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 ReadingSven Stuben (Master, Hamburg)

Beatriz Hernandez Salgado (Master, ULL)

Who am I?

IMBRAIN INVESTIGADOR BSc, University of Glasgow PhD, University of AberdeenImperial Cancer Research Fund, Fred Hutchinson Cancer

Research Center, Beatson Institute for Cancer ResearchFellow of the Royal Society of Edinburgh

Main Aim: “Targeting the DNA Damage Response (DDR) for Cancer

Therapy”

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)

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

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.

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!