Research Focus

The main research focus of the Morello’s lab is the functional characterization of novel genes, in particular those involved in bone formation, development, homeostasis and disease, collagens and the proteins involved in their post-translational modifications, animal models of connective tissue disease, osteogenesis imperfecta and its underlying pathogenetic processes, including mechanisms that impact respiratory function in OI patients.

 

Representative Publications

 

  1. 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 127 (2), 291-304, 2006.
  2. Gruenwald K, Castagnola P, Besio R, Dimori M, Chen Y, Akel NS, Swain FL, Skinner RA, Eyre DR, Gaddy D, Suva LJ, Morello R: “Sc65 is a novel endoplasmic reticulum protein that regulates bone mass homeostasis”. J Bone Miner Res. 29(3): 666-75, 2014.
  3. Heard ME, Besio R, Weis MA, Rai J, Hudson DM, Dimori M, Zimmerman SM, Kamykowski JA, Hogue WR, Swain FL, Burdine MS, Mackintosh SG, Tackett AJ, Suva LJ, Eyre DR, Morello R: “Sc65-null mice provide evidence for a novel endoplasmic reticulum complex regulating collagen lysyl hydroxylation”. PLoS Genet. 12(4); published April 27, 2016.
  4. Zimmerman SM, Dimori M, Heard-Lipsmeyer ME, Morello R: “The osteocyte transcriptome is extensively dysregulated in mouse models of osteogenesis imperfecta”. JBMR Plus 2019, (https://doi.org/10.1002/jbm4.10171).
  5. Dimori M, Heard-Lipsmeyer ME, Byrum SD, Mackintosh SG, Kurten RC, Carroll JL, Morello R: “Respiratory defects in the CrtapKO mouse model of osteogenesis imperfecta”. Am J Physiol – Lung C 2020 – in press.

 

Projects

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.

 

 

Grant Funding

 

1 R01 AI119380                              PI: Smeltzer, M                               7/01/15 – 6/30/20

$1,845,110 total direct cost                                                                        NIH/NIAID

Impact of Staphylococcus aureus in osteomyelitis and bone physiology

The focus of this application is to identify Staphylococcus aureus virulence factors that contribute to its predominance as a cause of bone infection.

Role: Co-Investigator (beginning July 01, 2016)

 

1 P20 GM125503-01                      PI: O’Brien, Charles                                        02/16/18 – 01/31/23

$7,500,000 total direct cost                                                                        NIH/NIGMS

This is a Center for Biomedical Research Excellence (COBRE) application to establish a Center for Musculoskeletal Disease Research (CMDR) at the University of Arkansas for Medical Sciences.

Roles:         Director of Core 002 (Bone Histology and Imaging)

Former mentor for project 04

PI of a Pilot project (March 2020 – February 2021)

 

 

1 R03 HD097559-01                        PI: Morello, R                                       01/11/19 – 12/31/20

$150,500 total direct cost                                                                                 NIH/NICHD

This project proposes to study the lung disease in mouse models of Osteogenesis Imperfecta.

 

UAMS Research Scholar Pilot Grant Award in Child Health   Morello, R        01/01/19-12/31/20

$50,000 intramural

Title: Respiratory Function in Animal Models of Skeletal Dysplasias.

 

 

Students/Postdocs (past and present)

 

Graduate students:

Sarah Zimmerman  (Ph.D. program) Interdisciplinary Biomedical Sciences

Advisor: Roy Morello, Ph.D. – 2013 – Graduated in 2018

 

Summer students:

2011          MaLeah Dunn                           Diversity Affairs Summer Program

2012          MaLeah Dunn                           Diversity Affairs Summer Program

2016          Sharon Amole                           Diversity Affairs Summer Program

2017          Sarah Ricks                              Diversity Affairs Summer Program

2018          Sarah Ricks                              Diversity Affairs Summer Program

2019          Karsten Winter Amezcua          Diversity Affairs Summer Program

2019          Seth Ransom                            M1 medical student

 

Post-docs

Roberta Besio, Ph.D.       Post-doctoral fellow – January 2013-May 2014

Melissa Heard, Ph.D.       Post-doctoral fellow – July 2014 – December 2017

 

 

Lab personnel, students and postdocs

– Milena Dimori, D.V.M.          Research Assistant