Using human pluripotent stem cells to model obesity in vitro│Dr. Florian Merkle

Summary: Obesity and neurodegeneration lead to millions of premature deaths each year and lack broadly effective treatments. Obesity is largely caused by the abnormal function of cell populations in the hypothalamus that regulate appetite. We have developed methods to generate human hypothalamic neurons from hPSCs to study how they respond to nutrients and hormones (e.g. leptin) and how disease-associated mutations alter their function. Since human hypothalamic neurons can be produced in large numbers, are functionally responsive, have a human genome that can be readily edited, and are in culture environment that can be readily controlled, there is an unprecedented opportunity to study the genetic and environmental factors underlying obesity. In addition, we are fascinated by the fact that mid-life obesity is a risk factor for dementia later in life, and caloric restriction, exercise, and certain anti-obesity drugs are neuroprotective, suggesting that there are shared mechanisms between obesity and neurodegeneration. Studies of HPSC-derived hypothalamic neurons may help bridge the mechanistic gulf between human genetic data and organismic phenotypes, revealing new therapeutic targets. Speaker Bio: Dr Florian Merkle obtained his B.Sc. in Biology from the California Institute of Technology in 2002, and a PhD in Neuroscience at the University of California, San Francisco in 2007 where he determined the lineage and potential of adult neural stem cells in the mouse brain. Florian then joined the laboratories of Kevin Eggan and Alex Schier at Harvard University, where he coordinated efforts to sequence the genomes of over 100 human pluripotent stem cell (hPSC) lines, was one of the first to demonstrate the efficient genome editing of hPSCs with CRISPR/Cas9 and pioneered protocols to differentiate them into hypothalamic neurons that regulate energy homeostasis and are of pivotal importance to obesity. In 2015, Florian joined the University of Cambridge where his laboratory has combined these tools to generate novel disease models of obesity. In particular, the Merkle laboratory studies the impact of environmental factors and obesity-associated mutations on the function of hPSC-derived hypothalamic neurons to uncover mechanisms that might be targeted to develop novel treatments for obesity. Florian is honoured to be a Roberston Investigator from the New York Stem Cell Foundation, and to be supported by the Chan Zuckerberg Initiative, Wellcome Trust, and Medical Research Council. Moderator: Mahmoud Maina, PhD, University of Sussex, UK. https://en.wikipedia.org/wiki/Mahmoud... Coordinator: Mosab Ali Awadelkareem, Al-Neelain University, Sudan. Society of Neuroscientists of Africa – SONA: https://sonafrica.org/   / sonaorg     / society-of-neuroscientists-of-africa-sona-...      / @societyofneuroscientistsof385   TReND in Africa: https://trendinafrica.org/ https://www.flickr.com/photos/trendin... https://twitter.com/trendinafrica?lan...   / trendinafrica   Worldwide Neuro: https://www.worldwideneuro.com/   / worldwideneuro