April 2021: Simunovic Lab
What is the main focus of your lab?
We study early human development. At the intersection of developmental biology and engineering, we build quantitative stem cell-based platforms to investigate the signaling and the mechanics of embryo implantation, gastrulation, and organogenesis. In applying our learned mechanisms, we are making experimental models that will shed light on early pregnancy disorders in hopes to advancing women’s reproductive health.
How long have you had your lab? When did you join Columbia University?
We opened doors in January 2020, just at the onset of the pandemic.
How big is your lab currently?
We are a multi-disciplinary lab with three PhD students from Chemical engineering, one from Genetics and development, a co-mentored student from Biomedical engineering, as well as four undergraduates, and an independent research fellow from Systems biology.
Where is your lab located?
We are in Lasker, along with several Engineering and Systems biology labs.
What are the most exciting projects/directions in the lab at this moment?
Organoids have seen a tremendous success in the past decade, with an explosive progress in the field of early embryogenesis over the last three or four years; however, current approaches heavily rely on tissue self-organization created by randomized internal signaling gradients. Where I see the future of the field is in combining efforts from engineering and biology so to recreate the signaling and the mechanical complexities that drive the actual development of tissues in vivo. This is the main direction of our lab. We engineer precise signaling gradients and biomimetic substrates so to reproduce the detailed complexities of early human organogenesis in vitro. This approach will not only help us understand the detailed molecular mechanisms of embryogenesis, but it will start to shed light on what makes us uniquely human.
What are the biggest accomplishments that your lab recently had?
In what took about one year, in the midst of a once-in-a-lifetime pandemic, we started from a completely empty space on an unoccupied floor and built what is now a fully equipped stem cell lab, comprising a vibrant and talented group of eleven researchers producing exciting results every day. I’ll call that a major accomplishment.
What are the model systems that your lab is using?
Our primary tools are human pluripotent stem cells, CRISPR genome editing, and tissue engineering. We inherited many cell lines created over the years in the Brivanlou lab at Rockefeller where I did my postdoc, but we are also creating new and exciting transgenic hPSC lines (fluorescent reporters of cell fate, cell cycle, cell polarity, as well as many knockouts of various signaling pathways), which we are happy to share.
What are the key techniques that your lab is using? Are you open to training scientists from other labs?
We are experts in manipulating signals and signaling gradients with genome editing, tissue micropatterning, microfluidics, and biomimetic matrices, which we create and develop in house. We would be thrilled to collaborate with other CSCI labs in developing quantitative platforms for reproducible and gradient-controlled organoids.
What's your best approach to mentoring trainees in the lab?
That’s a hard question to answer. I don’t think there is one best approach as no two students are alike. One thing that in my opinion is crucial though, is to never stop working on improving as a mentor. Each trainee at the beginning of their journey in our lab goes through a training pipeline to learn the ropes, usually starting with the proper sterile technique in the tissue culture room. Once that is out of the way, I like asking new members to make an organoid of choice, even if it’s not something they will focus on in the future. There is really nothing that will get you engaged in this exciting field quite like converting a cluster of cells into human cardiomyocytes that rhythmically beat on a dish right in front of your eyes.
Can you recommend courses/lectures in Columbia University that would be most beneficial for students/postdocs? Last year I started a new course, Synthetic Organogenesis, offered by Chemical engineering. It is a multi-disciplinary course, appropriate for both engineers and biologists, where we discuss, well… how to make human organs in a lab. We take on a historic journey in the field and tease out the rules of making individual organs: first in vivo, and then in vitro, focusing on organ on chip methods, organoids, and even human-animal chimaerae.
What would be your career advice for students/postdocs?
Celebrate every accomplishment, big and small. Don’t only celebrate when a paper is accepted, celebrate when it’s submitted! It’s such a milestone. Celebrate a successful gel, a good PCR result, a new transgenic line, a new observation. I think also in academia, there is a self-fulfilling prophecy that it’s not possible to succeed without a high impact paper. And while I recognize a lot of work needs to be done to break this value system, I would advise the trainees to embrace and appreciate their own unique career trajectories. Don’t hesitate to seek support from your mentors and your peers. It’s hard for me to imagine I would have accomplished anything without the right support.
Are you accepting rotating students at the moment?
We are always happy to consider new students, at any level, and from any background. We are highly committed to supporting students from underserved populations. Would you like to build mini organs from stem cells? Don’t hesitate if you don’t have experience or really don’t understand how it works. Very few students coming into our lab do, and we provide everyone the opportunity to learn.
Stem Cell Directions
What are the most important recent developments in the stem cell field?
We are now at the point where we can maintain human pluripotent stem cells in different states of naïveté, each with its own unique developmental potential, use CRISPR to manipulate their genomes at will, and employ sophisticated engineering approaches to direct cell fate acquisition in time and in space. In the near future, we will build on these breakthroughs to integrate such seemingly disparate disciplines to not only create better organoids, but to truly bring organoids much closer to regenerative medicine.
What was the main reason of you joining CSCI? What are the beneficial aspects of CSCI membership for your lab?
It really takes a village to make substantial progress. The future of our field is in finding ways to combine a multitude of expertise to truly elucidate human organogenesis and accelerate their use in elucidating fundamental questions in biology and evolution, and in personalized and regenerative medicine. No one lab can accomplish such an ambitious task on their own. The CSCI uniquely offers cross-disciplinary collaborations without the strict departmental boundaries, and in this way, I think, promotes new and innovative approaches to stem cell biology.
What do you plan to bring to the CSCI community?
Gastrulation and the onset of organogenesis are truly a black box in human development and early pregnancy, and I hope the CSCI community will appreciate our quantitative point of view in investigating these important phenomena.