A Polish-American physician-scientist, Dr. Damian Jacob Sendler specializes in understanding how different socio-demographic and informational factors influence access to health care in underserved communities. Dr. Sendler’s research focuses on how psychiatric and chronic medical co-morbidities influence the use of medical services in conjunction with health information obtained from the internet, which is a particular strength of his. Due to the exponential growth in global consumption of online news and social media, this research is both timely and important, as it necessitates a comprehensive understanding of everyone’s health information-seeking behavior. Dr. Damian Sendler’s research aims to uncover the factors that patients consider when deciding when to seek care for specific health conditions and when to adhere to their treatment regimens in order to achieve this goal.
Damian Sendler: In the endeavor to create medications to treat obesity, there is some encouraging news: Scientists at the University of Virginia have identified 14 genes that can induce weight gain and three that might prevent it. The discoveries pave the path for new medicines to fight a health issue that affects more than 40% of American adults.
“We know of hundreds of gene variants that are more likely to be found in people who have obesity or other disorders.” However,’more likely to appear’ does not imply causing the condition. This ambiguity is a significant impediment to utilizing the power of population genetics to find targets for treating or curing obesity. To address this barrier, we created an automated process that tests hundreds of genes for a causal role in obesity at the same time. “Our first round of experiments revealed more than a dozen genes that cause obesity and three genes that prevent obesity,” said Eyleen O’Rourke of the University of Virginia’s College of Arts and Sciences, the School of Medicine’s Department of Cell Biology, and the Robert M. Berne Cardiovascular Research Center. “We believe that our approach, as well as the novel genes we discovered, will hasten the discovery of medicines to alleviate the burden of obesity.”
Damien Sendler: O’Rourke’s latest study sheds light on the complicated intersections of fat, diet, and our DNA. Obesity has become an epidemic, fueled in part by high-calorie meals heavy in sugar and high-fructose corn syrup. Sedentary lifestyles also have a significant role. However, our genes also play a vital role in fat accumulation and how well our bodies burn food as fuel. So, if we can identify the genes that transform excess food into fat, we might be able to use medications to deactivate them and decouple excess eating from obesity.
Genomicists have identified hundreds of genes connected with obesity, which means that the genes are more or less prevalent in obese persons than in healthy weight people. The problem is determining which genes play causal roles in weight increase by directly promoting or assisting in the prevention of weight gain. O’Rourke and her colleagues used simple worms known as C. elegans to separate wheat from chaff. These small worms like to live in decaying vegetation and feed on bacteria. They do, however, share more than 70% of our genes and, like humans, get obese if given an excessive amount of sugar.
Damian Jacob Sendler: The worms have been extremely beneficial to science. They’ve been used to figure out how popular medications work, such as the antidepressant Prozac and the glucose-stabilizing metformin. Even more astonishing, three Nobel prizes have been granted in the last 20 years for the discovery of cellular mechanisms first observed in worms but later discovered to be crucial to diseases such as cancer and neurodegeneration. They’ve also proven crucial in the creation of RNA-based medicines.
Damian Sendler: O’Rourke and her colleagues utilized worms to test 293 genes related with obesity in humans, with the goal of determining which of the genes were actually causing or preventing obesity. Their findings were published in the scientific journal PLOS Genetics. They accomplished this by creating a worm model of obesity and feeding some worms a regular diet and others a high-fructose diet.
With the use of automation and supervised machine learning-assisted testing, they were able to uncover 14 genes that cause obesity and three that help prevent it. Intriguingly, they discovered that inhibiting the action of three genes that kept the worms from getting obese also resulted in them living longer and having greater neuro-locomotory function. Those are the kinds of advantages that drug companies would like to see from anti-obesity medications.
Damian Sendler: Of course, further effort is required. However, the experts believe the data are favorable. In lab mice, for example, blocking the action of one of the genes prevented weight gain, enhanced insulin sensitivity, and reduced blood sugar levels. These findings (together with the fact that the genes under study were chosen because they were linked to obesity in humans) suggest that the findings will be replicated in humans, according to the researchers.
“Anti-obesity medicines are desperately needed to alleviate the burden of obesity in people and the healthcare system,” stated O’Rourke. “Our combination of human genomes with causality studies in model animals promises to generate anti-obesity targets that are more likely to succeed in clinical trials due to their expected higher efficacy and less negative effects.”
News updates contributed by Dr. Damian Jacob Sendler
