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

Regulation and Function of P-Rex Family Rac-GEFs.

Welch HC

Small GTPases
2154-1256:0 (2015)

PMID: 25961466

P-Rex and Vav Rac-GEFs in platelets control leukocyte recruitment to sites of inflammation.

Pan D, Amison RT, Riffo-Vasquez Y

Blood
1528-0020: (2014)

PMID: 25538043

A rac1-independent role for p-rex1 in melanoblasts.

Lindsay CR, Li A, Faller W

The Journal of investigative dermatology
135 1523-1747:314-8 (2015)

PMID: 25075639

P-Rex1 directly activates RhoG to regulate GPCR-driven Rac signalling and actin polarity in neutrophils.

G Damoulakis, L Gambardella, KL Rossman

Journal of cell science
127 Pt 11:2589-600 (2014)

DOI: 10.1242/jcs.153049

PMID: 24659802

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