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Study shows prenatal cannabis use associated with low birth weights

With marijuana use during pregnancy on the rise, a new study led by the Colorado School of Public Health shows that prenatal cannabis use was associated with a 50 percent increased likelihood of low birth weight, setting the stage for serious future health problems including infection and time spent in Neonatal Intensive Care Units.

Cannabis Sativa leaf
New study shows association between prenatal cannabis use and low birth weights.

“Our findings underscore the importance of screening for cannabis use during prenatal care and the need for provider counselling about the adverse health consequences of continued use during pregnancy,” said the study’s lead author Tessa Crume, PhD, MSPH, assistant professor of epidemiology at the Colorado School of Public Health at the University of Colorado Anschutz Medical Campus.

The study was published last month in The Journal of Pediatrics.

Crume and her colleagues utilized survey data from 3,207 women who participated in the Colorado Pregnancy Risk Assessment Monitoring System in 2014 and 15. They found the prevalence of marijuana use in the state of Colorado was 5.7 percent during pregnancy and 5 percent among women who were breastfeeding.

Tessa Crume, assistant professor of epidemiology at the Colorado School of Public Health
Tessa Crume, PhD, MSPH, assistant professor of epidemiology at the Colorado School of Public Health

They also discovered that prenatal marijuana use was associated with a 50 percent increased chance of low birth weight regardless of tobacco use during pregnancy. Prenatal marijuana use was three to four times higher among women who were younger, less educated, received Medicaid or WIC, were white, unmarried and lived in poverty.

Crume said the numbers are surprising but also reflect changing attitudes toward marijuana, especially in a state like Colorado where it is legal.

“There is increased availability, increased potency and a vocal pro-cannabis advocacy movement that may be creating a perception that marijuana is safe to use during pregnancy,” Crume said.

The National Survey on Drug Use and Health suggests that cannabis use among pregnant women has increased as much as 62 percent between 2002 and 2014. At the same time, the potency of the drug has increased six or seven fold since the 1970s along with the ways it is consumed – eating, vaping, lotions etc.

“Growing evidence suggests prenatal cannabis exposure has a detrimental impact on offspring brain function starting in the toddler years, specifically issues related to attention deficit disorder,” Crume said. “But much of the research on the effects of prenatal cannabis on neonatal outcomes was based on marijuana exposures in the 1980s and 1990s which may not reflect the potency of today’s cannabis or the many ways it is used.”

The study found that 88.6 percent of women who used cannabis during pregnancy also breastfed. The risk of cannabis to the infant through breastmilk remains unknown. Various studies have found that cannabinoids are passed to the baby in this way. One of the study’s co-authors, Dr. Erica Wymore, MD, MPH, from Children’s Hospital Colorado and the CU School of Medicine, is currently conducting a study to evaluate this issue.

The researchers recommend that health care providers ask pregnant women about their cannabis use and advise them to stop during pregnancy and lactation.

“Obstetric providers should refrain from prescribing or recommending cannabis for medical purposes during preconception, pregnancy and lactation,” Crume said. “Guidance and messaging about this should be incorporated into prenatal care. And screening of pregnant women at risk for cannabis dependency should be linked to treatment options.”

The study co-authors include Ashley L. Juhl MSPH, of the Colorado Dept. of Public Health and Environment; Ashley Brooks-Russell, PhD, MPH, of the Colorado School of Public Health; Katelyn E. Hall, MPH, of the Colorado Dept. of Public Health and Environment; Erica Wymore, MD, MPH of the University of Colorado School of Medicine and Children’s Hospital Colorado and Laura M. Borgelt, PharmD, of the CU Skaggs School of Pharmacy and Pharmaceutical Sciences.

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Annual Department of Medicine Research Day 2018

Battling breast cancer, hepatitis C and the nationwide opioid-addiction crisis were just three of the research goals highlighted as part of the Department of Medicine’s sixth annual Research Day on the University of Colorado Anschutz Medical Campus.

Gathered in the Fulginiti Pavilion on April 6, the department within the CU School of Medicine recognized 22 students, faculty and staff for their outstanding research achievements as part of the event. Focused on showcasing the diverse accomplishments at CU Anschutz, the event encourages discussion and collaboration across the the Department of Medicine’s multiple disciplines.

This year, a diverse panel of faculty judges selected 22 outstanding abstracts – all submitted by Department of Medicine students, postdocs, fellows and junior faculty. The researchers were then invited to present their projects at Research Day, said Jennifer Kemp, director of the Department of Medicine Research Office.

“The Research Day poster session presents a unique opportunity for our researchers to present their latest work to a broader audience than is typically found at a more specialized conference,” Kemp said. “This broad audience brings the potential to spark new ideas and catalyze new collaborators in different fields.”

Cancer biology

Lynsey Crump shares her research in cancer biology.

Lyndsey Crump, a third-year student in the Cancer Biology

program in the Graduate School, works in Traci Lyons’s lab. Crump has been exploring how signaling proteins can affect breast cancer progression. Specifically, she has looked at SEMA7A (Semaphorin 7A) and how its presence may indicate a worse prognosis.

“I want to try to help people,” Crump said of her passion in cancer biology. “One day I want to see this lab work to translate to clinical work, to give patients another potential course of treatment.”

Hepatitis C and public health

Andy Bryant, MD, studies hepatitis C in special populations.

Andy Bryant, MD, is an internal medicine resident at CU Anschutz studying the treatment of hepatitis C in a “safety net” population, or those who are either uninsured or have Medicare or Medicaid.

“Until this study, this population was overlooked,” said Bryant as he walked onlookers through his research. “Unfortunately, these people usually come in a lot sicker than those with traditional insurance. This means that their prognosis isn’t very good.”

Recent studies have helped underscore the potential for a new drug (DAA) that can cure hepatitis C. Originally, Medicaid and Medicare did not cover this drug, but Bryant’s findings help show the long-term potential savings of administering DAA.

Opioid prescribing habits

Angela Keniston, MSPH, an instructor in the department of hospital medicine, studies the prescribing habits of health care providers across the world.

Angela Keniston researches cultural opioid prescribing habits.

“Specifically, we wondered, do doctors in the United States prescribe opioids more?” Keniston said. “The answer, one we’ve all suspected, was yes.”

 

In conjunction with her study, Keniston also looked into cross-cultural patients’ perceptions of pain across cultures.

In the long run, Keniston would like to help doctors understand their patients’ expectations of pain, and ultimately change prescribing habits. “Pain is a normal experience,” she said. “We need our providers to shape the conversation with patients to help curb this prescribing epidemic in our country.”

 

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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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Donors celebrated for transformational gifts

More than 430 people attended the Benefactor Recognition Dinner, a celebration of the passionate people behind philanthropic gifts to the CU Anschutz Medical Campus. The event took place in the Seawall Ballroom in the Denver Performing Arts Complex on March 29.

This year’s gathering was particularly special because, for the first time, the recognition dinner included a celebration of CU Anschutz’s partnership with University of Colorado Hospital, and an acknowledgment of how philanthropic support makes an impact all across campus. Hosts of the evening included CU President Bruce Benson and his wife, CU First Lady Marcy Benson; CU Anschutz Chancellor Don Elliman; and University of Colorado Hospital President and CEO Will Cook.

Learn more about our generous honoree benefactors in the video presentations on this page.

“Our vision at CU Anschutz is simple,” Elliman said. “We seek to rise higher among the country’s top medical destinations; to be the place where anyone who needs it can get the finest care in the world; where the science of that care is being pushed to new horizons; and where we train and prepare the health workforce of our future.”

When Cook stepped to the podium, he said, “I hope you’re getting a sense of the momentum of our campus. The tremendous promise we’re seeing realized is what drew me to the University of Colorado Hospital from UPMC (University of Pittsburgh Medical Center) 2 ½ years ago.”

He added, “We’re pleased to be partnering more closely than ever with the university, as we work to rise even higher among the ranks of the country’s top destinations for health, wellness and world-class medical care.”

Elliman thanked the benefactors for their generous gifts, which help fuel the campus’s unprecedented growth. “You are a vital part of our growth and progress,” he said. “Because of you, we are in great shape and getting stronger.”

2018 honorees:

 

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Share photos of your research at CU Anschutz

The University Communications social media team recently launched a mini-campaign that encourages the CU Anschutz community to share its research and/or lab pictures in an effort to bring attention to innovative research projects taking place on campus.

Because our social media team members found it can be difficult to bring a camera into labs and other campus areas, they’d like help from you – the researchers – in getting the pictures shown to the world.

The social media team will regularly share your candid lab photos – preferably along with the corresponding context provided by researchers – on the official CU Anschutz Facebook, Twitter and Instagram pages.

There is no end date on when the team will stop accepting and sharing photos, so they encourage you all to share away!

Here’s why we want your photos:

  • To show not only our community, but the world, how incredible, hard-working and passionate you all are.
  • To elevate research stories and projects to hopefully make more connections and growth opportunities for the researchers and scientists.
  • To strengthen CU Anschutz’s overarching identity as a world-class research campus.
  • To help people better understand what scientific work looks like on our campus and offer a lens into early- and mid-stage research.
Lucas Ellison shared this photo of Lane Bushman and Pete Anderson using LCMS to quantify HIV medication in people’s blood.

Here’s how you can show us your photos:

  • Add #ShareYourResearch in your Facebook, Twitter or Instagram captions when you post the research picture
  • Tagging @CUAnschutz helps!

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Discovery could speed clinical translation of stem cell therapies

A team of scientists from the University of Colorado School of Medicine and the Charles C. Gates Center for Regenerative Medicine at CU Anschutz has reported a more efficient approach to reprogramming a patient’s diseased skin cells into stem cells, raising hopes for future clinical trials and potential cures for critical illnesses.

The results were published on Feb. 21, 2018 in Nature Communications.

The team is reporting a clinically safe approach that consistently reprograms healthy and disease-associated patient’s skin cells into induced pluripotent stem cells (iPSCs) with an unprecedented efficiency.

Dr. Dennis Roop, director of the Charles C. Gates Center for Regenerative Medicine.
Dennis Roop, PhD, director of the Charles C. Gates Center for Regenerative Medicine.

Since its initial discovery in 2006 by Shinya Yamanaka, MD, PhD, iPSC reprogramming technology has created considerable interest in the field of regenerative medicine for its potential of providing an unlimited source of patient-specific cells suitable for transplantation. This technology involves the reprograming of adult skin cells taken from a donor into immature embryonic stem cell-like iPSCs. These iPSCs can be grown outside the body, genetically manipulated, converted into a variety of adult cell types and then either transplanted back to the same patient as an autograft or used as a platform for drug screening and research.

Despite significant advances, current methods for reprogramming adult cells into iPSCs are extremely inefficient and inconsistent, with less than 1 out of every 500-1000 adult human cells becoming iPSCs. The low efficiency of these protocols, coupled with the length of time in culture, increase the chances of accumulating harmful mutations in iPSCs, thus compromising the safety of this technology for clinical applications.

To address the issue of low reprogramming efficiency, the team from the University of Colorado Anschutz Medical Campus optimized the cellular delivery of modified mRNAs, encoding several reprogramming factors in combination with microRNAs, and improved cell culturing conditions to enhance the growth of cells undergoing conversion into iPSCs.

“Many groups had previously attempted to improve reprogramming efficiency by identifying novel modulators of the process,” said Ganna Bilousova, PhD, an assistant professor of dermatology and one of the study’s lead scientists. “Instead of looking for new reprogramming enhancers, we took advantage of the versatility of RNA molecules to control the precise levels of reprogramming factors and microRNAs in cells during their conversion into iPSCs. We were surprised at how simple manipulations of the timing and dosing of the RNA molecules could affect the efficiency of reprogramming.”

The researchers showed that the fine-tuning of RNA delivery and cell culturing conditions dramatically enhanced the efficiency of reprogramming and improved the consistency of the process for disease-associated skin cells.

“Initiating reprogramming at a reduced cell density was critical for improving reprogramming efficiency in our study,” said Igor Kogut, PhD, an assistant professor of dermatology at the Gates Center. Kogut is also one of the paper’s lead authors. “There is a direct correlation between the rate of cell division and the efficiency of reprogramming. Our optimal, combinatorial RNA delivery regimen, which reduced the toxicity of the protocol, made it possible to initiate the process at a reduced cell density, down to individually-plated single cells.”

The goal now is to move the technology from the laboratory into clinical trials. Gates Center Director Dennis Roop, PhD, who is also one of the lead authors on the paper, recognizes the magnitude of the team’s work. He believes it holds great potential for the development of new corrective stem cell-based therapies for currently incurable diseases, such as Epidermolysis Bullosa (EB). Roop has had a long-standing interest in finding a permanent cure for EB, a group of inherited skin diseases that results in severe blistering and scarring. EB affects thousands of people across the United States and worldwide, and is characterized by chronic skin wounds similar in property to thermal burns, and indistinguishable from burns induced by chemical agents such as mustard gas.

“There are no effective therapies for EB, and iPSC technology provides an opportunity to develop a permanent corrective stem cell-based therapy for these severe skin-blistering diseases,” said Roop. “Our breakthrough in developing a highly-efficient reprogramming method, that avoids the use of viral vectors, may allow us to get FDA approval for one of the first iPSC-based clinical trials in the U.S..”

To accelerate getting iPSC-based therapies for EB into the clinic, the CU Anschutz team has established a consortium comprised of the University of Colorado, Stanford University (Anthony Oro, MD, PhD) and Columbia University (Angela Christiano, PhD).

The “EB iPS Cell Consortium” was initially supported by the EB Research Partnership (EBRP), the EB Medical Research Foundation, and the SOHANA Research Fund. More recently, the Consortium has received funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases through the 21st Century Cures Act for the Regenerative Medicine Innovation Project, and the California Institute for Regenerative Medicine’s Partnering Opportunity for Translational Research Projects. The research teams at both Stanford and Columbia have adopted the University of Colorado’s reprogramming technology as the method of choice for generating patient-specific iPSCs for future clinical trials, and thus are setting the standards for future iPSC-based therapies for other diseases.

Prior to receiving the above sources of funding for the Consortium, this study was supported by additional funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the US Department of Defense, the Foundation for Ichthyosis & Related Skin Types, the Dystrophic Epidermolysis Bullosa Research Association (DEBRA) International, The King Baudouin Foundation’s Vlinderkindje Fund, the Linda Crnic Institute for Down Syndrome, the Gates Frontiers Fund and private donors.

Guest contributor: This article was contributed by Jill Cowperthwaite, Gates Center for Regenerative Medicine.

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Curiosity: It’s what makes new interim vice chancellor tick

Robert Eckel at desk
Dr. Robert “Bob” Eckel is serving as interim vice chancellor for research while a search for a permanent replacement is underway. Eckel has served as program director of the Clinical Translational Research Center Network of the Colorado Clinical Translational Sciences Institute (CCTSI) and the CU Adult General Clinical Research Center. He was only the second endocrinologist ever to serve as president of the American Heart Association.

It might have been what killed the cat, but to Dr. Robert “Bob” Eckel, the University of Colorado’s new interim vice chancellor for research, curiosity reigns in propelling a successful career and research program.

“It’s what drives the bus here,” said Eckel, MD, recently tapped for the job left vacant by Dr. Richard “Dick” Traystman’s death this fall, as CU administrators launch a search for a permanent vice chancellor.

Although “filling Dick’s shoes is impossible,” Eckel, an international expert in his field of lipid and lipoprotein metabolism and a recognized face on the CU Anschutz Medical Campus after nearly 40 years, said he hopes his ingrained curiosity can serve as a catalyst for furthering the research enterprise at an institution that has been good to him and his profession.

“There are many components to a successful career in science and medicine,” Eckel said. “But curiosity, in my opinion, is one of the most important factors. If curiosity is driving you, then grants, papers and quality research will follow.”

Fanning the curiosity flame

The curiosity flame was lit early in Eckel’s career. After conceding that he was no Vivaldi and ditching the thought of a profession in music (a passion that led him to his first wife, a talented violinist), Eckel decided his idea of medical school was more on track. “And I knew it would make my mother happier.”

But his vision of being solely a clinically-focused doctor soon vanished. “I found out during my residency in internal medicine that I was starting to get increasingly curious about what made people sick and why they weren’t responding to therapy,” said Eckel, an endocrinologist in both the School of Medicine’s Division of Endocrinology, Metabolism and Diabetes and Division of Cardiology. He also has an appointment in the Department of Physiology and Biophysics.

“I thought if I wanted to pursue that drive, that ultimately I needed to be trained in research,” said Eckel, crediting his subsequent research-fellowship experience at the University of Washington for fanning the flames. “I came out on fire for research.”

‘There are many components to a successful career in science and medicine. But curiosity, in my opinion, is one of the most important factors. If curiosity is driving you, then grants, papers and quality research will follow.’ – Robert Eckel, MD

Bringing a dual perspective

Eckel, who often calls himself a “cross-dresser” as a preventive cardiologist and endocrinologist, said he loves all components of his job. “As a clinician, I’m more of a preventive cardiologist, but as a scientist, I’m a metabolically-driven guy,” he said, adding that his physician-scientist perspective brings a different “twist” to the vice chancellor position.

As an investigator, Eckel thrives on being tucked in his lab, where he and Assistant Research Professor Kimberley Bruce, PhD, have expanded their longtime focus on how lipids (such as cholesterol and triglycerides) and lipoproteins (which carry lipids) relate to obesity, metabolic syndrome, diabetes and cardiovascular disease.

The two have joined forces with Wendy Macklin, PhD, a leading expert on glial biology in the Department of Cell and Developmental Biology, in investigating how lipids and lipoproteins play a role in neurological disorders, such as Multiple Sclerosis and Alzheimer’s disease, with a renewed funding award on Feb. 1.

“Myelin is loaded with lipids,” Eckel said, referring to the myelin sheath that protects the body’s nervous system. With MS, a disabling degenerative disease that affects an estimated 400,000 Americans, myelin is slowly destroyed. “So we are involved in understanding how lipids and lipoproteins can be processed to re-myelinate nerves that have been demyelinated.”

Eckel and wife at Nuggets game
Dr. Robert Eckel poses with Rocky and wife, Margaret, at a Nuggets game. Eckel credits the women in his life for much of his success.

Encouraging research partnerships

Bruce and Eckel have also teamed up with another top CU Anschutz Medical Campus researcher, SOM’s Department of Neurology’s Huntington Potter, PhD, in their work on the role of lipids and lipoproteins and the brain-degenerating Alzheimer’s disease. Alzheimer’s affects at least 5.5 million Americans, a number expected to soar with an aging population.

During her years working beside him, Bruce said Eckel has served as a great mentor and role model. “I’ve learned a great deal from Bob, not just about lipid and lipoprotein biology, but also about how to strive for scientific excellence while still keeping your feet on the ground,” she said. “I honestly can’t think of anyone better for this vice chancellor role.”

No stranger to cross-disciplinary collaboration, Eckel said researcher success also depends on networking. “None of us is an island anymore in science and medicine. There are no single-authored papers anymore. Science is really teamwork, and that’s something I will consider as I look at the big network of research on both campuses.”

Recognizing research’s influence

Eckel, winner of the Endocrine Society’s 2016 Outstanding Clinical Investigator Award, understands the power of research on both a professional and a personal level.

Diagnosed at age 5 with Type 1 diabetes, a disease he shares with two sons and opted early on to separate from his lab work, Eckel said he’s grateful for his colleagues who have made huge research strides in the insulin-related disorder.

“There’s been so much improvement in therapeutics for Type 1 diabetes,” he said. “I have a pump and a sensor,” he said, patting his lower chest, where a pump automatically infuses the insulin his body cannot make. “I’ve had this disease for 65 years now, and I’ve never felt better in my life. I feel fortunate to be alive, and that’s research,” he said.

Finding collaboration on all fronts

Eckel with family
Dr. Robert Eckel balances career and family, which includes three grandchildren and five grown children. Eckel, who emphasizes the importance of music in a well-rounded lifestyle, taught each of his kids piano until they were in sixth grade.

Eckel doesn’t just stand out in his field. In 2016, he won Father of the Year from the American Diabetes Association, for which he serves on the board. A devoted but humble family man, he doesn’t take the credit for his well-rounded success.

“It’s the women I’ve done it all with,” he said, acknowledging his first wife, who worked as a teacher while he went through medical school and then raised their five children before she died of breast cancer at age 45. “She was a great mom.”

Eckel eventually married his current wife, Margaret. “She stepped up and became a stepmom who’s now loved by all of my kids, and I’ve been married to her almost as long as I was my first wife. So I had great companionship and love from two women, and I probably didn’t deserve either one of them.”

On the professional side, Eckel said Bruce “runs the bus” in his research lab. “She’s smarter than I am. I’m lucky to have her.” With a retirement date set for July 1, 2019, Eckel hopes to have his research program ready to hand over to Bruce and to have fulfilled his new interim post to the best of his ability.

“I work at a great institution that’s been incredibly supportive, and it’s a privilege to serve,” said Eckel, who will not vie for the permanent post. “But right now, I’m neither intellectually nor emotionally ready to retire. The science is just too much fun.”

 

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CU Anschutz students present research to lawmakers at Capitol

More than 50 researchers greeted Colorado lawmakers entering the Capitol building on Jan. 19, with the aim of raising awareness of the importance of research. Colorful posters highlighting the young scientists’ projects lined the rotunda’s walls, as the presenters’ lively voices bounced around the room’s large marble structures while they explained their work.

Hannah Hathaway, PhD, is proud to share her research.

“This is such a great event,” said Hannah Hathaway, PhD, president of the University of Colorado Postdoctoral Association, as she stood amid the array of posters targeting a wide range of disciplines, from biomedical to atmospheric research. “Not only do we get to present our work in a unique way, but we also get to see other research going on in Colorado.”

Early-career scientists representing 11 state institutions of higher education, including the CU Anschutz Medical Campus, CU Denver and CU Boulder, attended the event, hosted by the CU Anschutz chapter of Project Bridge. Bruce Mandt, PhD, director of the CU Postdoctoral Office, and Jerry Johnson, the CU contract lobbyist for state relations, helped the group with the event.

Project Bridge

“The goal of Project Bridge is to give scientists more tools to succeed by teaching them to communicate outside the world of academia,” said Erin Golden, PhD, president of the national student organization. “We accomplish this through holding trainings, inviting speakers to campus and engaging in a variety of advocacy events like the Capitol Investment.”

Golden launched the CU Anschutz chapter last year after coming from Johns Hopkins University, where Project Bridge was founded.

Erin Golden, PhD, is excited with the turnout of Capitol Investment Day.

“It’s great to see everything come together,” Mandt said. “It is so important to showcase the broad range of scientific work from around the entire state of Colorado.”

Gov. Hickenlooper declared Jan. 19, 2018, “Early Career Scientist Day” to commemorate the event, aimed at showing lawmakers the importance of funding research. The event boasted 71 of 100 state legislators, who pledged their attendance as co-hosts.

Career Development

While waiting for the legislators to arrive, researchers shared their short presentations with one another. The presentations and posters were designed to be informal and jargon-free.

“This type of presentation is unusual for scientists,” Mandt said. “Our presenters are getting excellent experience in explaining their work to a lay audience. This is a wonderful career-development opportunity.”

“If I have accomplished something today, it would be relaying how impactful this scientific exploration is,” said Christopher Covey, a fifth-year graduate student in CU Anschutz School of Medicine’s Department of Immunology & Microbiology. “We’ve all worked so hard to approach scientific problems from new angles. Maybe one day we will uncover something that was previously overlooked.”

Golden hopes Project Bridge will grow to include more events and that Capitol Investment will become an annual event.

“We’re so excited with the turnout,” said Golden. “We really feel like we are making a difference in Colorado’s scientific community, while giving our peers the tools they need to succeed.”

Guest contributor: Photo at top by Katie Weeman, CIRES/CU Boulder.

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Research suggests why exercise slows Parkinson’s

Freed and Zhou
Curt Freed, MD, and Wenbo Zhou, PhD

While vigorous exercise on a treadmill has been shown to slow the progression of Parkinson’s disease in patients, the molecular reasons behind it have remained a mystery.

But now scientists at the University of Colorado Anschutz Medical Campus might have an answer.

For the first time in a progressive, age-related mouse model of Parkinson’s, researchers have shown that exercise on a running wheel can stop the accumulation of the neuronal protein alpha-synuclein in brain cells.

The work, published Friday in the journal PLOS ONE, was done by Wenbo Zhou, PhD, research associate professor of medicine, and Curt Freed, MD, professor of medicine and division head of the Division of Clinical Pharmacology and Toxicology at the CU School of Medicine.

Exercise in mice boosts protective gene

The researchers said clumps of alpha-synuclein are believed to play a central role in the brain cell death associated with Parkinson’s disease. The mice in the study, like humans, started to get Parkinson’s symptoms in mid-life.  At 12 months of age, running wheels were put in their cages.

“After three months,” Zhou said, “the running animals showed much better movement and cognitive function compared to control transgenic animals, which had locked running wheels.”

Zhou and Freed found that in the running mice, exercise increased brain and muscle expression of a key protective gene called DJ-1.  Those rare humans born with a mutation in their DJ-1 gene are guaranteed to get severe Parkinson’s at a relatively young age.

The researchers tested mice that were missing the DJ-1 gene and discovered that their ability to run had severely declined, suggesting that the DJ-1 protein is required for normal movement.

Study suggests positive human implications

“Our results indicate that exercise may slow the progression of Parkinson’s disease by turning on the protective gene DJ-1 and thereby preventing abnormal protein accumulation in brain,” Freed said.

He explained that his animal experiments had very real implications for humans.

“Our experiments show that exercise can get to the heart of the problem in Parkinson’s disease,” Freed said. “People with Parkinson’s who exercise are likely able to keep their brain cells from dying.”

Parkinson’s is a disease caused by the death of brain cells that make a critical chemical called dopamine.  Without dopamine, voluntary movement is impossible.  Most people with Parkinson’s disease take a drug called L-DOPA to treat their symptoms.  The oral drug is converted into dopamine in the brain allowing patients to get up and move.

In 1988, Freed and his colleague Robert Breeze, MD, performed the first transplant of human fetal dopamine cells into a Parkinson’s patient in the United States. His lab is currently working to convert human embryonic stem cells to dopamine neurons. These techniques should make it possible to produce unlimited quantities of dopamine cells for transplant.

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Expensive new cancer therapy may be cost effective

Researchers from the University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, selected to estimate the cost-effectiveness of the newly approved CAR-T therapies, have found the clinical benefit may justify the expensive price.

The treatments involve removing immune cells known as T-cells from the patient, genetically engineering them to kill cancer cells and then putting them back in the body. The therapy is known as CAR-T or chimeric antigen receptor T-cell therapy and is FDA approved for some B-cell cancers, including acute lymphoblastic leukemia in pediatric and young adult patients and those with adult lymphoma.

Jon Campbell, PhD, associate professor of pharmacy.
Jon Campbell, PhD, associate professor of pharmacy.

The evidence suggests a potentially great benefit from these therapies, but the treatments are costly. The leukemia therapy, known as Kymriah, costs $475,000 while the lymphoma treatment, Yescarta, costs $373,000. So the non-profit Institute for Clinical and Economic Review (ICER) enlisted the help of pharmaceutical outcomes research faculty Melanie Whittington, R. Brett McQueen, and Jon Campbell from the CU Skaggs School of Pharmacy to generate evidence on whether the treatments, already approved by the FDA, are cost-effective.

The draft report of their findings was published Wednesday on the ICER website. After a public comment period, the researchers in collaboration with ICER, will finalize the report and present the findings at a public forum on March 2, 2018.

In the draft report, they compared CAR-T therapies to chemotherapy, taking into account patient survival, quality of life and health care costs from the health care system perspective over the lifetime of a patient receiving the therapies.
“We take into account the clinical evidence, quality of life data, and health system costs to generate cost-effectiveness evidence,” said Whittington, PhD, research instructor at the CU School of Pharmacy.

According to Jon Campbell, PhD, associate professor of pharmacy, the cost-effectiveness findings for both CAR-T therapies were `promising’ and suggested that they may be a good use of our health care resources toward improving health. They significantly extended the lives of some patients, much more on average, than traditional chemotherapy.

“The CAR-T science is beyond whether the therapies work for certain patients and is now questioning its value,” he said. “CAR-T is promising on the clinical side but there is some feeling of sticker shock related to the price. Is it worth it? Yes, it seems to be.”

Does the cost-effectiveness of therapies matter in the U.S.?

“The straightforward answer to that question is yes,” said McQueen, PhD, assistant professor of pharmacy. “Insurance companies have a higher likelihood of providing access and payment for therapies that are considered good value for money.”

Campbell, who is director of pharmaceutical outcomes research graduate track at the Center for Pharmaceutical Outcomes Research at CU Anschutz, noted that cost-effectiveness doesn’t mean cheapest and it doesn’t mean denying access.

“It’s about ensuring patients have access to high value care while sustaining our health system for future generations,” he said.

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