We sat down with Giovanni Ferrari, MD, Associate Professor of Surgical Sciences and Scientific Director of the Cardiothoracic Research Program at Columbia University. Dr. Ferrari spoke with us about his new role as the co-director of the Surgical Cardiovascular Research Institute (CVRI).
What role do you see the Surgical CVRI playing here at Columbia?
The idea is to serve the Columbia University research community by providing a one-stop shop for everything related to cardiac surgery research within the Department of Surgery.
The institute is designed to be a hub, a place where collaborators, scientists can reach out to the Department of Surgery and connect with other researchers and resources.
Right now, each of our surgeon-scientists is working on their own project, and while we do have collaboration, we realize that we need to make it easier to connect. And there are a lot of researchers in the medical center and across Columbia who are constantly reaching out to us to involve us in their research, which may require a surgical model or access to resources like our human biobanking.
One resource with the department is the Columbia Biobank for Translational Studies (CBTS), which you direct. Can you tell us about how the biobank supports researchers?
This is a major resource that I've been developing for the past 15 years. When I was at Penn, I established the Department of Surgery Biobank. In 2017, I was recruited back to Columbia, where I established the current version of the Biobank, which is now called the Columbia Biobank for Translational Science.
There is a recognition that most of the cardiovascular diseases that we are studying currently don't have a good, reliable animal model, or a reliable in vitro or in silico model. Having access to human specimens that we collect during surgery is a unique resource that can be shared with collaborators within and outside the department.
So we created this biobank, which retrieves cardiac specimens that are otherwise discarded—obviously with informed consent and IRB approval. We collect blood, we collect tissue, we isolate primary cells. We isolate DNA and RNA. And these human specimens are then the base of basic translational and clinical research that really elevates the level of what we do.
We want to centralize this biobanking initiative within the cardiovascular institute. People will have a form to apply and request specimens for their research. And we will also work in close collaboration with other biobanking initiatives that the medical center has already established, such as the Columbia University Biobank. The difference here is that the Columbia Biobank is mostly a blood and genetic biobank, whereas we, as a department of surgery, have the actual physical specimens, the cardiac specimens that are resected during surgery.
Can you give us an example of how the Surgical CVRI hopes to connect potential collaborators?
One of the things that we are particularly excited about is centralizing the effort of our surgical residents and students. We have a unique opportunity here, both for innovation and educational purposes: putting our amazing surgeons-in-training at work in basic and translational research.
Usually, when an investigator at Columbia from outside of the Department of Surgery wants to do a surgical model, they have to reach out directly to individual PIs to connect with residents and medical students who can perform that surgical procedure. The institute will allow us to manage the workload of all our residents during what we call academic enrichment, where they take a break for clinical duty and they spend one or two years in the lab.
So the institute will help our residents to find a mentor or research project, but also help the investigators to reach the resident. We can provide this two-way exchange program between our resident that can do this amazing surgical procedure and the researcher outside of the department.
In the current climate, funding is a huge factor for research. Will the CVRI help researchers find financial support?
Absolutely. The institute is designed to support both our faculty and our residents as much as we can. One of the other benefits we will be offering will be internal awards. For example, when a faculty member is developing a resource program that is close to being funded through the NIH or another agency, but might be missing a key experiment, or need a bridge fund in between grants, we want to help. That's where the institute can step in and make sure that they continue to grow their research. That will help foster more academic and translational research within the department.
What other challenges do you feel that researchers are dealing with that this will help address?
I think there are two things that are critical to discuss. One is the collaborative nature of today's cardiovascular research, especially in surgery. Two classic examples are organ preservation outside of the body and designing implantable material. These are the intersection between engineering and medicine; we need engineering to help us refine the ex vivo system that preserves the heart outside of the body, and we need material scientists to help us develop new biomaterial for reconstructive heart surgery. It's very difficult, especially for young surgeons, to have the background and connections needed to develop this type of high-level collaborative work.
That's where the institute is stepping in. We will have a network of collaborators because senior faculty are involved in this institute. We can help junior faculty to develop their projects in this very complex world of interdisciplinary research. This will be a very effective way for the institute to help the next generation of surgeon-scientists.
The other thing that is important is that science today requires gathering a ton of data: imaging data, biomarkers data, genetic data, clinical data. We have an unprecedented amount of data, all requiring electronic storage.
So the hope is that the institute will be able to provide access to the expertise needed to harness that data: system biologists, computational biologists, AI support, to dig deeper into this hyper-complex, large data set that a department like ours collects. As a clinical department that receives a huge amount of information every day, developing access to these resources can obviously benefit our community.
Is AI an essential part of research now?
AI is a big reason why we need something like the CVRI. Our ability to recognize patterns is very limited. I mean, the human brain is fantastic in terms of analyzing small patterns. But when it is challenged to analyze a large dataset, that's where computational systems and artificial intelligence can really make the difference.
That’s why we are really looking at hiring faculty within the department and within the cardiovascular institute to help us develop this. And this will not be done just within the boundary of the CVRI; this is a Columbia University initiative that we would like to partner with others because this is going to be serving the entire CUIMC community.
But as a clinical department, we live on this large data set. Every patient coming for a heart surgery will have to have multiple types of imaging, multiple types of blood work, plus all their clinical history. So we are really living on a mountain of data that needs to be better characterized. And I think that's where AI can really help us. It is already helping us.
What are some technologies on the engineering side that you're excited about?
I think the next big thing for cardiac surgery is organ preservation; this is really changing the landscape. I mean, right now, a heart transplant is done whenever the heart is available; it’s never an elective surgery. The patients are on the waiting list, waiting for a call that might never come. When they finally come, they need to rush to the hospital, and we might perform the heart transplant at 3:00 or 4:00 in the morning, because that's where the organ is available.
But let's say we have a system now to preserve the heart for 24, 36, or even 48 hours? It's transformative. A surgeon can do the surgery at 9:00 AM. It improves logistics, improves utilization of the OR and ICU. It's much safer for the patient. The surgeons are fresh. Everyone benefits. We are very excited because surgery can have a central role in developing this ex vivo organ preservation.
We’re also excited about partial transplants. Right now, patients are receiving a heart, but very rarely there are techniques to transplant only a certain cardiac substructure, like a valve, for example. A living valve.
So this project of transplanting a living valve into a patient, not a bioprosthetic valve, but an actual living valve that can grow with the patient, is particularly important for pediatric patients for which we have very limited options. We have some of our surgeons developing this amazing technology of transplanting only part of the heart and maintaining it alive throughout the process.
And then the third thing is xenotransplantation. Transplantation of an organ from an animal to human obviously will be completely revolutionary because it will completely address the issue of organ availability. And Columbia is at the forefront of this technology; we are implementing genetic screening of animals that have minimal rejection.
And one of our surgeons is taking the lead of cell transplantation for adult and pediatric heart transplant. So that's actually very, uh, very important here at Columbia.
How about device development?
Device development is something that historically has been very important for the Department of Surgery. We have been one of the key players in the development of bioprosthetic valves, both for surgical and transcatheter implantation. My very own program is designed to modify the biomaterial that is used for bioprosthetic valves and medical devices to make it compatible with different patients. Right now we are implanting the same devices in a pediatric patient, or in a patient with diabetes, or in a patient with chronic kidney disease. But they all have a different biochemical signature in their blood, which is impacting the durability of this material.
We are working to customize the material to make them more resilient for different types of patients. The goal is to limit the number of reoperations that these patients have to undergo. For example, for pediatric patients, these valves fail rapidly. And the younger the patient, the more rapidly the valves fail. So designing a valve to specifically to resist the aggressive biochemistry and immune response in a pediatric patient will allow him to have maybe one valve replacement or two valve replacement in their lifetime instead of the multiple re operation that they're currently doing.
Is customizing valves for individual patients on the horizon?
I think so. The past decade or two has all been about the design and the delivery of this valve. We now deliver 70% of our valves using a transcatheter approach without full sternotomy. This is obviously a game changer for the patient; they can go home the day after. But now there is recognition that these valves, which are of biological origin, fail over time. This is inevitable. So we have two options: design a completely new polymeric valve with a material that is inert to structural degeneration, or take the current biomaterials and modify them to make them more resilient to the different types of patients.
We are working on both options. The polymeric valve will probably be the first one to reach the market; we already have one or two companies that are implementing clinical usage of this new polymeric valve. But I think there is a lot of room here to do both approaches and actually to modify this biomaterial as we learn more about biochemistry and how the blood material interaction is driving the structural degeneration.
Right now, we have an engineering problem: we figured out what the theory is and now we need to implement. There are a lot of different coating solutions and modifications to this biomaterial that are very promising; some of them have already reached preclinical testing in large animals. So I don't think we are very far from that potential solution coming to market.
Where do you see the Surgical CVRI in five, 10 years? Where would you like to see this developed towards?
I would like the CVRI to remain the small and dynamic institute that we are envisioning today. I would like to avoid it growing into something that is very difficult to manage and is going to overlap with all the other initiatives that are already being developed at Columbia. If we are able to maintain a small and centralized institute that can provide targeted support to our faculty and foster collaboration within the institution, I think that would be a game-changer.
I would also like to see the institute promoting institutional collaboration with other initiatives. For example, in addition to my position as a co-director of the CVRI, I'm also part of the Columbia Transplant Initiative. Our work with organ preservation and partial transplant has benefits outside the cardiovascular space. Here we are all working on our favorite organ, the heart, but the reality is that multiple organs crosstalk to each other, especially during disease progression.
And so I want to be able to bridge the research of a group working on liver transplant or on kidney transplant with the one on the cardiac, because the metabolic profiles of these patients often impact other organs.
I think this is one of the limitations of the current status of research. We don't know enough about cross organ interaction in disease, and physiology. I think this is something that an institute like ours, which has a 10,000 foot view of the problem, can really help.
I think it will be a powerful recruitment tool, as well. Because as faculty, we are asked: what will the next recruit be looking for? What will they need? And it's very difficult to just come up with ideas. But if we have an institute that is already looking at everything that is going on within the department, then it will be much easier to see where the gaps are.
And while it will make things easier for us to identify what we are missing, the CVRI will also be a great recruiting tool because if one of our possible new hires wants to do research, then they will be put in contact with me or with Dr. Geirsson. We can show them how we can help them to develop the research project that they have in mind.
The CVRI can help address so many obstacles. We can help our surgeons balance their time between research and the amazing clinical care they're providing every day. And as is required by a place like Columbia, we can help develop cutting-edge technology and drive transformational improvements in care.
Our milestone will be to see how many of our faculty are able to develop meaningful and impactful cardiovascular research projects. We’re excited to help them succeed.