EASO Speaker Spotlight Interview – Ana Domingos

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Greetings Ana. It was good to meet you at the European Congress on Obesity in Gothenburg. Please tell us a bit about yourself; where are you from, where did you grow up? Where do you live now?

I was born in Lisbon, and grew up in Portugal until my early twenties, when I left for New York to study at the Rockefeller University at the turn of the second millennium. Two years before, I lived in Paris for a year while conducting part of my undergraduate studies in mathematics. I moved back to Portugal 2.5 years ago to set up my lab at the Gulbenkian Institute. Time flies! One year ago I married a charming Dutchman and moved to an apartment in a lovely historical building right at the beach. We just adopted a big, adorable puppy dog!

Our readers will enjoy learning about your favourite activities, hobbies and interests outside of your professional work:

In addition to my bench work, I am also committed to reaching the public. Scientific education for the general public is the most important means of preventing stigmatization and prejudice against patients with obesity.

My participation in the Media Masterclass workshop at the European Obesity Summit in June 2016, involvement with patient organizations and various local TV shows in Portugal, as well as art projects that involve the science, such the Nexus Project at the KunstKraftwerkLiepzig, in Liepzig,Germany are important parts of my work – and my community activities.

I love to cycle! I have been a cycling commuter since my days as a student in NYC, and now I bike to work everyday along the beach.

Where I live there are few bike commuters and a big car culture, even though the weather is great. Cycling is a very efficient way to get vitamin D, exercise, and reduce my carbon print. I´m sort of a bike activist! It´s my hobby, and it takes time and engages me with the local community. Often it is like talking to a wall, but I am persistent!

We would like to learn about your work. Tell us why leptin resistance is the topic everyone is talking about!

Leptin resistance is a disease model that conceptually resembles that of insulin resistance, drawing a parallel between obesity and type 2 diabetes. Leptin resistance explains the kind of obesity that does not derive from leptin deficiency. The later can be cured by leptin injections, just as insulin deficiency can be managed with insulin injections. However, insulin injections do not cure insulin resistance in type 2 diabetes. Likewise, leptin injections do not cure leptin resistance in most cases of obesity. Thus finding biological ways to get around leptin resistance in the brain, would pave the way for the development of anti-obesity therapies.

Please tell us about your lab and current research projects.

I have 6 great female scientists working with me. My graduate student Roksana Pirsgalska, who is a fellow of the MIT/Portugal PhD Program, pushed forward a series of results which were recently published in Cell. We discovered that sympathetic (SNS) neuro-adipose junctions mediate lipolysis and fat mass reduction, and are a peripheral effector arm of leptin action in the brain. We discovered that local stimulation of SNS inputs onto white adipose tissues (WAT)  induces fat break-down and its consequent depletion. Thus targeted pharmacologic activation of SNS inputs onto WAT could represent a new strategy for the induction of fat loss that would circumvent central leptin resistance as well as the challenges of drug delivery to the brain, across the blood brain barrier. In one of our projects we aim to identify drug targets in SNS neurons innervating WAT, which are suitable for an anti-obesity therapy. We are also modifying potent anti-obesity drugs so that they target these neurons, and become suitable for long term use, and sustained weight loss without severe side effects.

How did your original interest in the field develop, and how did you come to focus on obesity?

I became fascinated by the topic of obesity when I first heard a talk by Jeffrey Friedman before he came to be my postdoctoral mentor at the Rockefeller University. This was the first time I heard about Jeff´s discovery of the hormone leptin –  a breakthrough discovery that changed the way we think about obesity. Jeff´s discovery of leptin transformed obesity into a biological problem, rather than a lack of will power relating to food intake and exercise.  The way he then explained the molecular and biological basis of obesity was truly a revalation to me, creating a new reality that is still unknown to many patients and health care providers. Jeff has been a role model and a valuable guide along with my PhD advisor Leslie Vosshall. Both are unique and interesting personalities who create science that can change society.  For me, they have been really inspiring.

Biography:

Before receiving a PhD in neurobiology working with Leslie Vosshal at New York’s Rockefeller University, Dr Ana Domingos studied mathematics at the Universty of Lisbon. She started her obesity research career in 2006 at Rockefeller as a postdoctoral associate of Jeffrey Friedman, who discovered the hormone Leptin. As a postdoc, Dr Ana Domingos used optogenetic tools to identify a neuronal circuit in the brain mediating the reward value of sugar. She discovered that Leptin has a regulatory effect on this circuit, influencing how much one likes sugar. In the fall of 2013, she started the obesity lab at The Gulbenkian Institute in her native Portugal. Domingos´ lab was the first to visualize the long-time conjectured peripheral neuron-adipose junctions in the adipose tissue. Furthermore, her lab demonstrated that localized activation of these peripheral neurons is sufficient for lipolysis and fat mass reduction. Thus direct and targeted pharmacologic activation of sympathetic inputs to adipose tissues could represent a novel strategy for the induction of fat loss, and a new anti-obesity therapy that would circumvent the challenges of drug delivery to the brain.

These findings were published in Cell, and were widely disseminated in Nature and Science as well as Cell Press. Dr Ana Domingos has received widespread international recognition, including awards from The Human Frontiers Science Program and the European Molecular Biology Organization.

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