Bringing the heart back to life
By Kimberly Eaton
Biomedical science can generally be broken down into two key areas: making new discoveries and developing new ideas. But for Mark Pepin, it began with a passion for solving problems.
“It’s a different way to approach the biomedical sciences,” said the 31-year-old South Carolina native. “As engineers, we tend to focus on the tools that make scientific discoveries possible, as well as their application to real-world problems.”
It was this passion for solving puzzles that led Pepin through his training in engineering, first with a bachelor’s in chemical engineering from Clemson University, followed by a master’s in biomedical engineering from University of California Davis. It was here that he recognized a strong desire to help patients as the missing puzzle piece in his training. The “secret ingredient” of biomedical science: medicine. He decided to develop his interest in both medicine and biomedical research as an MD-PHD student at UAB.
“It’s surprisingly hard to find universities that offer a balance of clinical competencies with cutting-edge research on campus,” Pepin said. “To be honest, UAB wasn’t on my radar when I started to apply, but when I arrived for the interview I found the perfect fit: innovative patient-centered research fully integrated within the clinical facilities. It is amazing.”
Through this dual-degree MD-PhD program, Pepin completed his first two years of medical school, and then transitioned into his PhD program in biomedical engineering. Although Pepin assumed he would look into muscular skeletal physiology and exercise, which was his background, his interests shifted to cardiology during his first two years of medical school.
“The heart is a more advanced machine than anything man-made; it is designed from materials that are alive, grow, and respond to their surroundings,” he said. “It really spoke to me as both a chemical engineer and medical doctor that we can study this amazing pump to treat patients with severe illness.”
That was Pepin’s introduction to cardiovascular medicine in science. From there, he chose Dr. Adam Wende’s lab because, among many reasons, it had “really cool tools” that were used to understand what goes wrong with the heart and why it fails.
The Wende Lab’s research focus is on understanding how alterations in the heart’s fuel supply can both cause heart failure and be disrupted in the heart when it fails. It studied these “metabolic causes and consequences” of heart failure, and Pepin’s project focused on epigenetics.
In broader terms, Pepin described his research using the analogy of a cookbook.
“In every cell or tissue, including the heart, there is a cookbook of DNA. The recipes used depends on the needs of the cell and the ingredients available to it. Epigenetics is a way of controlling which recipes of genes are available in this cookbook to determine how that cell functions.”
For Pepin’s project, he acquired human heart samples from UAB patients who had end-stage heart failure, “with their permission, of course!” They then looked at how the genes were being expressed inside the tissue, but also what the epigenome was doing and how the genes were being regulated in patients with heart failure.
“That was the core of my project – trying to understand how heart failure is associated with an epigenetic change called DNA methylation,” Pepin said. “It’s a modification that is known to regulate how recipes, or genes, are used. We were the first lab to show that DNA methylation is linked to how these hearts use different fuel sources for energy.
“When someone develops heart failure, as healthcare professionals we have treatments for patients based on what is causing their disease. My project helped to show that patients with heart failure display different epigenetic patterns that hopefully can be used to design better treatments in the future. At least, that’s the goal,” he added.
Pepin completed his Ph.D. in April 2019, and is now pursuing a postdoctoral fellowship in Germany.
“Despite having studied the theory and mechanism of heart failure for the past 6 years, seeing people suffer from it completely changed my understanding of it,” Pepin said. “Every patient is different. Some respond well to our current medicines, but others do not. This observation is what really excites me about my research. There are many ‘flavors’ of heart failure, and I think epigenetics will help us understand them better. Ultimately, we need medicine to treat each patient individually using therapies that address the underlying cause of disease.”
Pepin’s goal is to become a cardiologist and epigeneticist, which will require six more years of medical training. Regarding his long road of training ahead, he responds jokingly, “Is it still school when you’re having fun and making a difference? I already love what I get to do.”
Pepin hopes to start his own lab that studies epigenetics as a means of regenerating the heart.
“Currently, there is no way to fix a broken heart,” he said. “I want to change that.”
From menu to plate:
One doctoral student’s mission to improve nutrition in childcare centers
By Kimberly Eaton
Elizabeth “Lizzy” Kroeger had always loved children, so when it came time to pick a major, it made sense to choose elementary education. She wanted to be a kindergarten teacher.
She took her first semester of classes, and things were going great, but then a friend told her about this nutrition program she was in and Kroeger started wondering if she was on the right path.
“I had always loved reading nutrition magazines and learning about health and nutrition,” said the 29-year-old North Carolina native. “I would get so frustrated that one day you would hear something was good for you, like eggs, but then the next day you’d hear it wasn’t good for you. I always wondered why researchers couldn’t get the message right.”
It was this annoyance with the conflicting nutrition messages being shared with the public that caused Kroeger to not only change her career path, but also instill in her a desire to dive into research.
“I wanted to be able to answer some of these questions,” said Kroeger, a recent graduate of UAB’s Doctoral Nutrition Science program. “Now that I’m here, I realize it’s a little harder than I thought. I get why researchers have conflicting messages now.”
Kroeger chose UAB for her graduate studies because her mentor, Dr. Brenda Bertrand, had become UAB faculty about a year before. By the time Kroeger arrived, her mentor had established some funding to disseminate an existing curriculum that focused on infant and preschooler nutrition in an underserved community.
However, no one would show up to the educational sessions; the community was just not interested. It was Kroeger’s job to help identify next steps in order to make this project successful, and to make a positive impact on this community.
The decision was made to work directly with childcare centers, since the curriculum met the continuing education needs of the teachers and directors. It was through these conversations that Kroeger identified her research problem. Many childcare centers wanted help improving the nutrition at their center. Going this route would also be a little tricky. Kroeger quickly realized that each center had different reasons that contributed to the nutrition status of the center. Not every center was the same, so a one-size-fits-all approach to improve the nutrition at childcare centers was not going to work.
“A lot of interventions being done to improve the diet quality of children in centers were being done at the individual center level,” Kroeger said. “Researchers would go into one, try to improve diet quality and see if it worked, then go into the next one. That’s not the most effective strategy because it takes a lot of time. I wanted to look at all of the different characteristics that could influence diet quality in a childcare center and then create something similar to a Turbo Tax system. Each center fills out information about their center and then it spits out a guideline for improving diet quality in that particular center.”
Kroeger and her team of undergraduate honors students worked with 53 centers in eight Alabama counties. This did not include home-based centers. The centers also had to be within 50 miles of UAB and had to serve lunch to the children. These visits were completed between summer 2016 and fall 2018. Each center filled out a questionnaire that included information about the number of staff employed, the kind of kitchen equipment they had, general demographics about the center, as well as median income, food policies and more. The questions were selected based off current research, handbooks and guidelines and best practices from different academies, Kroeger said.
The team also did lunch observations where they observed three children at each center while they were eating lunch. The team recorded what the children were served and the amount, as well as what the children ate and the amount. Essentially, Kroeger was measuring diet quality in the centers in three different ways -- an analysis of what the children were served, what they actually consumed and what was actually on the lunch menu for that day – and comparing the three.
“When referring to diet quality we mean are the centers meeting the dietary guidelines set forth by the U.S. government,” Kroeger said. “The Healthy Eating Index just says how well you’re meeting the My Plate standards. A higher score means you’re eating better.”
Many times the diet quality on a childcare center’s menu was higher than what was actually served and what was consumed by the children, Kroeger said. This means that what was listed on the menu had a higher score, but what was being served had a lower score. Kroeger was not sure why there was a discrepancy but speculated it could be the center was worried the children would not eat what was listed on the menu, so they made substitutions.
However, what they found was that children were generally consuming what was served.
“We think children aren’t going to eat what we consider better diet quality, like vegetables, but what we’re seeing is if they’re served it, they’re consuming it” she said. “We just have this gap from what is on the menu to what is being served and that’s where we want to focus our interventions. Overall, diet quality is just poor in childcare centers, but the first step is making sure that what the children are served is what’s on the menu.”
There are also things childcare centers can do to improve diet quality that are fairly easy.
“Just sitting down during a meal and talking to them about new foods -- what does it look like, what color is it, how does it feel if you touch it,” she said. “Seeing the teachers and everyone else trying it as a group has been shown to help children try it themselves. Also, just expose them to a new food. If children are exposed to new food a certain amount of times then they are more likely to eat it later. Even if they hate it and throw it, at least you’re exposing them to it.”
Since this project specifically looks at diet quality in the childcare center, it doesn’t address diet quality once the child is at home. However, Kroeger said she is working with undergraduate honors students who want to develop a pilot nutrition curriculum that connects the home and childcare center so the children are hearing consistent messages in both places.
“When I first started this, I thought if I could help children improve their diet quality for the majority of what they’re eating, then that’s a start,” she said. “They’re usually at the center for eight hours and, during that time, they typically have breakfast, lunch and two snacks. Even if the center doesn’t serve breakfast, the children are still eating lunch and two snacks. They are consuming 75 percent of their daily caloric intake. That’s a majority of what they’re eating during the day. That’s my focus right now.”
Results from Kroeger’s study were published in the Journal of Nutrition Education and Behavior. She defended her dissertation in February of 2020 and is working on publishing the remaining findings. Kroeger is now an assistant professor in the department of nutrition sciences and the director of the Dietitian Education Program in the department.
A love of animals and reading leads to dream master’s degree
By Kimberly Eaton
Jessica Robbins has loved animals for as long as she can remember. She got her first puppy, Molly, at the age of 6, and the two were the best of friends until Molly went to “puppy Heaven” six years later. Over the years, more dogs would find their way into her heart, but when she discovered cats, she realized that was the animal for her.
Robbins had always wanted a career that involved animals, but her tender heart could not bear the thought of seeing them hurt, so being a veterinarian was out of the question. Little did she know that she would be able to combine her two passions – animals and reading – as a graduate student at UAB.
“I’m not a scientist so I never thought I would be able to study animals, but I didn’t realize there were people out there who studied animals in literature,” Robbins said. “I wrote my first paper about animals when I was a freshman, and it was probably the most pretentious thing you could imagine. It was about how animals were mistreated and I was grossly misinformed. It is hard to find reliable research about this topic because it’s so polarized.”
The 23-year-old Birmingham native transferred to UAB from Bevill State as a junior and received her undergraduate degree in English. Her goal was to work in higher education, and she knew she needed a master’s degree in order to do that, so she applied to the Master of Arts program in English.
Robbins discovered animal studies theory when she first started at UAB and wanted to learn more, but there were no other classes devoted specifically to that topic. So, Robbins developed her own, with the help of Dr. Rebecca Bach. The two developed a reading list and projects for the different books, and built a syllabus based on those two things.
“I went into it thinking this was going to just be a normal course, except I would be the only student, but because it was mine to do whatever I wanted with, I got so much more out of it,” Robbins said.
Initially, Robbins was going to complete a midterm and final paper, but she posed the idea of writing a literature analysis for publication and her professor was “all for it.” Robbins focused her energy on finding something she liked and spent the whole semester researching and writing, in addition to keeping up with her actual reading list.
After some digging, she finally settled on using Richard Adams “Watership Down” for the basis of her literature analysis. The novel looks at the domestication of animals, but Robbins noticed conflicting views in the reading and decided to study those views more closely through the “lens of these theorists” she had been reading all semester.
“Essentially, what the novelist is saying is that domestication is complicated,” she said. “One of the arguments is that he’s redefining what domestication means. It’s more than just a human that takes an animal and makes it into a pet or something sterile for the home. It’s more like taking all kinds of animals – human and nonhuman alike – and bringing them into a space where they can co-habitat with one another, whether that’s a bunch of rabbits or rabbits and humans or rabbits and birds. It’s a way of learning how to co-habitat with another animal under a set of rules that the two parties have learned to live with together.”
Her literature analysis looked at parts of the novel and analyzed where the contradictions come up and how that aligns with the theories that focus on ways animals work in real life. She used three primary theorists in her paper – Donna Harraway, Kari Weil and Erica Fudge.
Robbins said she used Harraway a lot in her writing because she loves her work as a theorist. Harraway looks at the “messy history” of humans and dogs and says, “multi-species living is the game of getting along together.”
“It’s the process of getting along together and all of the nastiness and all of the learning that comes with that because it’s never a clean process to learn how to live with another animal, even if it’s your spouse or someone you think you know really well,” Robbins said. “I felt the novel ‘Watership Down’ really embodies that.”
Another theorist that she read and had a close connection to is Cary Wolfe, who proposes the idea of approaching all relationships with skepticism. Robbins said she has tried to use that approach with not only animals, but also humans.
“It’s essentially the idea that you can’t predict how any interaction is going to turn out before it happens,” she said. “I really like the idea of approaching everything with curiosity as opposed to thinking you’re superior to it just because you think you know more.”
While the bulk of her semester involved reading “Watership Down” and writing her literature analysis, Robbins also read a slew of other books, including “Animal Farm,” “The Bear,” “Fantastic Beasts and Where to Find Them,” “Pride of Baghdad,” “Mastiff,” “The Open: Man and Animal,” some short stories and essays, “The Jungle Books” and more.
The result: an opportunity to present at a conference, which she was not expecting when she created the class, and, hopefully in the near future, a published paper. In addition, Robbins figured out her master’s thesis. Through reading “The Jungle Books” and “Tarzan of the Apes,” Robbins initially thought she would look at human behavior and human identity. The protagonists in each novel grows up in a world with animals and their identities change dramatically when they figure out they are actually human. However, her master’s thesis ended up being a little different from what she had originally planned. She decided to look at the ways in which the seal stories (“The White Seal” and “Quiquern”) in “The Jungle Books” push back against the idea of human exceptionalism. She defended her thesis and passed in April 2020.
“I really love reading children’s literature,” Robbins said. “There’s so much that children’s authors try to do with animals that’s weird and interesting. There’s just an endless amount of questions to ask, and the more I read, the more curious I become.”
Robbins is currently the Coordinator of Tutoring in the Learning Enrichment Center at the University of Montevallo. She manages and supervises the peer-tutoring program and helps students get connected to tutoring when they need it. While she was in graduate school at UAB, she had wonderful opportunities to work in both the writing center and in student-athlete support services, both of which prepared her tremendously for this position.
A journey based on curiosity
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- Written by: Kimberly Eaton
A journey based on curiosity
By Kimberly Eaton
Catherine Scull has always believed the best research comes from scientists who are curious and unbiased.
“Some of the most amazing discoveries in history came from someone who saw an interesting system and went after it, and now it’s become revolutionary to the field,” said the 28-year-old Florence native who, in March 2020, received her doctorate in biochemistry and molecular genetics.
It was this thought process that led Scull to her graduate research area – studying a system that could be used for cancer therapy.
“My goal was to study something I think is really cool, but also has positive benefits for human health,” she said. “I didn’t get into this area of research because I’m super passionate about curing all cancer, but I think the system is really cool to study. It wasn’t necessarily the disease, but the science around the disease that I found fascinating and the fact that it could really help people one day was a bonus.”
Scull joined the lab of Dr. David Schneider early on in her graduate studies because she loved the different types of research conducted in his lab. Since joining, she has explored everything from cancer research using cell cultures to purified systems using protein dynamics and kinetics. She spent a large part of her doctoral student career studying a protein called RNA Polymerase I, also known as Pol I. This protein makes the ribosome, and it is a potential target for cancer therapy, Scull said.
“The idea is that if we can decrease the number of ribosomes in cancer cells, then we can decrease their protein synthesis and that will inhibit the cell growth,” she said.
She initially executed studies on actual inhibitors of ribosome synthesis and those studies resulted in one published paper with a second paper currently in submission.
In these studies, Scull studied the rate at which Pol I synthesized ribosomal RNA by looking specifically at the changes that can be made to the polymerase to alter the rate of RNA synthesis. To do this, she grew cells in cell culture and used different techniques to measure ribosomal RNA levels in the cell. Scull then perturbed those RNA levels with potential therapeutic inhibitors to observe their effects on cell growth and viability.
Scull also executed a number of studies on the fundamental properties of Pol I while she was in graduate school.
“I take the polymerase, give it DNA and watch as it synthesizes RNA,” she said. “Then I give it a radioactive nucleotide, which allows me to visualize the process. So far, I’ve mostly just made changes to the polymerase, like getting rid of parts of the polymerase or changing parts of the polymerase from one thing to another, to see how that impacts the rate at which it adds nucleotides. When we change different parts of the structure, we can see how those parts contribute to the polymerase’s activity – how fast it goes, how well it binds to the DNA or how good it is at reading the DNA and making the right RNA.”
Scull’s overall goal is to understand the biological system. People and all eukaryotes have three Pols, but prokaryotes, like E. coli, only has one. Why? Scull said it turns out that the three Pols have specialized roles.
“So now, the question is how are they different, what implications does that have on the way they work and what does that mean for human health and different diseases that involve the three polymerases?” Scull said. “And, in the case of using it to inhibit cancer growth, how can we specifically target this Polymerase I versus inhibiting the other two?”
By the time Scull graduated, shepublished five papers, four primary literature studies and one review, and was first author on all of them. She currently has two additional first-author manuscripts in submission for publication. She has also presented at numerous conferences, seminars and poster sessions, and this year was awarded UAB’s Samuel B. Barker Award for Excellence in Graduate Studies.
Scull interviewed for postdoctoral positions at major scientific institutes around the country, and ultimately decided to pursue a position in the Department of Chemistry at the University of Michigan in the lab of Professor Nils Walter as a Michigan Life Sciences Postdoctoral Fellow. In the lab of Nils Walter, Scull will investigate RNA folding dynamics at the single-molecule level using cutting-edge technology. She believes a postdoc is a good time to branch out and explore somewhere new, but Scull said she would love to come back to UAB as a faculty member when she finishes her fellowship.
While Scull has been incredibly productive and successful as a graduate student, it was not without its challenges. She said her two biggest obstacles were public speaking and learning how to deal with negative data.
“Confidence is the one thing that graduate students have to learn,” she said. “The ability to take constructive criticism and not take it personally. You can’t take your science personally. I’ve had to overcome. All students have to overcome. Imposter Syndrome is real. There have definitely been times that I felt I didn’t belong in graduate school, but I just focused on the scientific questions and why I’m here and why it’s fun and the other stuff gets less scary.”
The Graduate School now offers automatic admission into a master’s program for exceptional high school students. Beginning with the Fall 2019 cohort, any high school senior who qualifies for UAB’s Presidential Scholarship is also offered admission into the Graduate School’s Early Acceptance (EA) program. This exciting new program offers guaranteed admission to any participating master’s program, provided the student meets necessary pre-requisites.
“Early Acceptance is a fantastic way for UAB to recruit and retain its best and brightest students,” said Jesse Keppley, Director of Student and Academic Services for the Graduate School. “It gives us a competitive advantage when recruiting and gives these students peace of mind knowing they don’t have to worry about graduate school. And we are able to offer them a wide range of interest areas, with eligible programs offered in every school across campus.”
But the benefits don’t end there. Applying to graduate school can be tedious and expensive, but EA students don’t need entrance exams and won’t pay an application fee. They can also use any unspent scholarship dollars for graduate courses even after their undergraduate degree is awarded.
Even in its initial year, Early Acceptance met with immediate success. In Fall 2019, the Graduate School sent out 1,851 letters to qualified applicants and ended up enrolling 351 Early Acceptance students.
“We initially thought we might get 200 students to participate,” Keppley said. “The immediate success of this program speaks to the strength of our graduate programs, and to the dedication these students have to their education.”
This success led to the hiring of Mellissa Taylor to serve as Accelerated Learning Opportunities advisor for UAB. Recognizing these are high school students, it’s likely their interests may evolve as they learn more about where their academic and professional interests lie. Taylor’s job is to bridge that gap and serve as a resource for these students.
“I am excited to serve this growing group of students through advising sessions and creative events to help them learn more about the various programs involved in Early Acceptance,” Taylor said.“While Early Acceptance is still so new, we are seeing the fruits of our labor as a handful of our Early Acceptance students beginning to enroll in Accelerated Bachelors Masters and Fast Track programs.”
Starting out with 11 participating masters programs, EA ballooned this past year to a robust 27 offerings. And student interest hasn’t slowed down either. For the 2020 cohort, 2,070 letters were sent out, and 369 students have already accepted their Early Acceptance offer.