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Oby: From the campus of Harvard Medical School, this is ThinkResearch, a podcast devoted to the stories behind clinical research. I'm Oby.

Brendan Keegan: And I'm Brendan, and we are your hosts. ThinkResearch is brought to you by Harvard Catalyst, Harvard University's Clinical and Translational Science Center.

Oby: And by NCATS, the National Center for Advancing Translational Sciences.

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Brendan Keegan: Grant funding is vital for clinical and translational research. Harvard Catalyst's Translational Innovator provides funding for projects that are high-risk, high-reward, and that may be outside of a researcher's typical field. As part of the program, Translational Innovator also provides project management support.

Hardeep Ranu, a project manager with Translational Innovator, meets with grant recipients regularly to discuss roadblocks that research teams may be facing and help connect them to resources. On today's episode, Hardeep talks about the Translational Innovator program and why getting to know grant recipients is important for helping them to be successful.

In the coming months, Think Research will feature interviews between Hardeep and Translational Innovator grant recipients, including previous guests Elena Aikawa and Georg Gerber, where they reflect on how support from Translational Innovator helped advance their research and career.

So Hardeep, thank you for coming on the show. Give us kind of an overview of what the Translational Innovator grants are-- like, how much money it is, and what the application cycle is like.

Hardeep Ranu: So typically we offer $50,000 per award or up to $50,000. And the application cycle, it varies. I would say at least once a year we'll have an opportunity available for people. What also happens is the theme of these change. So we don't have an open call for pilots. We'll have it along a specific theme.

So there's a microbiome set of awardees. We recently had a vision set of awardees. And earlier this year, we started a project, a group of awardees who are looking into environmental toxins.

Upcoming, we'll be having another pilot opportunity that's going to be around the five senses, and it's fairly broad, I would say. It isn't restricted to the biomedical research. It could be other areas. It could be walking aids or vision aids, that kind of thing.

Brendan Keegan: You are a project manager at the Translational Innovator, which is part of Harvard Catalyst. So maybe you could tell us a little bit about what you do at Translational Innovator.

Hardeep Ranu: What I do as a project manager in Translational Innovator is after projects are funded, I essentially meet with the investigators every four to six weeks to see how their projects are progressing, if there's anything I can do to help. And I think that's the most important part of what I do.

And then during that time, we get the investigators together every four months to meet each other and to present a catalyst leadership to see how their projects are progressing.

Brendan Keegan: And so you spend a fair bit of time talking with researchers and kind of learning about their work and visiting their labs. And you have a biology background or a science background?

Hardeep Ranu: [inaudible]. Yeah, I have a science background, yeah.

Brendan Keegan: Yeah. So just talk a little bit about what your favorite part is about maybe working with the researchers and what you enjoy about that.

Hardeep Ranu: Yeah, it is most definitely one of, if not the favorite parts of my job. And it's because of being-- having the background in science and having grown up being interested in science, to me it's a way in which I get to learn about other people's research where it fits into the context of the greater world around them.

And when I meet with the investigators, I like to get to know why they applied, what else are they doing in their lab, and who else are they collaborating with? And I really like going and visiting their labs and going to where they are to get a sense of who they are as well.

And I also-- what I like is-- obviously pre-pandemic-- I would go to-- in going to their labs, I would get to know areas of the affiliates. Or the Cambridge campus-- I would get to go and visit those buildings that normally I would never have had a chance to do so. So I get to know the links between the affiliates. That's something I really enjoy doing.

Brendan Keegan: Do you feel like getting to know the researchers on a more personal level, does that help when they're having an issue that they need your help with? Does it help to have a closer relationship?

Hardeep Ranu: I think so. I think that in my view, in order to be able to help and show up to them in a way that I'm supposed to, getting to know them personally kind of gets that connection with them. And in having that connection, I would hope that then they would feel comfortable reaching out to me if there is a problem in any way in which I can help, so that it becomes more of a collaborative type of relationship.

I think that's really important to establish that, that I'm not there to check up on them. I'm there to see how things are going. How can we help? Do we build collaboration with somebody else? Is there someone else that I have worked with previously who might be able to help? That's something that I think is important.

Brendan Keegan: Mm-hmm. And let's shift gears a little bit and talk about your interview with Elena Aikawa. She's been on the podcast before. Maybe you can just give a brief description of what their grant proposal was about, what their project was looking at.

Hardeep Ranu: Yeah, so that project was looking at heart valves. And what happens over time for some people these valves start to calcify, the calcium deposits build up, and there's no cure for it other than having open-heart surgery and having the valve replaced.

And so her research has been into building a model in which you can test different drugs, targets, in terms of being able to slow down or reverse that process. And that's essentially what she was funded to do is to look at building up this 3D model. And as her collaborator, her postdoc mark indicates in the interview that we had, it's sort of that 3D printing organ-on-a-chip type of project that they did.

Brendan Keegan: Cool. And in the interview, they talked about how they use some of the money, and they mentioned that a lot of the money was used for imaging at the Harvard Center for Biomedical Imaging, or HCBI. Because they have certain microscopes, but they don't have access to really cutting-edge resources that are at different parts of Harvard. So could you talk a little bit about how the-- or the importance of grant money like this to unlock these resources across Harvard?

Hardeep Ranu: Right. And for that particular project and the other awardees around that opportunity, we had allowed access to HCBI and CNS, which is the Center of Nanoscale Studies in the School of Engineering over at the Harvard campus. And what the money was useful for is that even though there is this thinking of there being one Harvard, in reality, in terms of funding, those people who are at partners-- Brigham Women's, Beth Israel-- if they want to use the HCBI or CNS, they are technically treated as external academic--

Brendan Keegan: Users or--

Hardeep Ranu: --in terms of funding, yeah.

Brendan Keegan: OK. So they're treated as somebody from BU or Northeastern would be treated.

Hardeep Ranu: Right. And it's to do with the funding. And so they get a different rate. And what we can do is because we are within Harvard University, we can get these other investigators at the affiliates access to these facilities at an internal rate. And that makes a big difference in terms of being able to use it and as a cost saving.

And also, like you had mentioned, the cutting-edge microscopes that they have at HCBI, and also at CNS, they also have electron microscopes. So in that regard, it's almost sort of game-changing, I think.

Brendan Keegan: Yeah. And, I mean, this is kind of-- these grants and these projects are on the-- would you say they're more of the pilot study, or they're-- I guess, what-- talk a little bit more about the-- like why getting that reduced rate is so important for this type of project, where maybe it's a little bit more exploratory, or it's like a high-risk, high-reward kind of thing.

Hardeep Ranu: Definitely. These projects are most definitely in that high-risk, high-reward. Oftentimes, it can be a sort of side project or something that would be sort of out of the investigator's field. And so therefore, getting funding to start off with may be difficult. And they're oftentimes some kind of proof of concept project. Because in reality, that's what $50,000 can do is a proof of concept. Can we build a 3D model, and will it be useful?

Brendan Keegan: At this stage, these projects are, like you said, maybe not at a point where the NIH is going to fund it because there isn't a treatment or like-- I don't know. It isn't the point at which they're going to get millions of dollars from industry or from government, so-- but they are still a very important research project to, like you said, proof of concept, in Dr. Aikawa's case, to show how these calcifications happen, which could lead to treatments down the road.

But at first, it's-- I mean, I guess it would be considered basic science, like understanding the mechanisms that these things happen. And because her lab doesn't have a-- I don't know how much an electron microscope costs, but they don't have this--

Hardeep Ranu: It's a lot of money. And you can't just put one in a lab.

Brendan Keegan: And it doesn't make sense for--

Hardeep Ranu: Yeah.

Brendan Keegan: Yeah, you can't just buy one on Amazon and roll it in and plug it in.

Hardeep Ranu: Right, right.

Brendan Keegan: Yeah, so-- but-- yeah, and the-- it's interesting the quirks of funding and how even within the same institution there are barriers.

Hardeep Ranu: I think oftentimes with these projects that we fund, the investigators don't have a track record of having a background in that area of research. So this funding is important in that respect, in that we can give them that sort of head start, if you will, into-- or kickstart, really, into getting that particular project up and running. And then hopefully, their proof of concept works, and they get enough data out of the project in which then they can now go to NIH and get more funding. And they can also publish to then establish that track record.

So with Elena, yes, this is her background. But in terms of building the model, that's an important part, that they hadn't been able to get a model established. And so what this allowed was for them to get the model established. And in order to do that, they had to be able to image those the models. And that's when they got access to HCBI.

Brendan Keegan: Right. What was it like getting a chance to talk to them? You've met with them a bunch and followed them through this project. What was it like to interview them about the grant and their work?

Hardeep Ranu: It was really great. I haven't spoken to them in probably close to a year, I would say, because their funding ended in February of 2020. And so it was great to catch up with them, and also to find out about their experiences with working with Harvard Catalyst and with me, and how they can reflect on that process, and how their research has continued on from there. I think that was really interesting to see how it's been built on and the opportunities that have arisen from that relatively small amount of money.

Brendan Keegan: Was there anything that they talked about that surprised you to learn?

Hardeep Ranu: I was surprised as to how valuable the meetings with Catalyst leadership, and having the other awardees present so everyone was presenting their work to each other, and how much they enjoyed that part of it. And also, how it also pushed them to think about their research, their project, in different ways in terms of, how do we push this forward? How-- what else is there that we can do? I was really surprised how much they thought that was valuable, really.

Brendan Keegan: So you talked with a couple of other grant recipients and we're going to share those episodes in the coming months. Can you talk about what is upcoming?

Hardeep Ranu: Upcoming are my interviews with Georg Gerber, who was part of the microbiome set of awardees. And his was primarily a project that was machine learning, and machine learning in terms of, is there a way to predict who will get a reoccurrence of a C. difficile infection, which if people don't know already, the C. difficile is a bacterium that primarily you would get infected by it in a hospital. And it is an absolutely terrible gastrointestinal pathogen. It's essentially the worst diarrhea you've had in your life, and probably several-fold worse than that.

And so as Georg mentions, the only way to treat it is by these very strong antibiotics, and so it goes away. And what can happen is that it comes back again. And so now these poor people have had it. Then they now have to go through it again and again.

And so Georg's project was basically saying, OK, is there a way of looking at the metabolites that are found in the people with a C. difficile infection versus healthy individuals-- is there a way to predict the differences between them?

Brendan Keegan: So to predict who will get recurrent infection?

Hardeep Ranu: Yeah. Is there a way? Is it possible to do that? And he has built a model, and it's open source. It's released to anyone who would like to use it. And he mentions that it was really important for him to be able to do that so other people can maybe build on it and use the algorithm and improve it.

Brendan Keegan: And was there another interview you did, too?

Hardeep Ranu: Yes. So I also interviewed Kate Jeffrey. She's an associate professor at Mass General Hospital. And she explains it in her interview that her research projects were mainly based on epigenetics. This project was something that she was interested in looking at.

Is there a way, again, to see if there are differences in the viruses that are present in those individuals who have inflammatory bowel disease or Crohn's disease or colitis versus others, and which of these viruses maybe contributed to those diseases?

And she's an immunologist by training. So this was a way-- this project and this funding was a way for her to get started in that field of what she describes as the virome. So the microbiome has been well-studied over the past 20 years. Now, it's sort of looking into the virome. How do viruses modulate certain diseases as well?

The result of this grant and the results that she's been seeing, and I'm guessing other work, that she has become now somewhat of an expert in her field.

Brendan Keegan: In the virome?

Hardeep Ranu: Yeah. Yes. In that respect, her career has really taken off, If I can say that. That's my opinion.

Brendan Keegan: OK. Well, that's great, and this-- so it speaks again to the importance of these grants to give people the opportunity to study something that's outside of their normal field, or try and validate a new model that has some promise but hasn't been tested. So that's great.

Well, thank you, Hardeep, and we look forward to hearing those interviews.

Hardeep Ranu: Thanks, Brendan.

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Brendan Keegan: Thank you for listening. If you've enjoyed this podcast, please rate us on iTunes and help us spread the word about the amazing research taking place across the Harvard community.

Oby: To learn more about the guests on this episode, visit our website catalyst.harvard.edu/thinkresearch.

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