The bioengineer investigating stem cell self-organization

Every year, Yale’s Faculty of Arts and Sciences welcomes exceptional scholars across the sciences, humanities, and social sciences. This series profiles six of the faculty joining the FAS in the 2025–26 academic year, highlighting their academic achievements, research ambitions, and the teaching they hope to do at Yale. Learn more about the incoming faculty joining the FAS.  

To become the person reading this, your body has had to undergo countless complex biological processes. 

One of the very first things your cells did was form an anterior-posterior axis. This central structure indicates where different tissues like the brain, heart, and gut should develop, and creates a blueprint around which the rest of the body takes shape. 

But how exactly our cells talk to each other, and how they decide which cell will become what part of that axis, is still a mystery—one that Harry McNamara is using every discipline in his toolbox to solve. 

“What I like about developmental biology is there's an argument that it's the most interdisciplinary and intersectional of scientific fields,” McNamara explains. “You have to understand molecular biology, genetics, cell biology—and understanding tissue morphogenesis is also a physics problem. You also have to think about all of this in the context of evolution and to understand how different developmental programs emerged.”

McNamara joined the FAS this past spring as Assistant Professor of Molecular, Cellular, and Developmental Biology, with a secondary appointment in Physics. 

As a developmental biologist with a PhD in physics (Harvard), master’s degrees in bioengineering and nanotechnology (Trinity College Dublin and Cambridge, respectively), and a dual-major bachelor’s degree in physics and Ethics, Politics and Economics (Yale), it’s no wonder McNamara brings a highly interdisciplinary approach to his work. 

“That's what I like about developmental biology,” he says. “You can draw from all of these different spaces and not have to limit yourself in one or the other.”

Cell communication: a question of basic science

McNamara is a firm believer in the power of basic science, and his research questions drive right to the heart of why it’s so important.

“I’m really interested in how cells communicate with each other to make decisions about what types of cells they should become, or what types of tissue structures they should build,” he explains. 

His lab focuses on two developmental paradigms: the formation of the body axes and the development of neural tissues and neural networks. It’s crucial for us to understand how cells self-organize early on, McNamara says, especially scientists working to discover how exactly the brain functions. “The things I think are most amazing about the brain are how it builds itself and how it self-organizes patterns of activity. I think there are deep connections between these fundamental questions about how cells self-organize early in development and how neural networks form and wire up.”

A developmental biologist with an engineer’s sensibility, McNamara’s lab is using stem cell models as miniature physics laboratories to try and understand the functional principles of how cells communicate with each other to build structures and organs. The models, also known as gastruloids (which model embryonic structures like the anterior-posterior axis) or organoids (which model the development of certain organ systems), are the perfect testing ground to understand how cells are building the body’s crucial tissues. “I come from a background in physics and engineering originally,” he notes, “so to me, one test of whether you understand a system is whether you can actually build it from the bottom up.”

His work with stem cell models now broadly uses three experimental approaches. The first involves using a signal recording technique to map how cells communicate to form the anterior-posterior axis. “We programmed cells with genetic circuits that could record memories of early signaling states,” he explains, allowing the investigators to look back in time and see how early signals guided cells’ eventual location. “This signal recording strategy gives a way to decode, if you will, how some of these self-organizing programs work.” 

McNamara’s lab is now extending the use of the signal recording technique to new types of stem cell models and organoid systems, including neural organoids. “A lot of these same signals that are used to make the early body axis get reused later, for example, to pattern different regions of the brain. So, you can take the same strategy and try to understand different developmental programs.”

The second approach McNamara’s lab is utilizing is optogenetics, a method for controlling patterns of biological signals using light. The third approach is a method called voltage imaging, used to look directly at electrical signaling activity in cells. This method enables new measures of neural activity during development and can also probe new roles for electrical signaling in other developmental processes. 

“As a bioengineer, you can take light-sensitive proteins from other organisms and essentially wire them up to cells’ developmental signaling pathways and get them to respond to light, rather than to the intrinsic signal,” he says of the optogenetic approach. “This is a way in which you can play back developmental programs and try to control the signals that drive pattern formation.” 

Though applications for his research could eventually include improved human disease modeling and cell therapy, right now McNamara is focused on answering questions about the fundamental mechanisms behind how cells communicate. 

“For me and my lab, at least for now, we think there's a lot of work to do just really understanding how these systems work.”

A new chapter at Yale

McNamara’s interests in developmental biology and neuroscience allow him to fit right in at both of his on-campus homes: the department of Molecular, Cellular, and Developmental Biology and Yale’s Wu Tsai Institute, an interdisciplinary hub that connects neuroscientists and data scientists to help accelerate our understanding of cognition.

The ambition to tackle huge questions is one thing he’s enjoyed about being part of Wu Tsai. “I've been really excited about how both interdisciplinary and frankly ambitious the community here is,” he says. “It's a place which does not shy away from big ideas and big swings.” And he appreciates the welcome he’s received from the MCDB faculty, who McNamara says are “really great neuroscientists and developmental biologists and microbiologists and plant biologists and people across all corners of biology” with similarly wide-ranging interests.

McNamara wasn’t sure how he’d feel being back at Yale, given the many special memories he’d made as an undergraduate in Branford College, but it’s been “a good balance of familiarity and refreshingly different,” he says. 

He’s come full circle this fall, teaching a neurobiology course with MCDB Professor Haig Keshishian—“one of the two MCDB courses I did actually take as an undergrad,” McNamara notes—and this spring he will co-teach a course on using math to model different biological processes.

He thinks it’s an important and exciting time to work at the intersection of developmental biology, neurobiology, and biophysics, particularly with new technologies including synthetic biology and optogenetics. 

“Certainly, there's a lot we’ve figured out in developmental biology, but there are a lot of really fundamental problems that aren't solved,” he says of the field's current state.

While classic developmental biology was about taking biological systems apart, he says, “now I think we can try to put systems together and understand not just the individual details, but the physical principles through which they work.”