Biagio Saitta, PhD
Research Scientist, Medical Genetics
|Regenerative Medicine Institute|
Awards and Activities
|East Coast Connective Tissue Meeting||1993|
|International Society for Matrix Biology||1995|
|International Society for Stem Cell Research||2005|
Understanding molecular mechanisms of abnormal growth plate development using patient-derived induced Pluripotent Stem Cells (iPSCs), to recapitulate dysregulated processes of cartilage development underlying the Skeletal Dysplasia (SD) disorders. SDs are a heterogeneous group of more than 450 genetic disorders and an important cause of congenital birth defects seen in 1:5000 live births worldwide. These disorders frequently result in disproportionate short stature with abnormalities in the size and shape of the limbs, trunk and/or skull and perinatal lethality. Many of the genes associated with SDs involve components of the extracellular matrix and its regulatory pathways. Having such patient-derived iPSCs as an in vitro model in place can then allow development and assessment of potential small molecule-based therapeutic approaches.
Developed multipotent mesenchymal stem cells (MSCs) from neonatal cord blood with shown diversity among MSCs and that they can be used successfully as in vitro models of musculoskeletal development. His expertise in extracellular matrix (ECM) regulation and in stem cell biology has resulted in collaborative federal grants with Schepens Eye Institute of Harvard Medical School, using MSCs to develop cell-based therapies for disorders requiring corneal transplants. Future goals involve combining stem cell technology with his background on ECM and collagen genes regulation to develop novel in vitro models of early stages of skeletal development and study degenerative conditions.
Current investigations include:
The research project combines the power of the material in the International Skeletal Dysplasia Registry, (ISDR) containing over 20,000 specimens representing the disease spectrum of SDs, with iPSC biology to reprogram cells from affected patients. In collaboration with the RMI iPSC core, we have successfully generated, using fibroblasts from SD patients with lethal and non-lethal forms of metatropic dysplasia, a total of 5 iPSC lines representing the full spectrum of metatropic dysplasia, carrying distinct dominant missense mutations in different regions of the TRPV4 gene, Transient Receptor Potential Vanilloid Family 4. The focus of the lab is to study the derived iPSCs, as in vitro model reflecting each disease state at the molecular level, by differentiating them into chondrocytes trough the different phases of the growth plate. Our goal is to demonstrate that the differentiation of derived normal iPSCs recapitulates normal chondrogenesis and that iPSCs derived from the fibroblasts of patients with TRPV4 SDs can model an aberrant cartilage developmental process. This work involves intercampus collaboration with established investigators in the molecular genetics of SDs.
- Anderson DG, Markova D, An HS, Chee A, Enomoto-Iwamoto M, Markov V, Saitta B, Shi P, Gupta C, Zhang Y: Human umbilical cord blood-derived mesenchymal stem cells in the cultured rabbit intervertebral disc: a novel cell source for disc repair. Am J Phys Med Rehabil, 92(5): 420-9, 2013
- Joyce NC, Harris DL, Markov V, Zhang Z, Saitta B: Potential of human umbilical cord blood mesenchymal stem cells to heal damaged corneal endothelium. Mol. Vis., 18: 547-64, 2012
- William DA, Saitta B, Gibson JD, Traas J, Markov V, Gonzalez DM, Sewell W, Anderson DM, Pratt SC, Rappaport EF, Kusumi K: Identification of oscillatory genes in somitogenesis from functional genomic analysis of a human mesenchymal stem cell model. Dev. Biol., 305(1): 172-86, 2007
- Markov V, Kusumi K, Tadesse MG, William DA, Hall DM, Lounev V, Carlton A, Leonard J, Cohen RI, Rappaport EF, Saitta B: Identification of cord blood-derived mesenchymal stem/stromal cell populations with distinct growth kinetics, differentiation potentials, and gene expression profiles. Stem Cells Dev., 16(1): 53-73, 2007
- Saitta B, Gaidarova S, Cicchillitti L, Jimenez SA: CCAAT binding transcription factor binds and regulates human COL1A1 promoter activity in human dermal fibroblasts: demonstration of increased binding in systemic sclerosis fibroblasts. Arthritis Rheum., 43(10): 2219-29, 2000
- Cicchillitti L, Jimenez SA, Sala A, Saitta B: B-Myb acts as a repressor of human COL1A1 collagen gene expression by interacting with Sp1 and CBF factors in scleroderma fibroblasts. Biochem. J., 378(Pt 2): 609-16, 2004