Regenerative Medicine: Bryan Brown

Bryan: Sort of came to realize that the only way that some things that we do as scientists are going to be able to have an impact on human patients is for somebody to take that out of the University more often than that that's going to have to be the person who invented it. Trying to push or figure out how to start the company either hand it off or stay involved.

Mike: From CTSI, this is the Products of Pittsburgh. A show about the people in Pittsburgh – innovators, scientists, community leaders – and the remarkable stories behind how they came to be and the work they’ve produced.  I’m Mike Flock.  On the show today, we meet with Dr. Bryan Brown, Associate Professor of Bioengineering at the University of Pittsburgh. 

Mike: In 2001, Bryan came to Pittsburgh to study mechanical engineering at the University of Pittsburgh where he would go on to obtain his PhD in bioengineering and become a faculty member at the university.    From winning multiple awards to co-founding a company, Bryan is well on his way to making an impact on health care innovation.  During his earlier training, Bryan spent time in China and Japan working as a visiting researcher. Although, it wasn’t his first timing living overseas.  As the son of a Naval officer, Bryan spent much of his earlier life on the move…    

Mike:  Where did you grow up? Where are you originally from?
Bryan:  So originally born in Yokosuka, Japan. My dad was in the Navy, so I moved every three or four years.  Japan, Florida, Virginia, DC area, back to Japan, to Colorado, and then eventually to Pittsburgh

Mike:  What was that like growing up in terms of school and having to move around every so often?

Bryan: Yea, it wasn't too bad actually because we ended up being most of elementary school was in Japan and then after we moved to Colorado my dad retired so we stayed there after that. So it was when I was very young when moved around a lot but you know once I was in middle school, high school we stayed put after that but yeah we have moved around a lot before that.

Mike: Did you have any earlier jobs as a kid growing up?

Bryan:  Yea, sure of course I did.  My first job was I was a waiter at a restaurant called The Village Inn in Monument, Colorado sort of like a Denny's, the Colorado equivalent.  I was a waiter.  I worked at a country club as a dishwasher and then eventually as a cook.  When I came here to the University of Pittsburgh, it’s not around anymore but there was a service called Tell a Fact for Fact.  It was a line that students or anybody could call in and ask questions about the University or anything else and we would try to answer just about any question that anybody would ask

Mike:  Wait, you basically had to respond to anybody calling in with a question about Pitt?
Bryan: Pitt or anything else you know to the best of our ability.  So really people calling about all sorts of things, settled bets you know but it was mostly directions or when is this open or how do I find X or Y or Z about the University but particularly Friday nights we’d get some interesting calls.

Mike: Interesting. I had no idea that existed nowadays that's a Google search.

Bryan: Now we have we have Google search to do most of those things for us shortly after that I started working with Steve Badylak and it was science after that.

Mike: When you were growing up as a kid did you have any ideas of what you wanted to be when you grew up?
Bryan:  Not really, you know going into college I got an undergraduate degree in mechanical engineering and was going in I thought I wanted to work on in a race cars are rocket ships or something like that mechanical engineering, building cars, but gradually moved more towards the bio side of things and didn't end up doing anything really mechanically related.

Mike: Why that transition from mechanical to more bioengineering?

Bryan: Yeah, after my sophomore year of undergrad decided I want to stay in Pittsburgh and started looking for an internship opportunity, really anywhere in that the Pittsburgh area.  A strange story still to this day I don't know how he got my resume at the time but Steve Badylak who is down at the McGowan Institute had just come to the University of Pittsburgh and needed people to help out putting things together essentially in his lab.  So I've been sending my resume out to a bunch of people at Pitt and I think his assistant or he got it and called and asked if I was still looking for position I said yes of course and went down and interviewed knowing absolutely nothing but he gave me a position and started by helping set up equipment in the lab and building chairs and things and slowly got more into the biology and just was so fascinated that it stuck and eventually ended up coming back to do PhD with Steve as well

Bryan: In between, I went and lived in China for a year.  I went and lived in China because my wife had a fellowship from the Department of Defense for studying language.  So she was going to China. I had the option to start into graduate school or take a year off and Steve was okay if I took a year off and came back after about a year.  So I went with her to China ended up studying Chinese language about 20 hours a week and then working in a laboratory about 20 hours a week.
Mike: Wow, so were you able to at the end or during –is it Mandarin – was that what you were able to speak?

Bryan.  Yea, we were in Beijing so we were learning Mandarin

Mike: Do you still have an ability to speak some of it today?

Bryan: I can understand a little bit, very few.  It’s very difficult language, but it's been close to 15 years since I was there.  At the time we were there, 20 hours a week.  We were married so we couldn't live in the student housing on the University so we lived in neighborhood where nobody spoke any English. So we learned very quickly sort of been in that environment but now it's mostly gone

Mike:  In retrospect, that experience in Beijing are their elements of that that you see today that you found to be beneficial or things that you would kind of take back or look back to that experience and say wow that really kind of helped mold me?

Bryan: That’s really hard question.  It was so different in so many ways and you know for my wife and I remove there four days after we got married.

Mike: That was your honeymoon

Bryan: In that respect a lot to learn. In other respects work-related respects I spend most the time that I was working at Tsinghua University actually editing papers and presentation.  I learned a lot about writing and editing and science.  So that part of that I think was really beneficial for me as well.

Mike:  It wasn't your only stint in Asia because you are also spend some time in Japan if I recall.

Bryan:  I've lived in Japan in three times.  Once when I was born times about 6 months old and then you know because my dad was in the Navy we moved back to the United States the second time lived in Tokyo, Japan for about four and a half years and then again at the end of my graduate studies. I had a NSF Fellowship that sent me to back to Tokyo and was working at Tokyo Women's Medical University for about 4 months then as well.

Mike:  International mobility is common among researchers and academics in part because science is a global endeavor.   Spending time in a foreign lab can offer exposure to new methods and ideas and help create new collaborations.  Eventually, Bryan came back to Pittsburgh and finished his PhD in 2010 and spent the following year and a half at Cornell University as a postdoc working on cartilage tissue engineering …in horses.    

Bryan: It was a pretty unique position between the biomedical engineering departments there and the department of clinical sciences in the veterinary school and we were working on trying to find ways to rebuild the airway cartilage in horses.  Unless you own a horse, you might not know, but horses have a lot of breakdown in their airways and particularly related to cartilage.  They get infections much more frequently than humans do obviously and they get weakness in the cartilage that causes their airway to collapse.  So we were both characterizing the airway in horses and trying to find ways to rebuild it. I was there for about a year-and-a-half before I had the opportunity to come back to the University of Pittsburgh.

Mike:  How did that happen?  Coming back to the University of Pittsburgh?

Bryan:  So the funding for my postdoc was running out and I was looking for other opportunities.  So I was back in Pittsburgh, talking with people here who were my mentors previously and was off cycle for applying for faculty positions wasn't sure what I wanted to do and essentially they said well I’ve got an office and if you want to come back for a year and work on some things here at Pitt while you sort of figure out what it is that you might want to do or if you can get some grant money and we'll see about staying here at Pittsburgh.  So I took that opportunity came back as a visiting assistant professor.

Mike: And have hit the ground running ever since.

Bryan: luckily yes. We're able to get some various kinds of funding along the way.  I was first a visiting assistant professor for about a year then research assistant professor for a few years and then on tenure stream at the department of bioengineering and eventually now a associate professor. So I think I’ve had all the faculty roles one can have between here and there.

Mike: Tell us a little bit about your research that you're doing here at the University of Pittsburgh and some of the things you're focusing on.

Bryan: We do number of different things starting with my PhD work with Steve Badylak mostly focused on looking at how the body's immune system interacts with implantable biomaterials.  When I was working with Steve it was mostly on materials that were naturally derived.  So tissue derived biomaterials removing all of the cells so that what you're left with is a sort of unique kind of tissue graft that's able to promote tissue regeneration and what we showed was that there are specific kinds of immune cells - macrophages, innate immune cells - that interact with particularly kinds of materials and when they interact with those materials they sort of shift from an inflammatory to a more pro-healing type of cell.  My PhD work was really on characterizing that transition, trying to understand how it happened you know moving forward into postdoc was mostly cartilage biomechanics in cartilage tissue engineering and when I came back here you went more back towards the immunology aspects of the work.  Since then we've done a lot of work on trying to build the kinds of cues that we saw coming from those extracellular matrix, decellularized tissue materials, into polymeric materials, started working with Pamela Moalli at Magee-Womens Hospital.  She’s an urogynecologic surgeon and works a lot on pelvic floor reconstruction.  In the pelvic floor reconstruction, they use a lot of polypropylene mesh materials, very similar to the kind of material that is used to repair hernia, and trying to understand the immune response to those and build cues onto surfaces of those materials to try to make them integrate better than they do currently trying to improve those outcomes

Mike: Meshes are used in surgery to act as a scaffold, allowing a person’s own tissue to grow and repair around it.  The amount and rate of tissue growth though depends on the properties of the mesh as well as the person’s innate immune system.  Bryan and his colleagues are working to understand why certain materials elicit more of an immune response than others and then using that knowledge can inform the development of better solutions to support recovery.

Mike.  The Pitt Innovation Challenge, you’re a two time awardee.  First in 2016 with a project called Neurogel at the time that now has since spun out and formed a company called Renerva. How did that proposal and project come together?

Bryan: Yeah so that that project came together actually originally as a collaboration with somebody at Cornell after I left, Dr. John Cheatham who is a large animal surgeon and scientist at the vet school at Cornell. He was also looking at ways of preparing the upper airway the larynx in horses other large animals and he's a specialist in the laryngeal nerve repair and so in those animals they have a lot of problems with laryngeal nerves.  Humans generally don't have the same kind of issues unless they have head and neck tumors and then those laryngeal nerves get cut or there other ways they can be damaged, but he's interested in repairing that and restoring function to the larynx because you need that for eating, breathing.  It’s an important part of body. We're talking about different ways that we might use some of the tissue engineering regenerative medicine concepts I was familiar with on repairing that and we came up with the idea of doing a decellaurized nerve material. Eventually we figured out how to turn that into an injectable gel.  We started looking more broadly than laryngeal nerve, peripheral nerve injuries are huge problem for people who have them.  Peripheral nerve injury can be anything from a crushed nerve to a cut nerve to a nerve that's now got a gap in it and needs to have a graft to be to be repaired.  Nerves can regenerate, they just don't do it very well. The material that we developed what we found was that one is injected at the site of a nerve repair or used to fill a gap between nerves it really accelerates the repair of the nerve, serves as a scaffold for nerve cells to grow on and facilitates the repair and faster and better recovery at the nerve

Mike: That's exciting and then of course then taking that idea and pitching it, a non-traditional approach to getting funding. What was that experience like?

Bryan: Right in and that came from a couple of different things you know one was John and I were working on the science and actually somebody at Cornell approached us and they had a program called the pre-seed workshop.  I think here Pitt we have a First Gear program to find out whether your idea has any commercial potential to it and so we participated in that started liking that idea and we're looking for more funding to do additional studies but also now thinking while if this works it might be a great commercial idea and there's a big problem that's an unmet clinic will need that we might be able to address. Part of the programs here at Pitt we got matched an executive residence Lorenzo Soletti who is now the CEO of Renerva but we work with Lorenzo for about 2 ½ -  3 years inside the University of Pittsburgh on things like developing pitches for the PInCh competition or the Coulter program.  The PInCh competition and the Coulter program are both things that give money towards clinical and commercial translation and we did some animal studies with that but we also looked at the regulatory pathways we also looked at manufacturing and supply chains.  We did a lot of non-traditional things that academics don’t usually do but at the end of those programs we were convinced that there was a good idea here and so we decided to spin that out. 

Mike: And of course more recently another project that came through the Pitt Innovation Challenge and won, CyteSolutions Lens. 

Bryan:  Right, so that was something that sort of grew out of an interaction.  One of my students with her physician. She has dry eye condition, her name is Alexis Nofli, Alexis has a dry eye condition and so she's always seeing her doctor about that and got to talking about what they work on and she was talking about how she works in the laboratory on building these anti-inflammatory ques into biomaterials and her physician Dr. Jhanji said, well hey do you think you could do this in a contact lenses, do you think you could do this for dry eyes, do you think you could do this  for other eye diseases.  And the answer was I don't know but we tried it and we found that we could actually coat these materials these cues onto contact lenses very effectively, very easily. That was really where that project was born and we want to use these cues these anti-inflammatory cues to try to change the progression of dry eye for patients and deliver it in a way that's easy and comfortable and familiar to patients.

Mike:  Bryan, his graduate student Alexis Nolfi, and colleague Dr. Mangesh Kulkarni teamed up with ophthalmologist and dry eye expert Dr. Vishal Jhanji on the CyteSolutions Lens project which won a Pitt Innovation Challenge 2019 award to further advance the technology.  They also participated in the Pitt Venture First Gear Program which guides researchers through the necessary steps in creating a go-to-market plan that can result in the creation of a new company or licensing agreement. Bryan has already co-founded one Pitt startup company in Renerva.  Time will tell whether CyteSolutions Lens follows similar path.   

Mike.  What about hobbies anything outside of work that you do or find interest in?

Bryan:  Yea, I’ve started going rock climbing. Indoor rock-climbing has become a hobby for me and that's something my wife was doing and really interested in it so I sort of picked it up and that's been excellent. I love espresso, making espresso, trying all the coffee shops in town kind of a hobby and spend most of the rest of my time doing stuff with the kids.

Mike: What ages?

Bryan: So the kids are 2, 4 and 7.

Mike:  That’s exciting.  So you’re starting seeing them develop into their own individual selves and perhaps own trajectories.

Bryan:  Very much, each one is an individual each one is great. 

Mike:  Well, you’ve been an undergrad here a graduate student and now faculty how has the university changed as you've gone through your different roles here at the University along the way?

Bryan: That's an interesting question and I think when I came here it was 2001 as an undergraduate. Oakland was obviously very different, different stores or lack thereof. I think Pittsburgh as a city has really grown over the last 10, 15, 20 years.  You have all of the restaurants, the arts scenes. Downtown coming back. So thinking in that way the city of Pittsburgh has changed a lot.  I think Pitt is changing too. I think particularly as it relates to some of the things you were talking about the spin out companies that rules and regulations that the Pitt has I think they're shifting more towards trying to support more entrepreneurship in ways that are really great, I think good for the Pittsburgh community, the biomedical engineering community in Pittsburgh.

Mike: Do you see yourself as an entrepreneur given some of the things that you've done is that something you envisioned becoming?

Bryan: It’s not something that I would say I ever envisioned becoming but now you know yes with Renerva I'm Chief Technology Officer of the company.  I'm involved in as much as I can possibly with the company but yeah I think it at this point I would consider myself an entrepreneur but it again it's not anything that I really ever set out to be a just so you know sort of over the couple of years of working with Lorenzo Soletti, going through Coulter program going through the First Gear program and things sort of caught on and sort of came to realize that the only way that some things that we do as scientists are going to be able to have an impact on human patients is for somebody to take that out of the University more often than that that's going to have to be the person who invented it. Trying to push or figure out how to start the company either hand it off or stay involved.  Both Lorenzo and I are tied to the to Pittsburgh area in a lot of ways, we wanted to keep the company here.  It’s been great that it stayed here so I can stay involved.

Mike:  One word that you can select to describe yourself, what would that one word be?

Bryan. The word I’m going to choose is lucky.  I've been very lucky to be able to come back here to the University of Pittsburgh, I've been very lucky in the mentors that I've had.  I have been very lucky in the collaborations that I've been able to be a part of, been lucky to be able to get the funding that we have to do the science and spin out companies. All of these things I'm just really grateful that we’ve been able to do that and be able to do it all of those things here in Pittsburgh.

Mike:  Bryan Brown, PhD, Associate Professor of Bioengineering at the University of Pittsburgh.

That’s our show.  Thank you for listening to the Products of Pittsburgh. Be sure to check out our website at ctsi.pitt.edu/podcast to hear more episodes as well as learn about CTSI programs and services.    I’m Mike Flock along with Zach Ferguson, until next time on the Products of Pittsburgh.