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Jon Carson: Another edition of Life at the Roost is now upon us! And so, I’m really thrilled to welcome Dr. Elie Zakhem, Manager of Process Development at RoosterBio. Dr. Zakhem joins us from work at ACell in Columbia Maryland, and about a decade’s experience in that cauldron of tissue engineering, Wake Forest. Welcome, Elie! Let’s kick this off… I thought I’d ask if you knew of any Anthony Atala legends or anecdotes, since it’s impossible to ignore what Atala and Co have done around WFU and for regenerative medicine, in general.

Elie Zakhem: Thank you Jon for having me today! When I first started working at Wake Forest, looking at Dr. Atala, he was like a legend in the field of tissue engineering and regenerative medicine. He was famous for his TED Talks on organ bioprinting, which is really fascinating. But I do still remember how he used to address us as grad students…even after when I became a post-doc…How he always encouraged us to keep doing what we were doing with the ultimate goal as treating patients. And really, he always ended his talks—whether speeches or presentations to students—by saying “Remember, whatever you’re doing now, keep in mind that someday the patient could be you.” That’s something that I carry with me everywhere I go. Whatever you do, you have high ethics in your work, because that patient could be you or any member of your family. So be the best you can. I really appreciated the words that he was always telling us, how to do research.

Carson: That’s wonderful! Sounds a lot like the Golden Rule, the categorical imperative, all that good stuff, high ethics [standards]. Now if I recall correctly, your mentor was Professor Khalil Bitar, and your work related to the repair of gut injuries. Could you tell me a little about what attracted you to GI tissue engineering with the Professor, and some of the problems you’ve helped to solve? What work you proud of, or pleased with, that someone could look up on PubMed for example?

Zakhem: Sure. I started working in the field of tissue engineering back in 2010, learning a lot about the scaffolds and biomaterials. And as I was looking up different labs with which to start my grad school—Dr. Bitar at the University of Michigan at that time was working a lot on the gut. And he had just started working on the tissue engineering part—he was mainly on the physiology part. So, when I talked to him, I proposed a couple of ideas to use scaffolds and biomaterials. He was very excited by the idea, and he took me on to his lab. This is where we really started working on the gut tissue engineering. The gut, as you know, is a tubular structure. I had experience developing tubular scaffolds during my master’s degree work in biomedical engineering, so I think that fit well in that application. I then started looking at the biocompatibility of the materials. Working in the gut, it’s such a complex system. There are smooth muscle cells, different layers, and neurons that are part of the enteric nervous system—which is a system that functions independently of the central nervous system. And other cell layers as well. So building a tubular structure to replace the gut is not as simple as it sounds. The challenges there are to find materials that are biocompatible that allow the smooth muscle cells to maintain the function, as well as the neural stem cells to actually be able to differentiate into the right neurons. Some of the diseases that we were targeting as part of my grad school were diseases that involve dysfunctional or lack of certain types of neurons, like relaxing neurons—such as with Hirschsprung’s disease, where kids are born with an enlarged colon, and they lose motility. So really, the goal there was to be able to develop a full, engineered gut tissue with the right muscle type, with the right neural cells differentiated there.

That was really amazing experience, because there were different aspects in my Ph.D. I was looking at biomaterials, their mechanical properties, their biocompatibility—but also the biology part of it, by co-culturing those cells and implanting into animals to see how those organs can function. What I’m really proud of—what came out of my Ph.D.—I want to start with the latest paper, which was in Nature Reviews, which really describes or summarizes the challenges as well as all the accomplishments throughout my Ph.D. I was also able to publish in high-impact factor journals like Biomaterials, looking at selection of the optimal biomaterial for this application… going into tissue engineering journals, looking at the actual anastomosis of those tissue in animals. It’s cool to see how the work is not only at the bench but you’re able to translate that to animals.

Carson: That’s amazing. Sounds like a ton of work! And congrats on the Nature review paper. So after Wake Forest, looks like you were in Phoenix for a little while. I, myself, have never lived out there, ‘cos collapsing from heatstroke holds just doesn’t appeal to me. You’re brave! So it’s nice to see that you survived the climate and could make it back East. Could you share a little bit about your post-academic journey to RoosterBio, and what brought you here?

Zakhem: When I finished my Ph.D., having started my work at the University of Michigan, then moving to Wake Forest with my professor at the Institute for Regenerative Medicine where I completed my Ph.D., looking back on it—some of the work that we did was really innovative. We had to work along with the Clinical Center at Wake Forest in order for us to scale up our tissue product that we were developing. So I stayed there for a post-doc for about a year and a half, working on translating whatever we developed in the lab. That introduced me a lot to quality control, to the manufacturing team, to process development. You know, when you were doing research as part of grad school, you were just doing it because you loved the research—but you did not have in mind all the quality control aspects or the manufacturing, how you’re going to translate or scale your product.

So I finished my post-doc there and then I moved to Phoenix, my first real job in industry as an R&D scientist. The heat was not pleasant I can tell you that for sure! But by nature, I’m always someone who looks for challenges in life. And another opportunity opened up in Columbia Maryland at ACell, where I joined as a senior scientist, staying in the same field of medical devices, looking at scaffolds, biomaterials, characterizing those… But also, a lot opened up for me by interacting with different departments. I started working with marketing, with the quality people as well. That really strengthened my industrial skills, I’d say. But I always had in mind that scaffolds are great, biomaterials are amazing. Tissue engineering is such an amazing technology. But without the cellular component, I don’t think we can achieve what we’re looking for. There’s definitely a need for the cellular part. This is actually why I looked at RoosterBio. Because I know that RoosterBio is the leading pioneer in materials for cell therapy, providing that cellular component that most researchers are really looking for. RoosterBio provides the high-quality cells and scaled-up manufacturing processes. So it really helps all the researchers, whether in academia or even industry, who are looking to have a product out there for the patient. RoosterBio is providing the necessary cells for that. I thought that RoosterBio would really complement the tissue engineering field by bringing up this cellular component. And so here I am at RoosterBio today, working in process development!

Carson: Wow. What a story, what a journey. We actually have a saying here, “Quality Begins at Inception”—there’s a nice [related] blog by Kathy Williams, our main Quality person. OK…What are some notable applications in gastrointestinal tissue engineering where MSCs or MSC-EVs could play a special role?

Zakhem: Good question. One of the lead challenges in gastrointestinal engineering is getting those neural stem cells, or neural progenitor cells, to differentiate into the right neurons. And I think part of it is co-culturing that with smooth muscle cells. But there are also additional factors that are needed. I believe MSCs are there to release those factors; are crucial for neural progenitor cell differentiation. Now MSCs are known to be “magic” cells, right? You implant those in vivo. You can’t track them for long, but they have some kind of “magic” effect by secreting certain molecules. Just recently we were looking at the MSC-EVs. This is what we’re really focusing on a lot at RoosterBio is the therapeutic effect of those EVs. You see a lot of papers out there looking at effect of EVs in so many diseases. And I believe, I’d assume, that if I’d come across EVs 10 years ago at that point—I’m sure we’d be looking at their big part in cell differentiation and cell-cell communication. As I said, the neural stem cell differentiation is a major challenge. And I believe EVs would provide—or they are—the cargo for affecting cell differentiation.

Carson: Yeah. Very interesting. I remember over the last 10-20 years, people once thought of EVs as just “cell excrement”—for lack of a better term. But clearly they do a lot more than that! They have very important roles as part of the MSC secretome. It would be interesting see to what they could do with GI tissue…So…having contributed greatly to biotechnology in both academic and industry settings, is there some advice you might have for one who is making that switch to industry?

Zakhem: Of course. I think spending some time in academia is good, because it really equips you with all the science and the knowledge that you need. It prepares you really well to go everywhere you want. So it’s definitely necessary. But I say if someone wants to move into industry, they need to have the passion, the excitement of being part of such a fast-paced environment. Keep in mind that we’re not just doing research just for the sake of doing research anymore. Someone wanting to go into industry has to keep in mind that there is commercialization, there is marketing that needs to be a priority. The business mindset is definitely an important part of it. I would say project management is an important facet as well, being able to multi-task and be able to manage multiple projects. But honestly, going into industry is really giving you a shortcut to having a faster impact on patients than being in academia. And if this is what you want I think industry is the right place for you.

Carson:  I completely agree. One thing that I might have noticed that was different [notable] regarding “industry vs. academia” is that you aren’t necessarily the “captain of your own ship” as you quite are in academia. You have to hand things off; you have to “say goodbye” to your deliverables and hand to another team. Right? So, if you can get used to that, you still have quite a bit of the adventure and fun, and the thrill of science, right there in industry.

Zakhem: Absolutely, I agree. I mean, you have to keep up with the science…

Carson:  For sure. Yeah, if the science isn’t real then what you’re doing isn’t real; that’s the baseline. So, at RoosterBio, a lot of people say that it’s all about industrializing the supply chain for cellular therapy solutions. Where do you fit in as the Process Development Manager? What does a regular day look like for you at the Roost?

Zakhem: Process development at RoosterBio really has multiple responsibilities. We work a lot on MSCs or EVs, with the goal of delivering to our customers—high-quality cells, and to develop processes that enable them to advance in their research or in their clinical trials. We work a lot internally on developing those manufacturing processes, making sure they are scalable, consistent, and reproducible. We have a great team of researchers here in order to ensure that. So, along with the manufacturing team, we help tech transfer all of our processes that we develop—or that we improve—within Process Development. And transfer those to our manufacturing so they can be implemented or incorporated in our products. Part of our job, as well, is working directly with customers through our Development Services group. So we make sure that if we get requests from customers, or clients, of if we develop some processes for MSCs, or EV productivity or purification, we make sure that we can transfer this technology so we can help those customers to get to their goals. So yeah, it is a fun place to be, because you get to work on some internal projects that are pure R&D/innovation, which is great—but you also get to feel that you’re having an impact on customers.

In terms of a “regular day,” the beauty of working at RoosterBio is that it’s never really the same every day. Other than having my cup of coffee in the morning here at the Roost, every day is different, which is something I like. But if I’m going to summarize what a week would look like, that goes from attending internal meetings, as well as extending some external meetings. We’re working with collaborators, developing scopes and proposals for new projects. I also work with my team, so I try as much as possible to go into the lab — check out what they’re doing. We have some state-of-the-art equipment in the lab that you do want to see working. And how all the proposals that we have been writing all translate there. And as well, working with the leadership team to relay to them the progress of the projects. I also spend some time developing and managing timelines as well as budget. There’s quite a bit of everything, which makes this job really exciting and challenging all the time.

Carson:  Yeah, I’ve seen some of your work, it’s really amazing, really spot-on. It can be a challenge, of course, to figure out how long something’s going to take and how much it costs! But at the same time, it’s thrilling to watch it mature and reach fruition. We certainly do have a lot of irons on the fire. Maybe you all [i.e., the readers] will hear about it ISEV-2022, I guess. Hmm, are you going to ISEV?

Zakhem: I’m not, but a couple of people from RoosterBio are going to ISEV; one of my team members is going to be attending (Stephen Lenzini, Ph.D.). He’s going to be presenting some of the really exciting work he’s been doing on increasing the EV productivity of MSCs. I hope it’ll get great exposure there, and I really feel that we are working super hard to make sure that we can deliver processes for generating those EVs from MSCs as well as purifying them.

Carson: You’ve surely seen how tissue engineering’s evolved in the past years… from stem cells, to biomaterials & scaffolds, to mini-organs… But looking ahead into the 2020s decade, what are some things that look exciting for you from your unique perspective?

Zakhem: There’s a lot of research in the field of regenerative medicine. It’s a great field to be in. A lot of promising results there. I believe there’s still going to be some progress happening there, with so many clinical trials targeting many different diseases using those technologies for treatment. But what I see, coming from my experience working at RoosterBio, I definitely see us going to more of a standardized treatment, moving more towards “off the shelf” products as opposed to going more into “customized” products. This is going to take a lot in terms of manufacturing scalability as well as consistency. The main challenge in tissue engineering and regenerative medicine is really the cell source. It’s not always easy to get autologous cells sourced for diseases. I see us going more into allogeneic cell sourcing. That could be one future that I see in regenerative medicine. So… off-the-shelf, standardized treatments.

Carson: Sounds interesting. I guess that kind of invites a question of… Maybe to help allogenic fit more into an industrial modality… Perhaps engineer the “upstream” as well as the “downstream…?” Upstream engineering might include something like CRISPRs. So, on that note, how do you see that gene editing and CRISPR tech might facilitate tissue engineering in the future?

Zakhem: I think it’s an amazing technology. For the different challenges that we have, the cell source is an issue. So being able to use the gene-editing technology to “edit” certain cells could alleviate the challenge of finding the right source of cells. I also see it—and I’m mainly talking about the gut tissue engineering—the gut microbiome, which are the natural bacteria found in the gut. It is thought that a lot of the diseases that happen in the gut such as inflammatory bowel disease (IBD) really result from some kind of disruption in the population of the gut microbiome. I think this is where gene editing really comes into play, by being able to modify those bacteria—either deleting certain genes or inserting certain genes that help you understand how those bacteria function to find treatment for diseases such as inflammatory bowel disease. I think gene editing tools will pave the way for treatments and advances in regenerative medicine.

Carson: Yeah. Applying gene editing to the microbiome? That’s fascinating, making it “more at home.” There was a company I was with, and we helped move along, called Actogenix. And they have this technology called “Actobiotics.” They engineer L. lactis to treat all kinds of diseases of the gut. They have them secreting IL-10. And then they have Type I diabetes treatment. Well…enough questions about work for a moment! What’s your opinion of daily life in central Maryland these days? Is it good for you?

Zakhem: Yes, I love living in Maryland. It wasn’t a big switch for me, going from Winston-Salem, North Carolina. I came to Columbia, Maryland. I was never a big fan of big cities, to be honest. Winston-Salem was such a small town for us, but it provided everything that you needed. You really didn’t need to drive more than five minutes to get anywhere you want. Coming to Columbia, to me, was just a bigger version of Winston-Salem. We really love it. There are so many states around us where you can go for hiking; the beach is not too far from us either. You get to explore and experience the four seasons, which is not something that you get everywhere in the States, so we love Maryland. It’s been great.

Carson: My family and I have been living here since late-2009. Definitely found our roots here. A good place to be.

Zakhem: Yes, a good place to be, a good place to raise a family.

Carson: I heard somewhere that you have a dog. My own Yorkie Bichon mutt thinks he’s a human and has been spoiled badly. What kind of dog you have? Would you recommend your kind of canine for others?

Zakhem: My current dog, he’s a mix of a border collie and an Australian cattle dog. So, two super-energetic breeds. I definitely recommend them for people who have a lot of energy. I had to learn it the hard way! He definitely keeps me on my toes. He’s crazy. But he really teaches you what a loyal best friend is. He’s always there; everywhere you go he’s following you. A great friend; a great companion throughout my career. I definitely recommend that type (or any) dog I would say!

Carson: Any other questions you’d like me to ask you before we finish up this interview?

Zakhem: Thank you again for having me today, Jon, and bringing back some really good memories of grad school.

Carson: Well, thank you so very much. I really enjoyed this, and I think our listeners and readers will too.