SearchThe principal focus of the Ginsberg laboratory is to delineate cellular and molecular mechanisms underlying cellular, synaptic, and dendritic reorganization following neurodevelopmental and neurodegenerative brain insults.
The Ginsberg laboratory employs the use of animal and cellular models of neurodegeneration as well as human postmortem brain tissues for functional genomic and proteomic based studies.
Dr. Ginsberg’s underlying hypothesis is that individual cell types are likely to have unique patterns of gene and protein expression under normative conditions that are altered in pathological states, which drives subsequent neurodegeneration. Indeed, the molecular and cellular basis of why certain neuronal populations are vulnerable to neurodegeneration, often termed “selective vulnerability”, can be elucidated by discrete cell analysis more readily than by utilizing regional and total brain preparations.
The hippocampal formation and cholinergic basal forebrain, brain regions critical for learning and memory, are the main structures analyzed, with particular emphasis given to identifying mechanisms that underlie changes within specific cell types, including cholinergic basal forebrain (CBF) neurons, dentate gyrus granule cells, CA1 & CA3 pyramidal neurons, and entorhinal cortex stellate cells.
Experiments are conducted on animal and cellular models of neurodegeneration, including mouse models of amyloid overexpression, Down syndrome (DS), and tauopathy. The Ginsberg lab also conducts parallel studies on postmortem human brain tissues accrued from subjects diagnosed with Alzheimer’s disease (AD), DS, mild cognitive impairment (MCI), and nondemented controls with no cognitive impairment (NCI).
Dr. Ginsberg is also spearheading a program to investigate selective vulnerability of specific pyramidal neurons and GABAergic interneurons in schizophrenia (SZ) and major depressive disorder (MDD).
The Ginsberg Laboratory has provided essential data in human and relevant mouse models that compare and contrast cells that degenerate (e.g., CBF neurons, CA1 hippocampal pyramidal neurons, and glutamatergic neocortical pyramidal neurons) versus cells that are relatively spared within these specific paradigms (e.g., dentate gyrus granule cells).
Dr. Ginsberg is one of the relatively few neuroscientists that conduct expression profiling research at the single cell level consistently.
Dr. Ginsberg developed his own RNA amplification technology termed terminal continuation (TC) RNA amplification which is employed in conjunction with microarray and qPCR based investigations of gene expression at the single cell level.
The Ginsberg laboratory has just developed a new technology for the amplification of microRNAs termed miRNA signature sequence amplification (SSAM) for biomarker discovery science. miRNAs are a short 17-25 nucleotide class of non-protein coding RNAs (ncRNAs) that have been shown to have critical functions in a wide variety of biological processes. One major obstacle when profiling miRNAs is their low expression level. miRNAs are estimated to constitute only 0.01% of total RNA. As a result, large quantities of starting materials were required for miRNA profiling until the advent of the developing SSAM technology.
