PhD MARGARITA CALVO

DIRECTOR OF THE MILLENIUM NUCLEUS MINUSPAIN

ACADEMIC DEGREE: DOCTOR IN NEUROSCIENCE AT KING’S COLLEGE LONDON

HOST INSTITUTION: PONTIFICIA UNIVERSIDAD CATÓLICA DE CHILE.

RESEARCH LINES: NEUROPATHIC PAIN MECHANISMS

CONYCYT RESEARCHER: LINK

CONTACT: mcalvob@uc.cl

BIOGRAPHY

Medical doctor from Pontificia Universidad Católica de Chile (2006). She completed a Master in Pain Management and then a PhD in Neuroscience at King’s College London (2010) under the supervision of Dr David Bennett. Later, she did a post-doctorate at the IMI EuroPain Consortium at Oxford University / King’s College London.

She recently completed a master’s degree in diseases of the peripheral nervous system in Milan (sponsored by the Peripheral Nerve Society). She is currently an Associate Professor at the Faculty of Biological Sciences of the Pontificia Universidad Católica de Chile and Director of the Núcleo Milenio MiNuSPain. Her laboratory is dedicated to research in neuropathic pain, which is complemented by her clinical work at the Pain Unit at the UC Christus University Hospital (Chile).

Brief History:

My research aim is to gain a better understanding of the response of the nervous system to injury in order to develop strategies to promote peripheral nerve repair and to prevent the development of neuropathic pain. This is complementary to my clinical interest in neuropathic pain and as such links with my clinical service at the Pain Unit at UC-Christus.

I employ a variety of techniques including cell culture, preclinical transgenic models and transcriptional profiling as well as biomarkers, and psychophysical studies in pain patients.

My PhD training was done at King’s College London under the supervision of Prof. David Bennett. I focused on understanding the role of the immune system in the generation of neuropathic pain. We published this work in high impact journals including Lancet Neurology (Calvo et al., 2012; 290 citations), Experimental Neurology (Calvo et al., 2012; 145 citations), Journal of Neuroscience (Calvo et al., 2010; 134 citations), and Glia (Calvo et al., 2011; 97 citations).

My postdoctoral training was at the EuroPain IMI consortium (https://www.imi.europa.eu/content/europain) under the supervision of Prof. David Bennett at Oxford University and Prof. Steven McMahon at King’s college London. We collaborated with several academic and industry groups within Europe and published four papers on animal models of chronic pain (Pain 2013; 77 citations, Pain 2016; 7 citations, Scandinavian Journal of Pain 2015; 9 citations, Science Translational medicine 2011, 84 citations).

In 2014, I moved back to my home country Chile and was granted funding from Conicyt to start my own laboratory. Together with the Early Career Research grant given to me by the International Association for the study of pain (IASP) in 2014, I was able to start my work at Pontificia Universidad Católica de Chile, where I am an Associate Professor.

Nowadays, I have a very functional and productive lab funded by a Fondecyt Regular, EB partnership and Debra international, and composed by 3 undergraduate students, 4 PhD students, and 2 lab technicians.

Currently I have two lines of research, both of which are highly translational. The first one is investigating how axonal degeneration of sensory afferents in the skin can produce neuropathic pain. We investigated a cohort of patients with Epidermolysis Bullosa (EB), a skin condition that produces severe blistering with consequent damage to skin fibers. We demonstrated that these patients suffer from a small fiber neuropathy, which is the cause of their chronic pain (von Bischhoffshausen et al., 2017, Brain, 9 citations). We are now investigating targets involved in the lack of regeneration of skin fibers after damage. Degeneration of skin fibres produces pain not only in EB but also in several common conditions such as painful diabetic neuropathy or chemotherapy induced neuropathy, and therefore understating the mechanisms will have a big impact in the treatment of chronic pain.

My other line of research is investigating the role of Kv1 potassium channels in modulation of chronic pain. In situations of axonal damage and consequent pain, these channels disappear and a neuronal hyperexcitation is generated, both in rodents and patients. But chronically following axonal damage, other Kv1 subtypes are expressed that are capable of inhibiting hyperexcitability and pain. We recently published these results in eLife (Calvo et al., 2017; eLife, 15 citations) and we are continuing this research with funds from a Fondecyt Regular 2016-2020.

My work has been done in collaboration mainly with groups in the UK (Prof. D.Bennett at Oxford University; Prof S. McMahon at King’s College London) and in Chile (Dr. Rodolfo Madrid USACH; Dr F. Court, Universidad Mayor). I have been invited to give lectures and chair sessions at: the 7th International Congress in Neuropathic pain (NeuPSIG 2019, London UK), the 17thWorld Congress in Pain (IASP 2018, Boston, USA), the 6th International Congress in Neuropathic pain (NeuPSIG 2017 Gothenburg, Sweden), the 16thWorld Congress in Pain (IASP 2016, Yokohama Japan), Neuropathic Pain Special Interest group (NeuPSIG, Santiago Chile 2014, Nice France 2015, and Gothenburg Sweden 2017), European Pain Federation, (EFIC 2015, Vienna Austria), and Peripheral Nerve Society (PNS, Saint Malo, France 2013, Sitges Spain 2017).

I am currently supervising 22 undergraduate students in their thesis and 4 PhD students. Until this year I was a member of the EarlyCareer Advisory Group of eLife (https://elifesciences.org/community). I am an IASP councilor member of the management board of NeuPSIG, member of the editorial board of PRF, and a member of the SIG Task Force Members of the IASP. I am a regular member of IASP, the NeuPSIG, the PNS, Sociedad de Biología Celular de Chile, and Asociación Chilena Estudio del Dolor.

PUBLICATIONS

Headline: Recessive dystrophic epidermolysis bullosa results in painful small fibre neuropathy
Headline: Altered potassium channel distribution and composition in myelinated axons suppresses hyperexcitability following injury
Headline: The role of the immune system in the generation of neuropathic pain
Headline: CXCL5 mediates UVB irradiation–induced pain

Headline: Neuregulin-ErbB signaling promotes microglial proliferation and chemotaxis contributing to microgliosis and pain after peripheral nerve injury

Headline: Following nerve injury neuregulin-1 drives microglial proliferation and neuropathic pain via the MEK/ERK pathway

Headline: La genética del dolor neuropático: desde los modelos animales a la aplicación clínica

GALLERY