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

Truncating PREX2 mutations activate its GEF activity and alter gene expression regulation in NRAS-mutant melanoma.

Lissanu Deribe Y, Shi Y, Rai K

Proceedings of the National Academy of Sciences of the United States of America
1091-6490: (2016)

PMID: 26884185

Norbin Stimulates the Catalytic Activity and Plasma Membrane Localization of the Guanine-Nucleotide Exchange Factor P-Rex1.

Pan D, Barber MA, Hornigold K

The Journal of biological chemistry
1083-351X: (2016)

PMID: 26792863

Small GTPases and their guanine-nucleotide exchange factors and GTPase-activating proteins in neutrophil recruitment.

Baker MJ, Pan D, Welch HC

Current opinion in hematology
23 1531-7048:44-54 (2016)

PMID: 26619317

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