Mizzou Research

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.

Another piece of the pathway: Stacey lab identifies enzyme key to regulating plant metabolism

February 24, 2022 By Balslew, Karly (MU-Student) in Research Tags: Mizzou Research, plant science

Mev. pathwayplant — Researcher Sung-Hwan Cho holds mutant Arabidopsis thalianas. The Gary Stacey lab used these mutant variations to study how plants react to external stressors. | Photo by Karly Balslew, Bond LSC

By Karly Balslew | Bond LSC

When we get hurt, our body signals our brain to warn us about stress and damage. We acknowledge the damage and then initiate the proper steps to heal.

Plants may have different receptors that read these stress signals, but the process is similar.

“When someone crushes the plant tissue, this triggers their immune system like us,” said Sung-Hwan Cho a researcher in the Gary Stacey lab at Bond Life Sciences Center. “Our focus is how the plant responds to their stresses, especially wounding.”

In plants, Adenosine triphosphate (ATP) plays a crucial role in regulating this process.

Cho explains that this signal is especially important because unlike humans, plants cannot move away from their stressors so they must adapt. Therefore, signals travel down a certain pathway to ensure the plant reacts appropriately to the damage. But without ATP, the process is lost.

As part of the Stacey lab, Cho recently published a recent paper in Nature Communications that detailed a key metabolite pathway in the ATP plant signaling process.

“What’s exciting about the mevalonate pathway is that the pathway is involved in producing so many molecules that are critical for plant growth and development,” said Bond LSC principal investigator Gary Stacey. “Such as a variety of different hormones and various lipids that are required. It means that purinergic signaling has a profound effect on plant physiology.”

Purinergic signaling is named after the purine compounds that are found in ATP. This signal is important as it helps researchers understand how plants handle external factors from their surrounding environment.

Purinergic signaling underpins a multibillion-dollar pharmaceutical industry for humans and animals. Hence, the hope is that, just as in these cases, further exploration of purinergic in plants will lead to practical means to alleviate stress in plants, improving plant health and, ultimately, yield.

Stacey explains that mevalonate kinase (MVK) is one of the first enzymes in the mevalonate pathway and impacts the metabolites, or functioning, of the plant.

Just like in humans, plants have metabolic functions that keeps the organism alive. When we eat food, our body breaks the food down into an energy form that the body can utilize. Plants do the same. These metabolite compounds are synthesized by plants and used for essential functions like growth and development. This process gets turned on or off by ATP.

ATP is predominantly the energy molecule of the cell. All the food that we eat eventually turns into ATP and provides us energy to function.

“You can think about it [ATP] as money. You can’t go to the store and do anything without money so the cell can’t do anything without ATP,” principal investigator Gary Stacey said.

When the body experiences stress, ATP is transported outside of the cell and acts as a signal to the rest of the body. However, when this idea was proposed in the 1970s, it was highly controversial, and many rejected the notion entirely explains Stacey. Since ATP is crucial to human and plant functioning, the idea that ATP was traveling out of the cell as a signal was ridiculed.

However, in the early 1990s, researchers identified the first receptors in humans that utilized this extracellular ATP. Researchers knew how important ATP is to the cell and realized how effective the molecule signal was. This is called purinergic signaling because it is triggered by nitrogen-based DNA building blocks named purines and compounds like ATP.

“If the cells make a receptor that’s recognizing extracellular ATP, then there must be extracellular ATP and it must act as a signal,” Stacey said.

Researchers turned to humans and studied their stress signals and the receptors.

However, the ATP receptors that were found in humans were not seen in plants. Researchers knew plants carried out these purinergic signals because plants reacted similarly to humans, but the receptor was unknown.

“Basically, what we do is we take the plant and then we screen for mutants that don’t recognize ATP. If the plant has a mutation in the receptor, then the plant will no longer recognize ATP. Once we identify the mutation, we can map the mutation and eventually identify the receptor,” Stacey said.

Stacey’s lab identified the first receptor, P2K1, back in 2014 through a genetic screening. Now the lab discovered another new receptor, P2K2. However, researchers also discovered that the enzyme mevalonate kinase (MVK) acts as a crucial component in the ATP signaling process.

“ATP can bind to the P2K1 and then the P2K1 interacts with the MVK. The MVK is then phosphorylated and activated to regulate diverse metabolites,” said researcher Daewon Kim, another author on the paper in the Stacey lab.

Yet even with new receptor and pathway discovery, more science is needed to fully understand this important signaling process. This research will move them closer to that understanding.

“Purinergic signaling is not just some side product but is really affecting a major pathway that is central to the way in which plants grow and develop,” Stacey said.

Read more about this work in the paper “Activation of the Plant Mevalonate Pathway by Extracellular ATP” published in January 2022 in the journal Nature Communications.

Sung-Hwan Cho is a Bond Life Sciences Center research scientist. Daewon Kim is a Bond Life Sciences Center research scientist. Gary Stacey is a curator’s professor of plant sciences and a Bond Life Sciences Center principal investigator.

Two SARS-CoV-2 strains cause independent infections only 19 days apart

August 5, 2021 By Suppes, Davis (MU-Student) in Research Tags: COVID-19, Mizzou Research

Increasing detection of reinfections and rediscovering brand new infections within days raises concerns for herd immunity and the durability of vaccine efficacy.

Cynthia Tang working to figure out how COVID-19 reinfections can bring us answers on how the virus is developing at Bond LSC. | photo by Davis Suppes, Bond LSC

By Davis Suppes | Bond LSC

Like many viruses, SARS-CoV-2 continues to develop and evolve with time. As the virus evolves it becomes more infectious and can produce worse symptoms and a higher fatality rate. While more people have been infected, we also learn more about it, including how different variants of the same virus can reinfect someone who already had SARS-CoV-2.

In a recent study led by Cynthia Tang, an MD-PhD student at the University of Missouri (MU) School of Medicine and Institute for Data Science and Informatics, her lab was able to identify a patient who got reinfected with a different strain of SARS-CoV-2 just 19 days after their initial infection. Her Systems Biology Laboratory is headed by Principal Investigator, Dr. Henry Wan, who directs the MU Center for Influenza and Emerging infectious Diseases.

“We found a case of reinfection that occurred during a shorter window of time than what we see in the current US Centers for Disease Control and Prevention (CDC) guidelines,” Tang said, “so we may be missing a subset of those reinfection cases.”

In October 2020, the CDC published investigative criteria for suspected SARS-CoV-2 reinfections. These criteria included: any individuals testing positive over 90 days after their first laboratory-confirmed SARS-CoV-2 infection, or symptomatic individuals testing positive 45–89 days after initial infection with paired respiratory specimens.

For this patient, nineteen days following her initial positive test in March of 2020, she returned for another SARS-CoV-2 test due to return-to-work requirements. Despite her symptoms fading to encompass only productive cough and fatigue she tested positive again. She continued to experience persistent cough, fatigue, and difficulty breathing until 55 days after her initial positive test.

Tang showed that the two samples contained two infectious variants of SARS-CoV-2 viruses. No diverse polymorphisms, or a mixture of different viruses, were identified among the sequences of the viruses from each clinical sample, suggesting true reinfection rather than a coinfection. One good news is that this case also suggests that reinfections may not be worse than the prior infection.

The CDC has encouraged symptom-based strategies for ending isolation rather than viral retesting for asymptomatic individuals or for individuals without new symptoms during 90 days after illness onset due to findings that detectable but noninfectious SARS-CoV-2 RNA can persist in respiratory samples. This means that even if you don’t exhibit symptoms there could still be traces of SARS-CoV-2 in your system, and those traces could be from an original infection or a reinfection.

This study suggested that reinfection could pose a challenge to infection control, especially as the Delta variants are surging around and new variants continue to emerge.

“People showing influenza-like illnesses are recommended to isolate themselves for ten days or wait for their symptoms to go away. We may not be catching cases where individuals contract another COVID-19 infection within a short amount of time,” Tang said.

“The COVID-19 vaccination has been proven to be effective in reducing the chances for people to become infected and reinfected”, Tang added.

This research was published in the Journal of Medical Virology in June 2021.

Bringing Protection Back in Line

July 23, 2021 By Suppes, Davis (MU-Student) in Research Tags: Mizzou Research

Research refines platform to address immune disorders

Dr. Esma Yolcu and Dr. Haval Shirwan, Co-pioneers of ProtEx technology

By Davis Suppes | Bond LSC

The things that protect you can also cause the most harm. That’s especially true when it comes to your immune system, which protects you against infections, but is also responsible for a host of diseases, including autoimmune disorders, such as type 1 diabetes.

More than 1.4 million Americans suffer from the self-harming condition of diabetes without an effective cure, but researchers Haval Shirwan and Esma Yolcu may have the answer.

The pair tackle the problem of diabetes and other autoimmune disorders by targeting the component of the immune system that does harm for modulation. DNA-based gene therapy has traditionally been used as a scheme to modulate the immune system.

“DNA-based gene therapy is a complicated, exhaustive and expensive technology,” said Shirwan, a NextGen Precision Health researcher at the University of Missouri and a professor in the Department of Child Health and Molecular Microbiology and Immunology at the School of Medicine. “We wanted to see if there was a more efficient and practical way to do immunomodulation.”

For conditions like Type 1 diabetes, where the immune system misfires and destroy beta cells producing insulin, they target to replace defective islets with healthy ones from another individual. Insulin is an important hormone that plays a role in regulating your blood sugar level. A major hurdle for islet transplantation is the immune rejection.

Shirwan and Yolcu co-pioneered ProtEx™, a proprietary platform that allows for generation of novel recombinant immune ligands and their positional display as single agents or in combination on biological surfaces, such as islets. This is a practical and safe alternative to gene therapy for localized immunomodulation.

In traditional methods of gene therapy, DNA must first be introduced into the cell, but ProtEx technology bypasses that step. Sticking the protein directly on the cell surface for immunotherapy via a test tube allows for a safer, more effective method than gene therapy. Islets engineered to stick on their surface proteins evade rejection by the immune system.

Shirwan’s translational research program’s goal is to develop safe and practical immunomodulatory approaches with applications to transplantation, autoimmunity, cancer, and infections. On the cancer side, Shirwan and Yolcu team has shown that the immune system of a healthy individual can be trained to surveillance the body for cells that may transform into cancer and eliminate them before cancer takes hold. “This is an exciting finding that has not been reported in the literature and sets the stage for

Shirwan’s focus of learning about the immune system and improving it came to him very early when he was a virologist for University of California, Santa Barbara. He developed an interest in immunology and wanted to learn more about immune defense mechanisms. Before bringing his talents to Mizzou he also spent time working at the California Institute of Technology, Allegheny University of the Health Sciences, University of Louisville, and Cedars-Sinai Medical Center.

He believes preventing these cancers and infections is the route we should be aiming toward, rather than trying to find new ways to treat them after they have already damaged the body to an extent.

“Things like cancer are so effective and harmful because they use the same mechanism as the immune system to evade it,” Dr. Shirwan said, “Just like how a runner can build muscle memory for running, our immune system can learn and build up a memory of these pathogens and infections to create a more effective response.”

“This is just the tip of the iceberg,” Dr. Shirwan said, “I am very excited to continue expanding on what our immune system is capable of.”

This type of research contributes to the University of Missouri System’s NextGen Precision Health focus. The NextGen Initiative unites scientists, government and industry leaders with innovators from across the system’s four research universities in pursuit of life-changing precision health advancements.

Dr. Shirwan and his team are moving to the new NextGen building on Mizzou’s campus in mid-September. He is very thankful for getting the opportunity to work in these facilities with these people, and he is excited for the next step of their research.

Shirwan believes we have only scratched the surface of what our immune system is capable of. Our immune system may not always know what is good and bad for itself but one thing is for sure, Dr. Haval Shirwan is good for it.

A scientist steps away from the bench

July 1, 2021 By Suppes, Davis (MU-Student) in Faces of Science Tags: Mizzou Research

After 40 years of hard work, it is finally time for David Pintel to pass the torch.

By Davis Suppes| Bond LSC

David Pintel is hanging up his lab coat after 40 years.

“It’s been an honor to be able to do my work at the University of Missouri. I’ve had a great group of colleagues both here and at the medical school,” Pintel said.

The Bond LSC virologist retired July 1 after a storied career. He spent 20 years at the School of Medicine before joining Bond LSC upon its completion more than 15 years ago.

Since then he has aimed to better understand the interaction between viruses and host cells. Pintel specialized in the study of parvoviruses, the smallest of all DNA viruses that infect vertebrates. In addition, the parvovirus adeno-associated virus (AAV) has been developed as a promising gene therapy vehicle.

On his last official day in his office Pintel was busy still packing up old memories while taking everything in.

“I’ve had tremendous students and tremendous colleagues, you know they were the important parts of my career,” Pintel said, “Going through all the old memories, you know, it’s gonna take a little while”

Pintel is a Curators’ Distinguished Professor as well as a Dr. R. Phillip and Diane Acuff Endowed Professor in Medical Research Molecular Microbiology and Immunology. He reflected on fond memories of his work here, but when asked what his favorite memory was his answer was the same, working with all of these people.

“It’s an emotional end, when you do something every day of your life for 40 years,” Pintel said. “I’m so thankful and grateful for the people that have worked with me, people that have been my friends here and allowed me to have a successful career.”

The future for Pintel will come in due time, but for now he is in no hurry and plans to enjoy some time off.

“To be determined,” Pintel said, “I think I will decompress for a while before I make any decisions on the next step.”

#IAmScience Lyndon Coghill

June 24, 2021 By Suppes, Davis (MU-Student) in #IAmScience Tags: bioinformatics, Mizzou Research

Lyndon Coghill is the new Director of the Bioinformatics and Analytics Core, and he is already making big moves at Mizzou.

By Davis Suppes | Bond LSC

Lyndon Coghill’s official title may be Director of Informatics for the Bioinformatics and Analytics Core, but his job branches out much wider than just a single label. Even as an undergrad, Coghill wore many different hats.

“I was incredibly excited about the way that the MU Office of Research and Economic Development recruited me,” Coghill said, “With these types of processes you can get an idea as to whether or not an institution is actually committed and excited about building something out.”

With his experience and range of expertise, Coghill was an easy choice for Mizzou to fill the role of Director of the Bioinformatics and Analytics Core located at Bond Life Sciences Center.

Before he achieved his doctorate in biology, he completed his undergraduate degree in zoology with minors in microbiology and geology at Western Illinois University. For his dissertation, the research he conducted was focused heavily on evolutionary genomics. Simply put, he wanted to know how changes in the genome lead to changes in a physical organism that allow them to adapt better to different environments and conditions.

With his doctorate in biology, he would go on to his first postdoc at The Field Museum of Natural History in Chicago in 2013, and then on to Louisiana State University where he began his role as a senior post doctorate in 2015. He continued to diversify his portfolio there working with the department of biology, focusing on computational biology. He was then promoted to research data scientist which had him take on an even more computationally heavy role. With this, he was able to help biologists learn how to talk to computer scientists, and assist them with building collaborative programs together..

As director, Coghill’s mission is to provide bioinformatics and data science support to all researchers across the UM system. He is creating a central hub where faculty who want to conduct domain- specific biological or life sciences-related research that is computationally heavy can get the help they need to come up with solutions. He does this by helping researchers wrangle incredibly large datasets and by helping them understand what that data is telling them from an information perspective in a meaningful way.

Coghill mentioned how interim Vice Chancellor of Research and Economic Development Thomas Spencer also made a personal effort to make sure Coghill understood his vision going forward on campus “and for me that was enough of a selling point that I wanted to be a part of that,” Coghill said.

In addition to the thorough recruitment process, Mizzou’s facilities and access were other huge factors that Coghill was looking forward to once he got here. With a hospital, vet school and productive biology program all on the same campus instead of in different cities, Mizzou offers a unique opportunity to build the integrated program all in one place.

“We’re trying to reach out to every department on campus to build these relationships because you can’t have true integration of ideas and solutions if you don’t talk to everyone who might be a benefactor or have knowledge about that,” Coghill said.

Coghill believes that to create a phenomenal translational research program, this core must interact with all these programs so that experts of different fields can come together to collaborate.

“Informatics research, especially bioinformatics is a program that really forces you to keep one foot in both worlds of computer science and biology, and there’s a limited number of people who do that kind of work,” Coghill said, “I think that was one of the big pushes for getting my experience here for this position, to bring in somebody who could bring these programs together and integrate across all these different fields.”

Coghill is excited to be working with the variety of researchers and programs across the MU campus and UM System, and learning from them at the same time.

“We may not know their biological system as well as they do and we may not know the high performance computing system as well as a full-time systems administrator, but we know enough of both that we can communicate with both teams and make sure that we can help get the researchers from the starting point to a meaningful result,” Coghill said.

Their goal is to provide Mizzou and sister campuses with research support allowing faculty to build translational research programs using computing power and informatics. This core brings new opportunities for Mizzou students as well.

“We’re going to have programs for students that can rotate through as part of the Informatics and Data Science Institute,” Coghill said.

This means that students who are interested in research fields can get direct experience related to career possibilities outside of Mizzou and academics by working in this program.

“Students can come to us and learn basic coding skills, learn informatics and bioinformatics, and that will help them build a skillset that will make them quite employable,” Coghill said.

Between helping researchers in their labs and analyzing quantities of data they are gathering for the first time, Coghill has a variety of jobs he has to understand and execute.

“So, I am the guy who wears a lot of different hats and allows these researchers from different domains to talk to each other,” Coghill said. “We’re trying to help them get to the point where their work could be as big as they want.”

Mizzou and Coghill know that there is no way to push modern research without computing, especially at the scale research is done today.

It would be extremely rare for someone who has a doctorate and spent their life trying to understand how one particular part of a biological process works to also have a doctorate in computer science, “That’s where we help… we’re providing researchers with the tools to do research at a scale using computing power, and asking questions that for many, might have only been dreamed about at other times in their careers,” Coghill said.

#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.

Homegrown researcher

October 16, 2019 By Mariah Cox in Research Tags: Mizzou Research

Years at MU lands student turned faculty tenure-track position

Maggie Lange-Osborn is a newly appointed assistant professor in the Department of Molecular Microbiology and Immunology. | Photo by Roger Meissen, Bond LSC

By Mariah Cox | Bond LSC

Where can passion, hard work and more than a decade worth of experience get you? They landed Maggie Lange-Osborn her own research lab on the University of Missouri campus.

Lange is starting down that path in Bond Life Sciences Center but will move to a permanent space in either the Medical Science Building or Schweitzer Hall eventually. She’s excited to spread her wings and establish herself independently of her past role in the Bond LSC.

In the meantime, she’s working arduously to build her lab from the ground up. From small materials such as plastics for cell culture, pipettes and pipette tips and chemicals to make buffers to large expensive equipment, Lange will eventually need it all.

“Walking into the lab, you don’t realize all of the things you need to do an experiment. When I walk into my lab space, I literally have nothing,” said Lange, a newly appointed assistant professor in the Department of Molecular Microbiology and Immunology (MMI). “You have to think about all of those things, you know it’s not just the equipment it’s the pipettes, the incubators, the hoods and then also the materials to put in those things.”

Luckily with 10 plus years in the building, Lange knows of all of the shared resources available to her, so she doesn’t have to invest in many expensive machines just yet.

“I cannot wait to do my first experiment with my own equipment,” Lange said.

Lange began her career at MU in 2003 as a Ph.D. student in the Molecular Microbiology and Immunology and Veterinary Pathobiology Graduate Program, whether she knew it at the time or not.

When applying for faculty positions, Lange worried that she would be placed in a box, unable to separate herself from her graduate work if she stayed at MU. With time, she’s found that hasn’t been the case.

“Even though I’ve been here for so long, I’ve been able to surround myself with people who know more than me and who have different areas of expertise than I do,” Lange said. “I can still branch off and learn a lot from other researchers, which is what I found really attractive about Mizzou.”

Her segway into research occurred during her first year as a graduate student in an MMI lab in the School of Medicine. Under Michael Misfeldt at the School of Medicine, Lange studied pattern recognition receptors in the innate immune system, which is the body’s first line of defense against a virus or bacteria.

The specific receptor she worked with recognizes a component of viruses. From there, Lange wanted to understand how a host is able to respond.

“After working on that I felt like I had a really good grasp of the host response side and I wanted to get more of the virus side to understand virus replication and what types of replication mechanisms work to signal the host from that perspective,” Lange said.

That led Lange to join Bond LSC in 2008 as a post-doctoral researcher in Donald Burke’s lab. Known for specializing in HIV research and viral biology, the Burke lab gave Lange the opportunity to understand virus side interactions.

Lange wasn’t quite ready to move on at the end of her post-doc, and the success with her research led Burke to invite her to stay on as an assistant research professor.

“During that time, I was more exposed to leading people and mentoring people in the lab. I was able to get some teaching experience in that role as well in the infection, immunity and advanced virology classes,” Lange said. “The position evolved into really enjoying all of the components that would be required for a tenure track position and it grew from there.”

In her sixth year as an assistant researcher, Lange decided she was ready to run her own lab. However, she knew it would be a challenge to secure a faculty position and even more difficult to stay at MU.

But, her experience in the Burke lab and her proven ability to obtain grant funding worked in her favor.

“It’s really nice to stay in Missouri because mine and my husband’s family are here,” Lange said. “When I was growing up, my dad was in the military and we moved around a lot, so I never got to know my grandparents or cousins. It’s really nice now that my kids get to have those relationships with their extended family.”

Her goal with her new lab is to combine her knowledge of viral interaction in the body and hosts’ response to infection.

Three projects currently in the works for grant submission focus on host-virus interactions and how different host factors and viral proteins interact during replication. One specific project looks at the host factors that are involved in HIV induced death caused by different HIV proteins.

“While HIV has been around for a long time, there are still things we don’t know about it. With the research, I’m getting back to my innate immunity roots and looking at exactly how viruses interact with innate immune receptors and signaling pathways and how that interaction dictates pathogenic outcomes,” Lange said.

Understanding the death pathways for HIV can lead to the development of a strategy to preserve T cells and facilitate the death of the virus. Additionally, it can lead to the development of therapies toward eradication.

Her excitement isn’t just for her new lab, it’s also for her newfound opportunity to provide students with lab experience and open up the possibility of research for those who haven’t had access to it.

“I’m from a rural community and I didn’t even know that a Ph.D. existed when I was in high school,” Lange said. “I’d really like to present those opportunities to people like me who have no idea that they’re even available. There are so many things you don’t realize are possible because of the environment that you’re in whether it be in rural or inner-city communities.”

While unknowingly launching her career at the outset of her Ph.D. program, Lange is grateful her path led her here.

“It’s been really fortunate for me, the way the whole process developed. I love this building and the awesome people I’ve met here, but I’ve been here since 2008, so having a fresh perspective elsewhere could be beneficial. I’ve worked a long time with both Marc Johnson and Donald Burke and being away from the building will allow me to meet new investigators and establish new collaborations,” Lange said. “While we still have very productive collaborations and have promising, active projects, it will help demonstrate that I’m separate from them and have my own interests as well.”

University funding moves cancer-targeting research forward

September 3, 2019 By Mariah Cox in Research Tags: Mizzou Research

Cross-collaborative research team looks to refine delivery of cancer treatments

David Porciani, Josiah Smith, Leah Cardwell, Mark Daniels, Bret Ulery and Donald Burke | Photo by Roger Meissen, Bond LSC

By Mariah Cox | Bond LSC

“When you want to use a tool to do something in the house, you have to use the right size tool. It does no good to use a large screwdriver to fix the tiny screw on your glasses.”

That’s Donald Burke, Bond Life Sciences Center lead primary investigator, as he begins to explain a project looking to optimize the targeting of cancer cells as part of a large cross-collaborative research team.

And the tools Burke is referring to are aptamers, single-chained synthetic DNA or RNA molecules. Aptamers are tricky molecules. Stemming from the Latin word “aptus,” meaning to fit, and “meros,” meaning part, aptamers must be complementary in size and shape to a certain cell-surface receptor in order to be useful as targeting tools, just like having the right size tool.

Last fall, Burke’s lab was able to identify aptamers as a specialized delivery method that have the potential to carry chemotherapy drugs and imaging agents, or cargo, as little backpacks to diseased sites. An important feature of aptamers is their three-dimensional structures which allow them to bind to target sites with high selectivity. That conceivably means they could deliver a drug to a particular part of the body, like a tumor, and not harm nearby tissues.

Now, the team, comprised of MU experts and researchers who specialize in surgery, radiology, molecular biology and immunology and chemical engineering, is hitting the ground running with a two-year research plan to refine the delivery of cancer treatments. The group was one of 19 innovative research projects across all four UM System campuses to receive a grant from a $20.5 million investment for research and creative works.

“Chemotherapeutics are not very specific and most of them act to block DNA replication or other functions of the cell in both healthy and cancerous cells,” said David Porciani a post-doc who started in the Burke lab in the spring of 2016 after finishing his Ph.D. in molecular biophysics in Italy. “Cells that are dividing are more susceptible to the chemotherapeutic effect, that’s why chemotherapy patients start losing hair.”

In general, therapeutic drugs don’t know to go only to tumors, and they don’t differentiate between cancer cells from healthy cells. The obstacle in only targeting cancer cells is to find specific indicative markers that are unique to tumors. Sometimes researchers have to make do with markers that are overexpressed on tumors cells, but those same markers can also be present in low levels on healthy cells.

The team is working simultaneously towards four major objectives – to identify a comprehensive panel of aptamers that target the majority of tumors, develop molecular tools to enhance the delivery of cargo specifically to cancerous cells, improve imaging for targeted delivery of radiopharmaceuticals, and enhance the efficacy of killing solid tumors through immunotherapy.

Each researcher bringing their unique expertise to the table play an important role in ensuring the project stay on track. Mark Daniels, an associate professor of Molecular Microbiology and Immunology and Surgery from the School of Medicine; Bret Ulery, an assistant professor in the Department of Biomedical, Biological & Chemical Engineering; and Donald Burke, a professor of Molecular Biology and Immunology in the School of Medicine and joint professor of Biochemistry, have been instrumental in the project since its beginning stages.

A collaboration years in the making

“Daniels, Ulery and Burke labs have been collaborating for a number of years, each of us excited about what the other could bring to the collaboration,” said Burke. “[Over the years] we’ve explored several ways of making things move forward, we’ve figured out some productive ways to work together and we’ve identified the key questions that we could pool our respective expertise toward answering,” said Burke.

Daniels’ subgroup of the project has been using flow cytometry, a technique used to detect and measure biochemical and molecular characteristics of tumor cells to see which ones are recognized by a set of different aptamers.

Additionally, Ulery has provided extensive insight into the different ways to package molecules together so that they can move around the body and get to where they need to go.

The grant comes as part of the combined UM system’s and all four campuses mission to supply funding for opportunities that will enhance the ‘well-being for Missouri, the nation and the world through transformative teaching, research, innovation, engagement and inclusion.’

For Burke, the grant couldn’t have come at a better time.

“This team has existed before the announcements were made that there would be these opportunities and so when they announced we said that this was tailor-made for us,” said Burke. “It was just the right time for us. Had they had the same competition three years ago, we weren’t ready for it. Had they had it three years from now hopefully we wouldn’t have needed it anymore and we would’ve already gotten the project to the next level.”

Another key player in the development of this discovery is David Porciani. He has spent three years trying to create ‘smart’ molecules that know exactly where to bind without damaging healthy cells, and he has been working on the project since its beginning.

David Porciani, a post-doc in Donald Burke’s lab at Bond LSC, sets up a reaction to obtain fluorescently labeled aptamer samples. | photo by Mariah Cox, Bond LSC

“There are several ways to target cancer cells. Even on campus, there are different groups that are trying to target cancer cells differently and, in my experience, every strategy has advantages and limitations,” said Porciani. “What I see for this aptamer strategy is that it can provide new molecules that can bind to receptors, and it can also identify new tumor biomarkers.”

Porciani’s portion of the project includes using the advanced microscopy capabilities of the MU Advanced Light Microscopy Core to visualize the kinds of receptors on the surface of cancer cells. This information can be very telling in identifying receptors that are specific only to cancerous cells.

Two HeLa Cells — A dividing HeLa cell captured using the MU Advanced Light Microscopy Core. The many green dots indicate single copies of receptors. Because these cells are from a cancer cell line, there is an abundance of green dots. | Photo by Alexander Jurkevich, Bond LSC

What the future holds

The project now starts down this ambitious road. In the first year, the collaborators are working on discovering their panels of aptamers, developing lung cancer-specific T cells which provide artificial cell receptors for the use of immunotherapy, and beginning testing of the specificity of aptamer-cargo constructs in samples acquired from the American Tissue Cancer Collection. By year two the group hopes to begin testing in biopsy tissues acquired from MU hospital patients acquired under informed consent and in lab mice.

“After we test a specific drug in cell culture samples and see an anti-cancer effect, killing only the cancer cells and leaving the healthy cells, we expect to see the same effect in biopsy tissue samples,” said Porciani. “Having a reduction of the tumor mass and not having side-effects is what we hope to see in biopsy tissues and mice.”

After the end of year two, the team is looking forward to expanding this research to other types of tumors to see if their tumor-targeting method can apply in different cancer types.

“Our team has been trying to piece this together for a long time and it’s been surviving on goodwill up to this point. This is the most substantial funding we’ve had for it to date and we’re really excited that the University of Missouri has chosen to support us on this,” said Burke. “We’re very hopeful that we can use it as the starting point for building a much larger enterprise centered around tumor targeting in general, whether it’s for therapeutics, diagnostics or other purposes.”

Donald Burke is a primary investigator in the Bond Life Science Center and is a professor of Molecular Microbiology & Immunology in the School of Medicine and a joint professor of Biochemistry and Bioengineering. David Porciani is a post-doctoral researcher in the Burke lab. Mark Daniels is an associate professor of Molecular Microbiology and Immunology and Surgery in the School of Medicine. Bret Ulery is an assistant professor in the Department of Biomedical, Biological and Chemical Engineering in the College of Engineering. Other key collaborators on the project include Diego Avella Patino and Jusuf Kaifi in the Department of Surgery and Jeff Smith in the Department of Radiology.

#IAmScience Henry Wan

August 22, 2019 By Mariah Cox in #IAmScience, Research Tags: Mizzou Research

By Mariah Cox | Bond LSC

Every year we all tend to pay a visit to the doctor to get ahead of cold and flu season. Nothing could be worse than being in the midst of a hectic time at work or school and being out of commission.

Many don’t think twice about the annual flu shot, it just becomes a part of their autumnal routine. But for Henry Wan, a new primary investigator in the Bond Life Sciences Center, a significant portion of his life revolves around understanding how flu viruses get transmitted from animals to humans and vice versa as well as tracking down more effective influenza vaccination strains.

Flu viruses caused more than 959,000 hospitalizations and 79,400 deaths during the 2017-2018 flu season in the United States, according to the Centers for Disease Control and Prevention. And influenza A virus (IAV), also known as the avian flu, has caused pandemics that resulted in millions of deaths in poultry, and fear of widespread transmission to humans and other mammals.

Wan’s interest in influenza started in 1996 after an outbreak of avian influenza (H5N1 virus) in South China. In 1997, this same virus caused another outbreak in Hong Kong that killed 40 percent of geese infected and crossed over to infect 18 humans, causing six of them to die.

While extremely noteworthy because the strain seemed to jump from poultry to humans, researchers weren’t able to pinpoint how these viruses were circulating in wild birds and predict which avian flu could transmit from wild birds to human and from human to human.

“Over the past decade, we’ve been trying to study how influenza emerged in the animal-human interface,” said Wan. “Influenza transmission among humans and different wild and domestic animals have been well documented for decades, however, the detailed mechanism is far from being understood. We still cannot predict emerging risks and provide precise alerts for influenza emergence for domestic animals and humans.”

Wan grew up in a small town in central China on the Yangtze River. After earning an undergraduate degree at Jiangxi Agricultural University in Nanchang, China, Wan decided to pursue an advanced degree in Avian Medicine at South China Agricultural University in Guangzhou, China. Afterward, he moved to the United States to obtain his Ph.D. in veterinary medicine and a master’s in computer science at Mississippi State University where he studied mycoplasmas in poultry rather than influenza.

While mycoplasmas weren’t the peak of his research interest, he still enjoyed studying them.

“I was a poor student from China and didn’t have the opportunities that are available now. The student assistantship at Mississippi State University provided by mycoplasmas study was a good opportunity,” he said. “While at MSU I also had an opportunity to study computer science while finishing my Ph.D. and that really helped me build a foundation in systems biology.”

Wan spent a short period at Oak Ridge National Laboratory in Tennessee before finishing his post-doc at the University of Missouri in the lab of Dong Xu.

From there, he started his teaching and research career at Miami University of Ohio, however, he didn’t get back to studying influenza until he moved to Atlanta to work at the Centers for Disease Control as a senior scientist fellow in 2007. Wan dived back into academics as a veterinary medicine professor to graduate students at Mississippi State University in 2009 and remained there until coming to MU this fall.

His focus on influenza will be helped by a recent $2.8 million National Institutes of Health (NIH) grant to develop and implement high-throughput technology to study and characterize influenza viruses’ antigenic properties and understand antigenic evolution of influenza A viruses. This technical-sounding purpose truly means his lab will work to advance the technology behind vaccine strain selection, especially for children, elderly and pregnant women, to provide a more universal flu vaccine strain for the general population.

Additionally, the project will explore the mechanisms that cause variation in influenza virus quasi-species and establish a history of prior human exposure to influenza viruses in an effort to improve strain selection.

“The mechanisms that cause variation in quasi-species will help us understand how influenza variants emerge in humans and help develop a better-targeted surveillance and prevention strategy through vaccination,” Wan said.

While Wan has only been at Mizzou since this summer, he’s jumped feet first into research collaborations here. He’s also involved in a cross-campus project funded by a University of Missouri System Tier-2 grant to build more research capacity for data-driven discoveries and a grant from the U.S. Department of Agriculture (USDA) to develop a broadly protective E. coli vaccine, among others.

When not in the lab, Wan enjoys spending time outdoors, running and biking along the Katy trail, as well as playing Ping-Pong with his friends. He believes in exercise as an outlet for brainstorming new ideas, rather than just sitting in a lab or his office.

“I think that’s critical, especially in science and research. A lot of the time I get a sparkling idea from exercise, not from sitting in this office. It’s from when you do something else another idea comes,” Wan said.

This research is funded by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health. Wan is a Bond LSC primary investigator and joint professor of Molecular Microbiology and Immunology in the School of Medicine, the Department of Veterinary Pathobiology and Electrical Engineering and Computer Science.

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