Dr. Biju Parekkadan is a professor of biomedical engineering at Rutgers University. He educates college and graduate students parallel to conducting research primarily focused on cell and genetic engineering to make next-generation medicines for human health.
Q: Can you give us a more in-depth overview of the research that takes place in your lab and the importance that it has?
A: The real end all is to try to make new cellular and genetic medicines. So when it comes to cell therapy, I think a lot of students have an understanding and awareness of things like blood transfusions, maybe even bone marrow transplants. These are cells that are administered to a person to combat some deficiency.
In the case of a red blood cell infusion, a patient is low in red blood cells and therefore is getting sick because they don’t have enough oxygen being delivered to their body. So those are the known examples in the current practice of medicine of using cells as a drug. Gene therapy is another term, where we might think of someone who was born with some protein deficiency.
To get that protein back in that person’s body, we deliver a gene that encodes for that protein into a person so that they can start expressing it normally and hopefully get their function and health back. In both of those cases, cell therapy or gene therapy, there’s an element of drug delivery.
The combination of those with drug delivery is really where my focus lies. So, why is the delivery of these agents important? Well, our body has natural mechanisms to destroy things that are deemed foreign. So cells and genes that are put into the body in their naked format are degraded by our body’s mechanisms. So drug delivery learns about what those mechanisms of elimination are and tries to circumvent them by using things like materials, new devices and other types of techniques.
Q: What is your current goal in the short term and what is the next stop in your research?
A: The current goal is to make cell and genetic medicines that in large part are next-generation in the sense that they can sense someone’s biology and their disease state, responding only in those states. So the way to think about this is using a term that we like to call a biosensor.
So we’re making genetic constructs that are triggered, i. e. turn on like a light switch when a certain signal in the body is present. For example, an inflammatory signal would turn on a gene that would encode an anti-inflammatory protein. In this way, we’re making medicines that are personalized and responsive only in certain states and therefore should have better safety profiles and work for longer periods.
We saw a similar use of sensors in Dr. Mitra’s work while using carbon nanotubes to measure blood glucose levels. In that scenario, the sensors were the carbon nanotubes themselves, and would selectively respond to molecules based on functional groups placed on the nanotube.
Q: What are other types of technologies and discoveries that have been essential to your work and designing these drugs?
A: I wouldn’t necessarily refer to it as a technology. There are a lot of tools out there. It’s kind of choosing the right tool for a given problem and a given scenario. So let’s say the approach that I bring to cell and gene therapy is trying to connect a deep sense of pharmacology, which is the study of drugs in the body to these new types of drugs.
When it comes to identifying what it is that’s preventing the use of these medicines in the body. You ask, well, what tools are available to potentially solve that problem?
So if, for example, the drug is being degraded and destroyed by someone’s immune system, are there ways to maybe combine a cell and gene therapy with an immunosuppressant for that cell or gene therapy to work better
Q: What are the difficulties that come with your research considering that it revolves around new therapies for the human body and the intricacies of the human body?
A: You’ll hear this from several academics, but some of these discoveries that are made, aren’t ready. You need to scale them up and manufacture these things with the quality, which is needed for clinical medicine.
There’s often what’s referred to as a valley of death. Those types of studies are developing sound manufacturing processes, testing perhaps in larger subjects before a human trial. Those areas are not very well supported by government agencies and other types of funding bodies. So I think a challenge in translation is going through that valley of death by securing resources that allow for “not so pretty” science, but really important science that takes discovery and translates it with rigor and reproducibility that’s going to be needed to make it a new medicine.
I think a second to that is constantly bearing in mind how important it is to keep things simple. Biomedical engineers and a lot of folks may suffer from overengineering creating things that have a lot of complexity. They often fail to get translated because other people can’t necessarily make them or reproduce them in the same fashion that is being done in someone’s laboratory.
This becomes very cost-prohibitive. There might be a lot of errors and deviations because of the complexity of making something. Just trying to find simple routes of production, testing, and translation is always important when trying to develop something that inherently is as complex as biological medicine.
Q: Have you been successful against certain diseases? Do you utilize certain therapies from one area or disease in another?
A: What I’m working on has this kind of platform nature, so it can be applied in many different areas of medicine.
We do have a sharp focus on certain applications. Particularly when it comes to the immune system, to cancer, and infectious disease. Those are kind of the three areas of biology and medicine that my lab focuses on. I think we’ve made a lot of inroads and progress while focusing primarily on the immune system.
For example when there’s overactivation of the immune system for things like trauma, blood loss, and severe organ failure that occurs after drug toxicity, your immune system is trying to stave off infection. But is a bit overzealous and oftentimes starts attacking other tissues that are innocent bystanders.
That leads to a patient going into shock, other types of organ injuries happening, and can lead to a lot of morbidity and mortality down the road. We try to bear those types of diseases in mind, things like sepsis, transplant rejection, and severe acute immunological injuries that can demand a really powerful medicine to try to counteract and rebalance the immune system.
It is extremely interesting to see that these cell therapies are not only being used to fight genetic diseases but also as drugs to prevent complications from injuries and infections. The ability to keep the body in equilibrium, whether it is the use of the immune system or another function can be utilized in so many different ways and is something we might look into further in the future with another interview!
Q: You’ve mentioned clinical trials. What do those partnerships look like, and what response have you gotten from the medical sector and patients in the general population?
A: The areas of medicine that we’re talking about, particularly severe immunological diseases, things like transplant rejection and autoimmune disease, have patients that are very enthusiastic to be offered something even experimental. There are very few options available for them.
I would say the same with the physicians that we’ve worked with. In translating some of these immunotherapies, they are often looking for something for their patients. The current standards of care are often managing a patient’s symptoms, but they rarely get to the root cause of the disease, which is why the person came to the hospital in the first place.
So they appreciate that we’re trying to move the needle in terms of the actual disease cure. There’s been a lot of enthusiasm there. When conducting early-phase clinical trials a wide network of people is critical. Physicians and patients are at the top of that list.
There’s also the hospital staff and people who are familiar with conducting experimental trials. There’s a lot of appropriate conduct that needs to take place including consenting a patient to work there, you know loved ones to receive experimental medicine. There’s a lot of testing that often has to happen before and after a patient is treated and that you know often leverages a lot of partners who are familiar with those types of clinical tests, whether they be in the hospital or outside of the hospital. We can run those kinds of blood tests or tissue testing or imaging that may be required.
So you know, conducting a clinical trial, even a small one, requires a tremendous amount of personnel, and it can go to the very top, which are the physicians and patients, But it also goes all the way down to couriers that are transporting these things.
Q: Another thing that you stress about connections in your group is looking for opportunities to translate work into partnerships or new ventures. So what does this look like? And why is it important to your lab?
A: I’ll answer the second part first. New ventures are where true elements of impact can be found. There are many different forms of impacting folks down to the trainees who are learning how to do science and how to translate things and up to making a societal impact on patients, their loved ones, the hospitals, and improving healthcare. It can even extend to lessening the economic burdens of healthcare. There’s a spectrum of impact, but the far end is having some of these medicines and innovations become a standalone treatment that is well-known, used, and has great results.
I think that’s kind of why we always start with at least a vision that where we begin is years, if not, you know, sometimes a decade away. But we have to bear that kind of end goal in mind in my laboratory and make sure that we’re driving towards it.
It may not be a straight path. It rarely ever is. But we always want to have that sight in our view. But when it comes down to it, conducting clinical trials and bringing forward a medicine is an extremely costly endeavor and also a timely endeavor. So the kind of route, at least that I often try is if there are existing personnel, experience, manufacturing abilities, and distribution abilities available by an industry partner. For example, if I made a new MRNA, I wouldn’t necessarily think of creating a new MRNA company per se. There’s already a lot of them out there. I might have that patent licensed to a company that already exists and has the know-how and ability to translate that quickly to patients. If that doesn’t exist, if there isn’t know-how, manufacturing ability, or distribution ability, then I might consider a second option of creating a new venture. So that would be more of a startup-type route. That would mean securing resources, personnel, and experienced people who’ve done things before to shepherd that invention from academia into its own entity so that it can be the focus of a dedicated team to begin translations to reach the populations.
Q: I think this brings me to my final section about your research, which is that you mentioned all of these ventures and the people that are involved in your research. But what involvement do students have in your group and what type of experience do you want them to have?
A: I would say, you know, the students are at the heart of the engine here. I might have some sort of vision or experience and network to move ideas forward. But the ideas themselves are nothing without the students who are also conceiving those ideas alongside me. Sometimes this is translating and conducting those studies. faithfully reporting data, presenting that data outward through publications, through conferences. I think there is a moving car and students are often the engine, the wheels, and the windshield wipers. They’re the ones who are really keeping that car functioning. They have an experience, not only a technical one, learning how to do these techniques and conduct these types of testing. But they’re learning how to approach projects, where to have decision points, and how to develop a team around an idea.
When it comes to teaching, I think that the areas of teaching that I focus on are really synergistic with my work. I like to think of teaching as an area where I continue to want to learn as well. Whether that be theory and biophysical courses in teamwork, there’s kind of a spectrum of classes that I instruct. I would say not only am I bringing the experience to bear, but I also want to continue to stay up to date with the current best practices in literature in those particular fields. It keeps me a student again.
Dr. Parekkadan’s research is a platform for many other areas of research and is something that can be easily specialized. Seeing the advancements he works toward in his research is inspiring, as he works for the future of cell and gene therapies, aims to transform treatment for countless diseases, and inspires students to take a similar route. Seeing this broad approach to disease treatment, are there any specific areas of disease treatment you would like us to explore next?