January 2020: Meet the Vunjak-Novakovic Lab

 

Background:

What is the main focus of your lab?

We are interested in tissue engineering approaches for advancing biological research and improving human health. Our lab investigates innovative technologies for engineering human tissues – including the bone, heart, lung, vasculature, bone marrow - by an integrated use of stem cells, scaffolds, and bioreactors. Our long-term goals are to develop personalized treatment modalities for regenerative medicine (through whole organ engineering), tissue models studies of development and disease, and “organs-on-a-chip” for use in precision medicine.

How long have you had your lab? When did you join Columbia University?

Our Laboratory for Stem Cells and Tissue Engineering was established in the summer of 2005, when I moved to Columbia University.

How big is your lab currently?

We have about 35 lab members (2 assistant professors, 2 clinical fellows, 9 postdoctoral scientists, 4 MD/PhD students, 10 PhD students, a research director, an administrative coordinator, a lab manager, a research engineer, 2 masters students and 2 research assistants). In addition, about 6-8 undergraduate students participate in our research.

Where is your lab located?

Our Laboratory for Stem Cells and Tissue Engineering is located at the Columbia University Medical Center, on the 12th floor of the Vanderbilt Clinic, and has the state of the art resources for stem cell and tissue engineering research. 

Current affairs:

What are the most exciting projects/directions in the lab at this moment?

The two main  directions are: whole organ engineering for regenerative medicine (bone, heart, lung), and “organs on a chip” platforms for modeling human patho/physiology (inflammation, cancer, adverse effects of drugs). In addition, our lab is the home of the national Tissue Engineering Resource Center that is funded by NIH to develop and implement advanced technologies for tissue engineering and to provide service, training and dissemination.

What are the biggest accomplishments that your lab recently had?

In the area of whole organ engineering, we recovered severely damaged lungs that would be rejected for transplantation, by using our interventional cross-circulation platform. This platform can support the lungs ex vivo for multiple days and enables applications of cell therapy (e.g., Guenthart et al., Nature Communications and J Heart Lung Transpl.; Hozein et al., J Heart Lung Transpl. and J. Thorac. Cardiovasc. Surg).

In the area of “organs on a chip” we published a methodology for maturing the engineering human cardiac muscle to an adult-like phenotype (Ronaldson-Bouchard et al., Nature Protocols), a human tissue model of ischemia-reperfusion injury (Chen and Vunjak-Novakovic Tissue Engineering), and the quantitative patient-specific evaluation of neuromuscular function during the development and disease using an optically responsive human tissue model (Vila et al., Theranostics – cover article).

Technology:

What are the key techniques that your lab is using? 

We work at two very different scales.

For regenerative medicine, we focus on whole organ engineering, and in particular on growing anatomically precise living bone (now in clinical trials through one of our start-up companies), heart repair (with emphasis on the use of extracellular vesicles secreted by iPSC-derived cardiomyocytes, and lung  recovery (by treating  ex vivo the perfused and ventilated lungs that are rejected for transplant).

For studies of disease and testing of drugs, we use patient specific “organs on a chip” platforms in which millimeter-sized human tissues of interest, all derived from the same iPS cells, are connected by vascular perfusion into functional physiological units.

It is interesting that the same biological principles form basis for the engineering designs at these two different scales, and that the knowledge generated at one scale can directly benefit the other one. Because the regulatory  path for “organs on a chip” is very simple compared to  regenerative medicine applications, these systems provide a fast track for translating issue engineering into commercial and clinical applications.

How much do you collaborate? Are you training scientists from other labs?

Tissue engineering combines principles of life sciences, engineering and clinical disciplines towards generating functional equivalents of our tissues. Therefore, our collaborations with the stem cell scientists, clinicians, experts in systems biology, cancer and many other disciplines are essential for our work. Collaborations help us identify the most critical needs, the approaches to address these needs, and proper methodologies for validating the tissue functionality.

Many of our projects evolved in response to a specific biological question that could not be addressed using existing techniques, such as the “organs on a chip” models (to meet the need for predictive testing of drug safety and efficacy in a native-like context) or whole lung bioengineering (to provide more lungs for transplant for patients with end-stage lung disease). Having a lab located at the CUIMC has been critical for these interactions. In 2005, we were the first bioengineering lab on this campus, and now we are a part of a strong and growing community of bioengineers.

What facilities or equipment does your absolutely lab rely upon? Do you use CSCI cores?

Our lab is equipped for work with human stem cells and bioengineered tissues. These studies require rather diverse equipment, from standard systems for cell and tissue culture to sophisticated equipment for microfabrication, on-line measurements of cell and tissue function, application of physical signals, and conducting small and large animal studies. The Tissue Engineering Resource Center in our lab serves as a hub for the development and dissemination of advanced technologies for tissue engineering, tissue models for biological research, and clinical translation. We also rely on the Stem Cell Core (for derivation of patient-specific iPS cells) and a number of other cores across both campuses at Columbia University.

Who shall be contacted with questions about equipment, resources and training?

Susan Halligan <sph2130.@columbia.edu> who also coordinates our Tissue Engineering Resource Center.

Training:

What's your best approach to mentoring trainees in the lab?

Science is awesome, but is difficult. Being in academia is not a “job”, it is a lifestyle. This is why we want our lab to be an inspiring, engaging, challenging, rewarding, supportive and friendly environment for everyone. Mentoring is the most difficult and most rewarding among all things we do. In our lab, postdocs and clinical fellows help mentor graduate students, they all mentor undergraduate students, and everyone is involved in some way in this most important dimension of our work.

Who were your most influential mentors/role models in science and what did you learn from them?

As a graduate student at the Chemical Engineering Department at the Belgrade University  in Serbia, I had a fantastic mentor who supported me in all possible ways as I was navigating through my thesis research, and starting as a young faculty.  When I went for a year to MIT in Boston to explore bioengineering, I was incredibly fortunate to meet the ever inspiring Robert Langer, who has been my mentor, colleague and friend ever since. From these two people I learned what it means to be a great mentor. From my father, also a chemical engineer, I learned that we are only as good as the people we train – if they do not become better than we are, we probably failed somewhere.

What would be your career advice for students/postdocs?

Think big, so you can make difference. Work on something you are really passionate about. Be selective, so you can become the best at something. And never, ever give up.

Are you accepting rotating students at the moment?

We routinely accept rotating students, but the lab is currently at a full capacity, with all rotations for the current year already scheduled. 

Lab management:

How do members of your lab celebrate accomplishments?

We are very good with celebrating. We have cakes for everyone’s birthday, play ball in Central Park, ice skate, sing karaoke, have holiday parties, and once a year go to “Kafana”, a really nice restaurant in East Village that we have all for ourselves. We really try to celebrate our individual and collective accomplishments.

What is the key to running a successful lab

I believe that the key ingredients are the young talent, intellectual freedom, and a friendly collaborative environment. I try to get the best people I can, and help them find an important question they are interested in, instead of asking them to work on a predefined topic. Working together, respecting and trusting each other, being honest, and being available whenever your students may need you are all key for runninga  lab.

What was the most exciting part about starting your new lab?

When I moved from Boston, my greatest challenge was to build the lab. This really was a new beginning. Over the 15 years, our most important job has been to recruit great lab members, which we always do together as a team.

What do you bring to the CSCI community?

I was involved in the CSCI from its inception, serving on the Executive Committee and as a scientific director of the Stem Cell Core at the time when this important facility was being established. Since then, with the current leadership, CSCI has made great strides, has built significant new facilities and developed remarkable research and training programs. Our lab brings engineering support to the CSCI community, through the advanced models for basic and translational stem cell research that we can offer.