R. Michael Roberts

Seeing the bigger picture through applied research projects

June 6, 2022 By Penquite, Cara (MU-Student) in Research Tags: applied science, basic research, biochemistry, Mizzou Research, research

Investigators at Bond LSC take steps to apply basic research

By Cara Penquite | Bond LSC

Yul Eum Song — Photo by Lauren Hines | Bond LSC

Scribbling in a lab notebook and planning experiments tucked between shelves of equipment, it’s easy to fixate on day-to-day lab operations. But scientists also face the challenge of finding how research can improve the world around us.

“The direction, the vision of the lab, ultimately comes from the principal investigator that bridges the research into applied directions,” said Jay Thelen, biochemistry professor and Bond LSC principal investigator

Despite the focus on basic research within the Bond LSC, many principal investigators choose to take their research to the next level with commercial partnerships.

Thelen’s lab researches ways to increase oil production in seeds and has three patents licensed to Yield 10 Bioscience, a sustainable crop innovation company who applies Thelen’s research to commercial crops. While seed oils like canola and soybean oil are known for their use in cooking, Thelen explains that increased production of these oils could play a larger role in sustainable fuel sources such as biodiesel and sustainable aviation fuel.

“We have to make more oil to balance out our need to eat it [and] our need to wean ourselves off of fossil fuels,” Thelen said. “To do that, we need to either plant more acres of oil seeds, or we have to raise the oil in existing oil seeds.”

Thelen researches enzymes with that potential application in mind. One is acetyl-CoA carboxylase, the enzyme which initializes the production of fatty acid chains found in plant oils.

“We’ve known this is an important enzyme, and we know that any tinkering you do with it has an impact on the oil production,” Thelen said. “In this case we’ve made new discoveries that permitted us to rationally engineer this enzyme to make it more active.”

Thelen suggests thinking of the enzyme as a “gatekeeper” to oil production which initializes the production of fatty acids and increases oil production. Thelen’s lab identified two different gene families that influence the activity of the enzyme in Arabidopsis and camelina plants. Yield 10 then applies these discoveries in other commercial plants.

While Thelen works closely with his commercial partner — having served on their scientific advisory board for three years and now stays in contact with Yield 10’s CEO to develop research projects — some labs stick with short-term arrangements.

Kamlendra Singh — assistant director of the Molecular Interactions Core at Bond LSC and Veterinary Pathobiology research assistant professor — studies HIV treatments. His lab identified a compound licensed by a commercial partner that targets the shell containing the virus’ genetic information.

Singh’s work in HIV started in 1994 with basic research investigating the enzyme that makes the viral DNA.

“I wasn’t into [studying] the drugs when I started working on HIV, I was mostly trying to understand how HIV enzymes works,” Singh said. “Once you know how the enzyme works, then you can target these enzymes for discovering the drugs.”

After years of studying how the enzyme works, Singh switched to HIV treatment. The first step to develop a treatment is to look for structures in the virus that the drug could potentially target to stop the viral replication. Singh targeted the shell around the virus’ genetic information known as the HIV capsid.

Building on previous research, Singh’s lab developed a compound able to bind the HIV capsid and prevent it from releasing the contained genetic information. Even with the licensing of his compound, Singh plans to continue researching ways to improve it.

“There are two reasons to keep working on it. One, well it’s my brainchild,” Singh said. “The second reason is as the company grows, we grow. We get more recognition and more funding. You can use it to [study] different viruses or use the same funding to improve upon it.”

While Singh plans to remain looking towards the applied side of his HIV research, he does not forget his roots in basic research.

“You have to put in time … [to] understand the system first, which is basic science, before you go to applied science,” Singh said.

Michael Roberts, a Chancellor’s Professor Emeritus of animal sciences and biochemistry who has had several patented projects, focuses on improving basic science projects and applies for patents if warranted.

“I don’t deliberately go into anything for commercial purposes,” Roberts said. “If I see something that I think does have commercial application, I’m happy to do it, but that is usually after you do [basic sciences].”

Whether starting a project with applications in mind or focusing on basic research, knowledge gained through research can be building blocks for the future.

“Science is simple. Even the most applied research project has its genesis in basic biology and basic research,” Thelen said.

Read more about how MU research leads to patents, inventions and licensing at https://research.missouri.edu/news/leveraging-mizzou-discoveries.

Bond LSC Researcher Wins Awards for 45-Year Career in Reproductive Biology

December 8, 2021 By Lauren Hines in Research Tags: preeclampsia, stem cells

By Lauren Hines | Bond LSC

Still in the lab after 45 years, chancellor’s professor emeritus Michael Roberts has received recognition for his career in reproductive biology research.

Roberts won the Marshall Medal from the UK Society for Reproduction and Fertility (SRF) in August and the Gold Medal and Honorable Membership of the Animal Reproduction Branch of the Chinese Association of Animal Science and Veterinary Medicine (CAAV) in October.

“It’s sort of a culmination of my career in reproduction,” Roberts said.

Since the mid-1970s, Roberts has studied reproductive biology including early pregnancy in cattle and sheep to stem cells models to exploring the causes of preeclampsia.

Roberts received the Marshall Medal largely for his groundbreaking research on interferon tau, a protein secreted by the embryos of cattle, sheep, and other ruminants, which is responsible for signaling to the mother that she is pregnant. In the absence of this signal, the pregnancy fails.

Roberts received the Gold Medal and Honorable Membership of the Animal Reproduction Branch for his long-term efforts in promoting academic cooperation with Chinese researchers in the field of animal reproduction science, including the training of young Chinese scientists.

Currently, Roberts’ lab is using various stem cell models to study the development of the human placenta and the origins of placental diseases, such as early-onset preeclampsia. This disease is life-threatening and initiated in the very earliest stages of a human pregnancy, although only first manifested late in the second trimester.

Even after so many discoveries, Roberts isn’t stopping when there’s still so much left to find.

To learn more, read about Robert’s latest work, his interferon tau discovery and his latest awards.

Turning Back the Clock

October 13, 2021 By Lauren Hines in Research Tags: COVID-19, preeclampsia, stem cells

Demonstrated Sample of Stem Cells — Megan Sheridan, a postdoctoral fellow working with the R. Michael Roberts lab, removes the base solution from a demonstrated sample of stem cells that will be grown into placental cells for study of their interaction with the Zika virus. | photo by Phillip Sitter, Bond LSC

By Lauren Hines | Bond LSC

At 24 weeks pregnant, a baby can hear the mother’s lullabies. At 30 weeks, her belly is a little over a foot large. At 40, the hospital bag is already packed and ready to go.

But imagine delivering only two weeks after the bump starts showing.

Preeclampsia makes induced birth necessary as life-threatening symptoms start 20 weeks into pregnancy, and delivery is the only cure. There is a lack of ways to detect it, and it’s difficult to ethically study the early stages of human reproduction. But what if it was possible to rewind the process to see when the source of the disorder took hold?

Different cellular models of the placenta might be that time machine researchers need to study early pregnancy disorders.

The Michael Roberts lab at Bond Life Sciences Center combines the knowledge and practices of three cellular models to learn more about early pregnancy and diseases.

“We can use these different models to study placental infection with viruses like Zika virus and, of course, COVID because there’s still a controversy as to whether COVID is a hazard in early pregnancy,” principal investigator Michael Roberts said. “And my suspicion is it probably is.”

The placenta is the brand-new organ generated by the embryo — the baby — before any of its other organs develop to give the baby nutrients and support as the embryo grows.

Megan Sheridan, postdoctoral fellow working with the Roberts lab, works on a project to combine 2D and 3D models to see how Zika and Dengue virus interact with the placenta and affect early pregnancy.

“[Complications] occur but you don’t necessarily know that until the end of pregnancy when the baby is delivered,” Sheridan said. “We really want to kind of go back in time and try to determine what’s going wrong in early pregnancy.”

Modeling early placental development is vital to see the beginning of disease complications, but the challenge is to get an accurate glimpse while not putting a healthy pregnancy at risk.

“It’s hard to get a good model to do research on that,” said Jie Zhou, postdoctoral fellow in the Roberts lab. “So that’s why we are working on different stem cells and trying to build up the best model to work on.”

So, the Roberts lab uses the BAP model. By working with a hospital, the lab first takes fibroblast cells from discarded umbilical cords after the baby is born. These fibroblast cells can be collected from mothers experiencing a normal pregnancy or pregnancies associated with complications, like preeclampsia. Then, as Sheridan puts it, they add a “cocktail of genes” to turn the cells into induced pluripotent stem cells. From there, the lab adds BAP — a mixture of growth factors and inhibitors that turn the stem cells into trophoblast cells.

Now the lab is back at the beginning of pregnancy except in a Petri dish of cells. In pregnancy, these trophoblast cells line the outside of the embryo.

From here, researchers can see what possibly caused the pregnancy complications in the first place.

“It’s trying to mimic pregnancy in a dish, essentially by using cells that will develop into placental-type cells,” Roberts said.

However, a flat Petri dish is nothing like a real placenta.

“It’s two-dimensional, and we can only culture the cells up to eight days after treatment so if we want to do long-term experiments, we can’t use this model,” Zhou said.

Two alternative models came out in 2018. The first model was by Hiroaki Okae et. al who created a 2D trophoblast cell line where trophoblasts can continually reproduce themselves long past eight days. The second model by Margherita Turco et. al also created a similar cell line, but in three dimensions.

This last model inches even closer to an early placenta. These 3D organoids float around inside a jello-like substance called Matrigel where they self-organize into a placental-like structure.

Together the two models give them a full picture. The 3D model gives a clue into how multiple cell types interact with each other while the 2D model allows researchers to see how a single cell type responds.

Since no model is perfect, the Roberts lab is combining their BAP model with protocols and growth conditions from the other two models to create a foundation for their experiments. Now researchers can start asking deeper questions.

While nothing is quite like a real womb, the Roberts lab will continue working backward.

“All of these models, put together, are really useful because we can kind of use them to their fullest potential and systematically assess which one might represent a certain disease or best answer a certain research question,” Sheridan said.

#IAmScience Teka Khan

April 9, 2021 By Becca Wolf in #IAmScience Tags: placentas, YEWOM

By Becca Wolf | Bond LSC

Growing up in the countryside of Pakistan, Teka Khan did not have a science class in high school. In fact, his first science class was in college and it was in English — a language he did not know at the time.

“First I had to understand the word meaning. So, what I did for physics, chemistry, and biology is I bought a dictionary,” Khan said. “I had to translate each and every word, and then I had to understand them, so I wrote down the meaning of each word. Sometimes I look back and think, ‘how did I do that?’”

Now a postdoctoral fellow in the Michael Roberts’ lab, Khan knows his stuff, and wants to give back to his community in Pakistan.

To do so, he helps with the Youth Educational & Welfare Organization in Mattani, Peshawar, Pakistan (YEWOM).

YEWOM promotes educational and welfare activities in hopes of improving the community and making students productive people in society.

“We usually have different types of activities,” Khan said. “We visit different schools to observe if there are any deficiencies in quality of learning, if there’s water or if there aren’t any toilets for the kids. Depending on the cost, we try to fix it. If the cost is beyond our limit, we try to find a funding agency or consult NGOs in the government organization.”

Khan was president of YEWOM for two years and still helps out even though he now lives over 7,000 miles away.

“From here, I usually give them suggestions,” Khan said. “So right now I’m contributing by sharing my own experiences, because I’m one of the senior most in the organization. We always promote the young people so they can learn how to lead the community. We provide them the platform to grow.”

Khan has always had a passion for helping others. To him, it is the best way to become a good person.

“It is necessary for each and every human being to do some work to live,” Khan said. “I’m a researcher, somebody will be a teacher, somebody will be a businessman, and so on. The ultimate goal is to get the resources for life, which we are doing for ourselves. But it doesn’t matter how much I’m a good scientist or how rich a businessman is, what matters is if we are good human beings, to me, that is most important. Everyone should be firstly a good human being then you can do other things.”

Toshi Ezashi, research professor in the Roberts lab, has witnessed this positive attitude firsthand.

“He spent a long time to come here but he never gave up and eventually came here in March [2020],” Ezashi said. “He tried to invite his family here around June, but then the pandemic happened. I think it was hard to him because he couldn’t see them for such an extended time. I don’t think they were able to join him until last November, but he didn’t complain. He just put all of his time and energy into the science and research. Even after his family joined him, he’s still passionate about his work.”

In the lab, Khan is working on developing trophoblasts in the early stages of the human placenta using embryonic stem cells.

“Sometimes experiments don’t work, but he doesn’t get upset,” Ezashi said. “He might be feeling bad, but he doesn’t project that onto others and never gets discouraged by failure. He just keeps pressing forward and tries to improve.”

This tenacity has paid off for Khan. He has developed protocol for isolating nuclei from trophoblast cells and is publishing that work soon.

Now that Khan has settled down here at Bond LSC, he plans on continuing to help others and promote educational opportunities.

“I like to say that as a biologist we can understand the nature of almost all animals,” Khan said. “We can understand if you are just doing things for yourself because every animal is doing things for themselves. As a social animal, humans give back to others. You have to try to give back to other people and help out.”

#IAmScience Shrikesh Sachdev

February 5, 2021 By Lauren Hines in #IAmScience Tags: cancer, stem cells, virology

By Lauren Hines | Bond LSC

Science is a pyramid. Every breakthrough and discovery are reached through incremental steps that build off the previous level.

Shrikesh Sachdev, a senior research associate in the Michael Roberts lab, thoroughly understands this.

“It takes many small steps to get to a treatment or a cure,” Sachdev said. “It very often takes decades, but it’s nice to be able to put in your little piece of the puzzle that might help lead to the discovery, if not a cure.”

Sachdev began his path to Bond Life Sciences Center when he left his home country of Canada in 1991 to earn his master’s degree in fisheries and wildlife from Mizzou.

Once he graduated in 1993, he felt his heart being pulled towards another field — disease and disease-related processes. That led him to conduct his Ph.D. in biochemistry doing cancer research with Mark Hannink lab in the Biochemistry Department at Mizzou.

After receiving his Ph.D. in 1998, Sachdev went to Munich, Germany as a Leukemia and Lymphoma Society Fellow for his postdoctoral research in Rudi Grosschedl’s lab, where he researched a developmental signaling pathway that has been implicated in cancer.

“Every scientist thinks, ‘I want to cure cancer, or I want to cure HIV,’” Sachdev said. “You always want to contribute to that, but I think the pursuit of knowledge should be our primary goal. Once we can understand the basics of how things work, then we can try and understand what is causing the diseases.”

While in Munich, Sachdev found a new type of SUMO E3 ligase enzyme that modulates a developmental signal transduction pathway. That was one of those underappreciated incremental steps.

“Science is incremental, but those ‘aha moments’ are what you live for,” Sachdev said. “I was thinking to myself, ‘I am the only person in the world that knows this right now…And it’s going to help people understand other things.’”

Currently, Sachdev works with research professor Toshi Ezashi to characterize and analyze induced pluripotent stem cells from patients with Smith-Magenis neurodevelopmental syndrome.

A mutation in the Retinoic Acid-Induced one (RAI1) causes the Smith-Magenis syndrome. Sachdev and Ezashi convert fibroblasts — skin tissue cells — into pluripotent stem cells which can turn into certain different types of tissue cells. Researchers use this method to understand the effects of the disease on a molecular level.

“Dr. Ezashi had a huge impact on introducing me to stem cells and really igniting a passion within me,” Sachdev said.

Ezashi has known Sachdev for more than eighteen years. The two started collaborating while Sachdev was near the end of his time in Munich.

“He’s very friendly and kind,” Ezashi said. “Whenever I need help, he never rejects me. He tries to help every time, which I do appreciate.”

While Ezashi has been working with pluripotent stem cells since 2003, Sachdev brings biochemistry and molecular biology expertise to the project.

“We have complementary backgrounds,” Ezashi said. “He has strengths that I don’t have, so we complement each other. We can cover each other’s deficiencies.”

The induced pluripotent stem cells will help the researchers do more since they won’t have to use embryo-derived materials that are restricting and complicated. However, both researchers have a long way to go in their study.

With a little luck, Sachdev’s multiple ongoing collaborations will each have their own set of incremental steps waiting to be found.

#IAmScience Toshi Ezashi

December 4, 2020 By Lauren Hines in #IAmScience Tags: placentas, stem cells

By Lauren Hines | Bond LSC

Despite his quiet demeanor, Toshi Ezashi leaves an impression on those who meet him in the halls of Bond LSC through his quiet intensity and constant courtesy.

The research professor was here before the “Joy of Discovery” sculpture in the atrium was built or the living plant wall was hung, calmly making progress with stem cells as part of the Mike Roberts lab team.

“I’m mainly doing research on trophoblast that compose the main component of the placenta tissue,” said Ezashi, who first came to Mizzou in 1995. “Using stem cell technology, we try to understand the pregnancy disease which happens in the placenta.”

Stem cells can be considered the ultimate source. They turn into all different types of the adult cells that make up the many tissues, organs and parts of a living thing. Induced pluripotent stem cells, on the other hand, are a little different. They start out as adult skin or blood cells but are pushed to revert back to an embryonic-like stage where they can once again turn into about any type of cell and self-renew.

Induced pluripotent stem cells were first discovered in a paper that appeared in Cell in 2006, and Ezashi excitedly presented it to his lab mates that same day.

“He knew instantly how important that was going to be,” said Laura Schulz, associate professor of Obstetrics, Gynecology and Women’s Health who works with the Roberts lab. “That’s just him. I think he really sees those things.”

Schulz has worked with Ezashi for the past 15 years.

“He’s just an incredibly kind person, but also a really very thoughtful, thorough and creative scientist,” Schulz said. “So, together those have made him a great collaborator.”

Currently, Schulz and Ezashi are studying trophoblast cells — stem cells from the placenta of early pregnancies. Ezashi is using these trophoblast cells to try to eventually understand preeclampsia, which results in dangerously high blood pressure and almost a rejection of the placenta. It is a potentially fatal complication that is only cured by the premature delivery of the baby.

Studying the placenta is difficult due to ethical issues and its ephemeral nature in relation to pregnancy. However, Ezashi generates placental cells that derive from umbilical cords left over after pregnancy to study the early stage of the placenta. This way, Ezashi and other researchers can figure out what causes the pregnancy complication.

“Right now, we don’t have any way to cure this disease,” Ezashi said. “The only option is to deliver the baby prematurely. Because of this issue being rooted in our lack of information of the time of the period, how the placenta works, we are expecting this study to provide important information to understand why this disease develops in this case.”

Ezashi has seen attitudes towards this kind of research shift in his many years working with stem cells.

“It was 2002,” Ezashi said. “We had this type of way of thinking that was just application. In those days, there was some understanding or social acceptance of stem cells, but we stepped forward to using stem cells in this field. I look back more than 17 or 18 years ago, but I still think it was the right move and decision to get into this field.”

Ezashi has grown along with attitudes and Bond LSC.

“He’s gained confidence and leadership skills I think over those 15 years, but actually he seems very similar to the person I met 15 years ago,” Schulz said. “He’s really just kind of a down-to-earth, quiet guy and the same careful scientist he’s always been.”

Even with 25 years under his belt, Ezashi isn’t leaving Bond LSC anytime soon.

“I know I have a different background, but by staying here to do something, I can uniquely contribute to society,” Ezashi said. “That means something. I can be a part of some message to the work, ‘How much can we achieve?’”

#IAmScience Jessica Milano-Foster

April 24, 2020 By Becca Wolf in #IAmScience Tags: Mizzou Research

By Becca Wolf | Bond LSC

The placenta is a crucial organ that develops in a woman’s body during pregnancy that provides oxygen and nutrients to the fetus. After her experience doing research on this organ while getting her master’s degree at the University of Kansas Medical Center, current MU Ph.D. student Jessica Milano-Foster has become passionate about studying it. To continue her education, she has teamed up with Laura Schulz’s lab in the MU School of Medicine and Michael Roberts’ lab at Bond LSC to look at the role of mitochondria in the placenta during early onset preeclampsia.

Milano-Foster did not begin her educational career studying the placenta or any sort of biology. In fact, she got her bachelor’s degree from Truman State University in chemistry.

“The initial goal was to be a forensic chemist,” she said, “But then, I was really bored in my forensic science class. So, I wanted to try research because I thought that might be interesting.”

The rest is history.

While doing research, she was introduced to epigenetics — the study of changes in organisms that are caused by modification of gene expression. This piqued her interest and led her to Dr. Souman Paul’s lab at the University of Kansas, which solidified her decision to not pursue forensic chemistry anymore.

“The thing that I really like about research is that you learn something new almost every day,” something she was not getting previously.

After her bachelor’s degree, Milano-Foster continued in Dr. Paul’s lab as a Master’s student and was first introduced to the placenta.

“His lab focuses on reproductive biology and I just kind of fell in love with the placenta along the way,” she explained. “I think it’s so cool because it’s something that we have to build in our bodies in order to create life. And then it goes away. And then it can come back again if you decide to be pregnant again. No other organ does that.”

The more she studied the placenta, the more she became fascinated by it. After finishing her Master’s degree at KU, Milano-Foster got an offer to stay in Dr. Paul’s lab for her Ph.D., but she declined because she was moving to Missouri with her husband who was starting medical school.

She began working as a lab technician for Tom Spencer, a MU professor of animal sciences studying neonatal uterine development in mice. While it was still in the realm of reproductive research, it was not focused on the placenta.

“It was interesting, but I wasn’t really motivated the way that I was in my Master’s to learn more and more and more about the placenta and epigenetics,” Milano-Foster said. “I wasn’t that excited about the uterus but, you know, I thought that as I learned more about it I’d get more excited, and I didn’t. It was just a matter of being honest with myself and honest with my advisor, and it worked out.”

After discussing this with Dr. Spencer, he agreed his lab would not be the right fit for her. There were no hard feelings and he helped look for opportunities at MU to conduct more research on the placenta. Turns out Dr. Laura Schulz had a spot open in her lab. Dr. Schulz’s lab focuses on how hormones and nutrition during pregnancy affect the function of the placenta and the health of the fetus, which was right up Milano-Foster’s alley. She has been with Dr. Schulz’s lab since last fall and now collaborates with the Roberts’ lab to continue her research.

“Because of the nature of my work, I have to be in the Roberts’ lab to do it,” she said, and she thinks it has been a good match so far. Roberts’ lab focuses on reproductive biology and stem cell research, allowing Milano-Foster to research early onset preeclampsia, a pregnancy complication characterized by high blood pressure that can have fatal consequences for the mother and the fetus. Her research focuses on mitochondrial dysfunction in the condition.

Despite only being here for a few months, Milano-Foster has already made progress conducting experiments on the mitochondria where she tests stem cells.

“They’re very picky,” she said, “You have to tend to them every single day. They have preferred growing matrices and everything.”

Milano-Foster not only learned how to control the cells, but also had to find a way to get them into small wells in order to conduct mitochondrial stress tests. It took some time, but she did so just as she had to go on maternity leave, putting the experiment on pause.

Her daughter is now a month old and Milano-Foster has about eight weeks of maternity leave left. She is eager to start working on her research again.

“I’m excited to jump back into that and get my replicates going. That way I can get some answers because right now my project is very much like we don’t know what’s going to happen,” she said.

Being out of the lab doesn’t excuse her from being a student as she still has to write and study for her Ph.D. She studies while her daughter naps, but has yet to get on a steady routine. Milano-Foster is also squeezing in time for her hobbies, “I work out every day and I’m hoping that while I’m on leave, I’ll have some more time to play the piano.”

Milano-Foster hopes to finish her Ph.D. here at MU within the next three years, four if necessary.

“A lot of that depends on how the project goes,” she said. After her Ph.D., she wants to continue doing her own research in a translational or clinical setting where she would be a senior scientist.

Between maternity leave and being forced to shelter-in-place due to COVID-19, Milano-Foster is taking things day by day for now. She is itching to get back to the lab and continue her passion and hopefully that day will come soon.

A return to mentor: Gant advises on PREP for Ph.D.’s

November 25, 2019 By Roger Meissen in Events and speakers Tags: Cheryl Rosenfeld, R. Michael Roberts

By Roger Meissen | Bond LSC

Kristal Gant is a long way from the student she was when she donned a lab coat and wielded a pipette in labs at Bond Life Sciences Center nearly four years ago.

As she stood in front of a group of MU students hoping to one day follow their own routes to graduate school, Gant recounted her long and winding path to her Ph.D. program at University of Wisconsin-Madison and how MU’s Post-Baccalaureate Research Education Program (PREP) Scholars helped her get there.

“I’m really passionate about wanting to give back and be kind of like a mentor, but also a motivational, navigational tool for these students,” Gant said. “In undergrad, I didn’t have any idea about research and I feel like it’s my duty to come back and talk about my experience. Most of these students have not seen people that look like them in graduate school, as Ph.D. candidates or doctors. They don’t even know that’s possible for themselves.”

Gant didn’t attend Mizzou for her undergraduate degree, but as a PREP Scholar here she gained the chance to hone her skills. It gives underrepresented groups opportunities for individual academic and professional development that range from mentoring and GRE preparation to mini courses and research experience. The end goal is to prepare them for applying to Ph.D. programs. Those in PREP spend one or two years refining their skills and knowledge.

Gant greatly expanded her experience in research during that time. She spent a year alternating between the labs of Cheryl Rosenfeld and Mike Roberts in Bond LSC, learning the ins and outs of research on reproduction and environmental chemicals like bisphenol A (BPA).

“It gave me a preview of what you go through in your first year of grad school. I knew I wanted to study reproduction, reproductive deficiency and disease, and was also interested in environmental and reproductive toxicology, initially,” Gant said. “When I came here, I had the best of both worlds; I had the BPA aspect with Dr. Rosenfeld looking at mouse models and how that affected their behaviors and I had the reproduction area where Dr. Roberts looks at placental development by converting embryonic stem cells to trophoblasts, the main cells responsible for placental function. The project was essentially perfect in accommodating both of my interests.”

Gant had a unique, sometimes turbulent path to her interest in science. She grew up and went to school on the Westbank of New Orleans, until ninth grade. She remembers first getting an interest in science in junior high when her teacher showed a time-lapse video about pregnancy and the development of a baby.

“I was really interested in like how the woman’s body knew to accommodate the baby and how it adapted to having another human inside of it. That really intrigued me, so I was like, ‘I want to do reproduction,’” Gant said. “That combined with “The Cosby Show” made me want to be a neonatal nurse or obstetrician. I pursued that initially, but then I was like, oh, whoa, I didn’t know you could actually research these things, and I was introduced to research careers and grad school in college and realized this could be a thing. So, yeah, I’m a nerd like that.”

Before she got there, life got a little derailed. When Hurricane Katrina hit, the 15-year-old girl got separated from her mother who was visiting her sister in Virginia, causing her to have to relocate to Texas with a family friend to avoid the storm. What started out as a few days of inconvenience quickly turned into a bigger situation.

“We saw on the news that there was extensive flooding and people were stuck on the roads, and our apartment was flooded out, so we lost everything,” Gant said. “My mom didn’t know if I had made it out or anything because the phone lines were down and we were separated two weeks before the family I was staying with in Texas flew me to Virginia where I ended up finishing high school.”

Gant completed a year of college at Virginia Commonwealth University before she moved to North Carolina to help her mother escape a domestic violence situation. They were left living in a shelter for abused women and children for a year before getting their own apartment, and Gant worked at McDonalds until she started college again at Elizabeth City State University. She graduated in 2014 and followed up with a couple internships before ending up in a customer service job.

“And I hated it because it was, like, I have a whole degree that I’m doing nothing with and I’m in debt from it and I need to do something with,” she said.

A former adviser recommended Gant apply for PREP Scholars to improve her chances of getting into grad school.

Kristal Gant talks with students eager to gain insight into applying to Ph.D. programs at Bond LSC in fall 2019. | photo by Roger Meissen, Bond LSC

Gant said her struggles helped her figure out what she wanted to do and shaped how she saw her future. Understanding it also aided her in writing personal statements for graduate school applications. She related that insight to those current PREP students looking to her for advice.

“It requires a lot of self-reflection to understand how your struggle got you to where you are. It doesn’t have to be family or a natural disaster or relationship troubles or whatever. It could be something within you that you yourself struggle with internally, whether it be confidence or fear or a feeling of not being good enough to do something,” Gant said. “It could be something so small that you struggled with, overcame and still, you pursued something you were deathly afraid to do. That shows that no matter what is supposed to stop you, you’re not gonna allow it.”

But her parting advice was some of the best.

“It really takes a passion, knowing what you’re trying to answer and putting in the work to figure it out. If you’re not passionate then you will be miserable and feel like you’re trapped in a prison,” she said. “But if you want the answers to your research questions and will not rest until you figure it out, then you should be in graduate school.”

Kristal Gant is a fourth-year Ph.D. candidate at the University of Wisconsin-Madison studying Endocrinology and Reproductive Physiology in the Department of Obstetrics and Gynecology. She was an MU PREP Scholar in 2015 and plans to graduate with her doctorate in 2021.

Learn more about the PREP Scholars program at prepscholars.missouri.edu.

The problem with placentas

April 11, 2019 By Danielle Pycior in Research Tags: placentas, R. Michael Roberts

MU scientists develop model to study complex pregnancy disease

Roberts Lab stem cells — Here, stem cells have undergone differentiation. The green shows the hormone used to diagnose pregnancy in humans and the ovals are nuclei, some of which stain a pinkish color, representing the protein GATA2.

By Danielle Pycior | Bond LSC

Researchers have been exploring the complicated and difficult world of pluripotent stem cells for 15 long years on the second floor of the University of Missouri’s Bond Life Sciences Center.

A type of stem cell that can be turned into any cell in the human body and self-replicate, scientist Michael Roberts and his lab have used these cells to study the early stages of pregnancy in the hopes of understanding preeclampsia — the number one cause of maternal mortality worldwide.

Roberts and his lab have been using an innovative technique to see what occurs at the early stages of the disease with the ambition of understanding the disorder. Their most recent advancements were published in Proceedings of the National Academy of Sciences in March.

Their work has focused on the complex interaction between a mother’s body and the placenta. This temporary organ connects a fetus via an umbilical cord to the uterine wall of the mother to provide nutrients, gas exchange and waste elimination for the developing child.

“The very fact that you can remove the placenta to cure the patient suggests that this maternal condition has its origin in the placenta” said Roberts.

Preeclampsia comes in two main forms, early-onset starting around 20 weeks of pregnancy, and late-onset occurring after about 35 weeks. Symptoms can range from high blood pressure to headaches, fatigue and other forms of stress in the mom. Severe forms of preeclampsia are life-threatening for mother and child, and the only treatment is removing the placenta, which forces the mother to undergo cesarean section, invariably prematurely.

Researchers have struggled to understand this disease for multiple reasons. While the underlying defect is generally believed to be shallow formation of the placenta and failure of certain cells called trophoblasts to invade sufficiently deeply into the wall of the womb, early detection in the first trimester is almost impossible right now, and, by the time doctors can detect it, the placenta has faced so much damage that it is of little use to researchers.

Working with University of Missouri Health Care physician Danny Schust and basic scientists Laura Schulz and Bond LSC’s Toshihiko Ezashi, Roberts’ lab acquired real-world samples of cells related to the disease. Mothers who came into MU Women’s and Children’s Hospital in Columbia diagnosed with early onset preeclampsia agreed to give part of the tissue from their umbilical cord after childbirth, which was then used to grow primary cultures of connective tissue cells. These were reprogrammed into stem cells that are essentially identical to embryonic stem cells. These induced pluripotent stem cells were then converted to trophoblast cells — the cells in the fetus that make up the outer layer of the placenta — and examined for abnormalities associated with the disease.

“If you do this successfully, you essentially recapitulate the early stages of the pregnancy that led to preeclampsia.” Roberts said.

Upclosetian — Yuchen Tian, a research specialist in Robert’s lab, worked on the most recent publication in Proceedings of the National Academy of Sciences, and helped with four other research publications. All five used stem cells to make discoveries.

After this, the researchers tested the cells under various conditions to try and figure out the early stages of the disorder, something that had been relatively impossible previously. Since preeclampsia is difficult to detect in early stages and early placentas from such patients are unavailable for ethical reasons, this approach has allowed researchers a unique look at what happens during a preeclamptic pregnancy.

They compared normal pregnancy cells with cells from preeclampsia pregnancies. By putting the cells in incubators, they observed them under different conditions and levels of stress. Under 5% oxygen, the cells acted similarly to the normal pregnancy, but under 20% oxygen, the cells were highly stressed, resulting in their inability to function properly.

“So, we essentially showed that at least one feature of these preeclampsia cell lines was that they weren’t able to cope with high oxygen and so invaded poorly,” Roberts said. “What we assume is that in the disease there is some sort of stress occurring that causes these cells to not behave properly.”

Roberts’ lab members Toshihiko Ezashi, a research professor at Bond LSC, and Megan Sheridan, a former MU graduate student in the Roberts’ lab who is now at University of Cambridge in England, discovered that there isn’t one gene that leads to preeclampsia, but a few genes within a large cohort of genes involved in controlling a trophoblast cell’s invasive properties.

HayashiTianEzashi — Chuyu Hayashi, Yuchen Tian and Toshihiko Ezashi all work in Robert’s lab. Tian and Ezashi helped work on the most recent published article, and Ezashi helped discover how preeclampsia is involved in multiple genes and not just one.

While this discovery narrows the search for answers, it still leaves a lot of questions being asked.

“We are still nowhere near creating a test for preeclampsia and we are certainly far from a cure because how can you prevent a disease before you know a woman has it?” Roberts said.

This arduous, complicated and incredibly intriguing work looks ahead to dissecting the genetic abnormalities of the disorder in the hopes of creating a successful test and treatment, which could make all the difference for women worldwide.

“This is a disease that affects a large number of women,” Roberts said. “In this country, women can usually find proper care, but in countries outside the U.S. without hospitalization, the woman is going to die and so is the baby.”

#IAmScience Rowan Karvas

June 15, 2018 By Roger Meissen in #IAmScience Tags: preeclampsia

ROWANKARVAS #IAmScience — Rowan Karvas, a Ph.D candidate at Mizzou, works in the Roberts Lab in Bond LSC. | photo by Erica Overfelt, Bond LSC

By Erica Overfelt | Bond LSC

Answering the unsolved questions is a lifetime commitment for fifth year Ph.D. candidate Rowan Karvas in the Roberts Lab at Bond LSC and Laura Schulz’s lab at the medical school in the Obstetrics and Gynecology department.

Originally from St. Louis, Karvas came to Mizzou and found her keen for science through her undergrad research working on adult muscle cells, but it wasn’t until she became a technician in a radiation oncology research lab at Washington University when she realized she wanted to continue research throughout her life.

“I remember a moment when a grad student, Danny Stark, and I were isolating quail embryos,” Karvas said. “We opened them up and I saw their beating tube hearts and all the details. Just looking under the microscope at them was so fascinating to me, I realized that I wanted to keep doing biological research.”

Karvas believes asking questions is what we often forget to do as a society, and in a scientific world with unlimited questions, she knows the one she’d most like to answer.

“I would like to solve pre-eclampsia,” Karvas said. “It’s a disease that’s most likely been with us since we have been human, and it is a disease that deserves to be solved.”

Karvas works on two projects researching human placental development. The pregnancy disease pre-eclampsia often goes unnoticed until later in pregnancy, but causes dangerously high blood pressure, kidney damage, and a placenta that is underdeveloped and has not invaded the maternal endometrium efficiently.

Karvas was eager to work on this problem and so she started grad school two months early.

“This disease if often very deadly for women and in the most severe forms causes death,” Karvas said. “It is the leading cause of maternal fatality in the developing world and is becoming a problematic issue in the states. There are no rock solid genetic, physiologic factors, or environmental stimulus that accurately predicts who will get this disease.”

And that’s why Karvas spends her time researching how and when pre-eclampsia develops during pregnancy.

In Karvas’s first research project, she is looking at modifications to the genetic code that could be responsible for pre-eclampsia and her second project is finding the answer to the question, “at what stage of pregnancy does our cell model represent?”

When Karvas isn’t in the lab you can find her aiding to bridge the gap between clinical scientists and basic science researchers as president of Interdisciplinary Reproduction and Health Group Trainees. The new group involves graduate students and post-doctoral researchers from animal sciences to biochemistry, all coming together to further explore reproductive science.

“It makes me happy and it is very satisfying to start the group and be a part of the groundwork for its continuation,” Karvas said. “Fostering these relationships with people you may have not met otherwise is important.”

When Karvas isn’t running her group or in the lab, you can find her playing the clarinet. Before discovering her love for science she wanted to be a professional performer.

“It is an opportunity to use the other part of my brain,” Karvas said. “I get to shut off the science part and bring on the musical part.”

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