Biomedical Sciences Graduate Program | University of California, San Francisco

Marta Margeta, MD, PhD
Synaptic function and neurologic disease

Selected Publications | Complete Publications

phone	(415) 514-0228
email	Marta.Margeta@ucsf.edu
additional websites	Department of Pathology Lab Website
secondary research affiliation	Cancer Biology & Cell Signaling

In most neurologic diseases, the pathologic process does not involve the entire brain. Instead, only specific subsets of neurons or glial cells are injured or die, and the nature of this selective brain injury determines the symptoms and clinical course of each disease. The long-term goal of our laboratory is to elucidate how neuronal signaling and synaptic plasticity contribute to the selective vulnerability of different neuronal populations and thus influence onset and/or progression of different neurologic disorders. To accomplish this goal, we use cell culture models and a combination of different approaches (molecular and cell biology, immunohistochemistry, in situ hybridization, imaging, biochemistry, and electrophysiology) to investigate two distinct but related areas:

(1) Intrinsic antioxidant defenses and neuronal signaling. Our aim is to define the role of endogenous antioxidant pathways in neuronal susceptibility to cell death, to elucidate how these pathways are regulated by neuronal activity, and to determine whether in turn they modulate neuronal signaling. Our current focusis on the Keap1/Nrf2/ARE pathway, which regulates the coordinated expression of a battery of antioxidant and phase II detoxification enzymes in response to a mild oxidative or ER stress in many different tissues, including the brain.

(2) MicroRNAs in synaptic plasticity and malplasticity. A complete loss of miRNA expression in the brain results in neurodegeneration in several animal models, but little is known about their role in normal brain function. The currently ongoing projects seek to identify miRNAs that are either transcribed or processed into mature forms in response to increased neuronal activity, to identify their candidate targets, and to establish whether they modulate synaptic strength through translational control of ion channel and receptor expression.

Our laboratory is also pursuing translational research with a goal to improve tissue-based diagnostics of neurologic disorders; our current focus is on tools for pathologic diagnosis of neuromuscular diseases. To learn more about ongoing basic and translational research projects, please visit our lab Website.

Selected Publications

Margeta-Mitrovic M , Grigg JJ, Koyano K, Nakajima Y and Nakajima N. Neurotensin and substance P inhibit low- and high-voltage activated Ca ²⁺ channels in cultured newborn rat nucleus basalis neurons. J Neurophysiol, 1997; 78:1341-52.

Margeta-Mitrovic M , Jan YN and Jan LY. A trafficking checkpoint controls GABA(B) receptor heterodimerization. Neuron, 2000; 27:97-106.

Margeta-Mitrovic M , Jan YN and Jan LY. Ligand-induced signal transduction within heterodimeric GABA(B) receptor. Proc Natl Acad Sci U S A, 2001; 98:14643-48.

Margeta-Mitrovic M , Jan YN and Jan LY. Function of GB1 and GB2 subunits in G protein coupling of GABA(B) receptors. Proc Natl Acad Sci U S A, 2001; 98:14649-54.

Margeta-Mitrovic M . Assembly-dependent trafficking assays in the detection of receptor-receptor interactions. Methods, 2002; 27: 311-7.

Keet CA , Fox CK, Margeta M, Marco E, Shane AL, DeArmond SJ, Strober JB and Miller SP. Infant botulism, type F, presenting at 54 hours of life. Pediatr Neurol, 2005; 32:193-6.

Layzer R, Lee H, Iverson D and Margeta M. Dermatomyositis with inclusion body myositis pathology. Muscle Nerve, 2009; 40:469-71.

Margeta M , Connolly AM, Widner TL, Pestronk A and Moore SA. Cardiac pathology exceeds skeletal muscle pathology in two cases of limb-girdle muscular dystrophy type 2I. Muscle Nerve, 2009; in press.

information last updated September 2009