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By Susanne Pallo

A University of Rochester Medical Center researcher is part of a team that is working toward characterizing where a certain type of RNA, called microRNA, is expressed in human cells. In a recent study, published in Genome Research, the team made a giant set of data about these RNA available to the public to guide research and foster the development of new therapies.

RNA, the close cousin of DNA, comes in many flavors - each with a specific role. MicroRNA (miRNA) help regulate which proteins are produced in a cell and how much. Fiddling with the level of proteins can have subtle or large impacts on that cell's activity and can even cause disease.

Several studies have linked miRNAs to diseases, either as the cause or simply a marker. While some of these links could lead to new treatments, others may just be red herrings.

"We've showed previously that when somebody claims a certain miRNA is a marker of a disease, at times it's just a marker of increased inflammation, which is a side effect of a lot of diseases," said Matthew N. McCall, Ph.D., assistant professor of Biostatistics and Biomedical Genetics at URMC and an author on the study.

According to McCall and study leader Marc K. Halushka, M.D., Ph.D., associate professor of Pathology and director of Oncology Tissue Services at Johns Hopkins University School of Medicine, before you can understand what miRNAs are doing, you need to know where they are.

And why is that important?

Within a given tissue in your body, there could be thousands of different cells types, serving different purposes. When measuring RNA in a tissue biopsy, you will get a mixture of RNA from all of these different cell types, whether or not they are relevant to the disease you are interested in.

For their study, Halushka's team pulled together all that was known about miRNA in human cells and conducted experiments to fill the gaps. Though it wasn't their specific intent, the researchers found that many miRNAs originally thought to be expressed in all or many cell types actually are not. Rather, they are expressed in cells that get into all or most tissues, like blood or inflammatory cells, and could be mistakenly associated with a disease.

All of the data from Halushka's study are available in an online database and in the University of California, Santa Cruz Genome Browser and will be updated regularly. Having access to this data should save researchers a lot of time and help weed out some those aforementioned red herrings. With just a few clicks, researchers can find all of the cells types that express a specific miRNA or all of the miRNAs expressed in a specific cell type.

Catherine Ovitt, Danielle Benoit, and Lisa DeLouise

A scientific team at the University of Rochester is using innovative technology to discover preventative treatments for salivary gland radiation damage typical for head and neck cancer patients—and recently received a $3.8 million National Institutes of Health grant to support their investigation.

Cancer patients can lose salivary gland function during treatment for head and neck tumors. The irreversible damage, which prevents patients from producing saliva, often results in permanent dry mouth and makes it difficult to eat, speak, and swallow. The team will develop salivary gland tissues using a unique chip technology called "microbubbles," which are tiny spherical wells or bubbles that can hold cells.

The use of the microbubble platform is based on several years of salivary gland research, led by Catherine E. Ovitt, Ph.D., associate professor of Biomedical Genetics, a member of the UR Center for Oral Biology, and an expert in the repair and regeneration of salivary glands, and Danielle Benoit, Ph.D., associate professor of Biomedical Engineering and an expert in drug delivery systems and hydrogel platforms for tissue engineering approaches. Together with Lisa A. DeLouise, Ph.D., associate professor of Dermatology and Biomedical Engineering, who developed and received several patents for the microbubble concept, the scientists are working as co-principal investigators on the NIH project.

Their goal is to find drugs that could be given to patients prior to radiation treatment that would prevent damage to the glands.

"Dr. Ovitt and I have shown through years of investigation that being able to develop functional salivary gland tissue for testing is the key to solving this problem," Benoit said. "So, it's microbubbles to the rescue."

Expanding cells and tissue outside of the body is elusive. In this case the process involves taking salivary gland cells that have been removed from humans undergoing surgery, expanding the cells, and studying their reaction to various drugs.

A major problem, however, starts to occur as soon as the tissue is removed from the body and isolated: Cells immediately begin to lose their natural function. In the body, cells send signals and secrete proteins that are essential for their survival. In a culture plate in a laboratory, however, these signals and proteins are diluted and dispersed, making the cells no longer viable.

DeLouise's technology at first glance looks similar to a cell culture petri dish, a round piece of silicone about the size of the large cookie. But within the dish are an arrangement of thousands of tiny round "micro-wells," each one comprising a minuscule compartment for cell growth and tissue formation. The unique shape of each microbubble creates a niche that concentrates the cells, allowing them to proliferate and form salivary gland units.

The microbubbles come in different sizes, and the beauty of the technology is that scientists can grow cells in thousands of bubbles at one time. DeLouise can make dishes the size of a dime that include more than 5,000 microbubbles. In addition, Benoit's lab has produced hydrogel materials that can be placed inside each microbubble that further allow the cell to maintain its structure and function.

If the team can successfully grow human salivary gland cells in the microbubbles, they say, they will also be able to rapidly test thousands of existing Food and Drug Administration-approved drugs on the salivary tissue using the microbubble technology.

"Only one treatment is currently available for radioprotection but it comes with many side effects, so most patients discontinue it," Ovitt said. "There is a great need for additional ways to either cure or prevent this debilitating condition."

The team is collaborating with Shawn D. Newlands, M.D., Ph.D., M.B.A., chair of the Department of Otolaryngology and member of the Wilmot Cancer Institute's head and neck oncology team, to collect salivary tissue from consenting patients undergoing salivary gland surgery. Salivary gland cells are isolated from these tissues for seeding into microbubbles for the investigation. Additionally, Paul Dunman, Ph.D., associate professor of Microbiology and Immunology, will provide high-throughput drug-screening expertise during the second phase of the project, which is contingent upon successful development of the human gland chips.

Several GDSC students and faculty attended the 5th Wilmot Cancer Warrior Walk this Sunday. Showing off our colors in form of this year's new GDSC T-shirts, the Team participated very successfully in the 10K, 5K and 1M events. Adam Cornwell, Andrew Albee, Xiaolu Wei, Fanju Meng, Justine Melo and Dalia Ghoneim were our "Runing Warriors" for the 10k and 5k events, with Andrew Allbee finishing overall 6th (44:05 min, 3rd 20-29yr old) and Adam Cornwell 7th (44:40 min, 1st 30-39yr old) in the 10k. Dalia Ghoneim ran the 5k and was the 3rd overall female finisher, and was 2nd in her age category (30-39 years). Her time was 23:33. Congratulations to all! The team was rounded out by Dashiell Na, Shen Zhou and and Anne Roskowski. Led by the scientific director of the Wilmot Cancer Center, Hucky Land, faculty also attended in force, including the whole Samuelson family, cancer biologist Mark Noble and the Pröschel's. Runners and walkers alike enjoyed a beautiful sunny day out and the positively uplifting company of cancer fighters and survivors! See you all again in 2018!

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