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Donald Leung, MD, pioneers new eczema treatments

The battle between good and evil is a theme usually reserved for blockbuster movies or literature. However, biomedical researcher Donald Leung, MD, PhD, is engaged in his own epic battle, pitting good bacteria against bad in order to treat atopic dermatitis or eczema – the world’s most common skin disease.

Donald Leung, MD, PhD
Donald Leung, MD, PhD

“The beneficial bacteria actually make natural antibiotics that kill staph aureus, the bad bacteria on the skin,” says Leung, medical director of the Clinical and Translational Research Center of the Colorado Clinical and Translational Sciences Institute (CCTSI)  and head of the Division of Pediatric Allergy & Immunology at National Jewish Health. “We know that eczema patients don’t have the good bacteria on their skin that’s needed to kill staph aureus. Our research has also shown that their skin immune system is also ineffective at eradicating staph aureus, so there is a double whammy plaguing these patients.”

Leung has been studying – and treating – atopic dermatitis for 30 years. Twenty percent of children and 10 percent of adults have it. And without effective treatment options, patients may suffer a lifetime of painful, itchy and often infected skin. The majority of these patients develop a problem with staph infections and receive treatment with antibiotics. As a result, many patients develop antibiotic resistant bacteria on their skin, which can be very dangerous.

‘Probiotic for the skin’

“Think of the good bacteria sort of like a probiotic for the skin,” says Leung. It may seem counterintuitive to apply bacteria to skin that is frequently plagued by bacterial infections, but the hope is that by applying good bacteria in a cream to eczema patients’ skin, a healthy bacterial balance will be restored.

Staph aureus
Staph aureus

Researchers hope that using the microbiome cream will offer a long-term solution where other treatments fall short. Powerful antibiotics are commonly prescribed for eczema, but they kill good bacteria on patients’ skin along with the bad. Creams containing corticosteroids are also often prescribed to eczema patients, but they come with harsh side effects, and patients usually can’t tolerate using them for long periods of time.

Eliminating bad bacteria

In a study that is being led by Leung and Richard Gallo, MD, PhD, of University of California San Diego, patients apply the bacteria-infused cream twice a day. Researchers are then able to analyze patients’ skin DNA to see if the bad bacteria have been reduced. The goal is to eliminate the bad bacteria on the skin altogether. The cream helps to restore the natural balance of bacteria on the skin, which will help improve the skin barrier required to keep harmful bacteria out.

Leung says in addition to strengthening the skin by using the good bacteria to restore a healthy microbiome, the study could also ultimately help people with antibiotic resistant staph infections such as MRSA who are running out of treatment options. For more information on how to participate in this study, or other eczema-related research at National Jewish Health, contact Sussmanj@njhealth.org.

Guest contributor: Wendy Meyer, director of communications and marketing, CCTSI.

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CU Anschutz wins $46.5 million NIH grant

The National Institutes of Health (NIH) recently awarded $46.5 million to the University of Colorado Anschutz Medical Campus and its Colorado Clinical and Translational Sciences Institute (CCTSI), a research partnership designed to speed up development of new treatments to address the greatest health needs of Coloradans.

In 2008, the CCTSI was launched with a grant of $76 million—the largest biomedical research and training award in the state’s history. This new five-year award brings the total funding from NIH to the CCTSI to more than $187 million.

Dr. Shikha Sundaram“The general public may not know the CCTSI name,” says Ronald Sokol, MD, CCTSI director and professor of pediatrics in the School of Medicine. “But they have probably benefited from the research that has come out of our institute over the past 10 years.” Examples include:

  • A cure for hepatitis C, which was made possible in part by dozens of clinical trials that were conducted by CCTSI investigators in our facilities over the past 15 years.
  • Precision medicine treatments for cystic fibrosis that target the defective protein caused by specific gene mutations and which have transformed the lives of patients.
  • Boosting the rates of health screenings that save lives in underserved Colorado communities, such as urban Latino, urban African American and rural eastern Colorado.
  • Decreased mortality rates in five Denver neighborhoods by developing community-based, culturally responsive approaches to tailor educational programs for cardiopulmonary resuscitation (CPR).

“The CCTSI is an engine that has enhanced the research enterprise on the Anschutz Medical Campus for many years,” says Dean John J. Reilly, Jr., MD, of the University of Colorado School of Medicine. “We are proud of their work and confident they will continue to provide essential support and leadership for the next generation of physicians and researchers.”

Over the next five years, the CCTSI will:

  • Develop, educate and sustain a diverse translational science workforce to ensure the highest research innovation, quality and safety.
  • Create a translational research environment in which team science and collaboration both locally and nationally are facilitated, supported and valued.
  • Engage local and national communities and stakeholders in all phases of the translational research process.
  • Create novel methodologies and resources to support and integrate research in special populations, including children, the elderly, the underserved and those with rare diseases.

“The grant will further establish the University of Colorado Anschutz Medical Campus, and all of our institutional partners, as biomedical research leaders, pioneers and innovators,” says Sokol. “We are thrilled to have the opportunity to continue to engage in the full spectrum of translational science to achieve our ultimate goal of getting more treatments to more patients more quickly.”

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Vascular problems associated with symptoms of menopause and quality of life measures

A new study shows that more frequent and severe menopausal symptoms such as hot flashes, sleep disturbance, loss of sexual interest, weight gain and other quality of life measures, were associated with markers of vascular aging, according to researchers at the University of Colorado Anschutz Medical Campus.

The researchers, however, found no association between these vascular markers and symptoms of depression. The study was published online today in Menopause, the Journal of the North American Menopause Society.

Kerry Hildreth, MD
Dr. Kerry Hildreth, MD, assistant professor in the Division of Geriatric Medicine, CU School of Medicine.

“The menopausal transition is a vulnerable time for women in terms of vascular health,” said the study’s lead author Kerry Hildreth, MD, assistant professor in the Division of Geriatric Medicine at the University of Colorado School of Medicine. “Many women also experience menopausal symptoms that can negatively affect their quality of life and can contribute to depression, which is an established risk factor for cardiovascular disease. We investigated whether these symptom and mood aspects of menopause were associated with markers of vascular aging.”

Hildreth and her colleagues studied 138 healthy women grouped according to the stage of menopause. They found that arteries were stiffer, and the endothelium, the layer of cells that line the blood vessels, was progressively less healthy across the stages of menopause. Menopausal symptoms and depression symptoms were greatest, and quality of life was lowest, in the late-perimenopausal and early postmenopausal stages. Importantly, more severe menopausal symptoms and lower quality of life were associated with worse vascular function.

Unique study

“To our knowledge this was the first study to examine the association of mood, menopausal symptoms, and quality of life measures with these key markers of vascular aging in a well-characterized population of women spanning the stages of menopausal transition,” the study said.

Dr. Kerrie Moreau, PhD, associate professor
Dr. Kerrie Moreau, PhD, associate professor in the Division of Geriatric Medicine, CU School of Medicine

Women entering menopause experience profound hormonal changes coinciding with adverse changes in cardiovascular disease risk factors like high blood pressure, weight gain and insulin resistance, the study said. This may help explain the acceleration of vascular aging during the menopause transition.

Although the majority of women do not experience depression during the menopause transition, the risk is two to three times higher than in premenopausal women. One hypothesis is that the brain has to adapt to the irregular fluctuations in estrogen, a potent neurosteroid, during perimenopause, and eventually to a new, lower baseline level after menopause. This may explain why depressive symptoms returned to lower levels in the late postmenopausal women.

But while the researchers did not find an association between depression and vascular dysfunction across the stages of menopause, they did find an association with common menopausal symptoms. These include vasomotor symptoms, such as hot flashes, palpitations and headaches, and general symptoms, such as sleeplessness, poor appetite, constipation, weight gain, and poor concentration.

Estrogen loss could play role

The reasons behind these changes are unclear but loss of estrogen could play a key role.

“Estrogen modulates the synthesis and uptake of serotonin which has neuromodulatory, thermoregulatory, and cardiovascular actions,” the study said. “Fluctuating and declining levels of estrogen with the menopausal transition may alter serotonin activity.”

Another culprit could be oxidative stress. Estrogen is a potent anti-oxidant and higher levels of oxidative stress are seen in estrogen-deficient, post-menopausal women compared to premenopausal women, according to the study. Hot flashes are also associated with higher oxidative stress.

Hildreth said the next step is studying the mechanisms underlying these associations between vascular aging and symptoms of menopause.

“A better understanding of these aspects of the menopausal transition will be important for developing effective lifestyle and therapeutic interventions to promote psychosocial well-being and cardiovascular health in women,” Hildreth said.

The other authors of the study include Kerrie Moreau, Ph.D.*, University of Colorado School of Medicine; Cemal Ozemek, Ph.D., University of Illinois at Chicago; Wendy Kohrt, Ph.D.*, University of Colorado School of Medicine, Associate Director of the Center for Women’s Health Research; Patrick Blatchford, Ph.D.*, Colorado School of Public Health.
*Also affiliated with the Eastern Colorado VA Geriatric Research, Education and Clinical Center

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CCTSI launches careers of young researchers through TL1 program

The Colorado Clinical and Translational Sciences Institute (CCTSI) TL1 program is making CU Anschutz a top-choice for students like Michelle Nelsen, who is pursuing her PhD in immunology. Nelsen heard about the program during a recruitment weekend event and was interested in additional opportunities to observe clinical medicine. The TL1 program opened doors for Nelsen to collaborate with physicians and researchers in her field.

Michelle Nelsen

Michelle Nelsen received valuable support for her research through the TL1 program.

“The TL1 program gave me the support of a program and made me comfortable talking to and asking to shadow physicians because I had the program to stand on,” Nelsen said. “This was important to me since I thought that clinical exposure would make me a better biomedical scientist.”

What is the TL1 program?

A program within CCTSI, the TL1 program launches careers in research by providing support for PhD students pursuing a Certificate in Clinical Translational Science. Students in the program are able to take advantage of research funding, as well as mentoring by faculty experienced in basic and clinical science.

The CCTSI is now accepting applications for the TL1 program. Deadline is May 2.

“For students in a PhD granting basic science program, partnering with an MD or other clinician gives a much better understanding of what impact your work can have on people suffering from life-threatening illnesses or other chronic issues,” said Emily Warren, programs manager for education,  training and career development within the CCTSI.

Additionally, students in the TL1 program are able to apply for one year of funding at the NIH level to support their research, alongside financial support for tuition and fees, research supplies and travel to the national meeting of the Association for Clinical and Translational Science.

“This program provides not only a stipend, but also an opportunity to interact with other students from other programs,” Warren said. “This is important as translational science enables students in the program to become someone who can bridge the gap between the lab and clinical practice. Team science collaborations between disciplines are becoming more and more prominent.”

Supporting research

Receiving a grant from the TL1 program has been helpful in Nelsen’s research in transplantation immunology. Nelsen is currently examining alternatives to immune suppression drugs that might exhibit fewer side effects and toxicity levels in transplantation patients. By using her clinical observations of patients to guide her laboratory experiments, Nelsen has helped identify key clinically-relevant situations when the new anti-rejection agents might fail in transplant recipients.

The grant has allowed her to free up resources that would normally cover her stipend and also purchase additional equipment that has enhanced the quality of her study. In addition, by using funds provided through the program to attend the national CTSA TL1 meeting, Nelsen has already begun building a professional network of peers.

“The program is an opportunity for us as basic scientists to learn about translational science, clinical medicine, and research opportunities,” Nelsen said. “It also gives us a better understanding of why we are answering basic science questions and how our work applies to patients.”

The experience in the program has been so profound that Nelsen now plans to attend medical school after graduating with her PhD so she will be able to work across disciplines in clinical and research environments.

“Because of my TL1 experience and being able to observe physicians and surgeons, I have decided to pursue a career as a physician scientist,” Nelsen said. “I want to be able to care for patients and also work to address current shortcomings in treatment.”

Translational science is team science

Allison Shapiro, who received her PhD in epidemiology from the Colorado School of Public Health in December 2015, participated in the TL1 program and received support necessary to design and implement the Baby Biology of Intrauterine Metabolic Programming (BabyBUMP) project, a study using mesenchymal stem cells (MSCs) as a model for human adipogenesis (forming fat cells) in response to nutritional influences.

Allison Shapiro

TL1 program participant Allison Shapiro describes translational science as “the core of her research.”

This ambitious study, which utilized patients from a cohort of 1,400 women from the Healthy Start Study at UC Denver, saw Shapiro and CCTSI research nurses collecting umbilical cord samples from more than 160 patients at delivery. She would then isolate, culture and examine the stem cells.

Reflecting on the project, Shapiro credits a team of faculty and clinical mentors across disciplines who collaborated to share knowledge, resources and experience necessary to complete her dissertation. She recognizes her project as a “true collaboration between scientific fields.”

“Translational science is the core of my research, and it’s constantly what I look to when I start thinking about new study ideas,” Shapiro said. “We don’t live in a world anymore where researchers can work alone, in silos. We live in a team science world, and translational science is the road to team science.”

Since graduating, Shapiro has leveraged the knowledge she has gained in designing studies, disseminating large data sets and gaining perspectives from other fields during her post-doctoral work. For the next two years Shapiro will be working alongside physicians and researchers at Children’s Hospital Colorado examining fetal and infant brain development.

It is Shapiro’s next step in a career that will focus on research.

“I live and breathe academia,” Shapiro said. “I feel fortunate to have this drive to want to write grants and design studies. This is my realm—my comfort zone.”

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