Ana Domingos
Portuguese neuroscientist
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Through Circulatory system and Paradigm
A trained mathematician, Domingos began her research career by pursuing a Ph.D. in neurobiology at Rockefeller University. Supervised by Leslie Voshall, Domingos studied the sensory systems facilitating our sense of smell. As a post-doctoral research scientist, Domingos worked under Jeffrey Friedman, investigating how one's metabolism can influence the brain circuitry involved in sweetener cravings.
Domingos founded her own laboratory in the Gulbenkian Institute in Portugal where she made a number of key discoveries. Firstly, her laboratory discovered that a hormone produced by fat, called leptin, interacts with the sympathetic nerves to control fat breakdown. Sympathetic nerves release a hormone called noradrenaline which is received by a molecular switch expressed by fat tissue, called a β-2 receptor. Activation of the β-2 receptor or "switch" causes the fat tissue to "burn off" as heat. Secondly, her laboratory was able to visualize how sympathetic neurons connect with fat tissue. Thirdly, the Domingos laboratory studied how "Pac-Man-like" immune cells close to sympathetic neurons, dubbed sympathetic associated macrophages, could contribute to obesity by absorbing the noradrenergic chemical signals sent by the sympathetic neurons to fat tissue.
Sympathomimetic drugs behave like the chemical signals produced by sympathetic neurons interacting with fat. Collaborating with scientists in The University of Cambridge, the Domingos' lab in Oxford hopes to improve upon sympathomimetics, by producing a class of compounds that do not interact with the central nervous or cardiovascular systems, thereby limiting side effects. These new and improved compounds are dubbed sympathofacilitators. To this end, the Domingos' group studies the circuit properties of sympathetic neural networks interact with fat and how they are regulated by immune cells, pioneering a new field of research coined Neuroimmunometabolism on which her lab has authored reviews.
Education
Between 1995 and 1999, Domingos studied mathematics up to MSc level at the University of Lisbon and in Paris. She then studied for a PhD in olfactory neuroscience at the Rockefeller University in New York City, supervised by Leslie B. Vosshall where she authored papers in Neuron and Current Biology.
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Career and Research
Between 2006 and 2013, Domingos did post-doctoral work with Jeffrey M. Friedman at the Rockefeller University. Domingos studied how metabolic signals affect neural circuitry underlying sweetener choices while in the Friedman lab, publishing several works.
She then returned to Portugal to work at the Obesity Laboratory of the Instituto Gulbenkian de Ciência in Oeiras near the Portuguese capital, Lisbon. While at Gulbenkian, the Domingos laboratory discovered that the sympathetic neuro-adipose axis mediates the liolytic effect of leptin. This discovery culminated in a seminal work, published in Cell in 2015. Following on from this discovery, the Domingos laboratory, provided the first visualization of adipose sympathetic neurons and demonstrated its necessity for fat mass reduction via norepinephrine signaling. Therefore, the Domingos group in Portugal characterized the peripheral efferent arm in the neuroendocrine loop of afferent leptin action in the brain. In Gulbenkian, Domingo's also discovered sympathetic neuron-associated macrophages (SAMs) contribute to obesity by importing and metabolizing norepinephrine.
In 2018, Domingos moved to Oxford in the UK to work at the Department of Physiology, Anatomy and Genetics (DPAG) of the University of Oxford as an associate professor in neuroscience. In 2022, Domingos advanced to the position of (full) Professor of Neuroscience where she heads a laboratory bearing her name. Her laboratory in Oxford, in a collaborative effort with the University of Cambridge, has developed a new class of anti-obesity compounds that could potentially avoid the harmful side effects of traditional treatments. Domingos aims to shift the treatment paradigm of obesity, through the development of a new class of anti-obesity drugs dubbed sympathofacilitators. Sympathofacilitators act as an energy sink by coupling thermogenesis to active heat dissipation. Sympathofacilitators improve upon sympathomimetic drugs by not interacting with the central nervous or cardiovascular systems, thereby limiting side effects.
Domingos also holds patents in the UK and US regarding pharmacological targeting of sympathetic associated macrophages to drive thermogenic activity.
Awards & Funding
Domingos leads a research laboratory consisting of three postdoctoral research scientists, four graduate (DPhil) students and a research assistant. Members of the Domingos laboratory have secured funding from Wellcome Immunology, the British Heart Foundation, Shineroad, NovoNordisk and Croucher Foundation to fund their projects.
As of 2023, the Domingos group is currently funded by competitive research grants from the Wellcome Trust, European Research Council, and the Pfizer ASPIRE Obesity Award. Notable previous prestigious awards include;
- 2023: American Physiological Society, Karl Ludwig Distinguished Lecture
- 2020: Marie Curie Postdoctoral Fellowship to fund project in Domingos group
- 2018: Marie Curie Postdoctoral Fellowship to fund project in Domingos group
- 2016: Human Frontiers Science Program
- 2015: EMBO, Young Investigator Installation Award
Media & Research Talks
Domingos promotes science communication. Listed below are a number of freely available research talks and media appearances.
- "Neuroimmunometabolism" by Ana Domingos at Global Immunotalks
- "Neuroimmunometabolism" by Ana Domingos at Oxford University Scientific Society
- "Optogenetics for neuroimmunity" by Ana Domingos at Society for Neuroscience
- "Mouse brains eavesdrop on their fat" by Alejandra Manjarrez, The New Scientist ft. Ana Domingos
- "Food for Thought" Ana Domingos interview on eLife