When you sit in the sun, or undergo chemotherapy, or age, or eat certain foods, millions of cells in your body respond. They must respond. They’re preprogrammed to respond because they need to survive. Sometimes, though, these adaptive responses go haywire and can play roles in diseases as diverse as cancers, Alzheimer’s disease, and gastrointestinal disorders.
Graduate student Patrick McCarter studies the mechanisms that control the responses inside cells. He wants to know how cellular signaling pathways operate in simple organisms, such as yeast, so that he can one day better understand the cell signaling underpinnings of human diseases.
We sat down with Patrick for a Student Profile to find out about where he’s from, why he chose biomedical research, and what he’s been working on at the UNC School of Medicine.
Name: Patrick Charles McCarter
Birthdate: April 28, 1987
Mentors: Timothy Elston, PhD, and Henrik Dohlman, PhD
Hometown: Parsons, Kansas
Education: BS in physics, NC A&T; masters in computational science and engineering, NC A&T. PhD student, bioinformatics and computational biology / program in molecular and cellular biophysics, UNC
Awards: Second place, best oral presentation, IMSD symposium at UNC
Dissertation: To understand how eukaryote cells respond to stress
Overall goal: To answer fundamental questions about cellular responses to environmental cues – such as hormones like insulin, or stressors like chemotherapy or radiation – to better understand the human response to disease
Extracurriculars: Mentor/tutor at Emily K center, basketball, tennis
“I was born and raised in Parsons, Kansas, a town of about 10,000 people in the southeast corner of the state. Mom worked for Ruskins , a manufacturing company. My dad still works for the U.S. Postal Service in Denver. My mom is now in Gastonia. She raised me. She always had higher expectations of me academically than I had. From the time I was a young kid, she pushed me to become well-educated, to go as far as I could. I don’t know if she thought I’d go quite this far – to a PhD. But she definitely wanted me to take advantage of opportunities she couldn’t take advantage of when she was growing up.”
“I didn’t know I wanted to get into science until my junior or senior year of high school. Before that, I thought I’d be a lawyer. I have older siblings, and I always seemed to win the arguments. At some point I thought, ‘maybe someone would pay me to do this.’ Also, in high school, I had some serious thoughts about things happening in society – some rulings in some pretty interesting cases about individual’s rights that I learned about in a pretty intense civics course.
“But then a neighbor moved in, and he was a civil engineer. He showed me some things he was working on and they seemed really fun and interesting. That’s when I decided I’d go into science. I wanted to become a physicist. That was my thinking going into college. So that’s what I majored in.”
Why North Carolina A&T SU?
“The idea of becoming a scientist was new to me, and I liked the idea of going to a place that would help me develop from the ground up. NC A&T SU is a Historically Black College and University (HBCU) with a small close-knit scientific community. That was important for me, more socially than anything else. Coming from Parsons, I thought I would be more comfortable learning there. It was good to meet peers of mine with similar interests. And its physics department was the right size for me"
“I did some really cool summer research in Newport News, Virginia, and in Ethiopia.
“After my freshman year, I had some interest in particle physics. The Thomas Jefferson National Accelerator Facility is in Newport News, and I was able to go there to help them design a particle detector. That was one of the benefits of coming from a small university; my advisor was a member of that facility.
“I worked on a very small component of the ultimate goal of the project. My job was to do simulations to help determine the final size of the particle detector for the accelerator– based on the type of particles they were shooting at it. This was interesting. It was my first experience doing simulations. Now I do them all the time.
“The summer after I graduated I went to Ethiopia to do geophysics with another advisor from college. This was great. Of the things I’ve done academically, this was the most enthralling, definitely one of the most fun times I’ve had doing research. That project wasn’t just about the research. We were looking for sources of fresh groundwater, which was really interesting. But it was also about the people I got to meet, the different cultures. It was about getting out of the bubble of the United States and North Carolina to see the rest of the world. It was just incredible.”
“I was part of a summer research program here as a master’s student. First, I wanted to do something in biology that was mostly physics applied to biology. I worked with Dr. Max Berkowitz in chemistry. I did some physics simulations of a small peptide. I loved it. I loved the idea of using my physics background to probe these biological systems quantitatively. Ever since then I’ve been hooked.
“UNC is such a great place. On a personal note, it’s really close to my family, which is mostly in North Carolina and Florida. And I had and still have an affinity for schools in North Carolina, especially coming from a different state and being able to look from the outside in. Once I was here, I didn’t see a good reason to move away. There are such great schools here, and UNC is one of the best in the country.”
Why two mentors?
“As a member of UNC’s bioinformatics program, you have the ability to choose an ‘experimental’ mentor and a ‘computational research’ mentor. Originally, I started out with Tim Elston, who does computational research. Tim and Henrik Dohlman have been working together for years. So it naturally progressed that I’d have a chance to model some of the data coming out of the labs. Now that I’ve been here a few years, I do modeling and experiments at the same time.
“Having two mentors helps me develop really interesting research questions from two different points of view – First, what are the best experiments that will help us build a really good model? And second, how can we use that model to propose some new experiments? So it’s one big circle.”
What’s your research about?
“I’m primarily focused on understanding stress response pathways. Our cells have preprogramed responses to some external stress. Ultraviolet radiation, for instance. A cell is hit by UV radiation and it has to undergo some process to respond and survive.
“What’ really interesting is that cells react in really robust ways to whatever goes on around them. But we don’t fully understand how cells sense and respond to changes in their environment.
“My research goal is to understand how a cell knows how much stress is being applied to it and how dangerous the extracellular environment is. Then once it understands how dangerous it is, how does it know when to start a response and when to stop the response? All of those processes are really important for the survival of the cell and, in essence, the entire organism.
“Our work is on the fundamental side. We want to know the key things that have to happen to get a response. We want to understand this in the simplest system, which for us is yeast. We can ask complicated questions in a simplified system and then try to extrapolate out to larger, more complex systems, such as humans.
“We just published a paper in January in Science Signaling, in which we experimentally showed that a protein has very interesting dynamics and then we were able to propose a mathematical model that could explain the behavior. We found that a key protein, called Hog1, which drives the stress-response of the cell, actually increases its own activity. It becomes activated by stress and then once activated it induces more activation of itself. In this case, it upregulates its own activity and then later in time, it down regulates its own activity. So you have this really dynamic profile for Hog1 in yeast. This is the first time that any lab has shown that it has a positive effect on itself.
“This is one of the most well-known and well-studied pathways we have available. It was known that Hog1 has a long-term negative effect on its own activation. That is, once activated, it later reduces its own activation. But interestingly, we found that early in the stress response, Hog1 also enhances its own activity through positive feedback loops.”
What do you hope to do with this?
“The ultimate goal is to take the expertise I acquire here and try to apply it to a more complex system. In this case, is there a human system that’s somewhat analogous to yeast where I could test some of these theories or models and find similar responses? Can we understand the human system as well as we can understand yeast? Or could we at least start going down that path where we find simplified systems so we can use some of these techniques to get meaningful insights into how disease states come about?
“We know that these stress response pathways have been implicated in everything from Alzheimer’s disease and ALS to cancers and tuberculosis to chronic diseases, such as Crohn’s disease.
“But when you move to a higher order of organism, how all these pathways work becomes more complicated. All kinds of proteins and pathways play roles together. So, it’s much harder work. But the way technology is going, I don’t think it will be impossible in the future to do this kind of research.”
What do you hope the future holds for you?
“I’ve always liked school, from the very first day of kindergarten to now. I like teaching and mentoring. My goal is to develop my own lab and teach, as well. I’d like to work with some undergrads and help them prepare for graduate school and the things they want to accomplish.
“I really enjoy mentoring. I’ve had great mentors for some time now, from A&T and UNC. But, I remember when I was starting my journey through education, especially when I moved here. I didn’t really have a main scientific mentor, someone helping me, guiding me, asking me the right questions, helping me to ask the right questions about what I might want to do. So that has always been something I wanted to do.
“I’d like to help students who have a similar inclination as I did and be able to say, ‘if this is what you want to do, then here’s the path I took. You should forge your own path, but here are a few things you should keep in mind.’
“It’s not purely altruistic. I get the satisfaction of helping someone else along their journey.
“But first things first. I hope to finish my PhD in another year and a half or so.”