CURRICULUM VITAE

Name: Vassilis Pachnis, M.D., Ph.D., FMedSci Date of Birth: 24 January 1953 Place of Birth: Athens,

Contact details:

National Institute for Medical Research Institute of Molecular Biology and Biotechnology The Ridgeway, Mill Hill, Foundation for Research and Technology‐Hellas London NW7 1AA, UK. N. Plastira 100, GR‐70013, Heraklion, Greece tel. (+44) 02088162113 Tel. (+30) 2810391100 email: [email protected] Email: [email protected]

Education: July 1980 University of Athens Medical School (Athens, Greece) M.D. magna cum laude June 1986 University of Pennsylvania, Philadelphia, PA (USA) Degree: Ph.D., Genetics Supervisor: Prof. Shirley Tilghman Nov 1986 – Mar 1988 Howard Hughes Medical Institute Center for Neurobiology and Behavior , New York, NY (USA) Postdoctoral Fellow in Prof. 's laboratory Apr 1988 – May 1991 Department of Genetics and Development Columbia University, New York, NY (USA) Postdoctoral fellow in Dr. Frank Costantini's laboratory

Present Post: ‐ Head of Division of Molecular Neurobiology, National Institute for Medical Research, Medical Research Council (London, UK) ‐ Director of the Institute of Molecular Biology and Biotechnology of the Foundation for Research and Technology‐Hellas (Heraklion, Greece)

Previous positions held: May 1991 – Feb 1997 Senior Scientific Staff, Group Leader, MRC National Institute for Medical Research, London (5/91‐2/97) Feb 1997 – Aug 2000 Tenured Senior Scientist, MRC National Institute for Medical Research, London

Honors/Awards ‐ Scholarship from the National Scholarship Foundation of Greece for Academic excellence in Medical School ‐ Special Fellowship Award from the Leukemia Society of America (Jul 1989‐May 1991) ‐ Janssen Award for Life Time Achievement in Gastroenterology (2002)

Membership in Academies ‐ Elected Fellow of the Academy of Medical Sciences, UK (2000). ‐ Elected member of EMBO (2007)

Committees and other Professional Responsibilities ‐ Member of Review Panel for the Evaluation of the Pasteur Institute (Athens, 2004) ‐ Member of Review Panel for the Evaluation of the Institute of Biology at the Research Centre “Democritos” (Athens, 2005)‐ Chairman K. Sekeris ‐ Member of Review Panel for the evaluation of IIBEAA (Athens, 2007)‐ Chairman G. Stmatoyanopoulos ‐ Member of Review Panel for the evaluation of CSIC Institutes (Spain) (2009)‐ Chairman I. Mattaj. ‐ Member of BBSRC panel for assessment of grant applications. ‐ Frequent reviewer of manuscripts submitted to International peer review Journals.

Meeting organisation ‐ Co‐organiser of an EMBO Workshop on Haematopoiesis and Neurogenesis (September 2007, Heidelberg). ‐ Organizer of the 2nd International Conference on ENS Development: Genes, Molecules and Signals (February 2009, London).

Publications: 1) Reid I. A., McDonald, M., Pachnis, V., and Ganong, W. F. Studies concerning the mechanism of suppression of renin secretion by clonidine. The Journal of Pharmacology and Experimental Therapeutics 192, 713‐721, 1975. 2) Pachnis, V., Belayew, A., and Tilghman, S. M. Locus unlinked to ‐fetoprotein under the control of the murine raf and Rif genes. Proc. Natl. Acad. Sci. USA 81, 5523‐5527, 1984. 3) Tilghman, S. M., Belayew, A., Pachnis, V., and Krumlauf, R. Genetic approaches to the regulation of ‐ fetoprotein synthesis: ‐fetoprotein and Genetic Disorders. p53‐46 Academic Press, 1985. 4) Pachnis, V., Belayew, A., and Tilghman, S. M. Studies into the raf and Rif genes. Current Topics in Microbiology and Immunology 122, 50‐52, 1985. 5) Pachnis, V., Brannan, C. I., and Tilghman, S. M. The structure and expression of a novel gene activated in early mouse embryogenesis. The EMBO 7, 673‐681, 1988. 6) Yoo‐Warren, H., Pachnis, V., Ingram, R. S., and Tilghman, S. M. Two regualtory domains flank the H19 gene. Mol. Cell. Biol. 8, 4707‐4715, 1988. 7) Pachnis, V., Pevny, L., Rothstein, R., and Costantini, F. Transfer of a yeast artificial chromosome carrying human DNA from Saccharomyces cerevisiae into mammalian cells. Proc. Natl. Acad. Sci. USA 87, 5109‐5113, 1990. 8) Pachnis, V., Pevny, L., Rothstein, R., and Costantini, F. Transfer of a Yeast Artificial Chromosome (YAC) into cultured cells: a new method for manipulating the mammalian genome. Mechanisms of Eukaryotic DNA Recombination (Academic Press, N.Y.) 1992. 9) Pachnis, V., Mankoo, S. B. and Costantini, F. Expression of the c‐ret proto‐oncogene during mouse embryogenesis. Development 119, 1005‐1017 (1993). 10) Schuchardt, A., D'Agati, V., Larsson‐Blomberg, L., Costantini, F., and Pachnis, V. Defects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor Ret. 367, 380‐383 (1994). 11) Schuchardt, A., Srinivas, S., Pachnis, V. and Costantini, F. Isolation and Characterization of a Chicken Homologue of the c‐ret proto‐oncogene. Oncogene 10, 641‐649 (1995). 12) Grigoriou, M., Kastrinaki, M‐C, Modi, W., Theodorakis, K., Mankoo, B., Pachnis, V. and Karagogeos, D. Isolation of the human MOX‐2 Homeobox gene and Localization to chromosome 7p22.1‐p21.3. Genomics 26, 550‐555 (1995). 13) Pachnis, V., Durbec, P., Larsson‐Blomberg, L., Mankoo, B., Schuhardt, A., D'Agati, V. and Costantini, F. Knock‐out mice for the RET oncogene. In Molecular Genetics of Cancer. Ed. J.K. Cowell. Bios Scientific Publishers, Oxford. (1995).

14) Schuchardt, A., D'Agati, V., Larsson‐Blomberg, L., Costantini, F., and Pachnis, V. RET‐deficient mice: an animal model for Hirschsprung's disease and renal agenesis. J. Int. Medic. 238, 327‐332 (1995). 15) Durbec, P., Larsson‐Blomberg, L., Schuchardt, A., Costantini, F. and Pachnis, V. Common origin and developmental dependence on c‐ret of subsets of enteric and sympathetic neuroblasts. Development 122, 349‐358 (1996). 16) Schuchardt, A., D'Agati, V., Pachnis, V. and Costantini, F. Renal agenesis and hypodysplasia in ret.k‐ mutant mice result from defects in ureteric bud development. Development 122, 1919‐1929 (1996). 17) Durbec, P., Marcos‐Gutierrez, C., Kilkenny, C., Grigoriou, M., Suvanto, P., Smith, D., Ponder, B., Costantini, F., Saarma, M., Sariola, H. and Pachnis, V. Glial cell line‐derived neurotrophic factor signalling through the Ret receptor tyrosine kinase. Nature 381, 789‐793 (1996). 18) M. Trupp, E. Arena, M. Fainzilber, A‐S. Nilsson, B‐A. Sieber, M. Grigoriou, C. Kilkenny, E. Salazar‐ Grueso, V. Pachnis, Arumae, U., H. Sariola, M. Saarma and C. Ibanez. Functional receptor for glial cell line‐derived neurotrophic factor encoded by the c‐ret proto‐oncogene. Nature 381, (1996). 19) Rothman, T.P., Chen, J., Howard, M.J., Costantini, F., Schuchardt, A., Pachnis, V. and Gershon, M.D. Increased Expression of Laminin‐1 and Collagen (IV) Subunits in the Aganglionic Bowel of ls/ls, but Not c‐ret ‐ /‐ Mice. Developmental Biology 178, 498‐513 (1996). 20) Marcos C. and Pachnis V. The effect of the ret‐ mutation on the normal development of the central and parasympathetic nervous systems. Int J Dev Biol.137S‐138S (1996). 21) Burton, M.D., Kawashima, A., Brayer J.A., Kazemi, H., Shannon, D.C., Schuchardt, A., Costantini, F., Pachnis, V. and Kinane, T.B. RET proto‐oncogene is important for the development of respiratory CO2 sensitivity. Journal of the Autonomic Nervous System 63, 137‐143 (1997). 22) Sainio K, Suvanto P, Davies J, Wartiovaara J, Wartiovaara K, Saarma M, Arumae U, Meng X, Lindahl M, Pachnis V, Sariola H. Glial‐cell‐line‐derived neurotrophic factor is required for bud initiation from ureteric epithelium. Development 124, 4077‐4087 (1997). 23) Marcos‐Gutierrez CV, Wilson SW, Holder N, Pachnis V. The zebrafish homologue of the ret receptor and its pattern of expression during embryogenesis. Oncogene 14, 879‐889 (1997). 24) Schuchardt, A., Durbec, P., Marcos‐Gutierrez, C.V., Pachnis, V. and Costantini, F. “The role of the ret receptor tyrosine kinase and glial cell line‐derived neurtrophic factor in development of the excretory and peripheral nervous system”. In: “Epithelial Morphogenesis and Disease”. W. Birchmeier and C. Birchmeier, eds, Harwood Academic Publishers (1997). 25) Grigoriou, M., Tucker, A.S., Sharpe, P. and Pachnis, V. Expression and regulation of Lhx6 and Lhx7, a novel subfamily of LIM homeodomain encoding genes, suggests a role in mammalian head development. Development 125, 2063‐2074 (1998). 26) Wynick D, Small CJ, Bacon A, Holmes FE, Norman M, Ormandy CJ, Kilic E, Kerr NCH, Ghatei M, Talamantes F, Bloom SR & Pachnis V. Galanin regulates of prolactin release and lactotroph growth. Proc. Natl. Acad. Sci. USA 95, 12671‐12676 (1998). 27) Attie‐Bitach, T., Abitbol, M., Gerard, M., Delezoide, A.L., Auge, J., Pelet, A., Amiel, J., Pachnis, V., Munnich, A., Lyonnet, S., Vekemans, M. Expression of the RET proto‐oncogene in human embryos. Am J Med Genet. 80, 481‐6 (1998). 28) Wynick D, Small CJ, Bloom SR, Pachnis V Targeted disruption of the murine galanin gene. Ann N Y Acad Sci 863,22‐47 (1998). 39) Pachnis V, Durbec P, Taraviras S, Grigoriou M, Natarajan D. Role Of the RET signal transduction pathway in development of the mammalian enteric nervous system. Am J Physiol. 275 (2 Pt 1):G183‐6 (1998). 30) Tucker, A.S., Yamada, G., Grigoriou, M., Pachnis, V. and Sharpe, P.T. Fgf‐8 determines rostral‐caudal polarity in the first branchial arch. Development 126, 51‐61 (1999).

31) Natarajan, D., Grigoriou, M., Marcos‐Gutierrez, C.V., Atkins, C. and Pachnis, V. Multipotential progenitors of the mammalian enteric nervous system capable of colonising aganglionic bowel in organ culture. Development 126, 157‐168 (1999). 32) Taraviras S, Marcos‐Gutierrez CV, Durbec P, Jani H, Grigoriou M, Sukumaran M, Wang LC, Hynes M, Raisman G, Pachnis V. Signalling by the RET tyrosine kinase receptor and its role in the development of the mammalian enteric nervous system Development 126, 2785‐2797 (1999). 33) Taraviras S, Pachnis V.. Development of the Mammalian Enteric Nervous System Current Opinion in Genetics & Development 9, 321‐327 (1999). 34) Mankoo BS, Collins NS, Ashby P, Grigorieva E, Pevny LH, Candia A, Wright CV, Rigby PW, Pachnis V. Mox2, is a component of the genetic hierarchy controlling limb muscle development. Nature 400, 69‐ 73 (1999). 35) Lavdas AA, Grigoriou M, Pachnis V, Parnavelas JG. The medial ganglionic eminence gives rise to a population of early neurons in the developing cerebral cortex. J. Neurosc. 99, 7881‐7888 (1999). 36) Natarajan, D and Pachnis, V. “Development of the Enteric Nervous System”. In “Development of the Gastrointestinal Tract”. Eds: W.A.Walker and I.R.Sanderson, Publishers: B.C.Decker Inc. (1999). 37) Parnavelas JG, Anderson SA, Lavdas AA, Grigoriou M, Pachnis V, Rubenstein JL. The contribution of the ganglionic eminence to the neuronal cell types of the cerebral cortex. Novartis Found Symp. 228:129‐ 39 (2000). 38) Holmes FE, Mahoney S, King VR, Bacon A, Kerr NC, Pachnis V, Curtis R, Priestley JV, Wynick D. Targeted disruption of the galanin gene reduces the number of sensory neurons and their regenerative capacity. Proc Natl Acad Sci U S A. 97(21):11563‐8 (2000). 39) Stamataki D, Kastrinaki M, Mankoo BS, Pachnis V, Karagogeos D. Homeodomain proteins Mox1 and Mox2 associate with Pax1 and Pax3 transcription factors. FEBS Lett. 22;499(3):274‐8 (2001). 40) de Graaff, E., Srinivas, S., Kilkenny, C., D’Agati, V., Mankoo, BS., Costantini F. and Pachnis, V. Differential activities of the RET receptor tyrosine kinase isoforms during mammalian embryogenesis. Genes Dev. 15, 2433‐44 (2001). 41) Sukumaran M, Waxman SG, Wood JN and Pachnis V. Flanking regulatory sequences of the locus encoding the murine GDNF receptor, c‐ret, directs LacZ ( ‐galactosidase) expression in developing somatosensory system. Dev Dyn. 222, 389‐402 (2001). 42) Aizenfisz S, Dauger S, Durand E, Vardon G, Levacher B, Simonneau M, Pachnis V, Gaultier C, Gallego J. Ventilatory responses to hypercapnia and hypoxia in heterozygous c‐ret newborn mice. Respir Physiolo Neurobiol. 131, 213‐222 (2002). 43) Natarajan D, Marcos‐Gutierrez C, Pachnis V and de Graaff E. Requirement of signalling by receptor tyrosine kinase RET for the directed migration of enteric nervous system progenitor cells during mammalian embryogenesis. Development 129, 5151‐5160 (2002). 44) Holmes FE, Bacon A, Pope RJ, Vanderplank PA, Kerr NC, Sukumaran M, Pachnis V, Wynick D. Transgenic overexpression of galanin in the dorsal root ganglia modulates pain‐related behavior. Proc Natl Acad Sci U S A.100:6180‐5 (2003). 45) Mankoo, B., Skuntz, S., Harrigan, I., Grigorieva, E., Candia, A., Wright, C.V.E., Arnheiter, H. and Pachnis, V. The concerted actions of the Meox homeobox genes is required upstream of genetic pathways essential for the formation, patterning and differentiation of somites. Development 130:4655‐4664 (2003). 46) Bondurand, N., Natarajan, D., Thapar, N. and Pachnis, V. Neuron and glia generating progenitors of the mammalian enteric nervous system isolated from fetal and post‐natal gut cultures. Development 130:6387‐6400 (2003).

47) Barlow, A., de Graaff, E. and Pachnis, V. Enteric Nervous System Progenitors Are Coordinately controlled by the G‐Protein Coupled Receptor EDNRB and the Receptor Tyrosine Kinase RET. Neuron 40:905‐916 (2003) 48) Kapur RP, Gershon MD, Milla, PJ and Pachnis V. The influence of Hox genes and three intercellular signalling pathways on enteric neuromuscular development. Neurogastroenterol Motil. Suppl 1:8‐13 (2004). 49) Fu, M., Lui, V.CH., Sham, MH., Pachnis, V. and Tam, P.KH. Sonic Hedgehog regulates the proliferation, differentiation and migration of enteric neural crest cells in gut J. Cell Biol. 166:673‐684 (2004). 50) Xouri, G., Lygerou, Z., Nishitani, H., Pachnis, V., Nurse, P and Taraviras, S. The licensing factor Cdt1 and its inhibitor Geminin are down‐regulated upon cell cycle exit and are expressed to higher levels in cancer versus primary cell lines. European Journal of Biochemistry 271:3368‐3378 (2004). 51) Fragkouli, A., Hearn, C., Errington, M., Cooke, S., Grigoriou, M., Bliss, T., Stylianopoulou, F. and Pachnis, V. Loss of forebrain cholinergic neurons and impairment in spatial learning and memory in LHX7‐ deficient mice European Journal of Neuroscience 21:2923‐2938 (2005). 52) Wong, A., Bogni, S., Kotke, P., de Graaff, E., D’ Agati, V., Costantini, F. and Pachnis, V. Phosphotyrosine 1062 is critical for the in vivo activity of the Ret9 receptor tyrosine kinase isoform Mol Cell Biol. 25: 9661‐9673 (2005). 53) Jukkola T., Trokovic R, Maj P, Lamberg A, Mankoo B, Pachnis V, Savilahti H and Partanen J. Meox1Cre: a mouse line expressing Cre recombinase in somitic mesoderm. Genesis 43:148‐153 2005. 54) Viemari JC, Maussion G, Bėvengut M, Burnet H, Pequignot JM, Nėpote V, Pachnis V, Simonneau M and Hilaire G. Ret deficiency in mice impairs the development of A5 and A6 neurons and the functional maturation of the respiratory rhythm. European Journal of Neuroscience 22: 2403‐2412 (2005). 55) Cassiman, D, Barlow, AJ, Libbrecht, L, Borght, SV, and Pachnis, V. Hepatic stellate cells probably do not derive from the neural crest. Journal of Hepatology 42, 312 (2005). 56) Fragkouli, A., Stamatakis, A., Zographos, E., Pachnis, V. and Stylianopoulou, F. Sexually dimorphic effects of the Lhx7 null mutation on forebrain cholinergic function. Neuroscience 137, 1153‐1164 (2006). 57) Stanchina, L., Baral, V., Robert, F., Pingault, V., Lemort, N., Pachnis, V., Goossens, M. and Bondurand, N. Interactions between Sox10, Edn3 and Ednrb during enteric nervous system and melanocyte development. Dev Biol 295, 232‐249 (2006). 58) Heanue, T. and Pachnis V. Expression profiling the developing mammalian enteric nervous system identifies marker and candidate Hirschsprung disease genes. Proc Natl Acad Sci USA 103, 6919‐6924 (2006). 59) Bondurand, N., Natarajan, D., Barlow, A., Thapar, N., and Pachnis, V. Maintenance of mammalian enteric nervous system progenitors by SOX10 and Endothelin‐3 signalling. Development 133, 2075‐ 2086 (2006). 60) Heuckeroth, R. O. and Pachnis, V. Getting to the Guts of Enteric Nervous System Development. Development 133, 2287‐2290 (2006). 61) Asai, N., Fukuda, T., Wu, Z., Enomoto, A., Pachnis, V., Takahashi, M. and Costantini, F. Targeted mutation of Serine 697 if the Ret tyrosine kinase causes migration defects in enteric neural crest cells. Development 133, 4507‐4516 (2006). 62) Liodis, P., Denaxa, M., Grigoriou, M., Yanagawa, Y. and Pachnis, V. Lhx6 activity is required for the normal migration and specification of cortical interneuron subtypes. J Neurosci. 27, 3078‐89 (2007). 63) Veiga‐Fernandes H, Coles MC, Foster KE, Patel A, Williams A, Natarajan D, Barlow A, Pachnis V, Kioussis D. Tyrosine kinase receptor RET is a key regulator of Peyer's patch organogenesis. Nature 446, 547‐51 (2007).

64) Heanue TA, Pachnis V. Enteric nervous system development and Hirschsprung's disease: advances in genetic and stem cell studies. Nat Rev Neurosci. 8, 466‐79 (2007). 65) Fogarty, M., Grist, M., Gelman, D., Marίn, O., Pachnis, V. and Kessaris, N. Spatial genetic patterning of the embryonic neuroepithelium generates GABAergic interneuron diversity in the adult cortex. J. Neurosci. 27, 10935‐46 (2007). 66) Butt, SJB, Cobos, I., Golden, J., Kessaris, N., Pachnis, V. and Anderson, S. Transcriptional control of pre‐ and post‐natal development of cerebral cortical interneurons. J. Neurosci. 27, 11847‐50 (2007). 67) Foster, K., Sheridan, J., Veiga‐Fernandes, H., Roderick, K., Bogni, S., Pachnis, V. Adams, R., Blackburn, C., Kioussis, D. and Coles, M. Contributions of neural crest‐derived cells in the embryonic and adult thymus J. Immunol. 180, 3183‐3189 (2008). 68) Heanue, TA. and Pachnis, V. "Ret isoform function and marker gene expression in the enteric nervous system is conserved across vertebrate species" Mech Dev. 125:687‐699 (2008). 69) Bogni S, Trainor P, Natarajan D, Krumlauf R and Pachnis V. “Non cell autonomous effect of Ret deletion in early enteric neurogenesis” Development 135:3007‐3011 (2008). 70) Fragkouli A, Pachnis, V and Stylianopoulou F. Sex differences in water maze performance and cortical neurotrophin levels of Lhx7 null mutant mice Neuroscience 158:1224‐1233 (2009). 71) Burns, A and Pachnis, V The enteric nervous system: bringing together cells, signals and molecules. Neurogastroenterology and Motility 21:100‐102 (2009). 72) Skuntz S, Mankoo B, Nguyen MT, Hustert E, Nakayama A, Tournier‐Lasserve E, Wright CV, Pachnis V, Bharti K and Arnheiter H. Lack of the mesodermal homeodomain protein MEOX1 disrupts sclerotome polarity and leads to a remodeling of the craniocervical joints of the axial skeleton Developmental Biology 332:383‐395 (2009). 73) Denaxa M, Sharpe P and Pachnis V. Lhx6 and Lhx7 LIM homeodomain proteins are required for the development of normal dentition Developmental Biology 333:324‐336 (2009). 74) Batista‐Brito R, Rossignol E, Hjerling‐Leffler J, Denaxa M, Wegner M, Lefebvre V, Pachnis V and Gord Fishell. “The cell‐intrinsic requirement of Sox6 for cortical interneuron development” Neuron 63:466‐ 481 (2009). 75) Laranjeira C and Pachnis V. “Development of the Enteric Nervous System: Recent Progress and Future Challenges” Auton Neurosci 151:61‐69 (2009). 76) Fragkouli A, Verhey van Wijk N, Lopes R, Kessaris N and Pachnis V “LIM homeodomain transcription factor‐dependent specification of bipotential MGE progenitors into cholinergic and GABAergic striatal interneurons” Development 136:3841‐3851 (2009). 77) Kioussis D. and Pachnis V. “Immune and Nervous System; more than just a superficial similarity Immunity (Oct 14, Epub ahead of print, 2009). 78) Karamitros D, Kotantaki P, Lygerou Z, Veiga‐Fernandes H, Pachnis V, Kioussis D and Taraviras S. J. Immunol. (2009 under review). 79) Vidaki M, Doulgeraki K, Kessaris N, Pachnis V and Karagogeos D. “Rac1 affects the development of cortical interneurons by regulating their cell cycle exit” (2009, submitted).