Breaking the cycle of unhealing wounds
From heart to lung to skin, Dr. Carlos Zgheib balances his career between academic research and biotechnology to develop drugs and therapeutics that not only heal wounds and scars, but can also save lives.
A chronic wound does not heal in an orderly set of stages or predictable amount of time. These wounds often remain in the inflammatory stage for too long, taking years to heal, or never healing at all.
Biomedical research uses regenerative medicine, tissue repair, nanotechnology, and various biomaterials to target chronic injuries like this. It’s important for researchers to focus on targeting an anti-inflammatory response within molecules, using regenerative techniques to combat oxidative and inflammatory stressors that would otherwise exacerbate the healing process.
For this episode of Science Talks, Amy Barber talks with Dr. Carlos Zgheib, an associate professor in the Division of Pediatric Surgery at the University of Arizona College of Medicine – Tucson. Dr. Zgheib leads the Laboratory for Fetal and Regenerative Biology with Ken Liechty and is the surgeon-in-chief at Diamond Children's Medical Center at Banner’s Children.
This interview had been edited for length and clarity.
We like to start off every podcast the same way with a couple of questions. What is your favorite city in the U.S. and why?
My favorite city is Denver. I lived there for nine years, and I liked it because it's a foodie town, multicultural, and you're close enough to the mountains for scenery and beautiful skiing.
What is something you could eat for a week straight?
Kenafeh - it’s a lot of cheese and simple syrup with dough. It’s served as breakfast, but I can eat it every day.
What is your dream car?
It’s always been a Lamborghini, a yellow Aventador. It is a sporty car with a lot of technology.
Can you tell us a bit about your background and what attracted you to science?
My mom was studying to be a doctor, but she could not continue. Then, my brother ended up going to medical school and becoming a cardiologist.
That influence from my family is why I became interested in the medical field and the science behind it. I was always interested in biology and chemistry during school. I have a bachelor’s in biochemistry then continued with a master's in pharmacology and cosmetology.
I received a scholarship to come to the U.S. for a three-month research internship at the Cardiovascular Research Institute at Texas A&M University. After finishing my internship, I went back to Lebanon to finish my master's. Eventually, I was accepted into two French universities to do a PhD, but I decided to apply for U.S. programs. I was accepted and did another master's and a PhD.
What brought you to the University of Arizona and to the BIO5 Institute?
My mentor and I were approached by the chair of the department of surgery at the University of Arizona College of Medicine - Tucson, Dr. Geoffrey Gurtner, with the possibility of joining the department and helping with pediatric surgery and bringing our research programs here. We felt it would be a good fit for our goals in biomedical and clinical research.
How did you get interested in the field of study you are in now? You have a lot of different research experiences, how does it all tie together?
I was focused on pharmacology, but also very interested in inflammation. During my doctoral studies, I was interested in when a patient has a heart attack and part of the heart dies and stops working, becoming fibrotic. A lot of that has to do with inflammation, which causes fibrosis in the tissue. I developed this concept that if you could control the arteries in the heart, they can help regenerate that muscle.
After my thesis, one of my advisors and longtime mentors offered me a position to join his team as a postdoctoral researcher. His lab was focused on fetal cardiac regeneration, and he thought I could bring my experience to push certain projects forward and finish them.
They had focused a lot on wound healing, particularly why wounds didn’t heal properly is due to this inflammatory cycle, making the wound chronic. The wound doesn’t get a chance to try to heal itself, and it all starts with inflammation.
Can you tell us about your current projects?
We base our research and drug development on what we learn from the fetus. When you mimic a heart attack in a fetal heart, it will regenerate as if it never happened, unlike in adults. Once an adult has a heart attack, there’s no going back, the heart is damaged. Depending on the severity, adult patients can die or go into heart failure. We also notice something similar with skin. When you wound the fetal skin, it regenerates completely. There’s no scar formation.
We were studying how the response differs between the fetus and the adult, knowing that difference can allow us to understand how tissues in adults could be changed to promote regeneration.
And that’s the basis of the nanotechnology we are using. It is a combination of nanoparticles and microRNA. The nanoparticle itself can deliver microRNA to the tissues. MicroRNA is also an antioxidant and anti-inflammatory, basically blocking inflammation So we can target both inflammation and oxidation in tissues, giving it a chance to heal itself.
When I was a postdoctoral researcher, we tested this concept in diabetic wounds and saw a lot of promising results. During COVID, we also focused on lung injury from people being on ventilators. We showed that we can not only block inflammation and reverse injury, but we can also restore lung function back to normal. This was huge because there’s no drug on the market right now that can treat lung injury. Now we're testing that drug in our drug pipeline and we’re sending it to the Food and Drug Administration (FDA).
We also recently received a Department of Defense (DOD) contract to develop a dry powder inhaler for patients that suffer from ulcerative colitis or Crohn’s disease, and we are collaborating with researchers here on campus.
We’re also working to develop two new areas at the University of Arizona, including developments for the treatment of sepsis and scarring from pregnancy complications. We need to understand why it scars while developing treatments to reduce scarring and promote healing.
Your lab’s focus is heavily surrounded by pioneering groundbreaking advancements that will shape the future of medicine and positively impact the lives of countless individuals around the globe. Can you tell us more about how that became an overarching goal for your lab?
It all started when I was a student with a passion for biomedical research and scientific discovery. As I developed that passion into my career, from the beginning I was focused on inflammation and inflammatory disease, but I began to expand into other areas.
You can build on developing one drug for one disease through developing the technology and receiving patents. As we were growing on the academic side, we also had to learn the business side of things. We started a company to bring this technology to market through clinical trials and eventually to patients. That’s when you start to think one drug is good, but more is better. So, you continue with research and development to develop more drugs and applications.
And all this is done by trainees. I trained for a long time, and now I’m training many students. We like to not only invest in potential therapies, but also invest in future scientists who can continue to innovate.
You work with ‘unhealing wounds’ - what does that mean?
Most people, when they have a paper cut, it heals within days. But some patients don’t have the privilege of healing that quickly, such as those who suffer from diabetes, especially in lower extremities. Those wounds take a long time to heal and can become infected. At some point, they need to be amputated or can even cause death These are called unhealing wounds.
There’s been a lot of research on diabetic wounds and why they don’t heal. It can be from inflammation, oxidative stress, infection, low protein, or low collagen. Understanding these mechanisms and dysregulations allows us to develop targeted therapies to push the wound and break the cycle to heal itself.
You have multiple patents as well as being a chief scientific officer of biotech companies, can you tell us how these experiences have impacted your work and life?
Along with being a faculty member at the University of Arizona, my other part time job is working at my company. We started Ceria Therapeutics in Colorado a few years ago to bring some of these technologies that we develop to clinical trials.
We moved the company to the University of Arizona at the Biosciences Research Laboratory (BSRL). Originally, I was only researching in academia in basic and translational research. But I realized if my end goal is to make a difference in patients' lives with these discoveries, I need to bring them to clinical trials. That was a whole different world for me.
When we first founded Ceria, we didn’t know the business side at all. We learned a lot and received a lot of help to start and develop that company, by hiring consultants and people who understand how to build a business. Now we have a CEO, CFO, CSO, president, lab director, employees, and opportunities for students to train from the University of Arizona.
Do you have a mentor who has impacted your life?
I had lots of mentors during my career since I was an undergraduate student. But one mentor stands out. He was my PhD thesis advisor who offered me a postdoc position after I graduated, and I joined his lab.
Since then, we have developed this special relationship. I went from a student to a postdoc to faculty and now a business partner. He’s been my mentor since 2009 and that relationship continues today. He’s the biggest mentor not only on the science and business side, but also in life as well.
What’s next for you?
I would like to continue innovating and pushing these technologies forward, as well as mentoring and training students and residents. Originally, I was only focused on healing, but today we are in different therapeutic areas. For example, we have a medical device for pressure injury as well and it’s ready for commercialization.
What is your "why”?
It’s the passion for scientific discovery and, more importantly, the goal of making a difference in patients' lives. It’s also personal – two of my family members passed away during COVID due to lung injury, which is one area I’m working on for therapies. So, it’s both because of my passion and personal connection.