Presentación del Dr. David Guillespie, investigador contratado por el CIBICAN - Universidad de La Laguna gracias al Proyecto Europeo IMBRAIN, en relación a los resultados alcanzados durante la ejecución del mismo y los planes de futuro. La misma se presentó durante las Jornadas IMBRAIN llevadas a cabo el 13 de Octubre de 2015 en la Sección de Física en la Universidad de La Laguna

1. DAVID AF GILLESPIE BSc, PhD, FRSE
Instituto de Tecnologías Biomédicas, Centro de Investigaciones Biomédicas
de Canarias, Facultad de Medicina, Campus Ciencias de la Salud, Universidad
de La Laguna, La Laguna 38071, Tenerife, Spain
Grupo de investigación (durante IMBRAIN):
Desiree Piscitello (Glasgow, CRUK)
Eun-Yeung Gong (Glasgow, WWCR)
Walter Vera Ortega (Master, ULL)
Felipe Fumagallo Reading
Sven Stuben (Master, Hamburg)
Beatriz Hernandez Salgado (Master, ULL)

2. Who am I?
IMBRAIN INVESTIGADOR
 BSc, University of Glasgow
 PhD, University of Aberdeen
 Imperial Cancer Research Fund, Fred Hutchinson Cancer
Research Center, Beatson Institute for Cancer Research
 Fellow of the Royal Society of Edinburgh
 Main Aim:
“Targeting the DNA Damage Response (DDR) for Cancer
Therapy”

3. My work at IMBRAIN
 Analyzed the regulatory mechanism of the DNA Damage-
activated Chk1 protein kinase
 Discovered that the Unfolded Protein Response (UPR)
controls DNA replication via a PERK, Claspin, and Chk1
(collaboration with Raimundo Freire)
 Developed unique cell lines that enable in vivo screening for
inhibitors of Chk1 and DDR signaling (validated with AZ7762)

4. Publications during IMBRAIN period - I
Smith, J., Larue, L., and Gillespie, DA. (2013) Chk1 is essential for the
development of murine epidermal melanocytes. Pigment Cell
Melanoma Res. 26: 580-585
Passaro C, Abagnale A, Libertini S, Volpe M, Botta G, Cella L, Pacelli R,
Halldèn G, Gillespie D, Portella G. (2013) Ionizing radiation
enhances dl922-947-mediated cell death of anaplastic thyroid
carcinoma cells. Endocr Relat Cancer. 20:633-47
Smits VA, Gillespie DA. (2014) Cancer therapy: targeting the poison
within. Cell Cycle. 13: 2330-3
Smits VA, Gillespie DA. (2015) DNA damage control: regulation and
functions of Checkpoint kinase 1. FEBS J. 282:3681-92

5. Publications during IMBRAIN period - II
Gong EY, Smits VA, Fumagallo F, Piscitello D, Morrice N, Freire R,
Gillespie DA. (2015) KA1-targeted regulatory domain mutations
activate Chk1 in the absence of DNA damage. Sci Rep. 3;5:10838-
56.
Liu EY, Xu N, O'Prey J, Lao LY, Joshi S, Long JS, O'Prey M, Croft DR,
Beaumatin F, Baudot AD, Mrschtik M, Rosenfeldt M, Zhang Y,
Gillespie DA, Ryan KM. (2015) Loss of autophagy causes a synthetic
lethal deficiency in DNA repair. Proc Natl Acad Sci U S A. 112: 773-8
Passaro C, Volpe M, Botta G, Scamardella E, Perruolo G, Gillespie D,
Libertini S, Portella G. (2015) PARP inhibitor olaparib increases the
oncolytic activity of dl922-947 in in vitro and in vivo model of
anaplastic thyroid carcinoma. Mol Oncol. 9:78-92.

6. Plans for the future….
 Publish two further manuscripts 1) on UPR/ DNA
replication and 2) on Chk1 auto-phosphorylation
 Develop “Phenotypic Reversion Screen” using FDA-
approved drug library (1018 drugs) to screen for
interactions with Chk1 and DDR signaling
 Investigate prospects for commercializing the
“Phenotypic Reversion Screen” technology
Gracias!