Jose lopez barneo

2005-present. Member of External Advisory Board of
Institute of Research Vall de Hebron (Barcelona).

2008-present. Member of external
Advisory Board of research
institutes in hospitals: Ramón
y Cajal (Madrid), San Pau (Barcelona), La Princesa (Madrid), Biodonostia (San Sebastián), Aragonés de Ciencias de la Salud
(Zaragoza), Biomedicine (Salamanca).

2010-present. Member of the
External Advisory Board of
the Ludwig Boltzmann Institute
for Pulmonary Vascular Research, Graz, Austria.

2007-2011 President of the Spanish Society of Gene and Cell Therapy.

3.3. Honors and awards

1978 Award of the University of Seville to the M.D and Ph. D. Theses

1993 National Research Award “King Juan Carlos I” in Science and Technology
1994 Medal of the Andalusian Government

1994 Wellcome Visiting Professorship Award. University
of Minnesota. USA 1998 National Research Award “King Jaime I” in Science and Technology
2000 National Research Grant of the Juan March Foundation

2002 Research prize "Maimónides" awarded by the
Andalusian Government 2003 Honorary Lecture "Teófilo Hernando",
Autonomous University of Madrid 2003 National Research Prize of the Lilly
Foundation

2003 Medal of the Spanish Ministry of Health

2004 Member of the “Real Academia de Ciencias de Sevilla”

2005 Corresponding member of the “Real Academia Española de Ciencias Exactas y
Naturales” 2006 Research prize Javier Benjumea awarded by
the Focus-Abengoa Foundation

2009 Prize FAMA to the Research Career by
the University of Seville

2010 Award Medal and Lectures “Chair Grisolía”, Foundation “Ciudad
de las Artes y las Ciencias”, Valencia. 2010 Honorary
Lecture “Carmen and Severo Ochoa”, Foundation “Carmen and Severo Ochoa”, Madrid

2012 Member of the “Real Academia de Medicina y
Cirugía de Sevilla”.

4.      Scientific/academic activity
and fields of interest

After obtaining his M.D degree, Dr. Lopez-Barneo combined for a short time his Ph.D. studies with work as a
family doctor. However, he
soon became a full time
investigator. His first research
interest was the neurophysiology of the oculomotor and vestibular systems using extracellular recordings in awake cats. He was
one of the pioneers of modern neurophysiological research in Spain. His most significant contribution was the
identification of neurons in the nucleus prepositus hypoglossi whose firing rate encoded eye velocity and position.
This work demonstrated that the prepositus nucleus, located in the lower brainstem, is a major center for gaze
control in mammals (see the most relevant contribution of this period in Lopez-Barneo et al., J. Neurophysiol.,
1982).

During his postdoctoral work at the U.S.A., Dr. Lopez-Barneo performed the most complete electrophysiological
study to date of the parathyroid gland. This work suggested the existence in parathyroid cells of a divalent cation
membrane receptor to explain
the dependence of parathyroid
hormone secretion on extracellular
calcium concentration (Lopez-Barneo &
Armstrong, J. Gen. Physiol.,
1983). This seminal observation
served of inspiration for the cloning of the receptor (that besides in the parathyroid gland is also found in neurons and other
cell types) and the opening of a new field of cellular physiology.
During this time Lopez-Barneo became also interested in the study of ion channels in the squid giant axon and the intrinsic electrophysiological properties of
central neurons (representative examples of the work performed in this period are in Armstrong
& López Barneo, Science, 1987; Lopez-Barneo & Llinas, J. Neurophysiol., 1988).

In 1983 Dr. Lopez-Barneo established an independent research group in the University of Seville aiming to the
study of ion channel function and modulation in different neuronal and non-neuronal preparations. His laboratory
was among the first to
set up in Spain several
techniques, now broadly used
in the study of cell
physiology, such as voltage and patch-clamping, amperometry
and microfluorimetry in single dispersed cells as well as in fresh
slice preparations. In subsequent years, the laboratory incorporated a whole set of molecular and cell biology
methodologies. The most relevant scientific achievements of Dr. Lopez-Barneo’s group are:

1. Analysis of the intrinsic electrical properties of septal neurons and their relationship with the generation of the
   theta rhythm (Alvarez de Toledo & Lopez-Barneo, J. Physiol., 1988). This work also included recordings of
   intradendritic action potentials, which are among the first ever performed.
2. Identification of the first oxygen-sensitive potassium channels in glomus cells of the carotid body. This pioneer
   work, summarized in several publications (e.g. Lopez-Barneo et al., Science, 1988; Ganfornina & Lopez-Barneo,
   PNAS, 1991; Ureña et al., PNAS, 1994), served not only to explain the chemosensory properties of the carotid
   body but, in addition, stimulated research on acute oxygen sensing in other organs. Acute oxygen sensing has
   become a quite attractive area of modern cellular physiology and pathophysiology (see Lopez-Barneo et al., Ann.
   Rev. Physiol. 2001; Weir et al., N. Eng. J. Med. 2005).
3. During a sabbatical stay
   at Stanford University, Dr. Lopez-Barneo
   worked on the identification
   of the molecular determinants for C-type inactivation and the interaction of external cations with the outer mouth of
   potassium channels. His observations,
   of major impact in the
   field (see Lopez-Barneo et
   al., et al., Receptor and Channels,
   1993), were followed by several contributions on the structure/function relationship in ion channels
   done at his laboratory in Spain. Among these, the most representative was the identification of the first non-
   conducting regulatory alpha subunit in potassium channels (Castellano et al., J.
   Neurosci. 1997).
4. A further step toward the full understanding of carotid body physiology was the development of the carotid
   body slice preparation (Pardal et al., PNAS, 2000). This allowed to show that, besides sensing changes of blood
   oxygen tension, carotid body glomus cells are also physiologically relevant glucose receptors (Pardal & Lopez-
   Barneo, Nature Neurosci., 2002; García-Fernández et al., Diabetes, 2007).
5. In parallel with the studies of the effect of acute hypoxia on ion channels, Lopez-Barneo’s group has also
   explored the possibility that ion channel-encoding genes are upregulated by chronic hypoxia. The first ion channel
   gene shown to be upregulated by hypoxia-inducible transcription factors is the T-type (alpha 1H subunit) calcium
   channel (del Toro et al., J. Biol. Chem., 2003). This group has also reported that the maxi-K+ channel beta1
   subunit (a gene whose expression is almost restricted to the cardiovascular system) is down regulated by chronic
   hypoxia (Navarro-Antolin et al., Circulation, 2005). This observation helps to explain why in some chronically
   hypoxic subjects (as for example in sleep apnea patients) altered vasoregulation can lead to hypertension. It also
   helps understand the mechanisms underlying hypoxic conditioning in heart muscle (Bautista et al., Circ. Res.
   2009).
6. The studies on smooth muscle cells have lead Lopez-Barneo’s group to the description of a new metabotropic
   role for voltage gated
   calcium channels, which might
   have major physiological and
   clinical interest. In the absence
   of calcium influx, activation
   of L-type calcium channels
   induce in arterial smooth muscle
   cells stimulation of the G protein-phospholipase C pathway, inositol trisphosphate production and calcium release (del
   Valle-Rodriguez et al., EMBO J., 2003; del Valle Rodriguez et al., PNAS, 2006, Fernández-Tenorio et al., Circ.
   Res. 2010, 2011).
7. The dopaminergic nature of carotid body cells suggested that they could be used for cell therapy applied to
   Parkinson’s disease. In 1997 Dr. Lopez-Barneo’s laboratory initiated a quite original project designed to test the
   efficacy of intrastriatal autotransplants of glomus cells to improve parkinsonism. The excellent results observed in
   preclinical research in rodents (Espejo et al., Neuron, 1998; Toledo-Aral et al., J. Neurosci., 2003) and monkeys
   (Luquin et al., Neuron, 1999) models, lead to carry out two pilot clinical trials in patients. A first safety trial, with
   moderately optimistic results, (Arjona et al., Neurosurgery, 2003) was followed by a second trial using PET-scan
   analysis (Minguez-Castellano et al., J. Neurol. Neurosurg. Psychiatry 2007). The technology used to prepare
   dopaminergic glomus cells and their transplantation to Parkinson’s patients is being refined based on the ability of
   carotid bodies to be expanded
   in vitro using stem
   cell techniques. Recently, Dr.
   López-Barneo’s group has reported
   the discovery of stem cells
   in the carotid body (Pardal
   et al., Cell, 2007). This
   is the first time neurogenesis
   is observed in the adult
   peripheral nervous system in
   mammals, an observation that
   may boost further developments on cell therapy applied to neurological disorders. Indeed, a patent derived from the stem cell
   work performed by Dr. López-Barneo’s group has been licensed by a biotechnological company, with the idea of
   facilitating the transference of this basic research to the clinics.
8. The increase in funding
   (mainly due to grants awarded
   by the Juan March and
   the Marcelino Botín Foundations allowed Dr. Lopez-Barneo’s group to setup independently the infrastructure necessary for the design
   and generation of genetically
   modified mice. The first
   knockout (Piruat et al., Mol.
   Cell. Biol., 2004) and
   transgenic (Mejias et al., J.
   Neurosci., 2006) mice ever
   produced in southern Spain have
   already been published. In
   addition, several other genetic
   animal models are being generated
   to study the mechanisms
   of oxygen sensing as well the processes underlying both cell death and neuroprotection in the nigrostriatal pathway.
   Recently, the absolute requirement
   of GDNF for maintenance of
   adult catecholaminergic neurons has
   been published (Pascual et al., Nature Neurosci, 2008). Identification of the GDNF-producing cells in the rodent striatum has also been
   recently achieved (Hidalgo-Figueroa et al., J. Neurosci. 2012). Other animal models with major phenotype are
   under study.

The research work of Dr. Lopez-Barneo has been published in more than 150 publications in highly ranked
international journals indexed in
PubMed and books. He has
given numerous lectures and
seminars in international meeting and research institutions all over the world. Dr. Lopez-Barneo is one of the most cited
physiologists in Spain and has been (or is being) serving as a member in the editorial committees of the most
prestigious international journals
in Physiology (Journal of Physiology,
Pflügers Archives, Physiological Reviews,
Physiology, etc).

In parallel with his research career, Dr. Lopez-Barneo has carried out an intense academic activity with a high
teaching load to medical and graduate students. He has already sponsored 25 Ph.D. students and more that 20
postdocs from Spain, the
USA and several other countries.
Numerous former Lopez-Barneo’s graduate
students are currently either physiology full/assistant professors or staff clinicians in Spanish hospitals and universities.
From the beginning of his career, Dr. Lopez-Barneo has been fully committed to the development of independent
research in Andalusia, a Spanish region with little academic tradition. Dr. Lopez Barneo’s has also devotedly
worked for the development of high quality biomedical research within the university hospitals, to favor the
connection between basic research and clinical practice. He has greatly contributed to the creation of one of the
first biomedical institutes (Instituto de Biomedicina de Sevilla) that bas been built within a Spanish university
hospital. Dr. Lopez-Barneo has also served as coordinator of the ENI (European Neuroscience Institute) in Seville
and from 2007-2010 he was Director of the National Center of Excellence for Research on Neurodegenerative
Diseases (CIBERNED).

1. List of 50 selected publications
   
   
   
   1. López-Barneo J, Darlot C, Berthoz A, Baker R. Neuronal activity in the prepositus nucleus correlated with eye
      movements in the alert cat. Journal of Neurophysiology
      1981; 47: 329-352.
   2. López-Barneo J, Armstrong CM. Depolarizing response of rat parathyroid cells to divalent cations.
      Journal of General Physiology
      1983; 82: 269-294.
   3. Armstrong CM, López-Barneo J. External calcium ions are required for potassium channel gating in squid
      neurons. Science 1987; 236: 712-714.
   4. Alvarez de Toledo G, López-Barneo J. Ionic basis of the differential neuronal activity of guinea pig septal
      nucleus studied "in vitro". Journal of Physiology
      1988; 396: 399-415.
   5. López-Barneo J, López-López J, Ureña J, González, C. Chemotransduction in the carotid body: potassium
      current modulated by pO₂ in type I chemoreceptor cells.
      Science 1988; 241: 580-582.
   6. López-Barneo J, Llinás R.
      Electrophysiology of mammalian tectal
      neurons "in vitro". I.
      Transient ionic conductances. Journal of Neurophysiology
      1988; 60: 853-868.
   7. López-López J, González C, Ureña J, López-Barneo J. Low pO₂
      selectively inhibits K⁺ channel activity in chemoreceptor
      cells of the mammalian carotid body. Journal of General Physiology
      1989; 93: 1001-1015.
   8. López-Barneo J, Castellano J, Toledo-Aral J. Tyrotropin-releasing-hormone and its physiological derivative
      TRH-OH inhibit Na⁺ channel activity in septal neurons. Proceedings of the National Academy of Sciences
      (USA) 1990; 87: 8150-8154.
   9. Ganfornina MD, López-Barneo J. Single K⁺ channels in membrane patches of arterial chemoreceptor cells are
      modulated by O₂ tension. Proceedings
      of the National Academy of Sciences
      (USA). 1991; 88: 2927-2930.
   10. Ganfornina MD, López-Barneo J. Potassium channel types in arterial chemoreceptor cells and their selective
       modulation by oxygen. Journal of General Physiology
       1992; 100: 401-426.
   11. López-Barneo J, Hoshi T, Heinemann S, Aldrich RW. Effect of external cations and mutations in the pore
       region on C-type inactivation of Shaker
       potassium channels. Receptors and Channels
       1993; 1: 61-71.
   12. Ureña J, Fernández-Chacón R, Benot A, Alvarez de Toledo G, López-Barneo J. Hypoxia induces voltage-
       dependent Ca²⁺ entry and quantal dopamine secretion in carotid body glomus cells.
       Proceedings of the National Academy
       of Sciences (USA) 1994; 91:10208-10211.
   13. Franco-Obregón A, Ureña J, López-Barneo J. Oxygen-sensitive calcium channels in vascular smooth muscle
       and their possible role in hypoxic arterial relaxation. Proceedings of the National Academy of Sciences (USA)
       1995; 92: 4715-4719.
   14. Montoro R, Ureña J,
       Fernández-Chacón R, Alvarez de
       Toledo G, López-Barneo J. O₂-sensing by
       ion channels and chemotransduction in single glomus cells.
       Journal of General Physiology 1996; 107: 133-143.
   15. Franco-Obregón A, López-Barneo J. Differential oxygen-sensitivity of calcium channels in smooth muscle
       cells of conduit and resistance pulmonary arteries. Journal
       of Physiology 1996; 491: 511-518.
   16. López-Barneo J. O₂-sensing by ion channels and the regulation of cellular functions.
       Trends in Neurosciences 1996; 19: 435-440.
   17. Molina J, Castellano A, López-Barneo J. Pore mutations in Shaker
       K+ channels distinguish between the sites of TEA blockade and C-type inactivation.
       Journal of Physiology 1997; 499: 361-367.
   18. Castellano A, Chiara MD, Mellström B, Molina A, Monje F, Naranjo JR,
       López-Barneo J. Identification and functional characterization of a K⁺ channel a-subunit with regulatory properties specific of
       brain. The Journal of Neuroscience
       1997; 17: 4652-4661.
   19. Espejo EF, Montoro RJ, Armengol JA, López-Barneo J. Cellular and functional recovery of parkinsonian rats
       after intrastriatal transplantation of carotid body
       cell aggregates. Neuron 1998; 20: 197-206.
   20. Luquin R, Montoro R, Guillén J, Saldise L, Insausti R, del Río J,
       López-Barneo J. Recovery of chronic parkinsonian monkeys after autotransplants of carotid body
       cell aggregates. Neuron 1999; 22: 743-750.
   21. Pardal R, Ludewig U,
       García-Hirschfeld J, López-Barneo J.
       Secretory responses to hypoxia
       and tetraethylammonium of intact
       glomus cells in thin slices
       of rat carotid body. Proceedings
       of the National Academy
       of Sciences (USA) 2000; 97: 2361-2366.
   22. Ortega-Sáenz P, Pardal R,
       Castellano A, López-Barneo J.
       Collapse of conductance is prevented
       by a glutamate residue conserved in voltage-gated
       K+ channels. Journal of General Physiology 2000; 116: 181-190.
   23. López-Barneo J, Pardal R, Ortega-Sáenz P. Cellular mechanisms of oxygen-sensing.
       Annual Review of Physiology 2001; 63:259-287.
   24. Pardal R, López-Barneo J. Low glucose-sensing cells in the carotid body.
       Nature Neuroscience 2002; 5: 197- 198.
   25. Toledo-Aral J, Méndez-Ferrer S,
       Pardal R, Echevarría M,
       López-Barneo J. Throfic restoration
       of the nigrostriatal dopaminergic
       pathway in long-term carotid
       body grafted parkinsonian rats.
       The Journal of Neuroscience 2003;
       23: 141-148.
   26. Ortega-Sáenz P, Pardal R, García-Fernández M, López-Barneo, J. Rotenone selectively blocks sensitivity to
       hypoxia in rat carotid body glomus cells.
       Journal of Physiology 2003; 548: 789-800.
   27. del Toro R, Levitsky
       C, López-Barneo J, Chiara MD.
       Induction of T-type calcium
       channel gene expression by chronic hypoxia.
       Journal of Biological Chemistry 2003; 278: 22316-22324.
   28. Arjona V, Mínguez-Castellanos A, Montoro RJ, Ortega A, Escamilla F, Toledo-Aral JJ, Pardal R, Méndez-
       Ferrer S, Martín JM, Pérez M, Katati MJ, Valencia E, García T, López-Barneo J. Autotransplantation of carotid
       body cell aggregates for treatment of Parkinson's disease.
       Neurosurgery 2003; 53:321-330.
   29. López-Barneo J. Oxygen and glucose sensing by carotid body cells.
       Current Opinion in Neurobiology 2003; 13: 493-499.
   30. Del Valle-Rodríguez A, López-Barneo
       J, Ureña J. Ca²⁺
       channel-sarcoplasmic reticulum coupling: a
       mechanism of arterial myocyte contraction without Ca2+ influx. EMBO
       Journal 2003; 22: 4337-4345.
   31. Piruat J, Pintado CO, Ortega-Sáenz P, Roche M, López-Barneo J. The mitochondrial
       SDHD gene is required for early embryogenesis and its partial deficiency results in persistent carotid body glomus cell activation with full
       responsiveness to hypoxia. Molecular and Cellular Biology
       2004; 24: 10933-10940.
   32. Villadiego J, Méndez-Ferrer S,
       Valdés-Sánchez T, Silos-Santiago I, Fariñas I, López-Barneo J, Toledo-Aral
       JJ. Selective glial cel line-derived neurotrophic factor production in adult dopaminergic carotid body cells
       in situ and after intrastriatal transplantation.
       The Journal of Neuroscience 2005; 25: 4091-4098.
   33. Muñoz-Cabello A, Toledo-Aral JJ, López-Barneo J, Echevarría M. Rat adrenal chromaffin cells are neonatal
       CO₂ sensors. The Journal of Neuroscience
       2005; 25: 6631-6640.
   34. Navarro-Antolín^, J, Levitsky KL, Calderón E, Ordóñez A, López-Barneo J. Decreased expression of maxi-K⁺
       channel b1 subunit and altered vasoregulation in hypoxia. Circulation 2005; 112: 1309-1315.
   35. Weir EK, López-Barneo J, Buckler K, Archer S. Acute Oxygen Sensing.
       New England Journal of Medicine 2005; 353: 1042-1055.
   36. del Valle-Rodríguez A, Calderón E, Ruiz M, Ordoñez A, López-Barneo J, Ureña, J. Metabotropic Ca2+-
       channel induced Ca2+ release and ATP-dependent facilitation of arterial myocyte contraction.
       Proceedings of the National Academy
       of Sciences (USA) 2006; 103: 4316-4321.
   37. Mejías R, Villadiego J, Pintado CO, Vime PJ, Gao L, Toledo-Aral J, Echevarría M, López-Barneo, J.
       Neuroprotection by transgenic expression of glucose-6-phosphate dehydrogenase in dopaminergic nigrostriatal
       neurons of mice. The Journal of Neuroscience
       2006; 26: 4500-4508.
   38. Ortega-Sáenz P, Pascual A, Gómez R,   López-Barneo J. Acute oxygen sensing in heme oxygenase-2 null
       mice. The Journal of General Physiology 2006;128: 405-411.
   39. Minguez-Castellanos A, Escamilla-Sevilla
       F, Hotton GR, Toledo-Aral JJ, Ortega-Moreno A, Mendez-Ferrer
       S, Martin-Linares JM, Katati MJ, Mir P, Villadiego J, Meersmans M, Perez-Garcia M, Brooks DJ, Arjona V,
       López-Barneo J. Carotid body autotransplantation in Parkinson disease: A clinical and PET study.
       Journal of Neurology, Neurosurgery and Psychiatry, 2007; 78: 825-831.
   40. Echevarría M, Muñoz-Cabello A M, Sánchez-Silva R, Toledo-Aral JJ, López-Barneo J. Development of
       cytosolic hypoxia and HIF stabilization are facilitated by aquaporin-1 expression.
       Journal of Biological Chemistry 2007; 282:30207-30215.
   41. Pardal R, Ortega-Sáenz P, Duran R, López-Barneo J. Glia-like stem cells sustain physiologic neurogenesis in
       the adult carotid body. Cell 2007;131:364-377.
   42. García-Fernández M, Ortega-Sáenz P, Castellano A, López-Barneo J. Mechanisms of low-glucose sensitivity
       in carotid body cells. Diabetes
       2007; 56:2893-2900.
   43. Pascual A, Hidalgo-Figueroa M,
       Piruat JI, Pintado CO,
       Gómez-Díaz R, López-Barneo J.
       Absolute requirement of GDNF for adult catecholaminergic neuron survival.
       Nature Neuroscience, 2008; 11:755-761.
   44. Levitsky KL, López-Barneo J. Developmental change of T-type Ca2+ channel expression and its role in rat
       chromaffin cell responsiveness to acute hypoxia. Journal of Physiology, 2009; 587:1917-1929.
   45. Fernández-Tenorio M, González-Rodríguez P, Porras C, Castellano A, Moosmang S, Hofmann F, Ureña J,
       López-Barneo J. Genetic ablation
       of L-type Ca²⁺ channels
       abolishes depolarization-induced Ca²⁺
       release in arterial smooth muscle.
       Circulation Research, 2010; 106: 1285-1289.
   46. Ortega-Sáenz P, Levitsky KL, Marcos-Almaraz MT, Bonilla-Henao V, Pascual A, López-Barneo J. Carotid
       body chemosensory responses in mice deficient of TASK channels. Journal of General Physiology, 2010; 135:
       379-392.
   47. Fernández-Tenorio M, Porras-González C, Castellano A, Del Valle-Rodríguez A, López-Barneo J, Ureña J.
       Metabotropic regulation of RhoA/Rho-associated
       kinase by L-type Ca2+
       channels: new mechanism for depolarization-evoked
       mammalian arterial contraction. Circulation Research, 2011;108(11):1348-1357.
   48. Hidalgo-Figueroa* M, Bonilla* S, Gutiérrez F, Pascual A, López-Barneo J. GDNF is predominantly expressed
       in the PV+ neostriatal interneuronal ensemble in normal mouse and after injury of the nigrostriatal pathway.
       The Journal of Neuroscience, 2012, 32:864-87.
   49. Romero-Ruiz A, Bautista L, Navarro V, Heras-Garvín A, March-Díaz R, Castellano A, Gómez-Díaz R, Castro
       MJ, Berra E, López-Barneo
       J, Pascual A. Prolyl hydroxylase-dependent
       modulation of eukaryotic elongation
       factor 2 activity and
       protein translation under acute
       hypoxia. Journal of Biological
       Chemistry. 2012, 287(12):9651-8.
   50. Sánchez-Danés A, Richaud-Patin Y, Carballo-Carbajal I, Jiménez-Delgado S, Caig C, Mora S, Di Guglielmo
       C, Ezquerra M, Patel B, Giralt A, Canals JM, Memo M, Alberch J, López-Barneo J, Vila M, Cuervo AM, Tolosa
       E, Consiglio A, Raya A. Disease-specific phenotypes in dopamine neurons from human iPS-based models of
       genetic and sporadic Parkinson's disease. EMBO Mol Med. 2012 Mar 8. doi: 10.1002/emmm.201200215. [Epub
       ahead of print]