PRIMARY FACULTY

Michael J. Schell, Ph.D.
Assistant Professor
Pharmacology
 
4301 Jones Bridge Road
Bethesda MD 20814
Office: 301-295-3249
Fax: 301-295-1996
mschell@usuhs.mil

Project 1: Control of actin structure and calcium signals in dendritic spines by IP3 3-kinase.
Dendritic spines are the tiny protrusions located on the receiving ends of most incoming excitatory signals in brain. Spines compartmentalize calcium and second messenger signals, which are integrated in the main dendrite to determine action potentials, signaling cascades, and changes in gene expression. On time scales of seconds to days, dendritic spines also undergo structural plasticity, as reflected in changes in spine shape, size and number. Such changes are controlled predominantly through the actin cytoskeleton. The signaling protein IP3 3-kinase A (ITPKA) is highly enriched in the dendritic spines of neurons, especially those neurons involved in higher learning and memory. ITPKA controls the lifetime of the second messenger inositol trisphosphate (IP3), which releases calcium from the endoplasmic reticulum intracellular stores via the IP3 receptor. In the course of turning off the IP3 signal, ITPKA also makes IP4, which is a possible second messenger whose role in signaling remains an active and controversial are of research. We discovered that ITPKA is also a filamentous actin (F-actin) binding protein in spines and we recently described how ITPKA is able to influence the structural plasticity of spines by modifying the shape of the F-actin microstructure. The laboratory has a strong interest in developing microscopic techniques for studying actin structure, dynamics, and calcium signals in living neurons. The long term-goal of this project is to delineate how ITPKA contributes to the synaptic plasticity that underlies learning and memory.

Schell Images

Project 2: Pharmaceutical control peroxisome number in brain cells.
Peroxisomes are organelles that specialize specialized biochemical reactions in all cells. The biogenesis and maintenance of peroxisome number is important, since defects in proteins that control peroxisome abundance lead to metabolic deficits that manifest most prominently in brain. Despite this, very little research has been done to investigate the molecular mechanisms controlling peroxisome abundance in neurons and glia. My lab has discovered novel pharmaceutical means of controlling peroxisome numbers in astrocytes via drugs that regulate cholesterol homeostasis in cells. We are investigating the molecules that regulate the transcription of genes that control peroxisome proliferation. We use a combination of cell biology, molecular biology, and microscopy to understand the pathways controlling peroxisome number and function. This research has medical relevance to metabolic disorders, neuronal migration, myelination, and Alzheimer's disease.

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