Schaefer remained in
Greengard’s lab as a research associate from 2007 to 2009 and was promoted to Senior Research Associate in 2009. Schaefer is currently a tenured professor in the Department of Neuroscience and Psychiatry at the Friedman Brain Institute at
Mount Sinai School and remains an adjunct faculty member at
Rockefeller University. In 2017, Schaefer co-founded the Center for Glial Biology at Mount Sinai and is now the co-director of the center alongside Dr.
Patrizia Casaccia. Since loss of miRNA led to cerebellar degeneration, her findings highlight the potential role for dysregulation of miRNAs in neurodegenerative diseases.
Histone methyltransferases are a key regulator in gene expression. They manipulate the state of DNA, which can be either open, referred to as
euchromatin or closed, referred to as
heterochromatin. She found that a deficiency in
argonaute 2 (a gene known to regulate the generation of
miRNA) in the
dopamine receptor 2 (Drd2) positive cells in the
striatum caused a decrease in the motivation to seek cocaine. When they suppressed this miRNA, aberrant motor patterns and fatal epilepsy resulted. When they suppressed BET proteins they found decreased neuronal gene expression and neuronal dysfunction which suggested a role for the BET-controlled gene network in ASD.
Epigenetics and microglia Another facet of Schaefer's work is understanding the impact of epigenetic regulation on neuroimmunity, with a particular focus on the innate immune cells of the brain,
microglia. They found that baseline phagocytic activity of microglia was high in the cerebellum but low in the striatum. They found that cerebellar microglial identity was driven by interactions between
CSF-1 and the
CSF-1 receptor, and was not reliant on the alternate CSF-1R ligand,
IL-34. The TRAP (Translating Ribosome Affinity Purification) methodology that is described in this patent provides a way to detect genes that are co-regulated within or across cell types, as well as discover candidate gene targets for treating specific neurological disorders and screen for modulators of those candidate genes. In 2013, Schaefer and her postdoctoral advisor, Dr. Paul Greengard, filed a patent for a therapeutic strategy to treat or reduce the likelihood of seizures. Schaefer and Greengard found that the microRNA miR-128 is involved in modulating neuronal excitability and motor activity. Their therapeutic strategy involves administering miR-128, an agent with 90% sequence homology, or an agent capable of increasing the expression or activity of miR-128 as a means to control dopamine receptor 1 (Drdr1) neuron excitability. The agent would be administered intrathecally, intranasally, or directly to the hippocampus or cortex via an injection. == Awards and honors ==