MicroRNAs have emerged as important master regulators in cells, since each one can shut down several target genes. Riding on top of the master regulators is Drosha, the RNA-cutting enzyme that initiates microRNA processing in the nucleus. Drosha and its relative Dicer have been attracting attention in cancer biology, because they are thought to beÂ behind a phenomenon where cancerous cells can â€œinfectâ€ their healthy neighbors via tiny membrane-clothed packets called exosomes.
At Emory, pharmacologist Zixu Mao and colleagues recently published in Molecular Cell their findings that Drosha is regulated by stress (experimentally: heat or peroxide) through p38 MAP kinase.
Although weÂ mention relevance to cancer above, this is one of those basic cell biology findings that may have applicability to several areas of medicine. Alterations in miRNA processing have been linked to neurodegenerative disease (Fragile X-associated tremor/ataxia syndrome, for one example). MicroRNA-packed exosomes are also being studied by biomedical engineers asÂ potential therapeutic tools in regenerative medicine, so knowing what cellular stress does to miRNAÂ production could be useful. Read more
Surveys indicate that many of us make New Yearâ€™s resolutions to eat more healthily or exercise more frequently, yet do not sustain the enthusiasm of January throughout the year.
What if the burst of energy and good intentions could be maintained over a longer period, perhaps with the help of a coach? What kinds of health benefits would appear?
Researchers from Emory and Georgia Tech recently published an analysis of the changes in the health profiles in 382 Center for Health Discovery & Well Being participants who completed a one-year evaluation.
The senior author is Greg Gibson, PhD, professor of biology and director of the Center for Integrative Genomics at Georgia Tech. Georgia Tech postdoctoral fellow Rubina Tabassum, now at the University of Helsinki, is the first author.
â€œWhat do most people in developed countries need to do? Eat better, exercise more regularly and stress less,â€ Gibson says. â€œItâ€™s unclear whether most of the impact comes from the interaction with partners, or simply from participation and goal-setting, but the overall effect is quite good.â€
The main points:
*These are â€œessentially healthyâ€ people — healthier than the general population in the United States â€“ but almost half started out with high blood pressure and cholesterol levels. There was no control group, and not everyone pursued the same exact program. The average age was 48 years and 28 percent of the group was considered obese. Thatâ€™s less than the United States population as a whole.
*On average, the 382 participants lost a moderate amount of weight (it works out to about three pounds) and saw their blood pressure and LDL-cholesterol go down significantly over that first year (121 to 116 mmHG for systolic BP, 112 to 105 mg/dL for LDL-C). They also reported lower scores for depression and anxiety.
Please welcome stem cell/cardiology researcher Hee Cheol Cho to Emory. Starting in September, Cho joined the Wallace H Counter Department of Biomedical Engineering at Georgia Tech and Emory, and Emory-Children’s Pediatric Research Center. He and his team will focus on developing gene-and cell-based therapies for cardiac arrhythmias. Their research will adding to and complement the research of several groups, such as those led by Chunhui Xu, Young-sup Yoon, Mike Davis and W. Robert Taylor.
Cho comes from Cedars-Sinai Medical Center in Los Angeles, where he specialized in understanding cardiac pacemaker cells, a small group of muscle cells in the sinoatrial node of the heart that initiate cardiac contraction. These cells have specialized electrophysiological properties, and much has been learned in the last few years about the genes that control their development.
Cho and colleagues from Cedars-Sinai recently published a paper in Stem Cell Reports describing how the gene SHOX2 can nudge embryonic stem cells into becoming cardiac pacemaker cells. Read more
Patients who receive more cells get significant benefits. That’s a key lesson emerging from a clinical trial that was reported this week at the American Heart Association meeting in Chicago.
In this study, doctors treated heart attack patients with their own bone marrow cells, selected for their healing potential and then reinjected into the heart, in an effort to improve the heart’s recovery. In the PreSERVE-AMI phase II trial, physicians from 60 sites (author list) treated 161 patients, making the study one of the largest to assess cell therapy for heart attacks in the United States. The study was sponsored by NeoStem, Inc.
“This was an enormous undertaking, one that broke new ground in terms of assessing cell therapy rigorously,” says the study’s principal investigator, Arshed Quyyumi, MD, professor of medicine at Emory University School of Medicine and co-director of the Emory Clinical Cardiovascular Research Institute. “We made some real progress in determining the cell type and doses that can benefit patients, in a group for whom the risks of progression to heart failure are high.” Read more
Cardiologist Bob Taylor and colleagues have a new paper in PLOS One this week, looking at the biomechanical forces behind plaque erosion.
Plaque erosion is a mechanism for blood clots formation in coronary arteries that is not as well-understood as its more explosive counterpart, plaque rupture. Plaque erosion disproportionally affects women more than men and is thought to account for most heart attacks in younger women (women younger than 50).
“We believe that this work has implications for our better understanding of the underlying biology of coronary artery disease in women,” Taylor says. The first author of the paper is biomedical engineering graduate student Ian Campbell, who now has his PhD. The team collaborated with cardiovascular pathologist Renu Virmani in Maryland.
Cardiologists have well-developed ideas for how plaque rupture works*; see the concept of vulnerable plaque. Cholesterol and inflammatory cells build up in the coronary arteries over several years. At one point in a particular artery, the plaque has a core of dying inflammatory cells, covered by a fibrous cap. If the cap is thin (the patterns of blood flows near the cap influence this), there is a risk that the cap will break and the contents of the core will spill out, triggering a blood clot nearby.
Plaque erosion is more mysterious and can occur more gradually, the researchers have found. Read more
What conferences likeÂ the HIV + Aging meeting recently held byÂ Emory in Decatur offer the visiting writer: anecdotes that illustrate issuesÂ of clinical care.
To illustrate her point that assumptions about who is likely to develop a new HIV infection may lead doctors to miss possible diagnoses, keynote speaker Amy Justice from Yale described a patient who was seen last year at Yale-New Haven Hospital.
AÂ 60 year old man reported fatigue and had lost 40 pounds over the course of a year. Despite those symptoms, and the discovery of fungal and viral infections commonlyÂ linked to HIV/AIDS, it took nine months before a HIV test wasÂ performed on the patient, a delay Justice deplored.
Sex and substance abuse do not end at age 50, she said, citing data showing that the risk of HIV transmission can be greater among older adults, and that substance abuse is more likely among adults who are HIV positive compared to those who are HIV negative.
Justice also highlighted the issue of polypharmacy (interactions betweenÂ prescription drugs at the same time), a concern even inÂ peopleÂ who are not living with HIV. Common blood pressure medications taken by older adults to prevent heart disease have been suspected of increasing the risk for falls. That’s a problem especially for people living with HIV, because HIV infection has been linked to weakened bone. Read more
Nature Medicine has a nice feature from Jeanne Erdmann highlighting the debate over how long donated blood can be stored. It sets the stage for two prospective clinical trials (RECESS and ABLE), which recently concluded but are still being analyzed. The trials were looking at how the age of stored blood affects patients undergoing cardiac surgery or in intensive care, respectively. Erdmann alsoÂ mentions that the NIHâ€™s Clinical Center already has tightened its standards for blood storage time.
Emory Blood Bank director John Roback and cardiologist Arshed Quyyumi have been participants in this debate, both theoretically and experimentally. In 2011, they proposed that depletion of the messenger molecule nitric oxide limits the benefits donated blood can provide to patients. In addition to nitric oxide depletion, the â€œstorage lesionâ€ is likely to include several changes, such as lysis of red blood cells, mechanical alterations in the remaining cells, and other chemical changes.
Since then, Emory research has shown that transfusion of donated blood more than three weeks old results in impaired blood vessel function in hospitalized patients, but in contrast, not in healthy volunteers. This informationÂ could allow doctors to prioritize fresher blood for patients with cardiovascular diseases.
Biomedical engineer Mike Davis reports he has obtained NHLBI funding to look into therapeutic applications of exosomes in cardiology. But wait. What are exosomes? Time for an explainer!
Exosomes are tiny membrane-wrapped bags, which form inside cells and are then spat out. Theyâ€™re about 100 or 150 nanometers in diameter. Thatâ€™s smaller than the smallest bacteria, and about as large as a single influenza or HIV virion. Theyâ€™re not visible under a light microscope, but are detectable with an electron microscope.
Scientific interestÂ in exosomes shot up after it was discovered that they can contain RNA, specifically microRNAs, which inhibit the activity of other genes. This could be another way in which cells talk to each other long-distance, besides secreting proteins or hormones. Exosomes are thus something like viruses, without the infectivity.
Since researchers are finding that microRNAs have potential as therapeutic agents, why not harness the vehicles that cells use to send microRNAs to each other? Similarly, if so much evidence points toward the main effect of cell therapy coming from what the cells make rather than the cells themselves, why not simply harvest what the cells make? Read more
One lab uses goopy alginate, another uses peptides that self-assemble intoÂ hydrogels. The objective is the same: protecting cells that are injected into the heart and making them feel like theyâ€™re at home.
Around the world, thousands of heart disease patients have been treated in clinical studies with some kind of cell-based therapy aimed at regenerating the heart muscle or at least promoting its healing. This approach is widely considered promising, but its effectiveness is limited in that most of the cells donâ€™t stay in the heart or die soon after being introduced.Â [UPDATE: Nice overview of cardiac cell therapy controversy in July 18Â Science]
Biomedical engineer Mike Davis and his colleagues recently published a paper in Biomaterials describing hydrogels that can encourage cardiac progenitor cells injected into the heart to stay in place. The first author is former graduate student Archana Boopathy, who recently started her postdoctoral work at MIT. Davis has been working with these self-assembling peptides for some time: see this 2005 Circulation paper he published during his own postdoctoral work with Richard Lee at Harvard.
How do these hydrogels keep cells from washing away? We donâ€™t have to go much beyond the name: think Jello. Researchers design snippets of proteins (peptides) that, like Jello*, form semisolid gels under the right conditions in solution. Helpfully, they also are customized with molecular tools for making cardiac progenitor cells happy. Read more