Harim Tavares dos Santos

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.

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.”