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Oby Ukadike-oyer: From the campus of Harvard Medical School, this is ThinkResearch, a podcast devoted to the stories behind clinical research. I'm Oby, your host. ThinkResearch is brought to you by Harvard Catalyst. Harvard University's Clinical and Translational Science Center, and by NCATS, the National Center for Advancing Translational Sciences.

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Happy holidays. We here at Harvard Catalyst will be out of the office for a couple of weeks. And the next two episodes will be a compilation of some clips from the past year and information about upcoming educational offerings. We hope you and yours enjoy a lovely holiday break. We will see you back here in the new year.

First up, we will hear from Dr. Meg Simione. Dr. Simione is a research scientist at Massachusetts General Hospital and an Assistant Professor of Pediatrics at Harvard Medical School. She is a clinician scientist with a focus on infant and child feeding and growth and implementing innovations to improve care delivery.

Meg Simione: We've been examining the quality of life with children, with pediatric feeding disorders. We've also been looking at, how are they able to participate in social activities? And we're hearing stories about how challenging that is for children and their families. In one of our studies, we did qualitative interviews where we interviewed families who had children with a pediatric feeding disorder. And we had a family who shared with us that she was told that they were glad that their child couldn't come to their birthday party, because they were a liability because they had such difficulty eating and drinking.

We're also looking at how caregivers are impacted by having a pediatric feeding disorder. We're looking at the financial impacts. And in one of our study where we used a national database, what we found is that children with feeding difficulties were more likely to have a family who had to leave their job to care for them. They had more out-of-office expenses than children without feeding difficulties and that they really needed to utilize more community resources to provide the care for their child.

And all of this has really led for us to think about, how do we alter care to make sure we are addressing what's important to families? And it's important for us to address the challenges that they're having with feeding and drinking. But we also need to think beyond that to truly support our families and make sure that they have the best quality of life.

In another line of our research, we have been exploring how we best support families and how we can alter care to make it contextualized to their life circumstances. A lot of this work comes from the work that we have done in childhood obesity. We know that there are systemic causes of childhood obesity. And an important piece is to connect families to resources.

We want to take it one step further and to make sure the recommendations that we are providing are contextualized to a family's life circumstances. And so what we are doing is we are doing surveys and interviews, and we're learning from families, clinicians, and community organizations what this might look like. How do we first identify that a family has their social risk factors or unmet social needs? And then once we do that, how do we make sure that we are referring to those services?

And many large health care organizations now have community health workers that are patient navigators that help with that. So that's a very important piece in this puzzle we're trying to solve.

And then we want to take it a step further. How can we adjust care? Rather than saying to a family who maybe lives in a community where it's not safe for their child to play outside, rather than just simply saying to them, well, your child should get more physical activity, go outside and play, really contextualize that. In their community, going outside to play isn't appropriate. So talking with them about ways to increase physical activity-- so maybe using different apps or maybe getting connected to an after-school program or a YMCA.

Again, really contextualizing our recommendations to that family's circumstance, and we believe that can promote better health outcomes rather than just giving generic recommendations. Many clinicians do this now without thinking about it. But the reality is that there are many clinicians who don't do this and aren't thinking about this. They feel like they're asking their families to do things. And then they're being met with, well, they're just not doing it.

And the reality is the family might not be doing it because it might be challenging for them, or they don't have the resources they need to be able to carry out that recommendation. And so I think it's on us as health care providers and as health care systems to start to think about that.

All of this that I'm talking about have been recommended through the national academies of medicine. And really, there's a breadth of research that has shown that we really need to integrate social care into the work that we do.

Ultimately, my aim is to have my research directly impact and improve health care for children. I want to do this through making sure that the evidence that we have is being used by clinicians and also making sure that the care we deliver is meaningful and family centered and that we are putting the family and the child at the center of the decisions that we are all making.

We need to better meet the needs of children and families. And by understanding what their needs are and addressing that in the care that we deliver, that truly is the only way that we will continue to improve health outcomes for children.

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Oby Ukadike-oyer: Next, we hear from Dr. Jason Vassy. Dr. Vassy is an Associate Professor of Medicine at Harvard Medical School, a Clinician Investigator at the Veterans Affairs Boston Health Care System and Brigham and Women's, and a founding member of Precision Population Health at Ariadne Labs. Join us as we hear him talk about the importance of genomics in medicine and the role it can play in an individual's health care.

Jason Vassy: We were learning a lot about the human genome in 2012, in 2015. And my career has kind of expanded as our understanding of the human genome has expanded. And because I'm a generalist clinician, instead of a specialist in a single disease, because I'm generally interested in primary care and all the things that might affect my patients, my own research interests started to include all the possible ways that a person's genome could help inform their own health care.

I still had a focus on primary care and disease prevention, but it wasn't limited to type 2 diabetes. It was all of the things that I think about for my patients, the diseases I try to prevent, the diseases I try to screen for. And so that interest-- when those genomic discoveries came along, my interest was always, how could I use this in the clinic? Or could I design a study that would use this information in the clinic?

Early on in my career, my projects looked at how primary care physicians and patients could use genome sequencing, so not just looking at type 2 diabetes but actually, what if you sequenced a person's entire genome and tried to glean from that all the information you could about the risks of diseases they had and how you might be able to prevent that? And in one study, called the MedSeq Project with a mentor named Robert Green, we gave primary care patients and their primary care physicians that information to the best of our ability to interpret it in 2013, 2014, 2015, and to observe what they did with that information.

The punch line of that research study was that they did fine. They were not scared. They did not overreact. So they didn't order unnecessary tests or institute unnecessary treatments. But some real disease risks were observed. And the patients and doctors managed that appropriately. When we performed chart review afterwards and ran it by a team of experts, the experts thought the primary care physicians were able to guide their patients through understanding what their DNA might mean for their health care.

Other projects that I've been a part of have looked at a certain kind of genetic test known as a pharmacogenomic test. So this is the idea that your genetic makeup can help you and your doctor make a better decision about the medications that will be most effective for you or have the fewest side effects based on your own unique genetic makeup, based on your own unique profile.

So pharmacogenetic associations have been identified for many medications that are commonly used by patients today, including cholesterol medications, blood thinners, antidepressants, medications that millions of people in the US and globally take. And we now know that there are certain DNA profiles that might make a medication work better for you or not as well for you compared to your neighbor who doesn't have that same genetic profile.

We still have a long way to go. Most patients know that their doctor is not ordering a pharmacogenetic profile test for them every time they walk in to the clinic. And there are a lot of reasons for that. Our EHRs, our Electronic Health Record systems, are not set up to facilitate that very well. Some insurance companies do not reimburse for that kind of test. Some primary care providers and other kinds of physicians don't know how to use that information. It was not a part of their medical school training. So there are a lot of implementation challenges, not only for pharmacogenetic tests but for a lot of the other genetic or genomic tests that I study in my research.

These days, I'm spending a lot of my research time looking at how a new type of genetic test called a polygenic score might help us improve disease prevention and screening. Polygenic scores are not a single yes/no kind of genetic result. Some of our classic genetic tests we think of-- does this patient carry risk for cystic fibrosis? Yes or no? Is our classic genetics 101 type genetics test.

But these polygenic risk scores instead are calculated from a person's DNA to put that person somewhere on a spectrum or a bell curve of genetic predisposition to a certain disease. So it's not, yes, you've got the risk factor, or, no, you don't. It's, where are you on that spectrum from low risk to high risk? And these diseases, there are dozens to hundreds of diseases that you could calculate a score for like this, such as diabetes, such as breast cancer, coronary disease, and dozens, dozens more.

And so many now in the field hypothesize that these scores might be able to help doctors and patients identify the low-risk people who maybe do not need to be screened for these diseases, who do not need to take preventive medications for it. You could actually deimplement some of the preventive measures we implement in primary care if they're thought to be unnecessary for those individuals. But also, perhaps more importantly, identify the people who are particularly high genetic risk for these diseases and target a lot of our preventive efforts to those individuals.

And preventive efforts could mean screening tests, like cancer screening tests. It could mean taking a preventive medication so that you don't develop the disease. Implementing a specific lifestyle modification, like changing diet or changing exercise to prevent disease. So this is an active area of research. Many hypotheses abound that this kind of information, this kind of polygenic score, can help better risk stratify patients moving forward.

So my team and I have looked at this in a few ways through a few different clinical trials. But currently, we're spending a lot of our time on the launch of a large randomized clinical trial of what we're calling precision prostate cancer screening. So you might know that prostate cancer is very common among men, and yet we don't have a great screening test in clinical care.

There is a blood test called the Prostate-Specific Antigen test, or PSA. And if it's high, that can mean that a person has prostate cancer, but it might also not mean that. And so it's not a great screening test in that it can't really distinguish the people who have cancer from the people who do not. And so, unfortunately, a lot of men get this test and then go on to get biopsies of their prostate and other invasive procedures and turn out not to have prostate cancer, which is good news for them. But it also means that they didn't need some of those biopsies to begin with.

So genetic information has really matured in the area of prostate cancer genetics. And so now this new study that we're launching, called the ProGRESS study, the Prostate Cancer, Genetic Risk and Equitable Screening study, is going to look at whether giving genetic information to patients and their physicians help them make more targeted decisions about their own screening approach to prostate cancer-- so identifying the low-risk men who might be able to forgo prostate cancer screening and identifying the high-risk men who might be especially encouraged to undergo prostate cancer screening and to follow up regularly with those screenings.

So that's a study that we're launching in early 2024. It'll go on for at least five years. And we're really hoping that we can improve the benefit-to-harm ratio of prostate cancer screening for a large population of men.

Oby Ukadike-oyer: Hi, ThinkResearch listeners. We're taking a quick break here to share with you that Harvard Catalyst now offers a selection of on-demand micro courses, full courses, digital certificates, and other resources, all available anytime, anywhere. Simply visit our website, and sign up for an offering. And start learning at your convenience. To explore our on-demand catalog, please visit ondemand.catalyst.harvard.edu. Thanks for tuning in, and enjoy the rest of the episode.

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In the final clip. Join us as we hear from Dr. Mayank Chugh. Dr. Chugh is a postdoctoral research fellow in the Department of Systems Biology with Sean Megason at Harvard Medical School. Dr. Chugh talked to us about his journey to his biology postdoctoral fellowship and how he pivoted his research direction and mission to investigate how social inequity, dimensions of race, gender, citizenship, and socioeconomic status shape STEM higher education, workforce, and innovation.

Mayank Chugh: Even as a child, I think I have been an advocate and action oriented about challenging socioeconomic dimensions of Indian society and culture. I was just sensitive. And I would speak out, even as a child, and I think which was uncommon.

So there was a dichotomy of what the culture was around for me and what my safe space was. And I think school was always my escape. I loved being in school. I was always fascinated by science, in particular biology. I mean, that thrilled me how we work.

So after winning a prestigious national fellowship from the government of India, I went to college at IISER, which is Indian Institute for Science Education and Research, where I got enchanted into this entire field that is called cellular and developmental biology. And I got really, really excited about, how do we become these complex organisms with trillions of cells and beautifully shaped and functioning organs, all from a single cell?

I came to Harvard to pursue my postdoc around the same questions. And I chose to work with fish because fish have external fertilization, so they lay their eggs outside. So you can actually study their embryos under the microscope and perturb cells and genes and study how the organs are being affected.

So this is what got me at Harvard. I joined in 2020. And during the pandemic, this was a rough time for every single living being on this planet. And I think it was also a time for asking yourself bigger questions like, how do we reshape? How do we do better as individuals? How do we do better collectively as a society? And I think that reinforced my own understanding of who I am and what my calling is.

I figured that social justice work is my calling. So during my PhD, I started to use my education and skills in advocating, for example, for equitable and inclusive practices and policies in the context of academia and STEM higher education. So I started working with nonprofits like ASAPbio and actively advocating for open-access publishing and transparent review process, which is the cornerstone and the heart of what we do as scientists. But at the same time, we want to ensure that taxpayer or people who pay for that-- like as scientists, we obtain funds from the government-- they have access to that.

I am privileged to be in a space in a lab where my postdoc mentor actually encouraged me to do so. Otherwise, you would think of any other lab, they would be like, hey, you're hired to do this work. Why are you delving into something else? And I think this asks the question of, what do we consider as postdocs? Or what are our expectations of mentees?

Is it always for PIs when they take in graduate student and postdoc understanding that they would go out in the world and be PIs? Or they could be successful human beings and skilled expertise and enrich our forward understanding in innovation, technology, or any way they would want to contribute.

Over the last three and a half years, I've been leading an informal research group here at Harvard Med School, and I was a chair of the Harvard Medical Postdoc Association, which is a postdoc body that caters to postdocs at HMS and HMS-affiliated institutions. So with that, leading all these teams, I think it gave me a vision that when I take on this role, I can actually delve into that social justice component that I've always wanted to work on.

So I created these informal teams with a vision of understanding how social dimensions of inequity of race, gender, socioeconomic status, and citizenship impact the STEM workforce and innovation. So this is not one-directional understanding. It is a bicyclical. It's a loop.

The first project, which was more focused towards the socioeconomic status broadly, but it will come down technically asking, what are the barriers to the retention of postdocs in higher education or academia? For example, if you look at the US faculty and workforce and you compare that to the demographics, you see the demographics are not representative of what the actual population really is.

From PhD beyond, we have this huge, tight bottleneck in that drop-out. Why we do not have more people of color and women of color and other marginalized identities representing these top echelons of our academic institutions? And I think we know that academia itself, it has been an exclusionary space from the beginning. But now is the time to go about and fix those small policies and fix those points where we might be able to elaborate those things.

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Oby Ukadike-oyer: Thank you for listening. If you enjoyed this episode, please rate us on iTunes, and help us spread the word about the amazing research taking place across the Harvard community and beyond. We are always looking to connect and collaborate with the research community and would like to hear from you. Please feel free to email us at onlineeducation.catalyst.harvard.edu to inquire about being a guest on the podcast.

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