Everyone is watching women’s sports. From the record-breaking of the 2024 NCAA women’s basketball title game to the two , and even , female athletes are finally having their moment.

Even though there’s much to celebrate, there are still some huge gaps. Pay is one example, with . Several common injuries also seem to haunt women鈥檚 sports, such as the ACL tears that . An ACL tear is two to eight times in the same sports.

, a 天美影视传媒 assistant professor of mechanical engineering, studies differences between how male and female tissues recover after sports injuries. Specifically, Robinson is interested in designing better methods to help female athletes train to prevent and recover from injuries.

With the Paris Olympics Opening Ceremony upcoming on July 26, UW News asked Robinson, who is also the endowed chair in women鈥檚 sports medicine and lifetime fitness in the orthopaedics and sports medicine department in the UW School of Medicine, to discuss common injuries for female athletes and how her research field is working to address them.

Let’s talk about ACL tears. We seem to hear about them happening in a variety of sports. Why?

ACL tears are extremely common in activities that require cutting, pivoting, quick turns of directions (high strain rate) and/or high-contact sports. We see this injury often in sports such as soccer, basketball, rugby, downhill skiing and football. I tore my ACL and my lateral meniscus playing soccer when I was 12 years old.

Why is it more common for women to tear their ACL?

There are many possible reasons including anatomical differences that lead to altered biomechanics, differences in tissue structure and properties, and sex hormone differences, including fluctuations that occur in women during the menstrual cycle.

How are ACL tears typically treated?

If the ACL is completely torn, it needs to be reconstructed. One method involves grafting a tendon from another part of the body. For example, using patellar or hamstring tendons are some of the most common options. But this can lead to additional risk for injury at the donor site 鈥� I strain my hamstring often because my hamstring tendon was used to repair my ACL tear.

Sometimes the reconstructions are torn again, which requires revision surgery. It鈥檚 not career-ending the first time this happens, but any subsequent injuries and/or post-traumatic osteoarthritis can make this career ending.

What makes an injury career-ending for female athletes?

I was just reading up on Olympian 鈥檚 total knee replacement this past spring. She鈥檚 39 years old and the typical age range for these types of surgeries is 60 to 70 years old. She鈥檚 had so many knee surgeries to treat multiple ACL, MCL and meniscus tears. That is career-ending.

This is personal for me. When I tore my ACL and meniscus, my orthopedic surgeon told me to stop playing soccer 鈥� I was 12 years old 鈥� to reduce the risk of additional injuries or post-traumatic osteoarthritis. When I was 16, I went back to the doctor with pain and they confirmed it was post-traumatic osteoarthritis. They told me again to just stop playing soccer, insinuating this wasn鈥檛 a major part of my life, a part of my identity, something I could make into a career.

If there has ever been a time to invest in ACL injury prevention, it鈥檚 now. For professional athletes, tracking ACL risk is critical for reducing the likelihood of degenerative conditions after acute injuries. These steps ensure athletes have long careers, livelihood and support for their families. Understanding ACL injury risk is also important for non-professionals, youth athletes, parents and coaches as well. It ensures a lifetime of peak physical and mental health.

How does your research focus on female athletes’ recovery from injuries?

We may think we know how women’s bodies operate. But we don’t. Most of the research is based on men’s bodies or bodies of undisclosed sex. Also, much of the research is based on what’s happening at the tissue and joint level without considering how the cells within the tissue are responding based on hormonal and mechanical signaling cues. But changes at the cellular level happen first and then lead to changes at the tissue level.

My research group is trying to determine what cues lead to tissue scarring versus regeneration so that we can develop processes that inhibit scarring and promote regeneration. How do sex hormones and mechanical cues regulate tissue structure and function? What happens to the cells in these tissues when there are different mechanical or hormonal changes?

We need this information to be able to design methods that reduce or prevent injury, provide clearer and more patient-specific surgical and therapy recommendations, and develop techniques to promote functional regeneration and reduce scarring.

Women’s sports are also having a moment in your research field. You’ve been attending multiple conferences that focus on women’s health and engineering. What are these conferences like?

This past summer I have been part of two meetings that bring together professionals in engineering for women’s health 鈥� the Engineering Research Visioning Alliance: Transforming Women鈥檚 Health Outcomes Through Engineering meeting and the ElevateHER meeting. They are both supported by the National Science Foundation and they aim to define the major questions we need to tackle in the next 50 years, especially around developing strategies to understand female physiology and address conditions that disproportionally impact women.

While I’m in these meetings, my thoughts have gone something like this:

• I’m so happy to be in a room with all these amazing researchers focused on women鈥檚 health! I鈥檓 pumped to continue working on these major questions
• Wow, there are so many basic questions that we don鈥檛 have any clue how to answer
• Oh, but the people in this meeting can figure it all out
• Wait, they don鈥檛 know how to approach these questions either
• Ahhh, we have so much to do
• OK, but there is hope because people are working in areas that we previously were clueless about and doing some really impactful research
• Now that we all know each other we can brainstorm and slowly but surely start to tackle these problems

This is a necessary step, and it’s been wonderful being in the same space with people who are all focused on women鈥檚 health and how to use engineering design principles and tools to tackle questions.

For more information, contact Robinson at jrobins1@uw.edu.

There are two major hurdles to overcome on the road to laboratory-grown organs and tissues. The first is to use a biologically compatible 3D scaffold in which cells can grow. The second is to decorate that scaffold with biochemical messages in the correct configuration to trigger the formation of the desired organ or tissue.

In a major step toward transforming this hope into reality, researchers at the 天美影视传媒 have developed a technique to modify naturally occurring biological polymers with protein-based biochemical messages that affect cell behavior. Their approach, published the week of Jan. 18 in the Proceedings of the National Academy of Sciences, uses a near-infrared laser to trigger chemical adhesion of protein messages to a scaffold made from biological polymers such as collagen, a connective tissue found throughout our bodies.

Mammalian cells responded as expected to the adhered protein signals within the 3D scaffold, according to senior author , a UW associate professor of chemical engineering and of bioengineering. The proteins on these biological scaffolds triggered changes to messaging pathways within the cells that affect cell growth, signaling and other behaviors.

These methods could form the basis of biologically based scaffolds that might one day make functional laboratory-grown tissues a reality, said DeForest, who is also a faculty member with the UW and the UW .

鈥淭his approach provides us with the opportunities we鈥檝e been waiting for to exert greater control over cell function and fate in naturally derived biomaterials 鈥� not just in three-dimensional space but also over time,鈥� said DeForest. 鈥淢oreover, it makes use of exceptionally precise photochemistries that can be controlled in 4D while uniquely preserving protein function and bioactivity.鈥�

DeForest鈥檚 colleagues on this project are lead author Ivan Batalov, a former UW postdoctoral researcher in chemical engineering and bioengineering, and co-author , a UW assistant professor of bioengineering and of laboratory medicine and pathology.

Their method is a first for the field, spatially controlling cell function inside naturally occurring biological materials as opposed to those that are synthetically derived. Several research groups, including DeForest鈥檚, have developed light-based methods to modify synthetic scaffolds with protein signals. But natural biological polymers can be a more attractive scaffold for tissue engineering because they innately possess biochemical characteristics that cells rely on for structure, communication and other purposes.

鈥淎 natural biomaterial like collagen inherently includes many of the same signaling cues as those found in native tissue,鈥� said DeForest. 鈥淚n many cases, these types of materials keep cells 鈥榟appier鈥� by providing them with similar signals to those they would encounter in the body.鈥�

They worked with two types of biological polymers: collagen and fibrin, a protein involved in blood clotting. They assembled each into fluid-filled scaffolds known as hydrogels.

The signals that the team added to the hydrogels are proteins, one of the main messengers for cells. Proteins come in many forms, all with their own unique chemical properties. As a result, the researchers designed their system to employ a universal mechanism to attach proteins to a hydrogel 鈥� the binding between two chemical groups, an alkoxyamine and an aldehyde. Prior to hydrogel assembly, they decorated the collagen or fibrin precursors with alkoxyamine groups, all physically blocked with a 鈥渃age鈥� to prevent the alkoxyamines from reacting prematurely. The cage can be removed with ultraviolet light or a near-infrared laser.

Using methods previously developed in DeForest鈥檚 laboratory, the researchers also installed aldehyde groups to one end of the proteins they wanted to attach to the hydrogels. They then combined the aldehyde-bearing proteins with the alkoxyamine-coated hydrogels, and used a brief pulse of light to remove the cage covering the alkoxyamine. The exposed alkoxyamine readily reacted with the aldehyde group on the proteins, tethering them within the hydrogel. The team used masks with patterns cut into them, as well as changes to the laser scan geometries, to create intricate patterns of protein arrangements in the hydrogel 鈥� including an old UW logo, Seattle鈥檚 Space Needle, a monster and the 3D layout of the human heart.

The tethered proteins were fully functional, delivering desired signals to cells. Rat liver cells 鈥� when loaded onto collagen hydrogels bearing a protein called EGF, which promotes cell growth 鈥� showed signs of DNA replication and cell division. In a separate experiment, the researchers decorated a fibrin hydrogel with patterns of a protein called Delta-1, which activates a specific pathway in cells called Notch signaling. When they introduced human bone cancer cells into the hydrogel, cells in the Delta-1-patterned regions activated Notch signaling, while cells in areas without Delta-1 did not.

These experiments with multiple biological scaffolds and protein signals indicate that their approach could work for almost any type of protein signal and biomaterial system, DeForest said.

鈥淣ow we can start to create hydrogel scaffolds with many different signals, utilizing our understanding of cell signaling in response to specific protein combinations to modulate critical biological function in time and space,鈥� he added.

With more-complex signals loaded on to hydrogels, scientists could then try to control stem cell differentiation, a key step in turning science fiction into science fact.

The research was funded by the National Science Foundation, the National Institutes of Health and Gree Real Estate.

For more information, contact DeForest at profcole@uw.edu.

The six UW faculty members who have been named as fellows are:

, professor emeritus in the School of Oceanography, is honored for his continuing work on the ecology of the plankton, the very small algae and animals that float with the currents. His career has focused on how plankton interact with light, temperature, oxygen, bound nitrogen, iron and other nutrients. At sea, Banse worked in the Baltic, the North Sea and Puget Sound, but especially the Arabian Sea. In other work, using an early color global satellite, he investigated the offshore seasonality of phytoplankton chlorophyll. With former students he also studied bottom-living polychaetous annelid worms and published identification keys for the nearly 500 species of these worms found between Oregon and southeast Alaska, between the shore and about 200 meters depth. Banse joined the UW faculty in 1960. The 90-year-old researcher became emeritus in 1995 and remains scientifically active.

, a professor of health metrics sciences and director of the at the Institute for Health Metrics and Evaluation, was selected for his research resolving infectious diseases in space and time in order to expose inequalities in health metrics and improve intervention strategies. He currently leads an international collaboration of researchers from a wide variety of academic disciplines to create even better maps of infectious disease. He has published over 400 peer-reviewed articles and other contributions, including two major, in-depth research papers published independently. His published works are cited more than 18,000 times each year, leading to more than 82,000 lifetime citations. With the support of the Bill & Melinda Gates Foundation, Hay has embarked on a project to expand this research to a much wider range of diseases to ultimately harmonize this mapping with the Global Burden of Disease Study, IHME’s signature project.

, a professor of microbiology, studies Kaposi鈥檚 Sarcoma Herpesvirus, a virus that alters the cells lining blood and lymphatic vessels. Those changes can cause Kaposi鈥檚 Sarcoma, a form of cancer that commonly affects AIDS patients worldwide and people in parts of central Africa. Lagunoff鈥檚 lab has studied how the Kaposi鈥檚 Sarcoma Herpesvirus interferes with endothelial cell signaling, gene expression and metabolism to promote the formation of tumors containing numerous blood vessels. His lab used RNA-sequencing, metabolomics, proteomics and other techniques to determine global changes in host-cell gene expression and signaling. This information has helped to identify key cellular pathways induced by the virus. His team is studying how the virus alters the host cell metabolism to mimic cancer cell metabolism, and is searching for novel therapeutic targets for Kaposi鈥檚 Sarcoma.

, a professor of pathology and genome sciences and an investigator at the , studies DNA damage and repair mechanisms, genome instability, and its role in cancer and other conditions. He is noted for his work on Werner, Bloom and Rothman-Thomson syndromes. These inherited disorders cause distinctive physical characteristics, such as premature aging in Werner鈥檚, and predispose to cancer. Monnat鈥檚 team explores how the loss of key proteins important to DNA metabolism may underlie these rare syndromes. Aberrant expression of those proteins may be common in some adult cancers and affect response to chemotherapy. Monnat and his group use certain genome engineering techniques to try to correct disease-causing mutations in patient-derived stem cells. His lab has also identified 鈥渟afe-harbor sites鈥� in the human genome where new genetic elements might be inserted without disrupting the expression of nearby genes.

, professor in the School of Aquatic and Fishery Sciences and the Department of Biology, is elected for her work in marine ecology. Her research focuses on seabird ecology, marine conservation and public science. A committed advocate of citizen science, she founded and directs the , which for two decades has enlisted coastal residents from California to Alaska to monitor West Coast beaches for dead birds and marine debris. Parrish spoke at the White House in 2013 about public engagement in science and scientific literacy. She holds the Lowell A. and Frankie L. Wakefield endowed professorship, and is associate dean for academic affairs in the UW College of the Environment.

, a professor of Earth and space sciences, is honored for his work in glaciology and climate science. Steig uses ice cores and other records to study climate variability over thousands of years. He works on the climate history and dynamics of polar ice sheets and mountain glaciers, and develops new tools to extract the chemical clues in samples of ice and other material. Steig was among the leaders of a project to drill the first deep ice core at South Pole, and was on the team that drilled a 2-mile-deep ice core in West Antarctica. His recent research has focused on the links between large-scale climate conditions and changes in West Antarctica, where glaciers are rapidly retreating. In addition to his research and teaching, he is committed to fostering greater public understanding of climate change, and is a founding contributor to RealClimate.org.

In addition, , an investigator at the Fred Hutchinson Cancer Research Center and an affiliate professor of genome sciences at the UW, was selected for his research on genetic conflict.

Proteins are key to this future. In our bodies, protein signals tell cells where to go, when to divide and what to do. In the lab, scientists use proteins for the same purpose 鈥� placing proteins at specific points on or within engineered scaffolds, and then using these protein signals to control cell migration, division and differentiation.

But proteins in these settings are also fragile. To get them to stick to the scaffolds, researchers have traditionally modified proteins using chemistries that kill off more than 90% of their function. In a published May 20 in the journal , a team of researchers from the 天美影视传媒 unveiled a new strategy to keep proteins intact and functional by modifying them at a specific point so that they can be chemically tethered to the scaffold using light. Since the tether can also be cut by laser light, this method can create evolving patterns of signal proteins throughout a biomaterial scaffold to grow tissues made up of different types of cells.

“Proteins are the ultimate communicators of biological information,” said corresponding author , a UW assistant professor of chemical engineering and bioengineering, as well as an affiliate investigator with the UW Institute for Stem Cell & Regenerative Medicine. “They drive virtually all changes in cell function 鈥� differentiation, movement, growth, death.”

For that reason, scientists have long employed proteins to control cell growth and differentiation in tissue engineering.

“But the chemistries most commonly used by the community to bind proteins to materials, including scaffolds for tissue engineering, destroy the overwhelming majority of their function,” said DeForest, who is also a faculty member in the UW . “Historically, researchers have tried to compensate for this by simply overloading the scaffold with proteins, knowing that most of them will be inactive. Here, we’ve come up with a generalizable way to functionalize biomaterials reversibly with proteins while preserving their full activity.”

Their approach uses an enzyme called sortase, which is found in many bacteria, to add a short synthetic peptide to each signal protein at a specific location: the C-terminus, a site present on every protein. The team designs that peptide such that it will tether the signal protein to specific locations within a fluid-filled biomaterial scaffold common in tissue engineering, known as a hydrogel.

Targeting a single site on the signal protein is what sets the UW team’s approach apart. Other methods modify signal proteins by attaching chemical groups to random locations, which often disrupts the protein’s function. Modifying just the C-terminus of the protein is much less likely to disrupt its function, according to DeForest. The team tested the approach on more than half a dozen different types of proteins. Results show that modifying the C-terminus has no significant effect on protein function, and successfully tethers the proteins throughout the hydrogel.

Their approach is analogous to hanging a piece of framed art on a wall. Instead of hammering nails randomly through the glass, canvas and frame, they string a single wire across the back of each frame to hang it on the wall.

In addition, the tethers can be cut by exposure to focused laser light, causing “photorelease” of the proteins. Using this scientific light saber allows the researchers to load a hydrogel with many different types of protein signals, and then expose the hydrogel to laser light to untether proteins from certain sections of the hydrogel. By selectively exposing only portions of the materials to the laser light, the team controlled where protein signals would stay tethered to the hydrogel.

Untethering proteins is useful in hydrogels because cells could then take up those signals, bringing them into the cell’s interior where they can affect processes like gene expression.

DeForest’s team tested the photorelease process using a hydrogel loaded with epidermal growth factor, a type of protein signal. They introduced a human cell line into the hydrogel and observed the growth factors binding to the cell membranes. The team used a beam of laser light to untether the protein signals on one side of an individual cell, but not the other side. On the tethered side of the cell, the proteins stayed on the outside of the cell since they were still stuck to the hydrogel. On the untethered side, the protein signals were internalized by the cell.

“Based on how we target the laser light, we can ensure that different cells 鈥� or even different parts of single cells 鈥� are receiving different environmental signals,” said DeForest.

This unique level of precision within a single cell not only helps with tissue engineering, but with basic research in cell biology, added DeForest. Researchers could use this platform to study how living cells respond to multiple combinations of protein signals, for example.聽 This line of research would help scientists understand how protein signals work together to control cell differentiation, heal diseased tissue and promote human development.

“This platform allows us to precisely control when and where bioactive protein signals are presented to cells within materials,” said DeForest. “That opens the door to many exciting applications in tissue engineering and therapeutics research.”

Lead author on the paper is , a UW doctoral student in chemical engineering. Co-author is , a UW undergraduate alumna who is currently an analyst for Point B Consulting. The research was funded by the National Science Foundation and the 天美影视传媒.

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For more information, contact DeForest at profcole@uw.edu.

Grant number: DMR-1652141.

Drug treatments can save lives, but sometimes they also carry unintended costs. After all, the same therapeutics that target pathogens and tumors can also harm healthy cells.

To reduce this collateral damage, scientists have long sought specificity in drug delivery systems: A package that can encase a therapeutic and will not disgorge its toxic cargo until it reaches the site of treatment 鈥� be it a tumor, a diseased organ or a site of infection.

In a published Jan. 15 in the journal , scientists at the 天美影视传媒 announced that they have built and tested a new biomaterial-based delivery system 鈥� known as a hydrogel 鈥� that will encase a desired cargo and dissolve to release its freight only when specific physiological conditions are met. These environmental cues could include the presence of an enzyme or even the acidic conditions that could be found in a tumor microenvironment. Critically, the triggers that cause dissolution of the hydrogel can be switched out easily in the synthesis process, allowing researchers to create many different packages that open up in response to unique combinations of environmental cues.

The team, led by UW chemical engineering assistant professor , designed this hydrogel using the same principles behind simple mathematical logic statements 鈥� those at the heart of basic programming commands in computer science.

“The modular strategy that we have developed permits biomaterials to act like autonomous computers,” said DeForest, who is also a member of both the and the . “These hydrogels can be programmed to perform complex computations based on inputs provided exclusively by their local environment. Such advanced logic-based operations are unprecedented, and should yield exciting new directions in precision medicine.”

Hydrogels are more than 90 percent water; the remainder consists of networks of biochemical polymers. Hydrogels can be engineered to ferry a variety of therapeutics, such as pharmaceutical products, special cells or signaling molecules, for purposes including drug delivery or even 3-D tissue engineering for transplantation into patients.

The key to the team’s innovation lies in the way the hydrogels were synthesized. When researchers assembled the polymer network that comprises the biomaterial, they incorporated chemical “cross-link” gates that are designed to open and release the hydrogel’s contents in response to user-specified cues 鈥� much like how the locked gates in a fence will only “respond,” or open with a specific set of keys.

“Our ‘gates’ consist of chemical chains that could 鈥� for example 鈥� be cleaved only by an enzyme that is uniquely produced in certain tissues of the body; or be opened only in response to a particular temperature or specific acidic conditions,” said DeForest. “With this specificity, we realized we could more generally design hydrogels with gates that would open if only certain chemical conditions 鈥� or logic statements 鈥� were met.”

DeForest and his team built these hydrogel gates using simple principles of logic, which centers on inputs to simple binary commands: “YES,” “AND” or “OR.” The researchers started out by building three types of hydrogels, each with a different “YES” gate. They would only open and release their test cargo 鈥� fluorescent dye molecules 鈥� in response to their specific environmental cue.

One of the “YES” gates they designed is a short peptide 鈥� one of the constituent parts of cellular proteins. This peptide gate can be cleaved by an enzyme known as matrix metalloprotease (MMP). If MMP is absent, the gate and hydrogel remain intact. But if the enzyme is present in a cell or tissue, then MMP will slice the peptide gate and the hydrogel will burst open, releasing its contents. A second “YES” gate that the researchers designed consists of a synthetic chemical group called an ortho-nitrobenzyl ester (oNB). This chemical gate is immune to MMP, but it can be cleaved by light. A third “YES” gate contains a disulfide bond, which breaks upon reaction with chemical reductants but not in response to light or MMP. A hydrogel containing one of these types of “YES” gates is essentially “programmed” to respond to its physiological surroundings using the Boolean logic of its cross-link gate. A hydrogel with an oNB gate, for example, will open and release its contents in the presence of light, but not any of the other cues like the MMP enzyme or a chemically reductive environment.

They also created and tested hydrogels with multiple types of “YES” gates, essentially creating hydrogels with gates that would open and release their cargo in response to multiple combinations of environmental cues, not just one cue: light AND enzyme; reductant OR light; enzyme AND light AND reductant. Hydrogels with these more complex types of gates could still carry cargo, either fluorescent dyes or living cells, and release it only in response to the particular gate’s unique combination of environmental triggers.

The team even tested how well a hydrogel with an “AND” gate 鈥� reductant and the enzyme MMP 鈥� could ferry the chemotherapy drug doxorubicin. The doxorubicin-containing hydrogel was mixed with cultures of tumor-derived , which doxorubicin should kill easily. But the hydrogel remained intact, and the HeLa cancer cells remained alive unless the researchers added both triggers for the “AND” gate: MMP and reductant. One cue alone was insufficient to cause HeLa cell demise.

DeForest and his team are building on these results to pursue even more complex gates. After all, specificity is the goal, both in medicine and tissue engineering.

“Our hope is that, by applying Boolean principles to hydrogel design, we can create a class of truly smart therapeutic delivery systems and tissue engineering tools with ever-greater specificity for organs, tissues or even disease states such as tumor environments,” said DeForest. “Using these design principles, the only limits could be our imagination.”

Lead author on the paper is UW doctoral student Barry Badeau. Co-authors are master’s alumnus Michael Comerford, student Christopher Arakawa and doctoral student Jared Shadish. The research was funded by the National Science Foundation and the 天美影视传媒.

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For more information, contact DeForest at 206-543-5961, profcole@uw.edu or on Twitter .

Grant number: DMR 1652141.

Morayma Reyes, professor of pathology and laboratory medicine, and Hannele Ruohola-Baker, professor of biochemistry and associate director of the Institute for Stem Cell and Regenerative Medicine, headed the 天美影视传媒 team that made the discovery. The first authors of the paper were Nicholas Ieronimakis, UW Department of Pathology; and Mario Pantoja, UW Department of Biochemistry.

They explained that the mice in their study, like boys with the gender-linked inherited disorder, are missing the gene that produces dystrophin, a muscle-repair protein. Neither the mice nor the affected boys can replace enough of their routinely lost muscle cells. In people, muscle weakness begins when the boys are toddlers, and progresses until, as teens, they can no longer walk unaided.聽 During early adulthood, their heart and respiratory muscles weaken. Even with ventilators to assist breathing, death usually ensues before age 30. No cure or satisfactory treatment is available. Prednisone drugs relieve some symptoms, but at the cost of severe side effects.

The disabling, then lethal, nature of the rare disease in young men presses scientists to search for better therapeutic agents. Reyes and Ruohola-Baker are seeking ways to suppress the disorder鈥檚 characteristic functional and structural muscle defects.

Ruohola-Baker鈥檚 lab originally identified the sphingosine 1-phosphate (S1P) pathway as a critical player in ameliorating muscular dystrophy in flies. Her lab did this through a large genetic suppressor screen using the fruit fly, Drosophila melanogaster. Sphingosine 1-phosphate is found in the cells of most living beings from yeasts to mammals. Named after the enigmatic sphinx, this cell signal is important in many activities of living cells, from migration to proliferation. The multi-talented, bioactive lipid is essential, Reyes said, in turning stem cells into specific types of cells, in regenerating damaged tissue, and in inhibiting cell death. Without cell receptors for sphingosine 1-phosphate, an embryo would fail to develop.

Other scientists had observed that levels of sphingosine 1-phosphate are lower in the muscles of mice with the muscular dystrophy mutation, and that certain cell repair pathways involving this signal are impaired. However, sphingosine 1-phosphate couldn鈥檛 be administered as a drug because it is rapidly used up.

Instead, Reyes and Ruohola-Baker sought to prevent the sphingosine 1-phosphate occurring naturally in the body from degrading. A fruit fly model of Duchenne muscular dystrophy allowed Ruohola-Baker鈥檚 lab to rapidly score small molecule therapy candidates for raising the level of sphingosine 1-phosphate. Flies with the genetic defect act normally after they hatch and fly around, but in a few weeks, due to muscle degeneration, they are flightless. By using insect activity monitors, the scientists assessed the effects of drug and gene therapy candidates on the flies鈥� ability to move.

This screening tool led to the discovery that a small molecule with a long name, 2-acetyl4 (5)-tetrahydroxybutyl imidazole, or THI for short, blocks an enzyme that breaks down sphingosine 1-phosphate.

鈥淚t鈥檚 interesting to note that THI is a trace component of Caramel Color III, which the U.S. Food and Drug Administration categories as 鈥榞enerally recognized as safe鈥�,鈥� said Reyes. The substance is also found in very tiny amounts in burnt sugar, brown sugar, beer, cola and some candies.

The researchers added a purified, concentrated form of THI to the food of young flies with the muscular dystrophy-like mutation. They confirmed that the THI alleviated muscle wasting in the flies. A few other drugs, including a THI derivative and an unrelated drug now in clinical trials for rheumatoid arthritis, also showed beneficial effects in fruit flies.

The study of THI then switched from insects to mammals. Reyes lab began by treating old dystrophic mice with direct injection of THI. Later, the researchers simply added the compound to the drinking water in the habitats of young dystrophic mice. These mice were comparable in developmental stage to human teens who have muscular dystrophy genetic variation.

鈥淲e observed that treatment with THI significantly increased muscle fiber size and muscle-specific force in our affected mice,鈥� Reyes said.聽 鈥淲e also saw that other hallmarks of impaired muscle regeneration 鈥� fat deposits and fibrosis [scar tissue] accumulation 鈥� were also lower in the THI-treated mice.鈥�

The research team linked the desired regenerative effects in the mice to the response of muscle-forming cells and the subsequent regrowth of muscle fibers. A type of sphingosine 1-phosphate, and cell receptors for it, also were observed in the cells in the regenerating muscle fibers. The researchers proposed that sphingosine 1-phosphate turned up the dial on the regulators for the biochemical pathways that mediate skeletal muscle mass and muscle function.

Now that they have shown proof-of-concept, the researchers hope to conduct additional animal studies on THI and other compounds that protect the body鈥檚 supply of sphingosine 1-phosphate necessary for muscle cell regeneration. If THI continues to show promise as a nutraceutical or food-based drug, medical scientists will head into pre-clinical studies of effectiveness and safety before advancing to human trials.聽 In addition to muscular dystrophy treatment research, similar studies might also be conducted in the future on loss of muscle strength during normal or accelerated aging.

While excited about the preliminary findings, the scientists cautioned that they are still at the very earliest stages of research, and that much more work needs to be done before any conclusions can be drawn about the potential of THI as a muscular dystrophy treatment.

Other members of the research team were Aislinn L. Hays, UW Pathology; Timothy L. Dose, Junli Qi, Karin A. Fischer, all of UW Biochemistry and the UW Institute for Stem Cell and Regenerative Medicine; Andrew N. Hoofnagle, UW Laboratory Medicine; Martin Sadilek, UW Chemistry; and Jeffrey S. Chamberlain of UW Neurology and the UW鈥檚 Sen. Paul D. Wellstone Muscular Dystrophy Cooperative Research Center.

The researchers have filed a federal patent on sphingosine 1-phosphate-promoting therapies for muscular dystrophy. They have not received any benefits from any organization with a financial stake in the research and have no competing financial interests in analyzing and reporting their findings.

The work was supported by the 天美影视传媒 Department of Pathology and Department of Laboratory Medicine, a Provost Bridge grant, a Nathan Shock Center of Excellence in the Basic Biology of Aging, Genetic Approaches to Aging Training Grant, and the American Recovery and Reinvestment Act of 2009 Challenge Grants 5RC1AR058520, R01GM083867, R01GM097372, and 1P01GM081619.

The scientists also received funding from the Washington Research Foundation, the Duchenne Alliance, RaceMD, and Ryan鈥檚 Quest.

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