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Canto-Soler brings visionary aspirations to Gates Center for Regenerative Medicine

Valeria Canto-Soler at CU Anschutz
Valeria Canto-Soler at work in the lab at the Gates Center for Regenerative Medicine.

When Valeria Canto-Soler, Ph.D., was a biology student in Argentina, she dreamed of a career studying elephants and other African wildlife in their natural habitat.

But life took her on a different journey. In July, Canto-Soler joined the Department of Ophthalmology and the Gates Center for Regenerative Medicine as the Doni Solich Family Endowed Chair in Ocular Stem Cell Research.

“I like to joke about it,” she says. “Instead of spending my life studying animals in the wilds of Africa, I’m in a dark room sitting in front of a microscope.”

After an international search, Canto-Soler also was named director of CellSight, the Ocular Stem Cell and Regeneration Research Program, in partnership with the Gates Center and the Department of Ophthalmology. She also will be an Associate Professor of Ophthalmology at the CU Anschutz School of Medicine.

Valeria Canto-Soler, Ph.D.
Valeria Canto-Soler, Ph.D.

This $10 million ocular stem cell and regeneration program initiative began with a $5 million grant from the Gates Frontier Fund to research the potential for stem cells to treat age-related macular degeneration, the leading cause of blindness in people ages 50 and older.

“I dreamed of launching a stem cell research program like this for years,” she says. “The leadership at both the Gates Center and the Department of Ophthalmology has the same vision that I have. Working together, we can make it happen.”

Growing up in Argentina

Canto-Soler grew up in Mendoza, Argentina, a city on the eastern side of the Andes Mountains. Similar to Denver in that it’s nestled in the foothills, Mendoza’s close proximity to the mountains gave her the opportunity to hike, explore and marvel at the natural wildlife she encountered.

But when it came to a career choice, it was more difficult for her to decide how to direct her love of nature and biology. In contrast to the U.S., students in Argentina have to decide on a career early.

“It’s a very important decision and there are very few chances for you to change your mind after that,” she says.

As a young biology student, Canto-Soler found herself drawn to the study of the human nervous system and how the sense organs work.

“Year by year, I felt more and more fascinated by the biology of the human body,” she says. “In the last two years of biology school, I started to work in a lab studying the nervous system. That defined my future.”

Canto-Soler earned a B.S. in Biology from the University of Cordoba School of Natural Sciences, Cordoba, Argentina in 1996. In 2002, she completed a Ph.D. in Biomedical Sciences at the Austral University School of Medicine in Buenos Aires.

A Johns Hopkins Fellowship

After she earned her Ph.D., Canto-Soler had the opportunity to explore new vistas. She was accepted as a Fellow with the Retinal Degenerations Research Center in the Department of Ophthalmology at Johns Hopkins University School of Medicine in Baltimore. She worked with renowned scientist Ruben Adler, MD, at the Wilmer Eye Institute.

“I was so excited – the focus of his research was the development of the eye,” Canto-Soler says. “It was perfect for me.”

She thought her fellowship would provide her the knowledge and experience she could take back to Argentina, but she found new challenges to keep her in the U.S. When her mentor, Dr. Adler, died in 2007, she took over his role at Wilmer to continue their work.

A New Discovery

In 2014, Canto-Soler and her team created a miniature human retina in a petri dish, using human stem cells. The mini retinas had functioning photoreceptor cells capable of sensing light. This cutting-edge research opened up the potential to take cells from a patient who suffers from a particular retinal disease, such as macular degeneration, and use them to generate mini retinas that would recapitulate the disease of the patient; this allows studying the disease on a human context directly, rather than depending on animal models.

Canto-Soler at CU Anschutz
Valeria Canto-Soler, Ph.D., hopes her research will someday result in cell-based treatments for vision patients.

This research could lead to personalized medicine and drug treatments for specific patient needs. At CellSight, Canto-Soler will work with clinicians and members of the Gates Center to create patient registries and cell banking. She hopes her research will someday result in cell-based treatments; retinal patches, for example, which could be transplanted into a patient’s eye, possibly curing blindness.

“Once you transplant a retinal patch, the cells have to establish all the right connections with the patient’s own retinal cells in order to process the information and produce a visual image,” she says. “No one really knows how to do that yet.”

But she’s confident the clinicians from the Department of Ophthalmology, and the researchers at CellSight and the Gates Center, will work together to make the dream a reality.

“I’m definitely a dreamer,” Canto-Soler says. “I never imagined we could generate human mini retinas in a petri dish. And to see that happen made me a believer. I believe our scientific dreams can come true if we pursue them in the right way.”

The letters and emails she receives from those who have family members or friends suffering from sight problems or blindness inspire her. They’re also looking for answers.

“It’s what gets me motivated to come to work every day,” she says. “I’m excited to think about how we could help people and the impact that would make in their lives.”

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Celebrating Loyalty

On Thursday, August 24, nearly 130 alumni, friends, faculty and staff gathered on campus for the 2nd annual Loyal Benefactor Celebration, an event honoring generous benefactors who support the University of Colorado Anschutz Medical Campus with loyal annual gifts, those who have included CU Anschutz in their estate plans, and faculty and staff who give through monthly payroll deduction. While the weather conspired to keep this year’s BBQ-style picnic indoors, guests enjoyed musical entertainment by local singer-songwriter Adrea LaRoche and conversation with friends, old and new.

Chancellor Elliman provided a campus update, reflecting on all that private support has helped accomplish since our move to the former Fitzsimons Army Medical Base just over 10 years ago and thanking dedicated supporters for advancing the university’s mission. He shared the story of recent UCHealth University of Colorado Hospital patient Sara Millard, who was born with severe kidney disease and hypertension, and who had endured more than 150 surgeries in her 31 years before finally undergoing a successful living donor kidney transplant here last spring that got her off of dialysis and back to her life. Chancellor Elliman thanked guests for making stories like Sara’s a reality, and emphasized the importance of a strong and dedicated community of support for making the impossible possible at the CU Anschutz Medical Campus.



Chancellor Elliman with Beth and Donald Kress, William Vandivier and Moumita Ghosh of the Flight Attendant Medical Research Institute

Amanda Brodie with Joan and Henry Strauss

Guests William Jackson and Lynne Bensten, David and Delores Claassen

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Doping in sports: official tests fail to pick up majority of cases

Doping is remarkably widespread among elite athletes and remains largely unchecked despite the use of sophisticated biological testing methods. This is according to Rolf Ulrich of the University of Tübingen in Germany and Dawn Comstock of the Colorado School of Public Health at the University of Colorado Anschutz Medical Campus. They are lead authors of a study in Springer’s journal Sports Medicine.

The researchers conducted anonymous surveys among athletes competing at two major sports events in 2011. At least 30-45% of athletes at these events acknowledged that they had used banned doping substances or methods in the previous year. This is a serious concern because doping not only compromises fair play, but it is potentially detrimental to the health of athletes.

Biological tests of blood and urine typically detect doping in only 1-3% of competitors at elite international competitions. However, the new study suggests that the true rate of doping is far greater, because cutting-edge doping schemes seem to make it possible for many athletes to beat the biological tests currently in place to detect prohibited doping.

“Given the numerous recent highly publicized doping scandals in major sports, one might guess that the proportion of such undetected cheats is high,” write Ulrich and his coauthors. In their paper, the authors cite several recent commentaries suggesting that technical, human, political and financial factors are all contributing to flawed results from current biological testing techniques.

The research team conducted anonymous tablet-based surveys of the prevalence of doping at two major sports events in 2011. These were the 13th International Association of Athletics Federations World Championships in Athletics (WCA) in South Korea and the 12th Quadrennial Pan-Arab Games (PAG) in Qatar. The surveys used a randomized response technique, a method that visibly guaranteed the anonymity of the respondent, thus permitting the athletes to answer honestly about their doping without fear of exposure. Surveys were completed by 2167 athletes at the two events.

Even after assessing statistically for various possible forms of bias in the results, the authors estimated that at least 30% of athletes at WCA and 45% of athletes at PAG had engaged in doping during the previous year. The statistical analyses suggested that, if anything, these figures may well have underestimated the true prevalence of doping at the two events. By contrast, on biological testing at WCA, only two (0.5%) of the 440 athletes tested positive for illegal substances. At PAG, 24 (3.6%) of the 670 athletes tested showed positive results.

“These findings suggest that biological testing greatly underestimates the true prevalence of doping in elite athletics,” Dawn Comstock, professor of epidemiology at the Colorado School of Public Health at CU Anschutz, said. “It indicates the need for future studies of the prevalence of doping in athletics using randomized response techniques to protect the anonymity of the athletes.”

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An Epic Sprint to aid clinics

In February 2011, the University of Colorado Anschutz Medical Campus took a major step toward fundamentally changing its health care delivery. The change would eventually affect every provider, researcher and staff member on the campus and beyond – and the reverberations continue today.

The revolution began with a handful of ambulatory clinics at University of Colorado Hospital that began using the Epic electronic health record (EHR). The aim: shelve dozens of discrete applications and towering paper stacks in favor of a single system that would allow all providers to view a patient’s entire medical record online.

Sprint Team Conference Room
Sprint team at work near the end of its four weeks of work in the OB/Gyn Clinic.

The Epic implementation included a massive training effort and a phased, multi-year rollout that ensconced the EHR on the Anschutz Medical Campus and at UCH satellite clinics. With the formation and growth of UCHealth, Epic now links hospitals and clinics up and down the Front Range and beyond.

But the challenges of ­working efficiently and effectively with an EHR remain. Memorizing sequences of clicks in record charting can be frustrating for providers focused on patient care. Patients now have an electronic conduit to their providers through My Health Connection; figuring out how best to route and respond to questions can be challenging and time-consuming for clinics. The basic Epic framework requires ongoing customization to meet the needs of dozens of specialists and subspecialists – most them with the CU School of Medicine – and their UCHealth patients.

These challenges help to explain why Epic training, in the form of tip sheets, webinars, emails, and other support, has never ended. The past year has produced a new twist: a dedicated team that gives clinic providers and staff focused, face-to-face help with making the most of the EHR.

On the run

The Sprint team, as it’s called, consists of Epic analysts, trainers, and a project manager, as well as a nurse and physicians who combine clinical and information technology skills. Together they help to define the clinical and operational needs of providers and staff and collaborate with IT, clinical and other experts to meet them. Their guiding principle: people learn best when they have face-to-face help from people who are interested in listening to them, answering their questions and solving their problems.

“It’s a collaborative effort,” said Christine Gonzalez, the Sprint team’s project manager. “When you need to make rapid changes, nothing beats live help. Providers and staff feel safe with working one-on-one.”

The Sprint team is a response to a problem that is both local and national, said Amber Sieja, MD, a physician informaticist for the Anschutz Medical Campus and an internist with the CU School of Medicine. Maintaining paper medical records might have been cumbersome, but for many providers meeting the demands of an electronic system has made practicing medicine more difficult than ever.

“The problem we face is that providers are burned out with their clinical practice,” Sieja said. She noted that in national surveys, providers routinely identify EHRs as a major contributor to that problem. “Locally, our providers have told us the EHR takes up too much time,” she added. “That’s our problem to solve.”

That’s a tall order, however. Epic is a dynamic tool that receives annual upgrades as well as ongoing customized changes for specific clinical areas. How to communicate the changes to the couple of thousand providers with the School of Medicine and UCHealth Medical Group? The Epic team has tried spreading the word with regularly scheduled Skype videos, newsletters, tip sheets, and open training sessions. It’s all fallen well short of reaching anywhere near most providers, Sieja said.

“The message we got is ‘we want somebody in our clinics,’” she said.

Face time

Sprint Team
Members of the Epic Sprint team outside the OB/Gyn Clinic at University of Colorado Hospital. Left to right, back row: Amber Sieja, MD – physician informaticist; Todd Andrews – lead analyst; Dan Golightly – analyst; Rob Lewis – analyst; Dan Kroening – trainer; Diane Pruitt, RN – clinical informaticist. Left to right, front row: Scott Carpenter – lead trainer; Barbara Noble – trainer; Christine Gonzalez – project manager; Megan Cortez – analyst; Tally Talyai, PA – physician informaticist.

That demand spurred the creation of the first “Sprint” in 2016. Sieja, fellow physician informaticist Katie Markley, MD, and UCHealth Chief Medical Information Officer CT Lin, MD, put together a team that parachuted into the Endocrinology Clinic at UCH for a two-week, hands-on helping stint. Their work drew praise from both providers and staff for helping to decrease burnout, reduce charting time and improve patient care.

The Endocrinology pilot wasn’t perfect, Sieja said. Most importantly, it showed that future Sprint projects would need more lead time to prioritize clinic needs, schedule rooms and meeting times, identify potential new EHR builds, and so on. They settled on 90 days of preparation, said Sieja, who used that time to develop a curriculum for the Neurology Clinic at UCH.

The Sprint project in Neuro, which began in January 2017, represented a major challenge. Its nearly 100 providers handled more than 26,000 patient visits in 2016. It also includes eight subspecialties, all with specific patient care needs. A major part of the work involved meeting with “clinical content leaders” to identify priorities for new Epic builds, such as flowsheets to help ensure that patients with neuromuscular diseases like ALS (amyotrophic lateral sclerosis, or Lou Gehrig’s disease) and other complex neurologic conditions receive evidence-based standards of care.

“These are tools that allow us to track patients over time,” said Laura Strom, MD, an epilepsy specialist who helped to lead the Sprint effort in the Neurology Clinic. “They are invaluable in Epic.” The flowsheets, however, had to be built from scratch, a time-consuming process, she added. All told, seven subspecialties requested and received customized builds as part of the Sprint project.

The Sprint team spent a pair of two-week stints, separated by a one-week break, in the Neurology Clinic, wrapping up the work in February. Much of the effort focused on helping providers use Epic more efficiently for their basic work: pulling needed information from patient charts; ordering labs, imaging studies and other tests; responding to patient questions and referral requests; and preparing to address patients’ chief complaints in advance of the visit. Providers learned to use templates, preference lists, keywords and phrases, and other shortcuts to reduce the number of clicks – and therefore time – they spend at the keyboard, Sieja said.

Making work simpler

The key is to reduce frustration with practical help, said Gonzalez, who handles the planning, coordination and other logistical details of each Sprint mission.

“I feel we come in to take a good tool [Epic] that we already have and make it better,” Gonzalez said. Many providers on the Anschutz Medical Campus, she noted, have not had additional guidance in using Epic since the first go-live six-plus years ago.

“Who doesn’t need more training?” Gonzalez asked. She cited the example of a UCHealth Colorado Springs provider who was surprised when she found how much time she could save by using Epic’s Dragon voice-recognition software for her progress notes instead of typing. The shortcut helped her get home to her family earlier.

“She told us the change helped her to become a better mother,” Gonzalez said.

Strom said more than 90 percent of the Neurology Clinic’s providers received the Sprint training in some form. The attention generally helped to increase individuals’ confidence in using shortcuts in Epic to trim their documentation time, she said. One example: “dictionaries” Epic uses to translate shorthand for frequently used terms into the real word.

“People applauded the one-on-one teaching,” Strom said. Some critics of Epic who had viewed it as nothing more than a “billing tool,” she added, changed their minds after the Sprint initiative.

“They saw that Epic could be used to take better care of patients and to help to improve the growth of understanding about their disease,” Strom said. A post-intervention survey showed that both providers and staff viewed Epic in a more favorable light than they had before the Sprint team worked with them. For example, the percentages of those who agreed that the clinic improved its use of the EHR and the patient care it provided increased significantly in both groups.

The Sprint team followed the Neurology Clinic assignment with a regular schedule of visits to UCHealth facilities in Northern and Southern Colorado as well as the Anschutz Medical Campus. For example, they worked with the respective Hematology/Oncology practices at UCHealth’s Memorial Hospital in Colorado Springs and Poudre Valley Hospital in Fort Collins. They wrapped up a four-week stint with the OB/Gyn Clinic at UCH – another with close to 100 providers and several subspecialties – on July 21. They are booked on a two-week on, one-week off schedule through June 2018 (with some extra time off for the next Epic upgrade this October), Gonzalez said.

Important challenges remain, including how to ensure that the positive changes in clinics visited by Sprint continue. Sieja points to the importance of super users and clinical content leaders to “carry the improvements forward.” Sprint success also brings to light questions of “scalability,” said Chief Medical Information Officer Lin, noting that it could be increasingly difficult for a single Sprint team to meet clinic demand. For now, the team splits to work with clinics with fewer providers and subspecialists.

“We need people to bring along others at the basic level,” Strom agreed. “But the sense of what is possible with Epic is now much more keen. More people are saying, ‘We really can use this tool.’”

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Researchers find creosote bush could treat Giardia and brain-eating amoeba infections

Compounds produced by the creosote bush, a desert shrub common to American Southwest, exhibit potent anti-parasitic properties against two deadly parasites responsible for Giardia infections (Giardia lamblia) and the amoeba that causes an often-lethal form of encephalitis (Naegleria fowleri), according to researchers at the Skaggs School of Pharmacy and Pharmaceutical Sciences at CU Anschutz and UC San Diego.

Daniel LaBarbera, PhD, associate professor of drug discovery and medicinal chemistry at Skaggs School of Pharmacy and Pharmaceutical Sciences.
Daniel LaBarbera, PhD, associate professor of drug discovery and medicinal chemistry at Skaggs School of Pharmacy and Pharmaceutical Sciences.

The findings, published online this month in PLOS Neglected Tropical Diseases, may give scientists the chance to widen their arsenal of antimicrobial agents effective against deadly parasitic infections. The current standard treatment for both infections involve antibiotics and anti-parasitic drugs.

The World Health Organization estimates giardiasis, a diarrheal illness, is linked to approximately 846,000 deaths worldwide each year. Infection usually occurs through ingestion of contaminated water or food. Though rarely lethal in the United States, it’s estimated there are more than a million cases of giardiasis in the country annually. Infections due to N. fowleri, sometimes called the `brain eating amoeba,’ are much less common than Giardia.

Compounds from the creosote bush may fight two deadly parasitic infections.
Compounds from the creosote bush may fight two deadly parasitic infections.

“However, it is a far deadlier parasite that is found in warm fresh waters and infects the central nervous systems of their victims through the nasal passages causing lethal brain damage known as primary amoebic meningoencephalitis (PAM),” said principal investigator Dan LaBarbera, PhD, associate professor of drug discovery and medicinal chemistry at the Skaggs School of Pharmacy and Pharmaceutical Sciences at CU Anschutz.

Due to its rapid infection cycle and high mortality rate, the CDC has been given special approval to provide the drug miltefosine to clinicians as a treatment option for N. fowleri infection. But it is still not FDA approved and has limited availability in the U.S. This new compound potentially provides a less expensive, more effective treatment option.

Scientists from CU Anschutz and UC San Diego collaborated as part of the Skaggs Scholars program, which matches investigators from Skaggs-funded schools of pharmacy with complementary expertise to discover potential drug breakthroughs. UC San Diego scientists provided expertise in parasitology, while the CU Skaggs School of Pharmacy provided expertise in natural products, compound libraries and active compounds from plants. The researchers investigated these tropical diseases because of their occurrence in Mexico and South America and found indigenous peoples treating infections with creosote compounds.

“The significance and intrigue about our study is that it shows the value of prospecting for new medicines from plants traditionally used by indigenous people as medicine,” said co-principal investigator Anjan Debnath, Ph.D., an assistant adjunct professor at Skaggs School of Pharmacy and Pharmaceutical Sciences at UC San Diego.

The creosote bush (Larrea tridentata), is a tough evergreen bush with small waxy leaves, yellow flowers and a distinctive turpentine-like scent. Native Americans in both the United States and Mexico have long used the plant for a variety of ailments, including intestinal complaints. There is also an existing body of scientific work documenting the plant’s pharmacologically active compounds, notably nordihydroguaiaretic acid (NDGA). NDGA has antiviral, antibacterial, anti-inflammatory and anticancer properties.  The study is the first to show that NDGA and five other compounds are active against both pathogenic parasites.

In other studies, NDGA has been shown to be a neuroprotective agent. It protects human monocytes and other cells and tissues through its powerful antioxidant activity.

“In our study the creosote natural product, NDGA, proved to be a more potent anti-parasitic agent against N. fowleri compared to miltefosine,” LaBarbera said. “Therefore, NDGA may lead to a more effective drug therapy option for N. fowleri infection.”

This research was funded in part, by a grant from The ALSAM Foundation and National Institutes of Health.


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Small cash incentives can encourage primary care visits

An economic experiment to inform policymakers considering Medicaid expansion shows small cash incentives to low-income people with new health care coverage can promote primary care visits that may significantly reduce costs overall. The study, by Cathy Bradley, professor of health systems management and policy at the Colorado School of Public Health at CU Anschutz, published today in the August issue of Health Affairs.

“This shows a potential for cost savings for a very small amount of money,” Bradley said. “Access to primary care does not necessarily mean a visit will occur. Establishing a primary care relationship with an initial visit helps prevent chronic conditions, avoids hospitalizations and use of emergency departments and provides better care to the patient.”

Some employers use cash incentives to encourage healthy behaviors among workers and the Affordable Care Act expanded the use of such incentives to public insurance programs.

“At the time this experiment began, Medicaid expansions were happening across the US,” Bradley said.

Previous studies reported that low-income patients could be especially responsive to financial incentives like cost-sharing responsibility for emergency department use.

“An emergency room visit would treat the patient’s immediate acute need and discharge them,” Bradley said. “A primary care doctor will do all the things that improve their well-being and prevent a medical crisis.”

In a randomized controlled trial with subjects in Virginia living 100 percent below the federal poverty level, researchers studied low-income adults newly covered by a primary care program to determine if a cash incentive could encourage them to make an initial visit to a primary care provider. Among four total participant groups, three were given a baseline survey by telephone and then either $50, $25 or $0 to visit their provider within six months. A control group received no incentive or contact from the researchers.

The findings also suggest that interaction with a health care program coordinator who shows low-income enrollees through the system may also encourage primary care visits without further cash incentives. In the $0 incentive group, more people sought and received care than the unpaid control group.

“It shows that for a small amount of money and a conversation you can get a person to obtain primary care,” Bradley said.

Subjects in the $50 and $25 incentive groups were more likely to see a primary care provider (77 percent and 74 percent, respectively) compared to the $0 group (68 percent). In the control group, 61 percent received care.

Study subjects were identified and enrolled through a community-based primary care program from a safety-net health care provider in Virginia serving low-income patients. All were newly enrolled in a health care program and had not seen a primary care provider or specialist in the previous nine months.

Overall, 1,228 participants were included in the three incentive groups and completed the baseline interview. There were 414 in the control group.

Bradley said the biggest limitation to the study was recruitment. A significant amount of potential subjects did not have stable phone connectivity, were homeless or incarcerated, making study enrollment a challenge.

The study was co-authored by David Neumark, professor of economics at the University of California, Irvine.



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