Roy Morello, Ph.D., is an associate professor in the Department of Physiology and Cell Biology at UAMS, with co-appointments in the Department of Orthopaedic Surgery and the Division of Genetics. He joined UAMS in 2009 and served as Director of the Bone Histology and Imaging Core in Phase 1 COBRE grant to establish the Center for Musculoskeletal Disease Research. Dr. Morello graduated from COBRE support when his project was funded by an NIH R01 in 2023.Dr. Morello received his bachelor’s degree in biological sciences from the University of Genoa (Italy) and then a Ph.D. in Molecular Biotechnology in 2000 from the University of Brescia (Italy). He then moved to the US where he trained as a post-doctoral fellow and then as a junior faculty under the supervision of Dr. Brendan Lee in the Department of Molecular and Human Genetics at Baylor College of Medicine, Houston, TX.

Research Focus:
In my laboratory, we study the function of novel genes, in particular those involved in connective tissue formation, development, homeostasis, and disease, with an emphasis on the skeleton. 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, proteomic and genetic approaches we characterize the phenotype of genetically modified 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.

Current Projects:
In 2023, Dr. Morello received a $1.54 million research grant to study better treatments for osteogenesis imperfecta, which is a rare genetic disorder of connective tissues, mainly caused by mutations in the genes responsible for producing Type I collagen, a protein that normally holds bones together and makes them strong. The four-year award from the National Institutes of Health will support his work investigating whether lung abnormalities in OI patients can be treated separately from OI’s bone- related defects.

Study of respiratory function in osteogenesis imperfecta (in collaboration with Dr. John L. Carroll at ACH)
The goal is to characterize the respiratory function in mouse models of OI with the hypothesis that type I collagen mutations causing OI also cause primary lung defects. We published the first manuscript on the characterization of the respiratory function and mechanics in CrtapKO mice and are currently working on the characterization (histology and respiratory mechanics) of two additional mouse models, the Amish (G610C mutation in Col1a2) and the oim/oim.

Study of the potential role of the prolyl 3-hydroxylation complex (Crtap/P3h1/CypB) in the post-translational modification (PTM) of surfactant D and A
The goal of this study is to understand if the prolyl 3-hydroxylation complex (Crtap/P3h1/CypB), that is responsible for fibrillar collagens post-translational modification, has a similar in surfactant D and A. We are using a human A549 cell line (type II pneumocytes) transfected with a Flag-tagged version of murine SP-D. The goal is to produce and isolate SP-D for mass-spec characterization of its PTMs and then assess these PTMs in A549 that lack expression of Crtap.

Study of the role of Rab33b in the skeleton (in collaboration with Drs. Lupashin and Storrie)
A new mouse model was generated using CRISPR/Cas9 and carrying a missense mutation in Rab33b identical to one that causes a rare human skeletal dysplasia. We are characterizing the skeletal phenotype of these mice and will also do in vitro work to characterize the effects of this mutation both on Rab33b and on the osteoblast/chondrocyte secretome.

Study of the cellular pathogenic processes in OI
We are interested in understanding what is the role of osteocytes in OI – are they passive players or active contributors to the pathogenesis of OI? We are also interested in better understanding the sub-cellular processes in osteoblasts that are affected in OI disease.