Angelman syndrome (AS) is a rare neurological disorder caused by loss of Ube3a protein in neurons. In all individuals, this loss occurs from the paternal allele due to genomic imprinting; at around week 10 of neuronal development, a long noncoding RNA, Ube3a-ATS, is transcribed from the paternal allele. Ube3a-ATS physically overlaps paternal Ube3a, thereby blocking its transcription. Individuals with AS have a complete absence of Ube3a expression in the brain due to a maternal loss of function.

Osteoarthritis (OA) is a chronic disease characterized by a progressive loss of hyaline cartilage, leading to restricted movement and painful joints. Due to a lack of vasculature, low cellularity, and the low mitotic activity of chondrocytes, hyaline cartilage does not spontaneously regenerate. Microfracture (MF) surgery can be used to treat OA and works by stimulating production of de novo cartilage in the treated areas. However, fibrocartilage rather than hyaline cartilage forms in the area following surgery.

Familial Dyskinesia with Facial Myokymia (FDFM) is a rare autosomal dominant movement disorder characterized by involuntary tremors in the limbs and facial muscles with a wide range in severity of symptoms. Mutations in a gene highly expressed in the striatum, the adenylate cyclase 5 gene (ADCY5), have been linked to FDFM with the most severe phenotype associated with a gain of function mutation linked to elevated cAMP levels at amino acid 418 (arginine to tryptophan).

Lymphatic vascularization is essential for ensuring tissue regeneration and repair due to lymphatic vessels’ crucial role in maintaining normal tissue fluid homeostasis. Localized stimulation of lymphangiogenesis, the formation of new lymphatic vessels, is a promising strategy for addressing a range of disorders and tissue damage via restoration of lymphatic function. Such functions include resolving inflammation, removing waste molecules and cell debris from tissues, and regulation of immune surveillance and trafficking.

In Dr. Nolta’s lab, we are developing novel immune deficient mouse models for use in human stem cell research. The goal of our project is to verify human Mesenchymal Stem Cells (hMSCs) transduced with a lentiviral plasmid containing a working copy of N-Sulfoglucosamine Sulfohydrolase (SGSH) cDNA (hMSC-SGSH) as a therapeutic for direct application and amelioration of Sanfilippo in a novel immune deficient disease mouse model. Sanfilippo Syndrome, is an autosomal recessive neurodegenerative lysosomal storage disorder which currently has no cure or effective treatment.

Genetics diseases are difficult to treat and the available drugs target small percentage of genetics diseases and provide no cures. With more understanding in human genome and CRISPR technology, genome editing could lead to cures. Dominate negative disease such as Charcot-Marie-Tooth provides a promising therapeutic targets for CRISPR technology to selectively inactivate the disease allele to test if cellular function can be restored.

Snyder-Robinson Syndrome (SRS) is a rare disease where patients harbor mutations in the spermine synthase (SMS) gene, resulting in multiple defects, including inadequate bone development. This defect has been suggested to be due to impaired osteogenic differentiation of bone marrow-derived mesenchymal stem cells (MSCs). To elucidate how defective SMS leads to impaired osteogenesis, we generated a lentivirus to deliver shRNA to silence SMS expression. Effective silencing of SMS expression was confirmed by RT-PCR.

Autologous Endothelial Cells (ECs) have become increasingly vital for providing vascular networks to regenerated organs and a source for autologous cell therapy of ischemic disorders. Additionally, new techniques are arising that make in utero transplantation of functional cells a viable alternative to treating congenital disorders. Here we explore the promise of direct reprogramming in which a mature cell type can be reprogrammed into a distinct mature cell type without passing through the pluripotent phase.

Recent advances in disease modeling with directed differentiation of induced pluripotent stem cells have offered alternatives to mouse models and given us the ability to understand disease on a cellular level. Familial Dyskinesia with Facial Myokymia (FDFM) is an autosomal dominant movement disorder. Characterized by involuntary twitches or tremors, FDFM has been causatively linked to several mutations in the adenylate cyclase 5 (ADCY5) gene, which is highly expressed in the striatum.

Malignant glioma is the most common primary brain tumor with approximately 20,000 new cases expected in the United states in 2018. It has been shown that approximately 12% of glioblastoma multiforme (GBM) and ⅓ of all adult gliomas display mutations in the isocitrate dehydrogenase 1 and 2 (IDH1/IDH2) genes. To date, no effective therapeutics exist that show specificity towards IDHMUT gliomas. In order to find a potential therapeutic for IDHMUT gliomas, the Persson lab conducted a high throughput drug screen of over 2,177 FDA-approved compounds.