UAMS.EDU

Roy Morello

Roy Morello
Assistant Professor
Ph,D., University of Brescia
Office (501) 526-4090
Lab (501) 526-4091
RMorello@uams.edu

In my laboratory we study the function of novel genes, in particular those involved in bone formation, development, homeostasis and disease. We utilize the power of mouse gene targeting and conditional gene-inactivation techniques to generate ubiquitous or tissue-specific mutations in the mouse. With the use of cell biology, biochemistry, cell microscopy and genetic approaches we characterize the phenotype of these mice to understand the underlying gene function. The objective is to learn from the animal model and make correlations with relevant aspects of human disease and hence gain mechanistic insights of biological function.

We recently characterized the function of the Crtap gene, a member of the Leprecan family of genes. Crtap knock-out mice have dramatic low bone mass and a functional defect in bone forming cells, the osteoblasts. We demonstrated that Crtap forms a complex in the endoplasmic reticulum with two proteins that have enzymatic function and such trimeric complex has essential collagen post-translational modification and chaperone activity. Importantly, while type I collagen mutations in humans cause autosomal dominant Osteogenesis imperfecta (OI – brittle bone disease), we identified CRTAP as the first gene whose mutations cause recessive forms of OI. Our discovery led the way to the recent identification of 4 new genes causing similar forms of recessive OI and involved in collagen intracellular processing. Currently, we are trying to further elucidate the Crtap protein function especially in the extracellular matrix.

We have also started a new project aimed at the characterization of another poorly understood member of the Leprecan family, Sc65. This protein has high similarity to Crtap and it is encoded by an evolutionarily related gene that may have retained a similar function. Current experiments are aimed at the study of Sc65 through the use of a mouse with an insertional mutation in the Sc65 gene.

We collaborate with the groups of Drs. Dana Gaddy and Larry Suva with whom we have joint lab meetings, and with other bone and non-bone researchers on campus.

Representative Publications

Homan EP, Rauch F, Grafe I, Lietman C, Doll JA, Dawson B, Bertin TK, Napierala D, Morello R, Gibbs R, White L, Miki R, Cohn DH, Crawford S, Travers R, Glorieux FH, and Lee B.: “Mutations in SERPINF1 Cause Osteogenesis Imperfecta Type VI. J Bone Miner Res. 26(12): 2798-803, 2011.

Ben Amor IM, Rauch F, Gruenwald K, Weis M, Eyre DR, Roughley P, Glorieux FH, and Morello R: “Severe Osteogenesis Imperfecta Caused by a Small In-Frame Deletion in CRTAP”. Am J Med Genet. 155A(11): 2865-70, 2011.

Gruenwald K, Castagnola P, Besio R, Dimori M, Chen Y, Akel NS, Swain FL, Skinner RA, Eyre DR, Gaddy D, Suva LJ, and Morello R: “Sc65 is a novel endoplasmic reticulum protein that regulates bone mass homeostasis”. J Bone Miner Res. 2013 In press.

Morello R, Bertin TK, Chen Y, Hicks J, Tonachini L, Monticone M, Castagnola P, Rauch F, Glorieux FH, Vranka J, Bachinger HP, Pace JM, Schwarze U, Byers PH, Weis MA, Fernandes RJ, Eyre DR, Yao Z, Boyce BF, and Lee B.  “CRTAP is required for prolyl 3-hydroxylation and mutations cause recessive Osteogenesis Imperfecta”. Cell 2006; 127 (2), 291-304.

Morello R, Bertin TK, Schlaubitz S, Shaw CA, Kakuru S, Munivez E, Hermanns P, Chen Y, Zabel B, and Lee B.  “Brachy-syndactyly caused by loss of Sfrp2 function”. J. Cell. Physiol. 2008; 217, 127-137.

Fratz-Zelman N, Morello R, Lee B, Rauch F, Glorieux FH, Misof BM, Klaushofer K, and Roschger P: “CRTAP deficiency leads to abnormally high bone matrix mineralization in a murine model and in children with Osteogenesis Imperfecta type VII”. BONE 46; 2010, 820-826.

Baldridge D, Lennington J, Weis MA, Homan E, Jiang M, Munivez E, Keene DR, Hogue WR, Pyott S, Byers PH, Krakow D, Cohn DH, Eyre DR, Lee B and Morello R: “Generalized Connective Tissue Disease in Crtap-/- Mouse”. PLoS ONE; published May 11, 2010.

Gabbay KH, Bohren KM, Morello R, Bertin TK, Liu J and Vogel P: “Ascorbate Synthesis Pathway: Dual role of Ascorbate in bone homeostasis”. J. Biol. Chem. 2010, 285: 19510-20.

Morello R. and Rauch F.: “Role of Cartilage-associated Protein in Skeletal Development”. Current Osteoporosis Report. Volume 8, Number 2, 2010, 77-83.

Link to Dr. Morello at PubMed