Mihaela Serpe, Ph.D.

The purpose of our research is to understand the mechanisms of synapse development and homeostasis. Synapse development is a highly orchestrated process coordinated by intercellular communication between the pre- and postsynaptic compartments, and by neuronal activity itself. Our long-term goal is to elucidate the molecular mechanisms, particularly those involving cell-cell communication, that regulate formation of functional synapses during development, and fine-tune them during plasticity and homeostasis. We focus on three key processes in synaptogenesis: (1) trafficking of components to the proper site, (2) organizing those components to build synaptic structures, and (3) maturation and homeostasis of the synapse to optimize its activity. My laboratory addresses the mechanisms underlying these processes using a comprehensive set of approaches including genetics, biochemistry, molecular biology, super resolution imaging and electrophysiology recordings in live animals and reconstituted systems. In recent studies, we also utilized single-cell RNA sequencing (scRNA-Seq) methodologies to describe various populations of neurons.

Because of its many advantages, we choose to study these events in a powerful genetics system, Drosophila melanogaster, and to use the neuromuscular junction (NMJ) as a model for glutamatergic synapse development and function. The fact that individual NMJs can be reproducibly identified from animal to animal and are easily accessible for electrophysiological and optical analysis makes them uniquely suited for in vivo studies on synapse assembly, growth and plasticity. In addition, the tremendous richness of genetic manipulations that can be performed in Drosophila permits independent control of individual synaptic components in distinct cellular compartments. Furthermore, the fly NMJ is a glutamatergic synapse similar in composition and physiology to mammalian central synapses. The Drosophila NMJ can thus be used to analyze and model defects in the structural and physiological plasticity of glutamatergic synapses, which are associated with a variety of human pathologies from learning, memory deficits to autism. The similarity in architecture, function, and molecular machinery supports the notion that studying the assembly and development of fly glutamatergic synapses will shed light on their human counterparts.

Dr. Mihaela (Ela) Serpe obtained her M.S. in Biochemistry from the University of Bucharest, Romania, then worked for two years in the Institute for Cellular Biology and Pathology “Nicolae Simionescu” in Bucharest. She completed a Ph.D. in Biochemistry at SUNY Buffalo in 1999 working with Dr. Dan Kosman on how yeast cells sense and acquire copper and iron from their environment. Driven by her interest in cellular signaling, she did postdoctoral studies on signaling by TGF-β growth and differentiation factors in the laboratory of Dr. Mike O’Connor at the University of Minnesota and Howard Hughes Medical Institute. Dr. Serpe started her own laboratory at NICHD in 2008. The long-term goal of her laboratory is to elucidate molecular mechanisms that regulate cellular communication during development and homeostasis. Dr. Serpe focuses on two related key questions in cellular communication: (1) how are tissues patterned and correctly connected by short- and long-range signals, and (2) how are cells’ structures and functions coordinated at short range with those of their neighbors. Her lab investigates these processes using the Drosophila model system and focusing on developmental patterning and the assembly, maturation and function of a specialized cell-cell interaction zone—the neuromuscular junction (NMJ).

Dr. Serpe's group has greatly contributed to understanding the mechanisms of synapse assembly and maturation through: 1) characterization of a key auxiliary protein of glutamatergic synapses, called Neto, that is essential for their development and function both in Drosophila and mammals, and the molecular dissection of its activities, 2) functional reconstitution of insect glutamate receptors in heterologous systems and characterization of channels gating properties, and 3) analysis of the action of the TGF-β pathway in synapse maturation and plasticity, and in particular the discovery of a novel mechanism by which local, non-transcriptional BMP signaling directly modulates synaptic structure and activity. More recently, the lab has assembled a comprehensive scRNAseq atlas of the larval ventral nerve cord, which shares many similarities with the spinal cord of vertebrates and has emerged as a major model for understanding the development and function of motor systems.