During my 2nd postdoc (Paris)

1. Autophagy as a novel therapy for age-related cognitive decline.

2. Effect of the systemic milieu in nervous system functions.

During my 1st postdoc (Barcelona)

1. 1.  Elucidate the hypoalgesic effects of NeuroHeal in neuropathic pain after peripheral nerve injury. We explored the effects of NeuroHeal in two in vivo models of neuropathic pain. Moreover, we observed that NeuroHeal may reduce painful sensations by the modulation of P2X4-BDNF-KCC2 pathway.

   2. Describe the effects of SIRT2 inhibition and its downstream mechanisms in motor axon regeneration after peripheral nerve injury. We used KO SIRT2 mice and in vitro models to analyze the role of SIRT2 in neuritogenesis and motor recovery after nerve injury. Here, we observed that the blockage of  SIRT2 promotes a p300-dependent axonal growth that includes GAP43 levels.

   3. SIRT1/Hif1a-dependent autophagy to recover proper function after a  peripheral nerve injury. SIRT1 is translocated to the cytosol when motoneurons need to regenerate their axon. This, promotes the stabilization of Hif1, which leads to an increase in autophagy flux that enhances motor regeneration after nerve injury.

   4. Elucidate the effects of NeuroHeal in muscle atrophy models. We deciphere the capacity of NeuroHeal to reduce muscle atrophydue to neurogenic denervation or disuse of the limbs. We observed that NeuroHeal modulates the autophagy associated with muscle atrophy.

During my PhD

1. Analyze the potential of Systems biology and artificial intelligence approaches to discover novel drug therapies for nervous trauma. With the aid of in vivo models of peripheral nerve injury, Systems biology, and artificial intelligence, we obtained novel drug therapies to neuroprotect motoneurons after nerve root avulsion. Afterthat, we discovered NeuroHeal therapy, which has wide-range protective effects (increases neuronal survival, activates Sirtuin1, promotes regeneration, and reduces gliosis).

2. Importance of SIRT2 and SIRT1 in MN death and neuronal endoplasmic reticulum stress. We used pharmacological treatments and transgenic mice (overexpressing SIRT1 or KO for SIRT2) to analyze the role of SIRT1 and SIRT2 in motoneuronal death after hypoglossal nerve axotomy and under endoplasmic reticulum stress.  Strikingly, we depictured that SIRT2 activity facilitates neuronal survival by modulating microglial reaction.

3. Role of SIRT1-dependent autophagy in neonatal motoneurons death.  We took advantage of an in vivo model of neonatal motoneuron death, to test the anti-apoptosis effects of NeuroHeal. We observed that NeuroHeal fine-tunes autophagy by SIRT1/AKT/FOXO3a axis, which reduces apoptosis and leads to increased neuronal survival after nerve injury during neonatal stages.