Penquite, Cara (MU-Student)

About Penquite, Cara (MU-Student)

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#IAmScience Reinier Suarez

February 18, 2022 By Penquite, Cara (MU-Student) in #IAmScience Tags: COVID-19, virology

By Cara Penquite | Bond LSC

When one of Reinier Suarez’s undergraduate professors suggested he go to graduate school, he was confused.

“I had never heard of a Ph.D. in my life,” Suarez said.

Three years later, Suarez is a first-year graduate student studying COVID-19 variants. Suarez came to Mizzou as part of the university’s Post-Baccalaureate Research Education Program (PREP), a stepping-stone between his undergraduate studies at Florida International University and his graduate studies at MU. He joined Marc Johnson’s lab at Bond Life Sciences Center as a PREP scholar and liked it enough to stay and continue his studies.

“Marc Johnson is a great [principle investigator], he really takes the time to talk to the students. He’s very honest,” Suarez said.

While Suarez started with HIV research, he soon switched his focus to coronaviruses when MU shut down at the beginning of the pandemic.

“[Johnson] saw it as a good opportunity to expand the lab, and I agreed,” Suarez said.

Suarez works on pseudotyped COVID-19 particles that allow him to study variants of COVID-19 without the dangers of using a live virus. Psudeotyped particles have the COVID-19 spike protein on the surface of the cell, but the virus genome is replaced with fluorescent proteins. Similar to a live virus, the pseudotyped particles can get inside healthy cells using the spike protein, but they release the fluorescent protein instead of the COVID-19 genome. A live COVID-19 virus would use the genome to hijack the cells and reproduce more virus, but the fluorescent protein in the pseudotyped particles only change the cell’s color under a microscope.

“If the [pseudotyped particles] infect a cell, the cells turn green … and then you can measure how much green there is in compared to all the cells that you have,” Suarez said.

By measuring the amount of green, Suarez measures how many cells were infected by the particles. Suarez uses this method to test different mutations of the COVID-19 spike protein to see which version increases infectivity.

Suarez also contributes to the lab’s other COVID-19 project testing wastewater samples from various locations in Missouri and around the U.S. to identify amounts of COVID-19 spike proteins in the water.

“You can actually see when a locality is about to hit an outbreak before they get there,” Suarez said.

As the only graduate student in the Johnson lab, Suarez has taken on greater research responsibilities as well as teaching undergraduates – a long way from his start in the lab as a PREP scholar.

As a PREP scholar, Suarez worked closely with Johnson to prepare for graduate school.

“It was clear that he had holes in his background which required chiseling,” Johnson said, but he also commended Suarez’s work ethic.

“His motivation has been second to none,” Johnson said.

As an undergraduate, Suarez studied at Florida International University where he pursued dentistry. Coming from Miami, it seemed like a natural step for Suarez.

“I started off with dentistry because I didn’t know what I wanted to do, I just knew I liked science, specifically biology,” Suarez said.

It was not until his last year of undergraduate studies that one of his professors suggested he look into grad school.

“I was taking her virology class and she said, ‘hey why don’t you go to grad school,’ and I was like ‘what is that, what is grad school,’” Suarez said.

Having no prior experience working in a laboratory proved an obstacle in the graduate program admissions process, but he was accepted to PREP which allowed him to improve his education and start research before attending a graduate program.

“The PREP program basically gives students the ability to see what grad school is like without having to be in grad school,” Suarez said.

During the PREP program Suarez rotated in various MU labs, but he credits much of his learning to Margaret Lange, Molecular Microbiology and Immunology assistant professor, and Johnson.

“[Lange’s] also an HIV researcher, so her and Marc Johnson work very close together,” Suarez said, “they kind of formed a co-mentorship.”

While Suarez experienced a “very nurturing environment” at MU, he still credits his decision to start research to his mentor during his undergraduate studies who suggested furthering his education.

“She set me on a path and that’s how I’m here today,” Suarez said.

Pancreatic tumor composition provides insight on treatment response

February 17, 2022 By Penquite, Cara (MU-Student) in Research Tags: bioinformatics, cancer, gene expression, mice

PanC_7 — Jing Zhou focuses the microscope through her computer. The microscope feeds its view directly to her screen so Zhou can see the pancreatic cells. | Photo by Cara Penquite, Bond LSC

By Cara Penquite | Bond LSC

Not all tumors are created equal, and potential treatments aren’t universal. When it comes to pancreatic cancer, surgery and radiation often do more harm than good due to its rapid growth and ability to spread to the liver.

Searching for alternative treatment options, Jing Zhou focused her research on immunotherapies. That led Zhou and her team to identify the sequences for over 9,000 cells from pancreatic tumors to out why some therapies don’t measure up.

“My professor said, ‘You have to do a lot of work to try and make sure your sample is ready [and] your experiments are ready. Otherwise, we [will] spend a lot of time, a lot of money, on [research] that doesn’t work,’” said Zhou, a NextGen graduate student who collaborated closely with Trupti Joshi’s bioinformatics lab at the Bond Life Sciences Center for the data analysis.

PanC_2 — Jing Zhou grabs a box with pancreatic tumor tissue samples in cover glass. Zhou can see the cancerous and normal cells by magnifying the samples in a microscope. | Photo by Cara Penquite, Bond LSC

Zhou identified differences between types of pancreatic tumors to understand why certain types of pancreatic cancer respond differently to treatment. Scientists analyzed RNA sequences for two different types of pancreatic tumors. While the project is continually evolving, her most recent findings were published online in the Journal of Translational Oncology.

Zhou focuses on a form of immunotherapy that increases the effectiveness of the immune system. Known as immune checkpoint inhibitors, the treatment turns off protein pathways that act as brakes on the immune system. In cancer patients, turning off the brakes allow immune cells, like T-cells, to attack more cancer cells.

“The cancer cells grow so fast, they expand a lot and that attracts a lot of T-cells. Normally, in a healthy tissue they don’t have so many T-cells, just a few of them to keep the body normal,” Zhou said, “But when you have a strong immune response, like in a tumor, it will have a lot of T-cells in that kind of environment.”

Not all types of pancreatic tumors respond well to immunotherapy.

“This was a very interesting project because what they were doing here is comparing four different types, [but] mainly two different types, of pancreatic cancers,” said Joshi, Bond LSC principal investigator and Assistant Professor at the Department of Health Management and Informatics in the School of Medicine and core faculty in MU’s Data Science and Informatics Institute. “One that is resistant to and one that is sensitive to this anti-PD-1 antibody treatment, what is known commonly as immunotherapy.”

PanC_4 — Jing Zhou selects a slide containing human pancreatic tumor cells to put into the microscope. While Zhou’s previous work was conducted in mice, surgeons now send human tissue samples to the lab for her to analyze as well. | Photo by Cara Penquite, Bond LSC

Tumors are composed of many types of immune cells mixed in with cancerous cells, and Joshi’s lab analyzed the composition to understand why two different types of pancreatic cancer react differently to treatment.

Unlike past analyses that relied on analyzing the tumors as a whole, the scientists used a process called single-cell RNA sequencing which allowed them to identify the various types of cells present and quantify the gene expression in individual cells. This quantification allowed the researchers to see which genes were turned on in each cell.

“The single-cell technology is the biggest advancement in sequencing technologies,” said Yuexu Jiang, a postdoc in Joshi’s lab who analyzed the single-cell RNA sequencing for the project.

Joshi suggested the analogy of a fruit smoothie to understand the concept of single-cell RNA sequencing. A fruit smoothie is a mixture of many fruits, and to understand what causes the flavor of the smoothie you must know how much there is of each fruit.

Single-cell RNA sequencing allows the researchers to quantify what types of cells are in the tumor, as well as identify the genetic makeup of the cells in the tumor.

“That really allows you to pinpoint that it is this particular gene expression in this particular type of cell which is really associated with what outcome you’re seeing in terms of these different tumors’ behavior,” Joshi said.

Pancreatic cancer is difficult to treat since surgery and radiation often do more harm than good. With its rapid growth rate and ability to easily spread throughout the body, a pancreatic cancer diagnosis comes with a 50% five year survival rate according to the American Cancer Society.

“I have been involved a lot of times in the surgery. I saw when the surgeon opened the [patient], and when they saw the metastasis, tiny things, on the liver, they just closed the [patient]. They won’t remove the cancer anymore,” Zhou said.

Immunotherapy provides another option for patients that need one.

“Getting a better understanding of the composition and what parts of the immune system are associated or involved in times when you see a cancer responding to immunotherapy […] that is really what this research was targeted towards understanding,” Joshi said.

This research published in the Journal of Translational Oncology November 9, 2021, under the title “Single-cell RNA sequencing to characterize the response of pancreatic cancer to anti-PD-1 immunotherapy.”

Outlining Omicron: researchers determine key mutations in the latest COVID-19 variant

February 2, 2022 By Penquite, Cara (MU-Student) in Research Tags: computer science, COVID-19, genetics

Bond LSC and UNMC scientists explain mutations unique to the Omicron variant

Austin Spratt Protein Models — Austin Spratt, undergraduate mathematics student in the Kamlendra Singh lab, shows protein models of the Omicron spike protein and the receptor it attaches to when infecting cells. “The genetic codes are used to identify the mutations, and then we use the structure to see how it would change over time. It’s going to give us more information about new mutations that occur,” Spratt said. | Photo by Cara Penquite, Bond LSC

By Cara Penquite | Bond LSC

It took eight days for Kamlendra Singh and his team to crack the code behind the Omicron COVID-19 variant. Although usually characterized by months of waiting, the peer-review process matched their pace, publishing their research a week later.

“That’s how quick it went because the editors and the general [scientific community] recognize that it’s very timely and important research,” said the Bond Life Sciences Center principal investigator.

Discovering 46 genetic mutations in the Omicron variant, their research explains Omicron’s ability to efficiently infect cells and evade antibodies. Their explanation predicted Omicron’s possibility for increased transmissibility a couple weeks before the beginning of the late December surge of COVID-19 cases in the U.S. The work published online December 10, 2021, in the Journal of Autoimmunity.

“You will see a lot of infections now because the vaccine-induced immune responses are not able to control the [Omicron] infection,” said Siddappa Byrareddy, a collaborator on the project and Professor and Vice-Chair of Research in the Department of Pharmacology Experimental Neuroscience at the University of Nebraska Medical Center (UNMC).

Genetic mutations to the spike protein on the surface of the virus increase Omicron’s ability to infect cells and evade antibodies. In Omicron, the mutations allow for a stronger bond between the spike protein and the healthy cell. The spike protein acts as a key enable the virus to get inside the cell by attaching to receptors on the surface of healthy cells. Once inside, the virus hijacks the cell and uses it to create more copies of the virus.

“What happens is, these mutations are in the receptor-binding domain. Which means, when these two things come together, when the spike protein tries to attach to the ACE2 receptor, these mutations cause it to bind more. When that happens, we have increased transmissibility or increased infectivity,” said Saathvik Kannan, a Hickman High School sophomore, and lead author from the Singh lab involved in identifying the mutations.

The spike protein is also the primary point of contact for antibodies designed to neutralize the virus. Since antibodies are not universal, the immune system must be exposed to a virus, either through infection or vaccination, before creating antibodies to neutralize that virus. Omicron’s mutations in the spike protein make it different from other variants of COVID-19, so antibodies that can neutralize other variants seem to be less effective in preventing Omicron infection.

“Antibodies are very specific. Any one mutation can completely abolish the binding,” Singh said.

While antibodies from previous infection or vaccination may not prevent Omicron transmission, Byrareddy emphasized that they are still decreasing hospitalization.

“Even though the vaccines are not effective [against Omicron] transmission, they still help the immune response to fight against the virus. That’s why we don’t [see] a lot of hospitalization,” Byrareddy said.

One potential solution to mitigate Omicron’s effect would be to create an Omicron-specific vaccine. While a new vaccine could decrease Omicron transmission, Singh warns that it would not necessarily prevent the emergence of further variants. This is a particular concern with Omicron because of its many versions.

“We’re seeing different Omicron versions where you have the Omicron, but with a couple changes. Those couple changes are making a big impact.” said Austin Spratt, another Singh lab researcher and MU undergraduate studying mathematics involved in the project.

Spratt’s role in the project was to create computer simulations of the spike proteins to see models of the mutations.

“[Omicron] has bigger mutations and different flavor mutations [than previous variants], and there are starting to be subcategories of that,” Spratt said.

Singh and Byrareddy’s labs are taking their research in the direction of antivirals with the hope of creating a drug that could reduce COVID-19 symptoms. The antiviral would block receptors on the surface of healthy cells so that the virus’ spike protein will not fit anymore. Without a key to get into the cells, the virus would not take over the cells.

While antivirals would not cut out all variants, Spratt believes they could help the problem as they did with other pandemics such as the Spanish Flu.

“I think it’s possible that they create antivirals that will slowly but surely cut out variants over time,” Spratt said.

This research published in the Journal of Autoimmunity December 10, 2021, under the title “Omicron SARS-CoV-2 variant: Unique features and their impact on pre-existing antibodies.”

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