Olga Baker

Receptors Found to Help Patients with Sjögren’s Disease

April 13, 2022 By Balslew, Karly (MU-Student) in Research Tags: salivary glands, Sjögren’s Disease

The Baker lab poses for a group photograph. The lab has been working with specialized pro-resolving lipid mediators in efforts to help patients with Sjögren’s Disease. Photo by Karly Balslew, Bond LSC

By Karly Balslew | Bond LSC

Saliva is probably not the first thing that comes to mind when we think about eating our favorite foods. The clear liquid washes away food debris and bacteria, and it plays a vital role in maintaining our dental hygiene and oral health.

You may take it for granted, but for patients with Sjögren’s disease, life without saliva is challenging.

“We’ve seen firsthand how patients suffer from Sjögren’s disease and what the consequences are in the oral cavity,” said Olga Baker, a Bond Life Sciences Center principal investigator studying the syndrome.

The autoimmune disease causes our body to attack the glands that produce tears and saliva. This destruction at the hands of our immune system causes dry mouth and dry eyes as it eventually kills the cells that perform this valuable service to our bodies. Without saliva, tooth decay and painful diseases like gingivitis are almost inevitable.

Sjögren’s disease affects approximately 4 million people in the United States. The severity of the disease varies in patients, but it destroys all exocrine glands and there is currently no cure. While the cause of the disease is still unknown, researchers are turning efforts to alleviate patient discomfort.

The Baker lab focuses on a class of drugs called specialized pro-resolving lipid mediators. These medications are derived from essential fatty acids and play an important role in decreasing inflammation and recovering salivary function.

Harim Tavares Dos Santos — a post-doctoral fellow in the Baker lab and lead author on a recent study of this drug —has seen success with restoring salivary functions with the specialized pro-resolving lipid mediator drug resolvin D1 (RvD1). Resolvins act as anti-inflammatory mediators and restores saliva flow rates. The lab will test a variety of drugs from the specialized pro-resolving lipid mediators’ class to see which one would yield the best results, but some receptors they affect within the salivary glands are unknown.

“The first step is to see if we know all the receptors for other drugs,” Tavares Dos Santos said. “Then, we test the different drugs to see which ones activate the receptor to possibly decrease inflammation and reach the goal of getting the saliva back.”

RvD1 activates the receptor ALX/FPR2 Tavares Dos Santos explains. This then triggers a signaling mechanism that promotes the survival of salivary gland cells and protects the cells tight junctions while increasing saliva secretion. Researchers used six human minor salivary from female subjects in this experiment to determine the expression of pro-resolving lipid mediators in patients with and without Sjögren’s syndrome.

Previously, the lab tested these drugs on mice models with Sjögren’s-like features and saw they can recover salivary function. However, researchers need more data to find other receptors that can maximize the positive response from the drug.

But mice aren’t the same as humans, and even when researchers test on humans it can be difficult to find patients with Sjögren’s disease willing to participate in the research.

“We don’t have a lot of literature in salivary glands to look for. Basically, what is known about resolvins and salivary glands is generated here in the lab,” Tavares Dos Santos said.

“Another challenge is that no one knows what causes the disease, so the research is mainly trial and error,” Baker said.

Baker explains that studies show people with Sjögren’s disease could have a genetic predisposition for it, but there are also environmental factors like viruses that could trigger the genetic components that lead to Sjögren’s disease.

“In the end, we want to create a drug that has all those properties to cure the patient so hopefully in the future, we can get a product on the market,” Baker said.

The Baker lab will present their progress with Sjögren’s syndrome at the 2023 Gordon Research Conference in Ventura, California. Both Baker and Tavares Dos Santos will co-chair the international conference that attracts researchers studying salivary glands and exocrine biology.

“This is a very important conference that will elevate Missouri,” Baker said. “The whole thing is really exciting.”

Olga Baker is a professor of Otolaryngology-Head and Neck Surgery and Biochemistry as well as a Bond Life Sciences Center principal investigator. Harim Tavares Dos Santos is a Bond Life Sciences Center post-doctoral fellow.

#IAmScience Harim Dos Santos

December 3, 2021 By Lauren Hines in #IAmScience Tags: Sjogren's syndrome

By Lauren Hines | Bond LSC

Don’t mistake Harim Dos Santos’ kind demeanor and introspective silence for a lack of ambition. On the contrary, his head is full of reflection and big dreams.

Coming from Brazil, Dos Santos has achieved quite a few of those dreams including researching at an American university. Dos Santos is now a postdoctoral fellow in the Olga Baker lab at Bond Life Sciences Center, developing ways to treat salivary gland damage in head and neck cancer patients and in Sjögren’s syndrome patients.

“I’m loving it [here], really,” Dos Santos said. “It’s good to see that there’s not only a dream. Things happen when you go for it.”

From Brazil to Mexico to Portugal, Dos Santos has been developing his career in dentistry and salivary gland research since 2012.

“In the beginning, it was hard,” Dos Santos said. “But now I see that I’m blessed. I’m blessed to be studying, working in different places … I feel like I’m going up.”

He says his biggest professional achievement so far has been joining the Baker lab. In 2018 he had a Skype interview with principal investigator Olga Baker, back when her lab was in Utah. At that time, Dos Santos was still learning English and practiced his interview answers to questions he thought Baker would ask.

“I remember I was really sad because I didn’t answer one question,” Dos Santos said. “I didn’t answer one question. It was not good.”

But then Baker sent him one of her papers. He had just 100 words to critique it and used 96.

He got the job.

“I just like, ‘Oh my gosh. I’m going to the USA,’ and I remember I started crying,” Dos Santos said. “I was like, ‘That’s my chance.’ Ninety-six words changing my life.”

To Baker, his organization and clinical experience made him a good candidate. What made him a great candidate, however, was when he pointed out she should be testing Sjögren’s disease in both male and female mice even though the disease mainly affects women.

“I see him as a future P.I.,” Baker said. “He has all the elements necessary. He’s very creative, very organized. He has leadership, and he is a go-getter. I ask him to do one thing. He does five.”

In May 2020 — the height of the pandemic — the lab moved from Utah to the University of Missouri. Baker drove cross country with her family, and Dos Santos flew over early by himself. For that first month, he came to Baker’s place many times to eat dinner, brainstorm protocol and help establish the lab.

“We became kind of a family,” Baker said.

Baker and her family showed him around Columbia, and they went to see the McBaine Burr Oak tree, known as one of the oldest trees in Missouri.

Olga Baker and Harim Dos Santos at Missouri's Largest Tree — Once they arrived in Columbia, principal investigator Olga Baker showed postdoctoral fellow Harim Dos Santos one of the oldest trees in Missouri. | photo contributed by Olga Baker, Bond LSC

Since then, the lab has been up and running without slowing down. Dos Santos’s work focuses on testing the effectiveness of different hydrogels to promote tissue regeneration in mice. These hydrogels are synthetic networks of crosslinked polymer chains that can take in large amounts of water.

He also recently published a paper focusing on finding specific receptors in the salivary glands of humans. For certain drugs to be effective, such as specialized pro-resolving lipid mediators, researchers need to find the receptors present in the target tissue.

“If the receptors are there, we know that we can use different combinations of drugs to try to improve it and decrease inflammation and also improve the quality of life of the Sjögren’s syndrome patients,” Dos Santos said.

In addition to his research, he’s organizing the prestigious Salivary Glands & Exocrine Biology Gordan Research Seminar as co-chair. The conference is in California in February 2023.

Dos Santos will keep going forward, while his dreams just get larger.

The Group Approach

January 5, 2021 By Lauren Hines in Research Tags: cancer, cell sheets

Cell sheet development promises better treatment for destroyed tissue

By Lauren Hines | Bond LSC

Imagine a sticker a few centimeters wide and as thin as a strand of human hair except made of cells. For medicine, this sticker — called a cell sheet — can regenerate tissue damaged by chemotherapy radiation wherever it’s placed.

Kihoon Nam uses cell sheet technology to help head and neck cancer patients who have lost the ability to produce saliva due to chemotherapy radiation at the Bond Life Sciences Center.

“[Without] saliva, you will have difficulties in eating, tasting and speaking,” said Nam, assistant research professor in the Olga Baker lab. “Sometimes you can get an infection. In that case, they would need to use medications, saliva substitutes or the other biomaterial, but current treatments provide only temporary relief and result in significant side effects. So, I wanted to make some nice new alternative approach for this kind of patient.”

Cell sheets are exactly as cool as they sound. They’re single or multiple layers of cells, similar to the top of a sticker. These cells come from a patient or donor and they can make an organ-like structure. If the cell sheet was produced using stem cells, they can turn into almost any type of cell or tissue.

Once the cells are harvested, they’re prepared using a temperature-responsive culture dish. As temperatures reach below 25°C, cells spontaneously detach, and the extracellular matrix adheres to the patient’s tissue like the back of a sticker.

For the Baker lab, cell sheets have the potential to help regenerate salivary gland tissue and therefore regain patients’ abilities to produce saliva.

Before cell sheets, doctors and scientists would try to restore cells damaged by radiation therapy by collecting healthy cells of the same tissue from the patient or a donor. Then, they isolate the cells using a certain enzyme and inject the cells into the patient to spread.

However, the enzyme caused cell damage, inhibited the cells from changing into other types of tissues, and caused side effects to the patient.

“If you use an enzyme to collect cells and use them for the treatment, you need additional glue-like polymer or biomaterials to transport cells,” said Nam. “If you add this kind of glue with cells, it may cause some side effects because it’s not our cell-derived materials. However, if we create this cell sheet with its own glue like the extracellular matrix, they cannot make any side effects.”

Kihoon Nam, assistant research professor in the Olga Baker lab, looks at a cell sheet under a microscope. | photo by Lauren Hines, Bond LSC.

Teruo Okano, the principal investigator at the University of Utah, started working towards a better system in 1984. After ten years studying temperature-responsive hydrogels, he went back to Japan where he worked with medical doctors to develop cell sheets

This new technology bypasses the need to use enzymes, and, instead, it uses polymers that change their structures as temperatures decrease in order to keep the cells together

“We can get the cells from the dish without any disruption in the cell and extracellular matrix protein,” said Kyungsook Kim, research assistant professor in Okano’s lab at the University of Utah. “So, this cell [therapy] is really functional.”

Cell sheet technology has been used in hospitals in Japan and Europe for eye, throat and heart tissue. The Okano lab has performed clinical research on periodontal, lung, middle ear, cartilage and heart tissue. However, cell sheet technology still has a way to go

“It’s a little expensive,” Nam said. “The other problem is that the cell sheet is very sensitive…the thickness of a cell sheet is about 100 microns. So, if you shake it, it is destroyed.

The technology also requires a high level of expertise, practice and environmental control care.

While cell sheets are in hospitals, it needs to be further developed for all kinds of tissues to make a difference for all kinds of patients. And so, the Baker lab continues to refine the process to develop them to restore salivary glands.

“If someone has cancer, they will get radiation therapy or chemotherapy,” Nam said. “In many cases, they lost their cell function and organ function. In that case, we can use saliva substitutes, but we cannot cure it 100%…We can keep patients’ cells before treatment. Then at the treatment with radiation therapy or other therapy, if they lost their organ function, we could cure this with their own cells.”

Read more about cell sheets and what else goes on in the Baker lab in their latest papers in Nature Regenerative Medicine and Cells.

Four months in, Baker lab hits the ground running and won’t be stopping anytime soon

October 19, 2020 By Lauren Hines in Research Tags: cancer, cell sheets, copper

Post doctorate Harim Tavares from the Baker lab works in “the hood,” which is a space used to prevent researchers and other outside factors from contaminating cells.

By Lauren Hines | Bond LSC

Saliva is often something people take for granted.

It helps break down food, maintain teeth and keep the oral cavity feeling comfortable. But head and neck cancer patients lose those benefits when chemotherapy treatments damage their salivary glands.

Olga Baker set out to research tissue regeneration for these cancer patients by collaborating with the Michael Petris and Gary Weisman labs after setting up shop four months ago as a new principal investigator at Bond Life Sciences Center.

Together, the Petris and Baker labs are looking at the role of copper in salivary gland damage.

“Nobody has asked what happens to copper metabolism during and after head and neck radiation,” Baker said. “Is copper related to the fibrosis that is developing in those patients, so they don’t make saliva? We don’t know. So, we are answering different questions…. We don’t have any data yet, but what we have is immunofluorescence studies showing that those copper transporters are present in salivary glands from mice and humans.”

If the two labs can learn how copper connects to salivary gland tissue regeneration, Baker can get a step closer to helping patients.

The Baker and Petris labs just published a paper with help from the Proteomics Center and the MU Molecular Interactions Core in the journal of Dental Research. Post doctorate Harim Tavares from the Baker lab is the leading author.

The study used synthetic networks of crosslinked polymer chains that can take in large amounts of water called, smart hydrogels. The smart hydrogels were used in the same mouse model as the cell sheets and promoted tissue regeneration on mouse salivary glands. The paper explored how different materials like smart hydrogels can improve tissue regeneration.

Baker’s other focus takes on cancer and tissue regeneration from a different angle in her collaboration with the Weisman lab.

“Dr. Weisman’s group has studied the mechanisms of salivary gland dysfunction for over 30 years, so between these two groups the tools are in place to provide a translational approach to understand and treat salivary gland disorders,” said Jean Camden, a senior research associate in the Weisman lab.

The two labs just submitted a paper on mouse submandibular glands and cell sheets, which are plastic-like sheets where cells grow and detach once it reaches a certain temperature. Kihoon Nam from the Baker lab is the corresponding author. The study transplanted submandibular gland cell sheets into a wounded mouse to see if cells could be transferred.

“We believe that is a good proof of concept for future use in radiation studies,” Baker said.

The Baker lab uses cell sheets with the Weisman lab to study the role of the P2Y2 receptor in salivary gland regeneration. P2Y2 is a plasma membrane receptor that binds the molecules outside of cells and serves as signals to trigger an action.

The Weisman lab previously showed that P2Y2 receptor activation encourages salivary gland cells to migrate together and form a unit capable of secreting saliva.

“At this time, we don’t know what the role of P2Y2R is in the cell sheets,” Camden said. “That is an aim we proposed in a recent TRIUMPH proposal.”

The TRIUMPH initiative — The Translational Research Informing Useful and Meaningful Precision Health initiative — is a pilot grant funding opportunity through the Missouri School of Medicine.

As if two collaborations weren’t enough, Baker is also working on saliva substitutes. The lab just submitted a grant to fund the project.

“If we get the money, we will be able to make a far better saliva substitute as compared to the Biotine, or Aquoral, or Oasis,” Baker said. “Those are the three leading brands. So, hopefully, we can make something better here at MU and commercialize the product.”

Newest Bond LSC faculty addition adds to focus on inflammation

May 22, 2020 By Lauren Hines in #IAmScience Tags: #IAmScience, cancer

#IAmScience Olga Baker — Olga Baker, professor of Otolaryngology, will join Bond LSC June 1, 2020, as our newest principal investigator with a focus on inflammation. | photo by Roger Meissen, Bond LSC

By Lauren Hines | Bond LSC

Olga Baker is the type of person who acts when she sees a problem.

In her home country of Venezuela, Baker worked as a dentist who was part of a team that treated head and neck cancer patients.

“They told me how much they suffered as I used to do their cavities and fix their teeth,” Baker said. “That’s how I became so motivated, because I saw their suffering myself.”

These patients stopped producing saliva due to radiation from their head and neck cancer treatments that destroyed their salivary glands.

“Because they look okay everybody thinks they’re normal and they’re healthy,” Baker said. “Nobody knows the suffering that is ongoing inside them, so this brings a lot of psychological burden for these patients.

That motivated Baker to enroll in a biochemistry Ph.D. program at the Central University of Venezuela which she completed in 2003.

Ever since, Baker has been studying salivary glands, tissue regeneration and Sjögren’s syndrome at multiple universities

That passion led Baker to Mizzou initially as a post-doctoral fellow in 2003.

Baker moved from her post-doctoral fellowship to become a senior researcher at Mizzou but left in 2009 for the State University of New York Buffalo to accept an assistant professor position as an independent investigator to gain more experience. In 2014, she then moved to the University of Utah School of Dentistry as a tenured associate professor.

Baker officially returns to Mizzou on June 1 as a full professor in the departments of otolaryngology-head and neck surgery and biochemistry to collaborate with former colleagues as LSC’s newest principal investigator

“I later on decided that it would be nice to be close to home because my husband is from Missouri,” Baker said. “So, working with many people who helped me to be here, I applied to MU and made my decision to come back after seeing all the possible scientific collaboration with great colleagues.”

This time around, Baker will have her own lab to find ways to treat salivary gland hypofunction and to develop the products that sprung from prior work at the University of Utah where Baker created her own business

She aims to further create and distribute saliva substitutes in her business venture using proteins in saliva called mucins. Baker isolates mucins from plants and animals to be used as a mouth spray to moisturize people’s oral cavity who otherwise can’t produce saliva.

“So then with that they can eat better, they can talk better, and that lasts long in their mouth,” Baker said.

Baker plans to bring it to market while working at Mizzou.

Due to having so much expertise in the salivary field, she’s also studying how to prevent COVID-19 from infecting patients through saliva

“COVID-19 is found in saliva, and that’s very important because we could find ways to prevent transmission if you block the entry into saliva. So that’s a new area of interest for my lab.

Baker will be opening her lab on the fifth floor working on inflammation. She plans on being part of the inflammation group at the LSC with Michael Petris and her former colleague Gary Weisman

“I think it will be very rewarding for us at Bond LSC if she locates a lab there because there are people ready to work in her area of research with her,” said Weisman, Curator’s Distinguished Professor of biochemistry.

Baker and Weisman plan on further studying Sjögren’s syndrome, an autoimmune disease that also causes dry mouth, dry eyes and a number of other systemic symptoms.

When Baker isn’t fighting for a cure, she enjoys her other passion — singing and dancing.

She was a lead singer of a band called, Peña Flamenca, who used to play in the Music Café (now known as Café Berlin) and also appeared on a TV show, Pepper and Friends, as part of Hispanic Heritage Month.

Even though she isn’t part of a band anymore, she still dances.

“I really enjoy that part of my life, being a singer and dancing and bringing joy to people,” Baker said.

Baker’s mission is to solve the oral health problems she encountered, and her journey isn’t over yet.