Michelina Iacovino, PhD

Michelina Iacovino, PhD

Investigator, The Lundquist Institute
Assistant Professor of Pediatrics, Division of Medical Genetics, David Geffen School of Medicine at UCLA

Contact

Development of vascular endothelium and stem cell therapies

Research Description

Dr. Iacovino’s laboratory is interested in developing stem cell therapies for rare genetic disorders that affect brain function. They are currently investigating the proof of concept to use Neuronal Stem Cell (NSC) derived from induced Pluripotent Stem Cells (iPSC) as a delivery tool for a missing protein into the brain. They are testing this approach for 2 rare genetic disorders: Sanfilippo B and Pitt Hopkins syndrome. Sanfilippo B is caused by a genetic mutation in a lysosomal enzyme (NAGLU) that is needed for heparan sulfate degradation. Pitt Hopkins syndrome is caused by a mutation in a transcription factor (TCF4) needed for neurodevelopment. We are also developing a brain organoid system to model Pitt Hopkins syndrome and understand how the missing protein impact brain development.

Dr. Iacovino is also interested in understanding the role of Hox Genes, essential transcription factors for organogenesis, in the developing heart and blood system. One project founded in the lab aims at understanding the role of HoxA3 during Cardiac Development. The other project in the lab regards the generation of HSC during development. Pluripotent Stem cell therapy is a future solution but is still unclear the mechanism governing HSC generation from embryonic tissue.

Education

  • PhD, 2004, University of Molise, Campobasso, Italy

Recent and/or Significant Publications

S. Le, S. Kan, D. Clarke, V. Sanghez, M. Egeland, K. Vondrak, T. Doherty, M. Vera, M. Iacovino, J. Cooper, M. Sands, P. Dickson. A humoral immune response alters the distribution of enzyme replacement therapy in murine mucopolysaccharidosis type I. Mol Ther Methods Clin Dev. 2017 Oct 5;8:42-51.
V. Sanghez, A. Luzzi, D. Clarke, D.P. Kee, S. Beuder, D. Rux, M. Osawa, T-F Chou, M. Kyba M. Iacovino. HoxA3 Induces Ligand cis-Inhibition of the Notch Pathway to Arrest Endothelial to Hematopoietic Transition (EHT). Plos One 2017 Oct 26;12(10):e0186818.
Liu J, Guo B, Chen Z, Wang N, Iacovino M, Cheng J, Roden C, Pan W, Khan S, Chen S, Kyba M, Fan R, Guo S, Lu J. miR-125b promotes MLL-AF9-driven murine acute myeloid leukemia involving a VEGFA-mediated non-cell-intrinsic mechanism. Blood. 2017 Mar 16; 129(11): 1491–1502.
Gong M, Antony S, Sakurai R, Liu J, Iacovino M, Rehan VK. Bone Marrow Mesenchymal Stem Cells of the Intrauterine Growth Restricted Rat Offspring Exhibit Enhanced Adipogenic Phenotype. Int J Obes 40, 1768–1775 (2016).
Zhang, X., Gui, L, Zhang, X, Bulfer, S.L., Sanghez, V. Wong, D., Lee, Y., Lehmann, L., Lee, S.L. Shih, P.Y., Lin, H.J., Iacovino, M., Weihl, C.C., Arkin, M.R., Wang, Y., Chou, T.-F. Altered cofactor regulation with disease associated p97/VCP mutations. Proc Natl Acad Sci USA 2015 112(14):E1705-14.