The Petritsch lab at UCSF investigates many processes of one of the most important organ in the body, the brain. One of your main goals is to understand the development and maturation of myelinating cells called oligodendrocytes (OLG). OLG cells constituting 2-9% of the total cells in the adult brain are the largest proliferating population. These unique cells originate from oligodendrocyte precursor cells (OPC) that express the NG2 chondroitin sulfate proteoglycan.
The Calos lab is focused on creating therapies for the treatment of various muscular dystrophies. Muscular dystrophies are a collection of diseases characterized by increasing muscle weakness and wasting as the affected individual gets older. The most progressive and lethal of these myopathies is Duchenne Muscular Dystrophy, DMD is the result of a mutation in the dystrophin gene. This disease is sex linked, affects 1 in 3500 live male births and causes wasting to the muscles of the skeletal and cardiac systems.
The Fan Yang Laboratory focuses in Biomaterials and Stem Cells engineering for tissue engineering and targeted drug delivery. One of the major focuses of the lab is the eradication of glioblastoma multiforme (GBM) using adipose derived stem cells (ADSCs). Due to the delicate anatomical location of GBM (the brain), surgical removal is often times precluded, dramatically reducing clinical outcomes. Adipose derived stem cells are an abundant source of adult stem cells that possess unique tumor-tropic abilities coordinated by a myriad of tumor-secreted signals.
Psoriasis is the most common inflammatory skin disease affecting 1-3% of the world’s population. Both keratinocyte cells and immune cells are central in the disease pathogenesis. The Marinkovich Lab at Stanford University has established that psoriatic keratinocytes have an intrinsic predisposition for Rac1 hyperactivation. Rac1 is a small GTPase known to regulate many important cellular processes, including those mediating cell cytoskeletal rearrangements, cellular migration, cell-cell adhesion, and the cell cycle.
Increasing evidence suggests cell-to-cell communication is possible via extracellular RNAs (exRNAs). Regulation of gene expression through microRNAs (miRNAs) has long been established as an endogenous mechanism for fine-tuning expression post-transcriptionally. These small RNAs can prevent translation by binding to the 3’-UTR (untranslated region) of a target mRNA transcript. Recently, many studies have suggested miRNAs can act intercellularly (as exRNAs), potentially broadening their role in many biological processes.
Genome editing is one of the forefront topics of science with vast potential uses. One large application is the effects that precise genome editing will have on the field of regenerative medicine. Precise genome editing for therapeutic purposes is difficult to achieve because it requires the pathway of homology directed repair (HDR) to be active rather than non-homologous end joining (NHEJ) which results in deleterious insertions or deletions in the DNA. These pathways are distinct and are regulated by different enzymes.
A heterozygous missense mutation in the H3F3A gene, which encodes a lysine-27-to-methionine substitution in the replication-independent histone H3.3, has been implicated as the main tumor driver in a subset of pediatric high-grade gliomas. This mutant histone variant, H3.3-K27M, alters normal histone marks and promotes a globally hypomethylated DNA landscape. Recent evidence has led to speculation that this mutation promotes gliomagenesis, exclusively, in oligodendrocyte progenitor cells (OPCs) to form diffuse intrinsic pontine gliomas (DIPGs).
Lethal Giant Larvae (Lgl1) is a protein involved in establishment of cellular polarity and is implicated in numerous cancers by expression or splicing aberration. Studies in the brains of mammalian models have shown protein knockout results in lesions exhibiting overproliferation and differentiation defects reminiscent of neoplasm. Our lab is examining the role of Lgl1 in regulation of key components of tissue homeostasis with emphasis on oligodendrocyte precursors.
Little is known about the growing number of gene mutations implicated in Autism Spectrum Disorder (ASD). Their mutations need to be studied in order to predict in vivo effects. We hypothesize that mutations found in ASD genes will cause dysregulation of GABAergic interneuron development. The aim of this project is to utilize a moderate throughput assay to identify in vivo functional changes that are caused by nonsynonymous mutations in candidate ASD genes. We will focus on CNTNAP2, an ASD susceptibility gene that has multiple mutant alleles that were identified in ASD populations.
Planar Cell Polarity (PCP) is required for proper orientation of a cell within a tissue and organ during development and regeneration. PCP has been described in adult neurons but its role during neuronal differentiation remains enigmatic. During postnatal cerebellum development granule neural precursors (GNPs) proliferate on the surface in the external granule layer, then start to migrate inward in a directed way to later form granule neurons (GN), the most abundant cell type in the brain.