Dr Daniel Gitterman | Staff Scientist

Gitterman, Daniel

My project aims to create a mouse model of rare and poorly understood kidney disorders. The model is generated using molecular biological techniques in embryonic stem cells to remove the mouse genes and replace them with the human ortholog.

A component of the immune system called Complement Factor H and its five related proteins (CFHR1 - CFHR5) have been found to play a key role in the pathology of several renal diseases which are poorly understood. By humanising the mouse locus containing these genes we hope to create a mouse model of the human pathology. One goal will be to investigate the utility of therapeutically targeting these proteins in the treatment of diseases such as atypical haemolytic uraemic syndrome (aHUS) and dense deposit disease (DDD).
The process of engineering mouse embryonic stem cells to contain the human rather than the mouse CFH locus relies on a number of genome engineering technologies. CRISPR/Cas9 is used for all steps targeting exogenous DNA sequences to specific positions in the mouse genome, which is required for excision of the mouse genes and preparation of the site for integration of the human genes. Sequential recombinase mediated cassette exchange is then used to insert human sequence in a step-wise fashion, gradually building up the human locus.

Publications

  • Isocitrate dehydrogenase (IDH) mutations promote a reversible ZEB1/microRNA (miR)-200-dependent epithelial-mesenchymal transition (EMT).

    Grassian AR, Lin F, Barrett R, Liu Y, Jiang W et al.

    The Journal of biological chemistry 2012;287;50;42180-94

  • Stretch-induced injury in organotypic hippocampal slice cultures reproduces in vivo post-traumatic neurodegeneration: role of glutamate receptors and voltage-dependent calcium channels.

    Cater HL, Gitterman D, Davis SM, Benham CD, Morrison B and Sundstrom LE

    Journal of neurochemistry 2007;101;2;434-47

  • Functional properties and pharmacological inhibition of ASIC channels in the human SJ-RH30 skeletal muscle cell line.

    Gitterman DP, Wilson J and Randall AD

    The Journal of physiology 2005;562;Pt 3;759-69

  • Capsazepine protects against neuronal injury caused by oxygen glucose deprivation by inhibiting I(h).

    Ray AM, Benham CD, Roberts JC, Gill CH, Lanneau C et al.

    The Journal of neuroscience : the official journal of the Society for Neuroscience 2003;23;31;10146-53

  • Nerve evoked P2X receptor contractions of rat mesenteric arteries; dependence on vessel size and lack of role of L-type calcium channels and calcium induced calcium release.

    Gitterman DP and Evans RJ

    British journal of pharmacology 2001;132;6;1201-8

  • Properties of P2X and P2Y receptors are dependent on artery diameter in the rat mesenteric bed.

    Gitterman DP and Evans RJ

    British journal of pharmacology 2000;131;8;1561-8

  • Effects of diadenosine polyphosphates (Ap(n)As) and adenosine polyphospho guanosines (Ap(n)Gs) on rat mesenteric artery P2X receptor ion channels.

    Lewis CJ, Gitterman DP, Schlüter H and Evans RJ

    British journal of pharmacology 2000;129;1;124-30

  • Reduced vas deferens contraction and male infertility in mice lacking P2X1 receptors.

    Mulryan K, Gitterman DP, Lewis CJ, Vial C, Leckie BJ et al.

    Nature 2000;403;6765;86-9

Gitterman, Daniel
Daniel's Timeline
2014

Wellcome Trust Sanger Institute

2010

Horizon Discovery

2008

Barker Brettell LLP

2005

Vernalis

2002

GlaxoSmithKline

2001

Laboratory of Molecular Biology, Cambridge

PhD, University of Leicester