USC Professor Megan McCain crafts an approach to tissue engineering

Megan McCain and family
Megan McCain and family (Photo by Adam Mueller)

Megan McCain has always liked using her hands to create things, ranging from art projects to human heart cells that grow on silicon chips.

“I’ve always loved building things and doing crafts, which drew me to engineering,” said McCain, who was recently awarded tenure as an Associate Professor and the Chonette Early Career Chair in the departments of Biomedical Engineering, and Stem Cell Biology and Regenerative Medicine at USC.

Growing up in St. Louis and Boston, McCain had dreams of becoming a Disney animator, and also excelled in math and science. She started her undergraduate studies as a graphic design major, but soon switched to biomedical engineering at Washington University in St. Louis.

“When I was younger and learning textbook knowledge, I didn’t really think about the process of discovering new knowledge. But as I matured and was exposed to more fields, I started seeing that there is a lot of creativity also in science,” she said. “I got especially excited about biomedical engineering because it is so interdisciplinary. It brings together a lot of different fields and types of skills to impact human health.”

The summer after her sophomore year, she had the opportunity to perform research as an intern at Pfizer in St. Louis. In the laboratory, she used human cells to test whether drugs caused arrhythmia or other toxic side effects on the heart. The following summer, she interned in an immunology lab at the National Institute on Aging in Baltimore. Back on campus at Washington University, she also did research during her junior and senior years in a laboratory that uses fluorescent dye to visualize the electrical signals that direct heart cells to contract and beat.

After experiencing the research environment at a drug company, in a government lab and in academia, she knew that her next step was graduate school. For her PhD, she joined the laboratory of Kit Parker at Harvard University.

“He’s a bit unconventional,” said McCain. “He was in the military and brings that leadership style to the lab. He holds his trainees to a very high standard and empowered me with the mindset to push the envelope.”

In the Parker Lab, McCain learned many of the tissue engineering techniques that she continues to use to this day.

Using a similar approach to how computer chips are manufactured, she began making tiny silicon wafers that could be seeded with heart muscle cells called cardiomyocytes. By engineering these “hearts on a chip,” she could grow rectangular cardiomyocytes with either the normal length-to-width ratio of healthy cells, or with the fatter or skinnier dimensions of diseased cells.

“If you have a heart attack, injured cardiomyocytes will be replaced with scar tissue, so the heart can’t pump as strongly,” she explained. “In response, the surviving cardiomyocytes will change their shape and therefore the force they generate. So by engineering cardiomyocytes that mimic the shapes of cells coming from a healthy heart versus a diseased heart, we could better understand the progression of heart failure after a heart attack.”

During her PhD, she also spent a year in Switzerland, where she learned a technique called “dual patch clamp,” which involves using electrodes to quantify the electrical current flowing between adjacent heart cells.

Her PhD thesis combined these different techniques to study how a cardiomyocyte’s shape, stiffness and other physical characteristics affect its function, including contractile strength and electrical signal propagation.

Most newly minted PhD scientists pursue several years of postdoctoral training before applying to faculty positions, but Parker encouraged McCain to dive directly into the job market. USC’s Department of Biomedical Engineering was hiring a faculty member with expertise in cell and tissue engineering, and McCain turned out to be a perfect fit.

“When I visited USC, I toured my current lab space, which was already being renovated with all the facilities I would need,” she said. “So I had a good feeling about the environment and support I would have at USC. I was also really excited by the opportunity to help lead and shape this brand-new area of the department.”

Before starting her faculty position at USC, McCain stayed in the Parker Lab as a postdoc for a year and a half to finish her projects and gain leadership experience in helping manage two large organ-on-chip projects.

Shortly after McCain began her faculty position in USC’s Department of Biomedical Engineering, she was invited to hold an additional appointment in the Department of Stem Cell Biology and Regenerative Medicine. Since then, she’s engaged in collaborations with several USC Stem Cell scientists to engineer better models of ALS and kidney disease, to grow more physiologically relevant skeletal muscle, and to build microfluidic devices to generate rudimentary mini-brains called organoids.

“Organs-on-chips used with human cells are so powerful for personalized medicine, but I’m not a stem cell biologist,” she said. “So my lab needs to work with  stem cell and developmental biologists, who are experts in making different cell types from human stem cells.”

In her own lab, her team is using devices with microfluidic channels that create an oxygen gradient to mimic what happens when a heart attack interrupts blood flow and oxygen supply. Along with scientists from Cedars-Sinai, she is studying how cardiomyocytes function and communicate during these “heart attacks on a chip.”

McCain recently embarked in a new direction when she received a prestigious National Science Foundation Career Award to develop a “uterus on a chip”—a platform to study the processes of labor and to screen for drugs that might be able to delay preterm birth.

“I got very interested in the uterus while I was pregnant with my first son,” she said. “And it’s a good thing, because there’s actually very little known about the uterus. It’s definitely been neglected in biomedical research compared to other organs. And I think bringing more light to women’s health in general is important.”

McCain also enjoys teaching undergraduate and graduate courses in tissue engineering and biomaterials, covering topics including stem cells and 3D printing. Starting in Spring 2022, her undergraduate course will incorporate hands-on lab work in a newly renovated space at USC Viterbi.

She has also worked with USC undergraduate volunteers to teach biomedical engineering to students from Orthopaedic Hospital Medical Magnet High School. With support from a USC Good Neighbors Campaign grant, she has guided the high school students in how to use Shrinky Dinks to make devices similar to the ones she uses for “organs on chips.”

“A Shrinky Dink is a thin sheet of plastic that you can color with colored pencils. Then you cut it out and put it in the oven and it shrinks into a stiff piece of plastic. It is usually used to make crafts like Christmas ornaments and key chains,” said McCain. “With the high school students, we printed designs for microfluidic channels onto Shrinky Dinks and then shrunk them down and used them as templates for making simple microfluidic devices. In my lab, we make organs on chips using similar processes, but with more precise tools. So this taught them the basic concept with cheap and available materials.”

Since being awarded tenure in March 2021, McCain feels like she can focus more on the projects that inspire her the most, and let the others fade away.

“Tenure has changed my mindset. I have more confidence in my ideas and leadership abilities,” she said. “I also feel like I have more freedom to explore different areas, and if things don’t lead to a publication right away, that’s okay.”

The pandemic provided an additional reminder to focus on what really matters in her life.

“Right now, my husband Leo and I spend all our time either working or taking care of our two boys. We are trying to enjoy it now since that will quickly change as they get older and more independent. Our younger son is only five months old but growing fast,” she said. “I started taking my older son, who is almost three, to toddler yoga classes in the park on the weekends. He learns animal poses, like frog and butterfly. I like to bake, too, so he helps me with mixing and stirring. One of the benefits of being faculty is we have flexibility in our schedule, so it is easier to make time for family.”

Mentioned in this article: Megan McCain, PhD