Dr Kimberly Mace

Kimberly Mace – Research Summary

Dr Kimberly Mace

My research is focused on the role of inflammation in tissue repair and regeneration. In particular we want to know how myeloid cells are recruited to injured tissue, what regulates their responses, and how their differentiation contributes to repair and regeneration. We are also interested in how aging and pathological conditions such as diabetes alter these responses.

During cutaneous wound healing, myeloid cells transition from a pro-inflammatory phenotype, which dominates the early wound environment, to a pro-healing phenotype, critical for later stages of healing. We have found that diabetes inhibits this macrophage transition, and that this is in part due to myeloid cell-intrinsic factors. These factors include dysregulated transcription factors and chromatin modifying enzymes. Together, they promote a chronic inflammatory state that is associated with impaired wound healing. We are investigating the mechanisms that underlie the regulation of this transition and how the diabetic environment affects myeloid cell development and differentiation. A better understanding of this process and what goes wrong in pathological conditions like diabetes will provide insights into how we can manipulate myeloid cells to improve wound healing in people with diabetes.

Publications

2016

Al Sadoun, H., Burgess, M., Hentges, K.E., & Mace, K.A. (2016). Enforced expression of Hoxa3 inhibits classical and promotes alternative activation of macrophages in vitro and in vivo. Journal of Immunology64(12). DOI: 10.4049/jimmunol.1501944

 2015

Wicks, K., Torbica, T., Umehara, T., Amin, S., Bobola, N., & Mace, K.A. (2015). Diabetes inhibits Gr-1+ myeloid cell maturation via Cebpa deregulation. Diabetes64(12). DOI:10.2337/db14-1895

2014

Campbell, L., Emmerson, E., Williams, H., Saville, C. R., Krust, A., Chambon, P., ... Crompton, R. A. (2014). Estrogen receptor-alpha promotes alternative macrophage activation during cutaneous repair.The Journal of investigative dermatology134(9), 2447-2457. DOI:10.1038/jid.2014.175

Wicks, K., Torbica, T., & Mace, K. A. (2014). Myeloid cell dysfunction and the pathogenesis of the diabetic chronic wound.Seminars in immunology26(4). DOI:10.1016/j.smim.2014.04.006

2013

Bannon, P., Wood, S., Restivo, T., Campbell, L., Hardman, M. J., & Mace, K. A. (2013). Diabetes induces stable intrinsic changes to myeloid cells that contribute to chronic inflammation during wound healing in mice. DMM Disease Models and Mechanisms6(6), 1434-1447. DOI:10.1242/dmm.012237

2012

Kachgal, S., Mace, K. A., & Boudreau, N. J. (2012). The dual roles of homeobox genes in vascularization and wound healing. Cell adhesion & migration6(6), 457-470. DOI:10.4161/cam.22164

Mahdipour, E., & Mace, K. A. (2012). Analyzing the angiogenic potential of Gr-1+CD11b+ immature myeloid cells from murine wounds. Methods in Molecular Biology916, 219-229. DOI:10.1007/978-1-61779-980-8-17

2011

Mahdipour, E., & MacE, K. A. (2011). Hox transcription factor regulation of adult bone-marrow-derived cell behaviour during tissue repair and regeneration. Expert Opinion on Biological Therapy11(8), 1079-1090. DOI:10.1517/14712598.2011.579096

Mahdipour, E., Charnock, J. C., & Mace, K. A. (2011). Hoxa3 promotes the differentiation of hematopoietic progenitor cells into proangiogenic Gr-1+CD11b+ myeloid cells. Blood117(3), 815-826. DOI:10.1182/blood-2009-12-259549

2010

Landry, Y., Lê, O., Mace, K. A., Restivo, T. E., & Beauséjour, C. M. (2010). Secretion of SDF-1α by bone marrow-derived stromal cells enhances skin wound healing of C57BL/6 mice exposed to ionizing radiation. Journal of Cellular and Molecular Medicine14(6 B), 1594-1604. DOI:10.1111/j.1582-4934.2009.00887.x

Mace, K. A., Boudreau, N., & Sen, C. K. (Ed.) (2010). Plasmid-Based Gene Transfer of Homeobox Genes and Improved Wound Healing. In Advances in Wound Care. (1 ed.). USA: Mary Ann Liebert, Inc.. Publication link: fa54b2ee-f9ab-49c1-8c3b-d5ca87fd2872

Restivo, T. E., MacE, K. A., Harken, A. H., & Young, D. M. (2010). Application of the chemokine CXCL12 expression plasmid restores wound healing to near normal in a diabetic mouse model. Journal of Trauma - Injury, Infection and Critical Care69(2), 392-398. DOI:10.1097/TA.0b013e3181e772b0

2009

Chen, A., Cuevas, I., Kenny, P. A., Miyake, H., Mace, K., Ghajar, C., ... Boudreau, N. (2009). Endothelial cell migration and vascular endothelial growth factor expression are the result of loss of breast tissue polarity. Cancer Research69(16), 6721-6729. DOI:10.1158/0008-5472.CAN-08-4069

Mace, K. A., Restivo, T. E., Rinn, J. L., Paquet, A. C., Chang, H. Y., Young, D. M., & Boudreau, N. J. (2009). HOXA3 modulates injury-induced mobilization and recruitment of bone marrow-derived cells. Stem Cells27(7), 1654-1665. DOI:10.1002/stem.90

2007

Mace, K. A., Yu, D. H., Paydar, K. Z., Boudreau, N., & Young, D. M. (2007). Sustained expression of Hif-1α in the diabetic environment promotes angiogenesis and cutaneous wound repair. Wound Repair and Regeneration15(5), 636-645. DOI:10.1111/j.1524-475X.2007.00278.x

Yu, D. H., MacE, K. A., Hansen, S. L., Boudreau, N., & Young, D. M. (2007). Effects of decreased insulin-like growth factor-1 stimulation on hypoxia inducible factor 1-α protein synthesis and function during cutaneous repair in diabetic mice. Wound Repair and Regeneration15(5), 628-635. DOI:10.1111/j.1524-475X.2007.00274.x

2005

Mace, K. A., Hansen, S. L., Myers, C., Young, D. M., & Boudreau, N. (2005). HOXA3 induces cell migration in endothelial and epithelial cells promoting angiogenesis and wound repair. Journal of Cell Science118(12), 2567-2577. DOI:10.1242/jcs.02399

Mace, K. A., Pearson, J. C., & McGinnis, W. (2005). An epidermal barrier wound repair pathway in Drosophila is mediated by grainy head. Science308(5720), 381-385. DOI:10.1126/science.1107573

 

Biography

2012 – present, Senior Lecturer, Faculty of Biology, Medicine and Health, The University of Manchester, UK.

2007 – 2012, Healing Foundation Fellow, Faculty of Life Sciences, The University of Manchester, UK.

2003 – 2007, Ruth L. Kirschstein NIH Postdoctoral Fellow, Department of Surgery, University of California San Francisco, USA. Advisors: David Young/Nancy Boudreau.

1997 – 2003, PhD, Division of Biology, Section on Cell and Developmental Biology, University of California San Diego, USA. Advisor: William McGinnis.

1996 – 1997, Research Associate, Department of Biology, University of Nevada Las Vegas, USA. Advisor: Deborah Hoshizaki.

1992 – 1996, BSc, Department of Biology, University of Nevada, Las Vegas, USA.

1986 – 1991, BFA, Drama, School of Theatre, University of Southern California, Los Angeles, California, USA.