Dr Georgina Caruana

Research Fellow

Dr. Georgina Caruana obtained her B.Sc. (Honours) and Ph.D at The University of Adelaide. In 1996 she undertook a postdoctoral position in the laboratory of Professor Alan Bernstein, at The Samuel Lunenfeld Research Institute (SLRI) in Toronto, Canada. Dr Caruana has experience in embryonic murine development, ES cell differation, molecular and cellular biology and gene discovery via gene trapping, microarrays and ENU mutagenesis. Dr Caruana has supervised 3 Honours students and 4 PhD students. 

In February 2001, Dr. Caruana commenced work as a Postdoctoral Research Fellow in the laboratory of Professor John Bertram  at Monash University to study the molecular and genetic regulation of kidney development. Dr Caruanahas performed a number of mircoarray and RNA in situ  hybridisation screens designed at identifying genes expressed in various sub-compartments of the developing kidneyand ureter. Isolation of these compartments has involved techniques such as fluorescence-activated cell sorting (FACS),  laser capture mirodissection (LCM) and manual microdissection. Dr Caruana is currently analysing the function of these genes with a focus on genes that are involved in the bone morphogenetic protein 4 (BMP4) signalling pathway sing kidney andureter organ culture systems. We have developed a ureter culture system in which the ureter undergoes peristalsis (See movie below).

Identification of novel CAKUT genes

BMP4 plays an important role in the regulation of ureteric budding and ureteric branching morphogenesis in the kidney and smooth muscle cell development in the ureter. Mice heterozygous for a null mutation in BMP4 (BMP4^+/-) develop renal and ureter abnormalities that very closely mimic those seen in human patients with congenital anomalies of the kidney and urinary tract (CAKUT). Many of the genes responsible for human CAKUT remain unknown. Utilising the microarray and RNA in situ hybridisation screens performed by Dr Caruana she is characterising the function of several candidate CAKUT genes. Another approach that is being utilised by Dr Caruana to identify novel CAKUT genes is through an embryonic mouse ENU screen which will generate novel mouse CAKUT models. In the future we wish to screen human CAKUT patients for mutations in these genes. 

Rescuing nephron number in TGF β2 heterozygous mice

We and others have shown that a variety of fetal/maternal perturbations and gene defects result in a permanent nephron deficit in the kidney. Offspring often develop hypertension and kidney disease in adulthood. In a recent finding, we have shown that mice with a reduced level of the growth factor, transforming growth factor β2 (TGF-β2) have 60% more nephrons than control mice. This is the first finding of increased nephron number in a setting of altered growth factor activity. We are analysing kidney structure and function in these mice as well as their blood pressure. We are also aiming to manipulate TGF-β2 signalling to see if we can rescue nephron number in mice born with a nephron deficit.

Dr Caruana has obtained funding from NIH, Kidney Health Australia and Monash University.

In 2007, Dr Caruana was appointed Lecturer and teaches in several units in the BSc major in developmental biology (first started in 2007) run by the Department of Anatomy and Developmental Biology. Dr Caruana teaches in DEV 2011, 2022, 3011, 3022 and 3990. Dr Caruana is Deputy convenor of DEV3011.

Contact Details

Dr Georgina Caruana
Department of Anatomy and Developmental Biology
STRIP2, Building 76, Level 3, Rm 325
Phone: +61 3 9902 9104

Email:georgina.caruana@med.monash.edu.au

10 career best publications

Stanford WL, Caruana G, Vallis KA, Inamdar M, Hidaka M and Bernstein A (1998). Expression Trapping: Identification of Novel Genes Expressed in Hematopoietic and Endothelial Lineages by Gene Trapping in ES cells. Blood 92: 4622-4631 (cover article).

Caruana G & Bernstein A. (2001). Craniofacial dysmorphogenesis including cleft  palate in mice with an insertional mutation in the Discs large (dlg) gene. Mol Cell Biol. 21(5): 1475-1483.

Voytyuk O, Lennartsson J, Mogi A, Caruana G, Courtneidge S, Ashman LK & Ronnstrand L. (2003). Src family kinases are involved in the differential signalling from two splice-forms of c-Kit. J Biol Chem. 278: 9159-9166.

Challen G, Gardiner B, Caruana G, Kostoulias X, Martinez G, Crowe M, Taylor DF, Bertram J, Little M, Grimmond SM. (2005).Temporal and spatial transcriptional programs in murine kidney development. Physiol Genomics. Oct 17;23(2):159-71.

Naim E, Bernstein A, Bertram JF & Caruana G. (2005).  Mutagenesis of the epithelial polarity gene, discs large 1 perturbs nephrogenesis in the developing mouse kidney. Kidney Int. 68:955-65.

Frese KK, Latorre IJ, Chung SH, Caruana G, Bernstein A, Justice MJ, Jones SN, Donehower LA, Garner CC & Javier RT.  (2006). Oncogenic Function for the Dlg1 Mammalian Homologue of the Drosophila Discs-Large Tumor Suppressor.  EMBO J. 25:1406-17. 

Mitchell EK, Taylor DF, Woods K, Davis MJ, Nelson AL, Teasdale RD, Grimmond SM, Little MH, Bertram JF, Caruana G.(2006). Differential gene expression in the developing mouse ureter. Gene Expr Patterns. 6:519-38.

Caruana G, Cullen-McEwen L, Nelson AL, Kostoulias X, Woods K, Gardiner B, Davis MJ, Taylor DF, Teasdale RD, Grimmond SM, Little MH & Bertram JF.   (2006).  Spatial gene expression in the T-stage mouse metanephros. Gene Expr Patterns. 6:807-25.

Moritz K, Wintour EM, Black MJ, Bertram JF and Caruana G. (2008). Factors influencing kidney development- implications for health in adult life. Adv Anat Embryol Cell Biol. 196: 1-78.

Sims-Lucas S, Caruana G, Dowling J, Kett MM, Bertram JF. (2008). Augmented and accelerated nephrogenesis in TGF-beta 2 heterozygous mutant mice. Pediatr Res 63:607-12.

contract.avi (2.8mb AVI)

Click on the movie above to see Peristalsis occurring in an E12.5 mouse ureter cultured for 9 days. As the ureter develops, in vitro, the appearance of smooth muscle cells and interstitial cells of Cajal, ultimately result in the commencement of peristaltic waves of contraction".