Life Sciences Research for Lifelong Health

Heidi Welch

We study the molecular mechanisms which regulate Rac, an important protein that controls cell shape, cell movement, gene expression and oxygen radical formation. In particular, we study the proteins which activate Rac, so-called Rac-GEFs. Rac can be activated by many different types of Rac-GEFs. A few years ago, we discovered a new type, the P-Rex family Rac-GEFs, and we have been studying the mechanisms that regulate their activity and their functional roles.

P-Rex family Rac-GEFs are important for the ability of our white blood cells to defend us against bacterial and fungal infections, for the shape and electrical functions of the nerve cells that control coordination of movement and for the distribution of skin pigment cells during animal development. Importantly, we have found that deregulation of the cellular amount or activity of P-Rex family Rac-GEFs contributes to inflammatory disorders, cancer growth and metastasis.

Currently, our lab is investigating new functional roles of P-Rex and other families of Rac-GEFs, particularly in inflammatory cells, as well as inventing new ways of monitoring and controlling Rac-GEF activity. One of these recent developments is a molecule which inhibits P-Rex which we hope will provide a useful basis for the future development of new anti-inflammatory drugs.

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Latest Publications

The guanine-nucleotide-exchange factor P-Rex1 is activated by protein phosphatase 1α.

MA Barber, A Hendrickx, M Beullens

The Biochemical journal
443 1:173-83 (2012)

DOI: 10.1042/BJ20112078

PMID: 22242915

P-Rex1 is required for efficient melanoblast migration and melanoma metastasis.

CR Lindsay, S Lawn, AD Campbell

Nature communications
2 :555 (2011)

DOI: 10.1038/ncomms1560

PMID: 22109529

Characterization of the Rac guanine nucleotide exchange factor P-Rex1 in platelets.

JE Aslan, AM Spencer, CP Loren

Journal of molecular signaling
6 :11 (2011)

DOI: 10.1186/1750-2187-6-11

PMID: 21884615

P-Rex1 and Vav1 cooperate in the regulation of formyl-methionyl-leucyl-phenylalanine-dependent neutrophil responses.

CD Lawson, S Donald, KE Anderson

Journal of immunology (Baltimore, Md. : 1950)
186 3:1467-76 (2011)

DOI: 10.4049/jimmunol.1002738

PMID: 21178006

P-Rex2 regulates Purkinje cell dendrite morphology and motor coordination.

S Donald, T Humby, I Fyfe

Proceedings of the National Academy of Sciences of the United States of America
105 11:4483-8 (2008)

DOI: 10.1073/pnas.0712324105

PMID: 18334636

Membrane translocation of P-Rex1 is mediated by G protein betagamma subunits and phosphoinositide 3-kinase.

MA Barber, S Donald, S Thelen

The Journal of biological chemistry
282 41:29967-76 (2007)

DOI: 10.1074/jbc.M701877200

PMID: 17698854