just to do medicine and train for a medical degree, for those, we have optional programs that the students can participate in to do research. And that's because the LCME (Liaison Committee on Medical Education), which is an authority that accredits medical schools in the U.S. and Canada, has specific standards that require medical schools to incorporate, somehow, programs that students can choose to do research if they want to. And this is a mandatory element for that reason. And so medical schools, like ours, spend a lot of time establishing programs like that and improving programs for research.

So students, therefore, that are enrolled just for the MD program are not required, but spend significant time doing research throughout the training.

[00:30:00] Host Amber Smith: So some of them, it's an elective for them, it sounds like.

[00:30:06] Dimitra Bourboulia, PhD: So, yes. So, there are different, I suppose, choices. There are electives, there are unique electives, and there are programs that our office offers to the students, especially during the first year, when they start medical school.

In fact, actually, I have students who contact our office even before they start medical school, while they know they will join, of course, our program. And so, they contact me directly and say, "Dr. Bourboulia, can you help us out, connect with faculty that do research?" before even they start the first year of medical school.

And so we have a great interest from students to start as soon as possible, hands-on research.

So what we have created throughout the years and what we have actually improved throughout the years is our summer program, is a fellowship (training program) that we offer to medical students between the first year and the second year.

And during that first year, students actually team up with faculty experts in research who have spent really the whole career learning about research, doing research and teaching and mentoring students, medical students, in the lab environment.

So, this summer program that we have developed, students spend almost eight weeks of full-time research with a faculty member. This is a very competitive program, attracts over 15% of the first-year medical students to apply for that.

And we have, as you know, over 30 different basic and clinical departments at Upstate. Some of the departments dedicate full-time on research, so students can just do full-time research, bench work (laboratory research), or they can just join a clinical department, and they can do more like a translational project -- I can explain that a little bit later.

So, there are different options for students to do any type of research they want.

[00:31:47] Host Amber Smith: So, the summer program, does that take place in Syracuse?

[00:31:52] Dimitra Bourboulia, PhD:

Yes. So, the summer program we offer is for medical students to stay in Syracuse and do research in Syracuse at the Upstate campus. Nevertheless, because of the COVID years, we had to try to change somehow this possibility, and so, we now offer remote projects. Students can go back home during the summertime, and they can connect through doing a remote research with faculty. And so that's also optional. And students, some students, prefer to do that because they don't need to stay, they don't need to pay rent, although the summer program offers a stipend to the students to stay and cover all the expenses they have. So, many students decide to stay, especially students that come from our area, but some students that are trainees here from a different state, they might want to go back home, and so that's also a possibility, and it can happen.

[00:32:43] Host Amber Smith: Do the students potentially publish medical journal papers related to their work from the summer program?

[00:32:51] Dimitra Bourboulia, PhD: The majority of the students that I know in this program publish. There are different types of research they can do. As I said, they can be physically in Syracuse, and they can do research here. They can go back home and do research remotely. Ultimately, the projects could be from lab work to translational to being in a clinic, and even do remotely. For example, doing epidemiological studies, computational studies, artificial intelligence studies that you don't need to be here physically to do, as long as you connect with a mentor.

And we find, they find, we help them find, the best mentors they can to actually complete this project during the summer. It's interesting though, allow me to say that many students decide to continue doing research even if they finish during the eight weeks, because they enjoy so much doing that, and they can actually decide how much time to spend. And even if it's a part-time, they can produce several types of publications, from reviews to a research paper. They can collaborate with other peers. They can collaborate with graduate students who are just doing a PhD, so they can learn more than just doing their own little research.

[00:34:05] Host Amber Smith: And what is translational research?

[00:34:09] Dimitra Bourboulia, PhD: Let me explain a little bit about just the basic biochemical research, which is more like dedicating time in the lab, doing a research specifically with, let's say, molecules and try to understand a mechanism behind a disease, I would say.

But there are projects, for example, where you want to test a drug to see if it has any side effects, or you want to test an antibiotic, or you want to test a system where you need more than just a test tube. So you might want to have cells to work with, you might want to have animal models.

You want to have models that you can test, and it's more like physiologically relevant to a disease that happens in a patient. Or you want to, let's say, test an instrument that you have designed, with, of course, the help of the mentor, and you want to test it to see whether it fits in a patient.

So these types of projects are more translational projects.

[00:35:05] Host Amber Smith: This is Upstate's "HealthLink on Air," with your host, Amber Smith. I'm talking with Dr. Dimitra Bourboulia. She's the director of the Office of Research for Medical Students.

Why do you think it's important for students to have the opportunity to do real medical research during their training?

[00:35:24] Dimitra Bourboulia, PhD: Thank you so much for this question. This is very important question. Studies have shown it's widely accepted, that promoting research education through programs and initiatives that we have at Upstate and, of course, other medical schools do, early exposure on research experiences, those boost long-term student career profiles. That's one part: Students benefit long term.

And it also increases the idea and the culture of evidence-based research. We base our research on facts, and we try to take our data, our results, for clinical practice.

There is no better way to describe the importance, but just to give some examples of how research by a medical student has benefited humankind, for example, I'll give you heparin, which is an anticoagulant and used very much in medicine and in surgical procedures, was discovered by a medical student, a second-year medical student at Johns Hopkins, back in 1916, and, of course, we still use it.

The anesthesia process: again, a medical student. It was William Clarke, who used it in surgery, and that helped, for example, remove a tooth without pain.

So, ultimately, you want to know that the student has the ability and wants to and is motivated enough to go and do research and discover something new, because if it's not new, there is no point of doing the research.

Some discoveries are small, but some discoveries big, and some discoveries can last forever. But the interesting part that I can say is our students want to do research, and they're very enthusiastic, and they look forward to discover, even if it's small or big.

[00:37:05] Host Amber Smith: Does having solid research experience help make students more competitive for residencies and fellowships (training programs) after medical school?

[00:37:13] Dimitra Bourboulia, PhD: Yes. Many residency programs actually require research experience from the candidates they interview. So, students, as you mentioned earlier, publish while they're at medical school. They need to publish the research activities to show this is a productivity process. You need to produce something to show that you have done research.

Mentioning that you are doing research is not enough. So we always, in our office, and me personally, I always encourage students to talk to the mentors and discuss publication, and how they can contribute, how can they create in, maybe, a new field, or how they can improve the field they're working on, by writing the results and publishing it before leaving medical school.

So, this is very important, and a lot of residencies actually look for those publications. The research experience, also, students acquire mostly career profile, and also they can be employed later on. Publication as an undergraduate or while you are trained as a medical student has long-term implications for doctors as well.

There are many surveys out there, there are many studies on that. Academic physicians found that the career research success is associated with how much research they have done during the medical school. Physicians who undertook extracurricular research produce many times more publications than the peers that haven't done this.

And publication is very important for a student, even now, while they're training, or even later on, when they're doing residencies and fellowships, especially if you want to become a physician scientist. It also contributes to students' CV (curriculum vitae, or résumé), and also, I would say that it boosts the confidence of the student later on to come out and discuss the research they have done in a more specializing way.

They know what they're talking about, and other people listen to them.

[00:39:05] Host Amber Smith: Let's talk about some of the research that students at Upstate have done. Can you share some examples from the area of cancer?

[00:39:14] Dimitra Bourboulia, PhD: Yes, absolutely. Upstate has, as I said, over 30 different departments, many basic departments, dedicated research, clinical departments, so students have the opportunity to connect with multiple different fields and multiple focuses on research.

So, with regards to cancer, for instance, we have students that participate in brain, breast, bladder, kidney, prostate: There is quite a variety there. But the interesting part is our students have a different kind of focus. They want to do different things while they are in medical school, and so some of them do lab-based research, but some of them may do more like the translational research I mentioned earlier.

So you can see students doing, for example, research on immune disorders or cancer in children. You can see students who are doing artificial intelligence projects. And then we're going to the other side, neurological projects, for example, students work on blindness or stroke or the effect of blood pressure on stroke or neurodegenerative disorders.

I don't want to leave anything out. I can talk about viral infections, COVID: During the COVID years, many students actually participated in research on COVID. We can even move to zoonotic diseases, like Lyme disease, which is very prominent in our state throughout the year.

You can have students participate in our projects in the psychiatry department, for example, attention-deficit disorder, depression, metabolic diseases.

So all these options, our students can see projects that are available, areas of research that they are jumping on immediately, as soon as they start medical school.

[00:40:54] Host Amber Smith: Many of the medical students at Upstate graduate and become physicians taking care of patients. Do you think having research experience makes a physician a better physician?

[00:41:05] Dimitra Bourboulia, PhD: Yeah, that's a great question. Many studies have shown that this is the truth, this is real. I would just say: Research -- what is research?

Well, research is needed to understand the world we live in, if it is a microcosm or if it is looking at the stars in the sky. You need to understand the world we live in, and you cannot do this without research.

Every treatment, every drug, every knowledge we have, on a disease, on diagnosing a disease, or even prognosis or even the treatment, is because of research. And so being involved, no matter the time spent, contributes to the advancement of medicine.

Any medical doctor needs to help the community they live in, if it is one person or it is the whole group of people, here in our city or in the state will live in or nationwide. And so it also provides the opportunity to learn why a disease has specific symptoms, for instance. That's, again, because of research.

Reporting a new case a doctor might see in the clinic requires them to understand what has been done already, what's the background of this disease, if it existed before, or if it's something new. And you need to know how to address this problem.

And also, the more knowledgeable you are on a specific problem that the patient has, they listen to you. The patient listens to you. You have a voice that brings responsibility. You have a duty to describe, to be able to describe, what is happening with that person you try to treat. All the policy makers are listening to the doctor who has this extensive knowledge of detail of a disease that happens in the community.

And so, that brings me to the answer to the question. Yes, of course, research. The more you spend on research, the more time a student spends on research, the better clinician they will be, a physician will be, in the end because they will know more, and they will know how to treat a patient.

[00:43:02] Host Amber Smith: Thank you so much for making time for this interview, Dr. Bourboulia.

[00:43:07] Dimitra Bourboulia, PhD: Thank you for the invitation. It was a pleasure to be here.

[00:43:11] Host Amber Smith: My guest has been Dr. Dimitra Bourboulia. She's an associate professor in the department of urology and the assistant dean for undergraduate and graduate medical education, and she's also the director of the Office of Research for Medical Students.

I'm Amber Smith for Upstate's "HealthLink on Air."

Here's some expert advice from Dr. Sharon Brangman, chief of geriatrics at Upstate Medical University. How do you advise adult children when it's time to take the car keys away from a parent?

[00:43:39] Sharon Brangman, MD: Well, this is one of the toughest things that we deal with in geriatrics. There is no set age when somebody should stop driving. This is a very individual thing. We should not have a one-size-fits-all. The aging process, in and of itself, can make driving more risky. For example, someone could have arthritis in their neck, and they can't turn their head to look over their shoulder when they're changing lanes, or they may have a weakness in their legs that could keep them from pressing down hard on the brakes. There are also vision problems that occur, or hearing problems that can make it difficult to drive. And of course, if you have any kind of memory problem that impacts your ability to make decisions or have appropriate reactions when you're driving, that could be another red flag.

So what we usually tell adult children is that they have to have a plan. You can't just do this overnight. You have to look and see how you are going to supplement the driving needs of their parents, for example, when they have to stop driving. And we live in a society, and especially in our city, we don't have a very walkable city, and most of our services are out in the suburbs. So when you stop someone from driving, you can cut them off from everything from groceries to the pharmacy, to going to church and socializing. So you have to have a plan. You have to have a process so that you can figure out who's going to fill in those gaps. A lot of adult children feel ambivalent because they can't do it, but we now have lots of driving services, and there are actually people who do this now as a living, who can come and help drive. And yes, you may have to give up some of your spontaneous ability to come and go, but you can still be able to get the things you need appropriately, if you don't have a car yourself.

And we always want to stop before there's a terrible accident. And I don't have a crystal ball to predict when that might happen for any one person, but we don't want to wait for someone to get hurt before we make that decision. And that's the part that gets tricky because again, that's a very individual thing.

There are driving evaluation programs that can be helpful, where an older adult can go and get a driving test by someone objective to just see how they are behind the wheel, and if there's any adaptations that might be helpful or anything that can be done to help them stay on the road safely. We have some patients who stopped driving at night, or they don't drive during the busiest times of the day when the roads are quieter, and that's sometimes is an adaptation that works. But unfortunately, there does come a time when it is time to hang up the car keys to keep you safe and to keep others safe, as well.

[00:46:49] Host Amber Smith: You've been listening to Dr. Sharon Brangman, chief of geriatrics at Upstate Medical University.And now, Deirdre Neilen, editor of Upstate Medical University's literary and visual arts journal, The Healing Muse, with this week's selection.

[00:47:10] Deirdre Neilen, PhD: There is now awareness and emphasis on mental health. Two of our poets gave us a sense of how a child's struggles with such illness also affects the parent. First is poet W.F. Lantry, who describes what the illness does to his son in his poem "Extreme Ways."

There is an epigram to Ernest Dowson:

"-- Those scentless wisps of straw, that, miserable, line

His straight, caged universe."

He had to discard everything, his songs,

and everyone who tried to hold him close.

It's like he lived inside a Moby riff,

played endlessly, shut down within his mind,

his thought unknowable, a hieroglyph

I cannot read. Did he forget his dose,

or tell himself, again, he didn't need

what others knew? I could not intercede.

In other times, he held the chickens' wings

quite gently while I clipped one half their flights

so they'd be grounded close to earth, confined

within their fence. My reckless heart delights

in memory the images it brings:

once, walking with his mother on a strand,

I fell behind, and saw him take her hand

to help her balance on the title stones.

But where's the balance now? These double doors,

Locking behind us, buzz in turn, designed

to block out everything our sense adores,

reduce his worlds to exclusion zones,

and hold him where no conscious love belongs.

Ann Weil has stark images and searing emotions in her poem "Choices for the Mother of a Son with Mental Illness."

I could ...

Cut a slit and peel back the dewy blanket of grass.

Crawl beneath the sod, pulling its cover over my head.

Let the earth, warm with the spring sun, heal my ache.

Stand on the street corner and rage-scream at the traffic.

Fall to my knees, gutted by panic's sharp knife.

Run fast and far, a rabbit fleeing the rabid dog.

Climb to the jagged peak of understanding.

Know too little and too much.

Cover the wounds with powder and blush.

Bargain with the Devil, make a deal with God.

Open the cupboard of my chest.

Squeeze my heart, bring it back to life.

Knock gently on his door, wait for the invitation.

Ask, How are you today? Prepare his favorite foods.

Tell him he is loved. Hold him as he weeps.

[00:50:00] Host Amber Smith: This has been Upstate's "HealthLink on Air," brought to you each week by Upstate Medical University in Syracuse, New York.

Next week on "HealthLink on Air," what's holding back research into gun violence prevention?

If you missed any of today's show or for more information on a variety of health, science and medical topics, visit our website at healthlinkonair.org.

Upstate's "HealthLink on Air" is produced by Jim Howe with sound engineering by Bill Broeckel.

This is your host, amber Smith, thanking you for listening.