In the News
Novel Approach Reveals More Diversity in the Human Brain
A collaborative effort from the University of California San Diego, The Scripps Research Institute (TSRI), and Illumina has led to the classification of neuronal single-nuclei transcriptomes from the cerebral cortex of the human brain. The new findings were published June 23 in the Journal of Science.
Classification of single neurons into subtypes has often posed a challenge because of the lower signal-to-noise ratio in cell subtypes than other typical single-cell datasets. Dr. Rizi Ai (Wang Lab at University of California, San Diego), the leading researcher and co-first author in the new Journal of Science paper, developed a new bioinformatics algorithm to iteratively classify 3,227 single-cell transcriptome datasets across the six brain regions. Dr. Ai's algorithm called "Clustering-and-Classification" is able to sensitively measure the most variant gene expressions at each splitting level and determine the cell subtypes based on the active/inactive genes iteratively. The algorithm successfully revealed a lot more diversity in human brain than previously thought by dividing 3,227 individual neurons into 16 neuronal subtypes that are correlated with functions. Besides, Dr. Ai also developed an automatic analysis pipeline to automatically process and analyze large volumes of high-throughput sequencing data such as RNA sequencing data of neuronal cells.
Dr. Rizi Ai had this to say when contacted through email:
"Our research is beyond classifying cells into cell types, we wanted to look more deeply and classify single neurons into cell subtypes. This process is important in further understanding how different brain regions could function differently. With the shortfalls of traditional clustering methods I worked around the clock to create the novel bioinformatics algorithm, Clustering-and-Classification. This new algorithm is sensitive enough to reveal heterogeneity in cell subtypes and capturing transcription variation signals from different neuronal subtypes. "
The Journal of Science article that Dr. Rizi Ai co-first authored is a huge step forward in understanding neuronal subtypes in the human cerebral cortex and provides a framework for comparing individual neurons. This data can also be useful for further research into neurological disorders like dementia, Alzheimer's, Parkinson's, schizophrenia, and depression, as well as seeing if changes in heterogeneity of neuronal subtypes plays a role in these diseases.
SOURCE Wei Wang's Lab
Study Finds Potential Treatment for Non-Alcoholic Fatty Liver Disease
Researchers report in the journal Cell Reports a targeted molecular therapy that dramatically reduces the initial development of Non-Alcoholic Fatty Liver Disease (NAFLD) in laboratory mouse models of the disease.
The study, published online June 30, found increased levels of an enzyme called cdk4 in patients with NAFLD and in mouse models. Researchers at Cincinnati Children's Hospital Medical Center report that when they used two drugs that inhibit cdk4 in mouse models of NAFLD (flavopiridol, PD-0332991), this significantly reduced development of hepatic steatosis—the first stage of the disease.
"This is the first study to show that cdk4 triggers development of NAFLD and that inhibiting this enzyme can both prevent and reverse the first step of the disease," said Nikolai Timchenko, PhD, senior author and head of the Liver Tumor Biology Program at Cincinnati Children's. "Both of the cdk4 inhibitors we tested are approved by the FDA and in clinical trials for liver cancer, so it should be possible to initiate clinical trials for NAFLD with these drugs soon."
NAFLD is an abnormal buildup of extra fat in liver cells that is not caused by alcohol. The disease—which affects up to 25 percent of the US population—usually develops in people who are overweight, obese, or have diabetes and high cholesterol. The first stage of the disease, hepatic steatosis, can progress to a condition called NASH (non-alcoholic steatohepatitis) and ultimately cirrhosis or liver cancer.
Timchenko said new therapies for NAFLD are needed because, short of weight loss and lifestyle changes, there currently are no safe or effective treatments. There are new treatments being tested in clinical trials with promising results, but these studies have revealed evidence of serious side effects.
Unraveling a Mystery
Despite technology advancements in molecular analysis, study authors said that very little has been known about key biological events that cause NAFLD. In people, the disease is usually linked to age and an inappropriate, high-fat diet that initially leads to the disease's first stage.
Timchenko and his colleagues turned to what they say is one of the best biologically relevant animal models for the disease—mice put on a high-fat diet that researchers have learned mimic the main steps of NAFLD development in people.
The researchers started making progress in unraveling the molecular progression of NAFLD when they bred genetically engineered mice that developed first-stage disease much faster than normal wild-type mice. The genetically bred mice had elevated levels of a complex of enzymes, suggesting to the researchers a particular enzyme might trigger the disease.
After repeated testing—including analysis of donated liver tissues from human patients—the researchers found an association between elevated levels of cdk4 and NAFLD in humans and mouse models. Mice that were bred to not express high levels of cdk4 did not develop the initial stage of NAFLD, according to the authors.
Because NAFLD is a progressive disease with several stages, the researchers are now conducting tests to see if using drugs to inhibit cdk4 not only stops or reverses the progression of hepatic steatosis, but also the later disease stages of NAFLD.
Funding support for the study came in part from the National Institutes of Health (R01DK102597, R01CA159942, AR052791, AR064488) and from Cincinnati Children's.
About Cincinnati Children's
Cincinnati Children's, a non-profit, pediatric, academic medical center established in 1883, is internationally recognized for improving child health and transforming delivery of care through fully integrated, globally recognized research, education, and innovation. A destination for children with complex medical conditions, it also served patients from all 50 states and nearly 70 countries during the past year. Additional information can be found at www.cincinnatichildrens.org.
SOURCE Cincinnati Children's Hospital Medical Center
GD Biosciences Announces PULS Cardiac Test Distribution Partnership With Cleveland HeartLab, Inc.
Irvine, California-based Global Discovery Biosciences (GD Biosciences), a biotechnology company dedicated to research and development of innovative solutions to some of the biggest challenges in healthcare, announced that it will partner exclusively with Cleveland HeartLab, Inc. to distribute the PULS Cardiac Test to physicians in the United States. Formed in 2009 as a spin-off from the Cleveland Clinic, Cleveland HeartLab, Inc. offers its testing to thousands of leading clinicians focused on health and wellness as well as corporate wellness plans through its CAP accredited and CLIA-certified clinical lab, and shares Global Discovery Biosciences’ commitment to preventing heart disease.
Heart disease remains the leading cause of death and disability worldwide, but is 80-percent preventable with early detection and lifestyle modifications. Most patients present with no signs or symptoms before a fatal or debilitating heart attack. Nearly half of all heart attacks are silent according to a study published on May 16th, 2016 in the American Heart Association Journal Circulation. The ability to identify these individuals before they have a heart attack has high clinical value.
The PULS (Protein Unstable Lesion Signature) Cardiac Test is an affordable, non-invasive blood test that has the ability to find these individuals before they experience a heart attack. The PULS Cardiac Test quantifies endothelial damage, measures the body’s immune response to the damage, and predicts risk of an acute coronary syndrome (ACS). The PULS Cardiac Test incorporates the most significant predictive markers and risk factors to provide a powerful indication of coronary artery endothelial damage and a risk for potential ACS. Measured and validated against the current gold standards in cardiology, the PULS Cardiac Test is a potential game changer in uncovering asymptomatic patients at real risk of heart attacks who are missed by current conventional methods.
Already being used by select physicians in the US, United Kingdom, Canada, and countries with growing heart disease problems such as Indonesia, China, Middle East, and India, the PULS Cardiac Test is a diagnostic and predictive blood test that detects the body’s immune response to early coronary artery endothelial damage, often in patients with no symptoms of heart disease (the Vulnerable Patient). The immune response frequently causes formation of unstable cardiac lesions that are like blisters or pimples in the coronary artery wall. These lesions can become unstable and rupture, forming a blood clot. This process blocks blood flow to the heart muscle and is the most common cause of heart attacks (75 percent).
“The PULS Cardiac Test is becoming a critical tool for physicians to identify apparently healthy patients with silent disease who are at risk of heart attack. We tend to focus too much on cholesterol and the structural defects in heart disease, and not enough on the functional defects,’” said Douglas S. Harrington, MD, CEO of GD Biosciences. “Free radicals, including oxidized cholesterol, cause damage to the coronary arteries. The body has the ability to repair this damage. In order to do so, it receives a signal from the injury to activate the immune response and repair the damage. We detect the body’s immune response to this injury with the PULS Cardiac Test and predict the likelihood of a heart attack in a 5 year timeline. This allows physicians to implement potentially life-saving prevention plans and improve patient care.”
Jake Orville, CEO of Cleveland HeartLab, Inc. commented “Numerous studies have shown that 50 percent of heart attack victims have normal cholesterol levels. Recently, the American Heart Association’s “Get with the Guidelines” revealed that over 70 percent of patients hospitalized with a first Acute Coronary Syndrome (Heart Attack) event were well within guideline targets for lipids. Cleveland HeartLab is focused on providing breakthrough innovations to the market and the PULS Cardiac Test complements our industry leading menu of cardiac tests and enhances our ability to provide Doctors and patients with actionable results.”
About GD Biosciences
Global Discovery Biosciences (GD Biosciences) is a pioneer in the field of diagnostic medicine and focuses on turning academic discoveries into innovative clinical products for global clinical applications. Its CLIA-certified and GMP laboratory performs a menu of clinically effective tests targeting key health issues. Our goal is to equip physicians with the tools they need to transform health care—one patient at a time.
About Cleveland HeartLab
Cleveland HeartLab Inc. (CHL) is the premier cardiovascular disease (CVD) Management Company with a comprehensive array of propriety tests focused on improving the early identification of those with CVD risk. In addition to its industry leading approach to inflammation testing, CHL manages a robust R&D program to accelerate the clinical use of scientifically proven and medically relevant biomarkers. CHL’s biomarkers have been validated in more than 100 peer-review studies published in leading medical and scientific journals. For more information about CHL visit us at www.clevelandheartlab.com. For more information on CVD visit www.knowyourrisk.com.
SOURCE GD Biosciences
NIH Funds Zika Virus Study Involving US Olympic Team
Researchers supported by the National Institutes of Health will monitor potential Zika virus exposure among a subset of athletes, coaches, and other US Olympic Committee (USOC) staff attending the 2016 Summer Olympics and Paralympics in Brazil. The study, funded by NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and led by Carrie L. Byington, MD, from the University of Utah, Salt Lake City, aims to improve understanding of how the virus persists in the body and to identify potential factors that influence the course of infection.
“Zika virus infection poses many unknown risks, especially to those of reproductive age,” said Catherine Y. Spong, MD, acting director of NICHD. “Monitoring the health and reproductive outcomes of members of the US Olympic team offers a unique opportunity to answer important questions and help address an ongoing public health emergency.”
USOC established an Infectious Disease Advisory Group (IDAG), chaired by Dr. Byington, to help prepare the US Olympic team for travel to Brazil, which is the epicenter of the Zika virus outbreak in the Americas. Dr. Byington proposed the project, which aims to enroll at least 1,000 men and women, in response to an NIH announcement designed to expedite review and funding for Zika-related research projects.
“We partnered with the USOC to improve knowledge of the dynamics of Zika infection, so that we can better protect the health of athletes and staff who will participate in the 2016 Games,” said Dr. Byington. “This ongoing relationship also opens avenues for long-term research that promises to benefit not only the Americas, but also other regions facing the emergence of the virus.”
The current study seeks to determine the incidence of Zika virus infection, identify potential risk factors for infection, detect where the virus persists in the body (blood, semen, vaginal secretions, or saliva), evaluate how long the virus remains in these fluids, and study the reproductive outcomes of Zika-infected participants for up to one year.
To prepare, USOC and the University of Utah conducted a pilot study in March and April 2016. The study was fully enrolled in two days and included 150 participants. Notably, one-third of the pilot group indicated that they or their partner planned to become pregnant within 12 months of the Olympic Games.
Participants in the current study will complete health surveys and provide samples of bodily fluids for the detection of Zika and similar flaviviruses, such as dengue. Zika virus infection typically does not cause symptoms in adults, so routine sampling will detect asymptomatic infections and help shed light on symptomatic versus asymptomatic infections. Zika virus testing kits and training on how to use the tests will be provided by the US Centers for Disease Control and Prevention.
Before traveling to Brazil, all USOC staff, including athletes and coaches, will be briefed on a number of items, including the Zika outbreak. IDAG will provide educational materials to athletes and staff and answer questions. During this time, the NIH-funded researchers will present the study and enroll as well as consent USOC staff who are interested in participating. Approximately 3,000 USOC staff members are expected to travel to Brazil. In addition, spouses or sexual partners who are traveling to Brazil may be eligible to participate.
The 2016 Summer Olympics will take place in Rio de Janeiro, from August 5-21, 2016, and the Paralympic Games are scheduled for September 7-18, 2016.
About the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
NICHD conducts and supports research in the United States and throughout the world on fetal, infant and child development; maternal, child and family health; reproductive biology and population issues; and medical rehabilitation. For more information, visit NICHD’s website.
About the National Institutes of Health (NIH)
NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.