Navigation

Researchers at UCD

researcher

Debra Higgins

Lecturer/Assistant Professor

School Of Medicine
Conway Institute
Belfield
Dublin 4

Tel:
Email: debra.higgins@ucd.ie

Biography

 Dr. Debra Higgins is an Assistant Professor / Lecturer in Pathology. Debra graduated from UCD in 1995 with a first class joint honours degree in Botany and Molecular Genetics, and in 2001 completed her PhD in Prof Matthew Harmey's laboratory studying differential gene expression techniques. Debra was one of the original twelve Conway Post-doctoral Fellows to be recruited and studied molecular mechanisms of kidney disease with Profs Hugh Brady, Catherine Godson, William Watson and John Fitzpatrick at the Mater Misericordiae Hospital prior to the opening of the Conway Institute. She was awarded the first Conway Post-doctoral Fellows prize for Best Oral Presentation at the Conway Festival of Research in 2001.
 
 In 2002, Debra moved to the University of Pennsylvania to work with Dr. Volker Haase, and studied the role of hypoxia and HIF in the progression of kidney disease. During her time in the US, she was awarded  American Heart Association post-doctoral fellowship.  In 2009, Debra returned as a Research Fellow to the Diabetes Complications Research Centre based in the Conway Institute to further her research into acute and chronic kidney disease, and was lead investigator on industry sponsored projects by Boehringer Ingelheim and Roche.

 In 2011, Debra was awarded a HRB Fellowship in Translational Medicine to investigate the potential of hypoxia-responsive proteins as diagnostic biomarkers for early detection of renal disease and as therapeutic targets for treatment of kidney injury. This research is being further developed through an SFI TIDA awarded in 2017.

 Debra has a total of 37 publications, of which 14 are senior author papers, in journals such as the prestigious Journal of Clinical Investigation (IF 15.43, >550 citations), Journal of American Society of Nephrology (IF 9.66), Kidney International (IF 8.56), Development (IF 6.46), Molecular and Cellular Biology (IF 5.76), FASEB Journal (5.72), and the American Journal of Physiology- Renal (IF 3.79).

Professional

Honours and Awards

Year: 2010.
Title: IEPG Outstanding Postdoctoral Award
Year: 2007.
Title: Keystone Symposium Scholarship
Year: 2007.
Title: ASN Outstanding Scientific Abstract - Oral Presentation
Year: 2002.
Title: INS Best Presentation Award
Year: 2001.
Title: Conway Research Fellows Best Presentation Award
Year: 1998.
Title: IBM Best Speaker Award
Year: 1996.
Title: Lord Edward Fitzgerald Scholarship

Associations

Association: International Society of Nephrology, Function/Role: Member
Association: European Foundation for the Study of Diabetes, Function/Role: Member
Association: The Adult Stem Cell Foundation of Ireland, Function/Role: Board of Directors
           

Education

Year 2001 Institution: University College Dublin
Qualification: PhD Subject:
Year 1995 Institution: University College Dublin
Qualification: BSc Subject: Botany and Molecular Biology
 

Consultancy

Client: Boehringer Ingelheim
Client: Roche
     

Publications

     

Peer Reviewed Journals

Börgeson E, McGillicuddy FC, Harford KA, Corrigan N, Higgins DF, Maderna P, Roche HM, Godson C. (2012) 'Lipoxin A4 attenuates adipose inflammation'. FASEB Journal, 26 (10):4287-4294. [Details]
Beaton H, Andrews D;Parsons M;Murphy M;Gaffney A;Kavanagh D;McKay GJ;Maxwell AP;Taylor CT;Cummins EP;Godson C;Higgins DF;Murphy P;Crean J (2016) 'Wnt6 regulates epithelial cell differentiation and is dysregulated in renal fibrosis'. American journal of physiology. Renal physiology, . [DOI] [Details]
Borgeson, E,Docherty, NG,Murphy, M,Rodgers, K,Ryan, A,O'Sullivan, TP,Guiry, PJ,Goldschmeding, R,Higgins, DF,Godson, C; (2011) 'Lipoxin A(4) and benzo-lipoxin A(4) attenuate experimental renal fibrosis'. FASEB Journal, 25 :2967-2979. [DOI] [Details]
Higgins DF, Kimura K, Iwano M, Haase VH (2008) 'Hypoxia-inducible factor signaling in the development of tissue fibrosis'. Cell cycle (Georgetown, Tex.), 7 (9):1128-1132. [Details]
Kimura K, Iwano M, Higgins DF, Yamaguchi Y, Nakatani K, Harada K, Kubo A, Akai Y, Rankin EB, Neilson EG, Haase VH, Saito Y (2008) 'Stable expression of HIF-1{alpha} in tubular epithelial cell promotes interstitial fibrosis'. American Journal of Physiology-Renal Physiology, 295 (4):F1023-F1029. [Details]
Higgins DF, Kimura K, Bernhardt WM, Shrimanker N, Akai Y, Hohenstein B, Saito Y, Johnson RS, Kretzler M, Cohen CD, Eckardt KU, Iwano M, Haase VH (2007) 'Hypoxia promotes fibrogenesis in vivo via HIF-1 stimulation of epithelial to mesenchymal transition'. Clinical Investigation, 117 (12):3810-3820. [Details]
Rankin EB, Higgins DF, Walisser JA, Johnson RS, Bradfield CA, Haase VH (2005) 'Inactivation of the Arylhydrocarbon receptor nuclear translocator (Arnt) suppresses VHL associated vascular tumors in mice'. Molecular and Cellular Biology, 25 (8):3163-3172. [Details]
Higgins DF, Biju MP, Akai Y, Wutz A, Johnson RS, Haase VH (2004) 'Hypoxic induction of Ctgf is directly mediated by Hif-1'. American Journal of Physiology-Renal Physiology, 287 (6):F1223-F1232. [Details]
Higgins, DF,Lappin, DWP,Kieran, NE,Anders, HJ,Watson, RWG,Strutz, F,Schlondorff, D,Haase, VH,Fitzpatrick, JM,Godson, C,Brady, HR; (2003) 'DNA oligonucleotide microarray technology identifies fisp-12 among other potential fibrogenic genes following murine unilateral ureteral obstruction (UUO): Modulation during epithelial-mesenchymal transition'. Kidney International, 64 :2079-2091. [Details]
Higgins, DF; Lappin, DWP; Isaka, Y; Watson, RW; Godson, C; Imai, E; Fitzpatrick, JM; Brady, HR; ; (2002) 'Transcriptomic responses underpinning renal tubulointerstitial fibrosis as identified by DNA oligonucleotide microarray technology'. Journal of the American Society of Nephrology : JASN, 13 (NA):560-560. [Details]
 

Conference Publications

Kavanagh, D., Gaffney A., Murphy, M., Faherty, N., Andrews, D., Higgins, D., McKay, G., Maxwell, P., Godson, C. and Crean, J. (2012) Wnt 6 is increased in diabetic nephropathy and modulates de novo tubulogenesis and opposes TGFbeta mediated epithelial cell differentiation in vitro American Society of Nephrology [Details]
                                                                                           

Comment

Higgins DF, Murphy M (2014) Epigenetic unsilencing reverses renal fibrosis. Comment [DOI] [Details]
                   

Research

Research Interests

Chronic Kidney Disease (CKD) affects approximately one in twenty five people in Ireland. There is no cure for CKD and current treatment therapies are aimed at slowing disease progression to end stage renal disease, which requires patients to undergo renal replacement therapy such as dialysis or kidney transplantation. Treating patients with kidney disease in Ireland consumes approximately 10% of the total Irish health care budget.

Diabetes and hypertension are two major causes of CKD. Diabetes is a global health problem with approximately 250 million suffers worldwide and this number is estimated to increase by more than 50%  over the next ten years. Given that approximately 30% of diabetics develop kidney disease, there is an urgent need to identify new techniques for early identification of at risk patients and to discover and develop new treatment therapies to halt and regress kidney disease. Towards this end, my research has focussed intensively on the molecular processes which are altered in diseased kidneys compared with healthy kidneys.

I have identified many key molecules which control development of renal disease including connective tissue growth factor (CTGF), bone morphogenetic protein-7 (BMP-7), and lysyl oxidase (LOX) proteins and have investigated the role of these factors in regulating pro-fibrotic processes such as epithelial injury and activation, extracellular matrix accumulation, cellular adhesion, migration, proliferation and apoptosis. My research employs a variety of pre-clinical models of kidney disease along with analysis of CKD patient samples.

In addition, my studies have identified hypoxia, or insufficient oxygen, as a critical micro-environment which controls both pro-inflammatory and pro-fibrotic processes which are fundamental to kidney disease progression. Hypoxia, via activation of hypoxia inducible transcription factors (HIF), regulates progression of kidney disease and I am currently examining how these pathways may be exploited in an effort to develop novel diagnostic and treatment strategies for DN.

Research Projects

Sponsor : F. Hoffmann-La Roche Ltd.
Title : The effect of Roche compounds in in vitro and in vivo models of fibrosis
Start Date / End Date : 01-FEB-11 / 31-OCT-11
Sponsor : Biochemical Society (BS)
Title : Elucidating the molecular mechanism underlying BMP-7 protection against renal injury
Start Date / End Date : 01-JUL-13 / 30-AUG-13
Sponsor : Biochemical Society (BS)
Title : Role of hypoxia inducible transcription factors HIF-1 and HIF-2 in macrophage differentiation towards pro-inflammatory M1 or pro-resolution M2 phenotypes
Start Date / End Date : 01-JUL-13 / 30-AUG-13
Sponsor : Irish Research Council (IRC)
Title : Promoting resolution of inflammation to protect kidney function
Start Date / End Date : 01-OCT-15 / 30-SEP-19
Sponsor : Health Research Board (HRB)
Title : LOX proteins as predictors of renal disease
Start Date / End Date : 01-DEC-11 / 30-NOV-15
   

Collaborators

Internal Collaborators

Prof. Catherine Godson
Prof. Finian Martin
Prof. Cormac Taylor
Dr. John Crean
Dr. Eileen Nolan

External Collaborators

Dr. Yvonne O'Meara, Mater Misericordiae Hospital
Dr. Denise Sadlier, Mater Misericordiae Hospital
Dr. John Holian, St. Vincent University Hospital
Prof. Cormac Kilty, Argutus Medical
Prof. Matthew Griffin, REMEDI, NUIG
Prof. Peter Conlon, Beaumont Hospital
Prof. Elaine Kay, Beaumont Hospital
Prof. Amato Giaccia, Stanford University, CA
Prof. Barbara Murphy, Mount Sinai, NY
Prof. Volker Haase, Vanderbilt, TN
Prof. Kai-Ewe Eckardt, Erlangen University
Prof. Masa Iwano