Howard Group

Genetic modification of stem and progenitor cells 

Stem cells and progenitor cells show great promise as treatments for diseases and repair of tissue damages. These cells are also useful tools to study developmental processes in a human system in vitro. 

Our group is interested in genetically modifying stem cells to (i) to better understand how they function and (ii) to enhance their therapeutic potential. Using viral vectors we can efficiently overexpress proteins in cells (figure 1, overexpression of GFP in an oligodendrocyte progenitor cell), or we can deliver short hairpin RNAs (shRNAs) which reduce the levels of protein in cells (figure2 showing that 2 shRNAs reduced the production of NG2 by astrocytes).

Comparison of stem and progenitor cells from healthy volunteers and patients with diseases 

Stem and progenitor cells can be used autologously ( where a patient is given their own cells) or allogeneically (cells are obtained from a donor).   It is possible that cells from patients with chronic diseases and/ or older patients may not grow or function as well as cells from young healthy donors. We are studying cells from patients with conditions such as critical limb ischaemia and type II Diabetes Mellitus to determine how they compare to cells from healthy donors.  

Ireland’s first clinical trial of an ex vivo expanded progenitor cell was conducted at NUI Galway and Galway University Hospital with GMP clinical grade cells produced at the Center for Cell Manufacturing Ireland (CCMI). Patients with ‘no option’ critical limb ischemia were given their own cells.  While the therapy was safe we observed that it was more difficult to manufacture the required cell dose for older patients than for young healthy donors. We are continuing to determine how patient cells compare to healthy young cells and whether patient cells can be altered to enhance their function.

Genetic modification strategies to enhance recovery after spinal cord injury. 

Spinal cord injury can have a devastating impact of a patient’s quality of life. This condition is the focus of research efforts all over the world.  

Following spinal cord injury a glial scar is formed, initially this has a protective function, but it inhibits repair and regeneration of the damaged spinal cord. Our group, in collaboration with Dr Siobhan McMahon in Anatomy are developing gene therapy approaches to removing or / breaking down the glial scar. The efficacy of these approaches are tested in ex vivo organotypic cultures. (Figure 2) In addition we are evaluating strategies to provide factors such as neurotrophins which enhance repair and regeneration.

Please see here for research publications.