Cynthia St. Hilaire, PhD & Milka Koupenova, PhD

January 2020 Discover CircRes

January 2020 Discover CircRes

This month on Episode 8 of the Discover CircRes podcast, host Cindy St. Hilaire  speaks with Nikki Purcell and  Sean Wu, the chair and vice-chair of the BCVS Early Career Committee. The episode also features an interview with the 2019 BCVS Early Career Finalists, Dr Luigi Adamo, Dr Swati Dey, and Dr Jihoon Nah. In addition, we highlight three featured articles from the January 3 and January 17, 2020 issues of Circulation Research.   Article highlights:   Souza, et al. Upregulation of Plasma SPM by Enriched Marine Oils   Paredes, et al. Metabolic Control of VSMC Phenotype   Ritterhoff, et al.  ACC2 Deletion Prevents Aspartate Synthesis Transcript Dr St. Hilaire: Hi. Welcome to Discover CircRes, the podcast of the American Heart Association Journal, Circulation Research. I'm your host, Dr Cindy St. Hilaire, and I'm an assistant professor at the University of Pittsburgh. The goal of this podcast is to share with you highlights from recent articles published in the Circulation Research Journal. But today, we're going to have a special edition focused on early career. The American Heart Association has 16 different councils. One of which is basic cardiovascular sciences,  or BCVS. The BCVS Scientific Sessions is held annually and brings together basic and translational cardiovascular scientists from around the world. It has become the go-to meeting for intra and interdisciplinary cross fertilization of ideas in basic cardiovascular research. The overarching goal is to integrate molecular, and cellular, and physiological approaches to address problems relating to functional genomics, cell signaling, myocardial biology, circulatory physiology, pathophysiology, and peripheral vascular disease. In addition to highlighting new approaches and discoveries from the general scientific community, the BCVS Council also plays a pivotal role in training the next generation of junior scientists and trainees. At the recent meeting in Boston, I had the opportunity to interview the chair and vice chair of the BCVS Early Career Committee, Dr Nicole Purcell from UCSD, and Dr Sean Wu from Stanford University, as well as the three finalists of the Outstanding Early Career Investigator Award competition, Dr Luigi Adamo, Dr Swati Dey, and Jihoon Nah. Hope you enjoy. Before we get to our interviews with the BCVS early career committee chairs, and the finalists of the BCVS Outstanding Early Career Investigator Award, I want to give you a few highlights from three articles that were published in the January 3rd and January 17th issues of Circulation Research. The first article I'd like to highlight is titled Enriched Marine Oil Supplements Increase Peripheral Blood Specialized Pro-Resolving Mediators Concentrations and Reprogram Host Immune Responses: A Randomized Double-Blind Placebo-Controlled Study. The first authors are Patricia Souza and Raquel Marques, and the corresponding author is Jesmond Dalli, and they are from Queens Mary University of London. So, this study is attempting to answer the longstanding question of whether I should or should not take fish oil supplements. Once ingested into the body, essential fatty acids, which is a group that includes those that are found in fish oils--those fatty acids are converted into molecules called specialized pro resolving mediators, or SPMs. SPMs can reduce inflammation and can also promote a process called phagocytosis where immune cells can essentially eat up dead cell debris and also micro-organisms like bacteria. While these actions are beneficial, whether ingesting fish oils translates to beneficial cardiovascular effects in humans, is unclear. Some studies show the oils reduce inflammation, while others have shown no effect. And part of the lack of clarity on this is that in previous studies there was no impartial measure of the clinical efficacy of the supplements. So to combat this, Souza and colleagues performed a double blind, placebo-controlled crossover study to determine the effects of marine oil supplementation, which by the way was tested at three different concentrations on both SPM levels and on immune cell function. Now for those of you who are unfamiliar with the clinical trial lingo, that means that both the patients, and the scientists, and the doctors did not know who got what pill, whether they got the placebo or the fish oil, and each patient was tested with both the placebo and with the fish oil so that they could be somewhat used as their own control at the end of the study. The scientists then obtain the blood from the patients before and then during the experiment at several time points. Blood samples from the subjects revealed a dose dependent increase in SPMs that was significant in the two high dose groups. Meaning the more fish oil they took, the more beneficial effects we're seeing. These effects peaked a few hours after they ingested the fish oil. Further, they found that high dose blood samples, monocytes and neutrophils, so those are inflammatory cells, those cells had increased phagocytic activity, while leukocyte activation, which is a sign of inflammation, was decreased. These beneficial effects persisted after SPM levels returned to baseline. These results suggest that SPMs are not only likely mediators of fatty acid-induced immune effects, but perhaps they could be useful efficacy indicators for future trials. The second article I want to share with you is titled Mitochondrial Protein Poldip2 Controls VSMC Differentiated Phenotype by O-Linked GlcNAc Transferase-Dependent Inhibition of a Ubiquitin Proteasome System. The first author is Felipe Paredes and the corresponding author is Alejandra San Martin, and they are located at Emory University in Atlanta, Georgia. So, I've said it before and I'll say it again, we all learned in elementary school that the mitochondria are the powerhouse of the cell. The nuclear encoded protein, Preliminaries Interacting Protein Two or Poldip2, is required for the activity of the TCA cycle, which is called the tricarboxylic acid cycle. It's also known as the citric acid cycle, and it's also known as the Krebs cycle. So interestingly, this nuclear protein, Poldip2, has effects on mitochondria, which as we also know have their own DNA encoding some of their proteins. So, Poldip2 deficiency reduces the activity of the citric acid cycle, which then induces a shift in the metabolic reprogramming, which leads to a lower rate of oxidative metabolism, and a higher glycolytic rate. So previously, this group found in mice that were heterozygous knock-outs for Poldip2, that these mice exhibited no avert phenotypes at baseline, but after an injury they actually showed protective effects. This was done with a wire induced injury that causes neointima formation, and also in an experimental aneurysm model. In normal healthy vessels, smooth muscle cells reside in a quiescent state. However upon injury, they can be induced to lose their fully differentiated smooth muscle cell phenotype, and acquire a more plastic, undifferentiated state. And in that state, these cells can migrate, proliferate, and in some cases even transdifferentiate where they acquire non-smooth muscle cell-like markers. The investigators, because of these phenotypes in response to injury, decided to look at the role of Poldip2 in metabolism in the phenotypic switching of smooth muscle cells. They found that reduced levels of Poldip2 in vascular smooth muscle cells in vitro induced the expression of transcription factors that are necessary for the expression of smooth muscle specific markers. And further, repressed the transcription factor KLF4, known to promote the loss of the smooth muscle contractile phenotype. Poldip2 deficient mouse aortas expressed high levels of contractile proteins, and more significantly did not de-differentiate or acquire macrophage-like characteristics when exposed to known stimuli, cholesterol, or PDGF. These effects are caused by inducing the enzymes that perform protein glycosylation, which helps to stabilize smooth muscle specific transcription factors yet repress the differentiation factor KLF4. Altogether, this work suggests that mitochondria metabolism and mitochondria-induced signaling plays a main role in the maintenance and phenotypic switching of vascular smooth muscle cells, and that this access could be targeted to modulate smooth muscle phenotype during vascular diseases. Sticking with the metabolism theme, the last article I want to share with you before our interviews is titled Metabolic Remodeling Promotes Cardiac Hypertrophy by Directing Glucose to Aspartate Biosynthesis. The first author is Julia Ritterhoff, and the corresponding author is Rong Tian, and the work was completed at the University of Washington School of Medicine in Seattle, Washington. Cells of hypertrophied hearts switch from using fatty acids for energy production to glucose. This is less efficient. It has been shown that preserving fatty acid oxidation prevents the pathological shift of substrate preference, which then preserves cardiac function, and improves energetics, and reduces cardiomyocyte hypertrophy. While the effects of preserving fatty acid oxidation are well known, it remains unclear whether substrate metabolism regulates cardiomyocyte hypertrophy directly, or whether this metabolic shift is a secondary effect of improving cardiac energetics. So to that end, the investigator sought to determine the mechanisms of how preservation of fatty acid oxidation prevents the hypertrophic growth of cardiomyocytes. They went about this in two ways, in vitro and in vivo. And so for in vitro, they took some cultured adult rat cardiomyocytes, and they grew them in a medium that contained glucose and mixed chain fatty acids and induced pathological hypertrophy by supplementing these cells with Phenylephrine. This hypertrophy in a dish caused increase glucose consumption and higher intracellular aspartate. Interestingly, adding aspartate alone was enough to promote hypertrophy. In vivo, they found that fatty acid oxidation prevented the metabolic shift to anabolic energy production, which further prevented cardiac hypertrophy, and overall improved myocardial energetics. Together their data shed new light on the contribution of intermediary metabolism, specifically aspartate to the hypertrophic growth of the heart. They found that aspartate synthesis is a rate limiting step, and they found that specific mechanisms for aspartate production support growth and proliferation of postmitotic cells, and these studies now provide potential therapeutic strategies to target for reducing cardiac hypertrophy. Okay, well I'm here with the BCVS Vice Chair and Chair of the Early Career Committee, Nikki Purcell and Sean Wu. Thank you for coming. Nikki Purcell: Thank you for having us. Sean Wu: Yeah, thank you. Dr St. Hilaire: Yeah. I was wonder if you could just introduce yourselves and maybe a little bit about where you are in your career. Sean Wu: I'm Sean Wu. I'm at Stanford University. I'm part of the Stanford Cardiovascular Institute. I do both clinical work as a general cardiologist, and I also work on research in stem cell and developmental biology. Dr St. Hilaire: And how long have you had your lab? Sean Wu: I have had my lab for about 10 years now. Dr St. Hilaire: That's good. Success story. How about you, Nikki? Nikki Purcell: All right. I am at the University of California, San Diego, in the Department of Pharmacology. I'm an Associate Professor there. My research deals with phosphatases in the heart and their role in cardiac hypertrophy and heart failure. And I've gotten my position as a professor for about eight and a half years now. Dr St. Hilaire: Excellent. So, my lab just had its fourth birthday, so we're still on the, okay, we're moving up. We're moving up. Nikki Purcell: Congrats. Dr St. Hilaire: Yeah. Sean Wu: Congrats, yeah. Fantastic. Dr St. Hilaire: Yeah. Thank you. So, what is the role of the BCVS Early Career Committee? Nikki Purcell: So, the real role of the Early Career Committee is to support early career investigators. And our role in the AHA is, one, to keep the early career investigators engaged in the AHA and BCVS, but also to help them with their questions as they transition from either their predoc to their postdoc, or getting their first faculty position. So, we try to make events where they can network, and get the mentorship they need, and help them along the way. Sean Wu: And also, the Early Career Committee serve as a connector between the early career and the bigger AHA with all the different activities that we have. But it also connects the early career member with each other because we feel like having an opportunity for them to be able to meet people in their similar stages of training, they can share stories with each other, and build a network of scientists themselves as they grow up into being full faculty. Dr St. Hilaire: Great. So, what kind of events are these that you use to either help bring them together or help them move along? Nikki Purcell: We've done multiple along the years. One of the ones that is really popular is probably our mentor lunches where we actually have established PIs from all different fields come in, and the one that's worked we've done the speed dating, but that's hard to get everybody in. And the last one we did was we had 12 to 13 people around a table with two PIs and that worked amazing. And they had that chance because a, early career sometimes don't like to talk as much- Dr St. Hilaire: You're a little shy. Nikki Purcell: ... but other people are going to ask questions they want to hear. So, it was a great opportunity. And for network we had a mentoring talk. So, that's one of the things we do is to try to connect people with other people in their field that maybe they are afraid to normally just go up to. But it's a much more relaxed setting I would say. Sean Wu: We also have some of the mainstream session, so having well known people come up and talk about their career, like the ones that we just now have with Litsa Kranias describing her long and distinguished career as a scientist with some of the lessons that she's learned along the way. But we also like to offer people opportunity to experience what the careers of people who have not necessarily done in academic, but into industry, in the legal world, or into the venture world to give the trainees some ideas of what they could do with their career. So, that's one of the sessions that we have this time called, Oh, The Places That You'll Go, so that they can actually see what the opportunities that they have as they complete their training in science and looking forward to the next stage of their career. Dr St. Hilaire: That's so important because I mean, what is it, maybe 10% to 20% of people actually stay and go on in academia? Nikki Purcell: And we get a lot of questions on mentors, and how do we find our mentors. And so, the other session that we're having is our Lunch and Learn really is to show new faculty with their chairs, postdocs with their mentor, and graduate students with their mentor, and really get it that the early careers can ask them questions. Especially if you're leaving the lab, how are you taking your project? How did you work that out with your mentor? You're a new faculty, how did you negotiate? All those questions that they don't teach you maybe so much along the way. Dr St. Hilaire: No. They don't. Nikki Purcell: So, we're having the panel up there so that they can throw questions at them- Dr St. Hilaire: That's great. Nikki Purcell: ... and really ask from Chair down to the graduate student. Dr St. Hilaire: And so, we're at the BCVS conference right now recording this, but you have events also at the AHA Scientific Sessions in the fall? Nikki Purcell: Yes. Sean Wu: Mm-hmm (affirmative). Dr St. Hilaire: Is there any non-conference related things? Do people ever kind of cold call the ECC saying, "I need advice," or is that a thing? Nikki Purcell: We've gotten emails, yeah. Sean Wu: Yeah. Right. Nikki Purcell: Yeah. We're really accessible. Yeah. Sean Wu: We've had inquiries, too. Dr St. Hilaire: Yeah. Sean Wu: Yeah. Besides things that we do at the meetings, we just now have this brand-new mentoring program with the BCVS where a young investigator, if they like to be able to interact with certain established investigator, can now make a request and apply to be able to make a travel visit. Dr St. Hilaire: Very nice. Sean Wu: And so, we have a full list of mentors who are willing to either sponsor the person, or both sponsor and provide some financial support for the training to come. Dr St. Hilaire: Wow, so you've already gotten buy-in from these senior mentors. Sean Wu: Yeah. Right. Nikki Purcell: Yeah. Dr St. Hilaire: That's wonderful. Nikki Purcell: We have over 30 mentors who have said yes, and we're always looking for more. So, if there's faculty out there. And what's great is also it gives a chance for let's say you want to transition to a different field, if you're a grad student postdoc it gives you that chance to meet that lab in that new field that you're interested in. And it's also for young PI, so if you're just starting out your lab, and you want that little help in that field, so it's open to that, too. So, we're really excited about that new program. Sean Wu: And I think it provides them a lot of opportunity to get exposure. Because that's one thing that the young scientists always tells us about, it's hard for them to really get to meet people or get other people to know who they are and what they do. And the Early Career Committee is one that really helped facilitate giving people opportunity, and put them in front of other people to help getting leadership training, and getting exposure. Nikki Purcell: And this year, we're actually having the poster competition, which we've never had before. So again, three established judges will definitely come to all these posters and speak to them, and that also gets them exposure. So, we're giving out five awards to both the early career trainees as well as postdoctoral. Dr St. Hilaire: That's wonderful. Nikki Purcell: Yeah. And so, we'll have some honorable mentions, too. The more people we can recognize, the more names we can get out there. Dr St. Hilaire: Absolutely. I remember one of my very first conferences as a postdoc, we just kind of made this discovery of a new disease, and I had written down the names of five big names that I was like, "I know they're going to be at that meeting. I really want to meet them." And I just had business cards at the ready, "Please come to my poster. Please come to my poster." That's the biggest fear as a poster presenter, what if nobody comes? What if I can't share this? So, I think that's an amazing avenue of interactions you've created. Nikki Purcell: And we have over 200 that have applied for our award, but there's 600 posters. And we know that a large proportion of those are Early Career. Sean Wu: Yeah, yeah. Dr St. Hilaire: That's great. If there's one thing a trainee, or a postdoc, or even junior faculty could do at a conference, of this size at BCVS we're about I think 500 to 1,000 people. Nikki Purcell:1,000 this year. Dr St. Hilaire: 1,000 this year. Amazing. Nikki Purcell: 1,000. Biggest conference ever. Dr St. Hilaire: That's wonderful. Oh, that's great. Sean Wu: Yeah. That's right. The first time. Dr St. Hilaire: So, 1,000 at BCVS versus, I don't know, the tens of… Nikki Purcell: Yeah. 13,000. Dr St. Hilaire: 13,000 at Scientific Sessions. What can someone who just feels lost in this little sea of all these big people do? What would you recommend as advice to a more junior person to interact? Nikki Purcell: I would say one, find us, because if we know your name and we know what you do, we promote the early careers, and we try to, and I would introduce who I'm with. In our social event that we have at Tuesday night brings together not only early career but the established investigators. It's everyone can come in, and we try to welcome that. My biggest thing, and when I met with a small group the other day of postdocs and students, is just grab people. You see people walk past your poster, start saying, "Are you interested in seeing what I'm doing?" Engage them. People are going to look at your poster and keep walking, but if you engage and are excited about what you do, they're going to be excited to say, "Oh, okay. I'm going to stop and listen." So, my big thing is get out of your comfort zone and just engage. Sean Wu: I do think that it is a little daunting. If you were just starting out as a new graduate student, and you have never been to an AHA meeting, and especially if you go to the annual session in November, it does feel a little bit like you're just overwhelmed by too many people, too many sessions, too much- Nikki Purcell: It's too much walking. Sean Wu: Right. Too much going on. And I do think that the Early Career Committee is what gives you a little bit more of a home for you as a trainee because by, at least, starting out meeting other people in the specific sessions that we create for them, now they can start building their network from a much more cozier, comfortable environment of the Early Career Committee activity. And before eventually moving out to get to know more people in other councils and the bigger AHA. Hopefully that also allows people to get excited about taking on more of a leadership role in the AHA down the row in the future as they become more familiar. Dr St. Hilaire: Well, thank you so much Dr Sean Wu and Dr Nikki Purcell. Everyone come to BCVS and meet them in person. Nikki Purcell: Thank you. Sean Wu: All right, thank you. Dr St. Hilaire: Yes. Thank you. Nikki Purcell: Thank you so much. Dr St. Hilaire: All right, so now we're going to talk with the three finalists of the outstanding Early Career Investigator Competition that's held annually at the BCVS Conference. With me today is Dr Luigi Adamo, Dr Swati Dey, and Dr Jihoon Nah. So, welcome all of you. Jihoon Nah: Thank you. Thank you for inviting us. Dr St. Hilaire: Yeah, thank you. Swati Dey: Yeah. Nice to meet you. Dr St. Hilaire: Congratulations again on becoming the finalists. I don't know how many submitted, but I know it's always very steep competition. Jihoon Nah: Well, thank you. It's an honor to be here. Dr St. Hilaire: Maybe we can all take a turn, and you can just give a quick introduction. Say where you're at, and what stage you're in in your career. Jihoon Nah: Yes. So, I'm Jihoon Nah in Rutgers University, and I'm now a post doctorate fellow in Dr Sadoshima’s lab. Dr St. Hilaire: How long have you been there? Jihoon Nah: I came to USA three years ago from South Korea. Dr St. Hilaire: Oh, goodness. How do you like it? Jihoon Nah: Yeah, very good. Dr St. Hilaire: Very Good? Jihoon Nah: Yeah. Dr St. Hilaire: Good. Luigi Adamo: So, hi, my name is Luigi Adamo. I'm a physician scientist. I'm a cardiologist at Washington University in St. Louis, and I just concluded this long training as a physician scientist doing residency fellowship, advanced fellowship, postdoc final, and faculty. I'm an instructor of medicine there, and I'm looking for starting my own lab. So, it's a transition phase. Dr St. Hilaire: Ah, so maybe we can use the podcast to promote you. Luigi Adamo: Oh, anybody want a motivated physician scientist in cardio immunology? Please send me an email. Dr St. Hilaire: Perfect. Okay. Wonderful. Swati Dey: So, my name is Swati Dey. I am a new PI. I started my lab at Vanderbilt University Medical Center a couple of months ago. So, it's a really new experience for me right now. I did my postdoctoral training from Johns Hopkins for about four years with Dr Brian O’Rourke, and then for two years I was a junior faculty. And like I said, I recently transitioned. Dr St. Hilaire: Yeah, yeah. Excellent. So, we got kind of three different spots in the career. I'm also relatively new faculty. I got my lab in 2015, so we just had our fourth birthday, and I have at the same time feelings of I've been here forever and I'm still brand new. Hopefully we can share some of the early career ups and downs with everybody who's listening. So, thanks again for coming. Dr St. Hilaire: I was actually wondering, how did you guys ... We're all in the cardiovascular field, and at this conference in a little bit more cardiology than the rest of it, so how did you get into this field? What was your path? Swati Dey: So for me, it was I don't know how I got there. I have been very lucky. Dr St. Hilaire: It just happened. Swati Dey: No. So, my PhD was from Ohio State. I got a PhD in microbiology. Dr St. Hilaire: Interesting. Swati Dey: And then, I was looking for postdocs. So when I was young, my mother, she passed away due to a cardiac condition. So, when I got an opportunity to start a postdoc in a cardiovascular lab studying cardiovascular diseases, I just couldn't believe that this would just fall in front of me. I just went with the flow. It was a little hard in the beginning because the learning curve is essentially longer. Dr St. Hilaire: I'm sure. Swati Dey: I had no background in cardiac physiology, electrophysiology, anything related to cardiac. But it was also fun. I was learning so many new things. Everything I did was just brand new, and it made my postdoctoral training period so exciting, and I was just feeling proud of myself, everything I accomplished. Dr St. Hilaire: Well, the title of your talk, I'm not going to read it because it's very long, but essentially, you're looking at the neurocardiac access, and how that can be manipulated to help with myocardial infarction treatments. You've gone from teeny tiny bugs to ... Swati Dey: Absolutely. Yeah. It's been great. So yeah, this work essentially focuses on nonischemic heart failure. So sudden cardiac death, like if you have been to my talk, it talks about it happens in patients with even before the signs and symptoms of heart failure appear. Like very early stages of heart failure. I could be doing late stage of heart failure, too. So, there's no signs and symptoms for sudden cardiac death. Swati Dey: And to prevent that, there are very few treatment options available. There are ICDs, the defibrillators, but they are expensive, and if you go running they might just shock you,. So there are very appropriate shocks, but there are also inappropriate shocks. So, the quality of life for these patients are very poor. And I remember when I started working on this project, we got some human samples of patients who were my age, and they had defibrillators, and they were in such poor health that they had to go through this new surgical treatment. And it was so exciting to study the underlying mechanisms because I could see it translate into the real world. Dr St. Hilaire: And in people young enough to really benefit from it. That's wonderful. That's a great story. Luigi Adamo: Great story. Dr St. Hilaire: Yeah. I started in microbiology, too, actually with a fungal genetic lab. Swati Dey: Oh, wow. Dr St. Hilaire: Yeah. Now I do valve research, so it's funny where it takes you. Swati Dey: Yeah, exactly. Dr St. Hilaire: Luigi, how'd you get in this field? Luigi Adamo: So today, I presented work about B-cells in the heart. I think God has a good sense of humor, and also kind of serendipitous stories. So, I've always wanted to do cardiology. My dad is a cardiologist. But so, I did a PhD in hemodynamics, and then when I joined the physician scientist, phew, I actually ended up doing cardiac inflammation and heart failure just because I was so strong there. And I picked a mentor, Dr Doug Mann, a giant in cardio inflammation, but he didn't want to study B-cells, I didn't want to study B-cells. So, I started doing a different experiment, and then a friend was teaching me how to do a flow cytometer and heart samples gave me as a control an anti B-cell antibody. Luigi Adamo: And then, I remember telling her, "Why do you give me this?" It was like, "Whatever. We need a control in that color." And then in my model, I saw this dramatic effect on B-cells, and then I kept doing my experiments, and all my hypotheses were wrong, and there was always a signal on B-cells- Dr St. Hilaire: Oh, that is so funny. Luigi Adamo: ... and it was you know what? I think I need to study B-cells. Dr St. Hilaire: I think there's a B-cell there. Luigi Adamo: And it was a blessing because I might be one of the very few people in the world studying B-cells in the heart, and that's what I think sometime make people interested in my work because there's very little known about it. Dr St. Hilaire: Yeah. And how about you? What's your story? Jihoon Nah: So when I was a PhD student, I was working on some molecular biology in neurons. But it was a little bit basic in the field, and I just focusing on some cells, some intracellular cells And after I got my PhD, I want to move my field from basic to more clinical field. And I have a lot of interest in autophagy and mitophagy, and I tried to find some post doctorate position in more some clinical field which focusing on autophagy. And fortunately, I can join Dr Sadoshima’s laboratory, focusing on autophagy and mitophagy in cardiovascular disease. That's what I can do in this field. And I think autophagy is a very important role, especially in non-dividing cell like a cardiomyocyte. And I can allow many news and knowledge [inaudible 00:26:54] in this cardiovascular field, and I knew there are many things that are known about the role of autophagy or mitophagy in cardiovascular disease. And I think I want to stay this field, yeah, to find- Dr St. Hilaire: Yeah? You don't think you'll switch? Maybe like the microbiology, that hard switch. Jihoon Nah: Yeah. I really like this field. Dr St. Hilaire: Well, you say that. We're going to come back in five years and we'll see. Dr St. Hilaire: So, everyone's a little bit early career. So, what's really been a hard hurdle for you to overcome? Whether it was in a particular experiment, or paper, or just in the career itself. Swati Dey: It wasn't a hurdle, but one thing which took a long time to learn and was very hard was grant writing. So as a postdoc, so Hopkins is a great institution, but also you're competing with people who are equally, or well, actually smarter than you. Dr St. Hilaire: Well and also, if it's English as a first language versus English as a foreign language, I can't imagine. Swati Dey: Exactly. So, the tools and techniques to write your science on paper is not easy to communicate such that I understand my science, but to make another person convinced that my science is good, it's not easy. So, I think grant writing has been the hardest thing I had to learn. Because as a graduate student, you don't write. So, other things I knew I could do, it was in my control, but grant writing required so much rigorous training. And I'm happy I had colleagues and my mentor who took the time out to actually make my entire grant red. It came back with all tracking and comments, and- Dr St. Hilaire: Oh, yeah. I know. It's so disheartening. Swati Dey: It's actually so helpful. Dr St. Hilaire: Yeah, yeah. Swati Dey: But yeah, they took the time out. They thought that they were invested in my success, and my colleagues, and my mentor. Dr St. Hilaire: So essentially, you kind of formed a mentoring team that really helped train you or teach you how to properly write a grant. Swati Dey: Yeah. Dr St. Hilaire: That's really good advice for people to have. Swati Dey: And it doesn't really have to be someone who is very senior. Maybe someone who is recent. You have to find people who have been successful in that particular phase of science. Let's say grant writing, or maybe networking, which is also very important, or doing certain techniques. Reach out to different people, seek help, and learn from them, and never think that you are just too good or someone is going to judge you. That's the problem more that we think that if we go to someone with our weaknesses, they're going to judge that, "Oh, you're not good enough," but we all are not good enough in some parts. Dr St. Hilaire: Yeah. We're all weak at some point. Exactly. Swati Dey: Yeah. Dr St. Hilaire: Oh, that's really great advice. Luigi Adamo: I agree with all that. It sounds like very wise and very thoughtful. I am a physician scientist, as I mentioned. For me, one thing that has been very hard has been the length of the path because when you try to do both things, and you have the passion for both, it just takes a long time. And then, there are people that ... people who did their PhD with me, and they did it well as I did, or maybe a little bit more, I don't know, but then they were already an established investigator, and I was a trainee back to the bottom. And then, I was doing medicine, and then my classmates were leaving and getting big jobs, and I was back in the lab. And it just it takes a very supportive family, a lot of dedication. I think if you have that fire and passion for science and for medicine, it just keeps you afloat. But sometimes it's hard. Dr St. Hilaire: How about you? Any big hurdles yet or not? Jihoon Nah: No. So fortunately, I think with the experiment. I think I have a very small some problems, and I can overcome every time. But in my case, it always feels a little bit difficult to grant-writing because using English is very difficult to me. And also, in my case, I came USA around the two and half years later after I got my PhD degree. And many of fellowship, or first doctor fellowship, or grant has some time limitation within four years of the PhD degree. So, it's very tough to me to get a grant. Dr St. Hilaire: No, that's a really good point. I don't think enough graduate students fully understand all the different requirements of getting the postdoc, and then knowing if you want to write a K grant you need to have a project at year two because you'd have to submit it about twice, and you need the timeframe to resubmit it. And that's the thing that's really important that I don't think we spend enough time teaching trainees on. Swati Dey: My PhD was not in cardiovascular sciences, so I did not know what a K grant was. Dr St. Hilaire: Sure. Swati Dey: So when I came in, after two years I started seeing, okay, people are talking about this Dr St. Hilaire: What is this K99? Swati Dey: What is it? And apparently, a lot of my colleagues they had this in their life plan. They planned this out when they were still in their, probably med school, or in the graduate school, and I had no clue. Dr St. Hilaire: I was similar. I'm actually the first one in my family to go to college, let alone get a PhD and become a professor. And I can remember at every step of the way always finding people who I was like, "How did you already know this? How did you know what this award was, or to apply for this grant, or to go to a conference?" And I think that's partly why we want to have these conversations and get them out there is so that people in similar situations at least hear what these are in time, and have those opportunities. Dr St. Hilaire: All right. So, we'll end with a question that hopefully can help everybody else. If you could go back and give yourself any piece of advice, or any bit of nugget of knowledge that would help you had you known it then, what would you say? What would be one little thing you'd want to tell your past self? Swati Dey: Meet with your PI very early on, and sketch out your career plan. Luigi Adamo: I actually…I was about to say the same thing. I've been blessed with great mentors, but I think it's very important to have open communication about expectation and goals because very appropriate goals could be different in the minds of people. Then, there are personal needs, there are personal feelings about things. And in the end, a good mentor, if you set a goal, will help you work toward that goal. Dr St. Hilaire: How about you? You're still early, early, but that's okay. What would you tell your grad school self? Jihoon Nah: I'd say it's very interesting question. So, when I was a PhD student, I didn't want to learn some new techniques, and I think I was a little afraid to learn new techniques. And also, I feel it's very difficult and I frustrated my PI to set up new things in the laboratory. I think if I can beg, I want to say I just want to learn new techniques, and I just want to try to push my PI to set up new things because it’s very important to support our hypotheses. Swati Dey: No, he said something very important. I noticed this. Some of my fresh PhD friends, I asked them to apply to a good lab for postdoc. They're like, "Oh no, I am molecular biology. I can only do what will ... If I switch fields, I can't learn anything new." Dr St. Hilaire: Yeah. I can't do that. Swati Dey: Yeah. That's not true. You can switch fields. Go from engineering, to science, to English, to anything if you want to. Dr St. Hilaire: Absolutely. Jihoon Nah: And one more thing then. In my case, I came USA a little bit late after I got PhD degree. I just want to recommend to somebody who want to go some overseas to study, I think it's better to decide earlier, and try to just go to overseas as soon as possible. Dr St. Hilaire: Yeah. Do you guys want to add anything else? Luigi Adamo: I would say thank you. Jihoon Nah: Yeah, I'm very happy. Swati Dey: Yeah, me too. Dr St. Hilaire: Thank you. This has been really fun. Thank you for coming, and we'll talk again soon. Jihoon Nah: Thank you. Luigi Adamo: Thank you. Dr St. Hilaire: That's it for this special early career focused edition of Discover CircRes. Thank you for listening. Dr St. Hilaire: This podcast is produced by Rebecca McTavish, and edited by Melissa Stoner, and sponsored by the editorial team of Circulation Research. I'm your host, Dr Cindy St. Hilaire, and this is Discover CircRes, your source for the most up to date and exciting discoveries in basic cardiovascular research.

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