Professor, Division of Biological Sciences
Bio: Eduardo Macagno received his Ph.D. from Columbia University in 1968. He was on the faculty of Columbia from 1973 to 2000. From 1993 to 2000 he served as Associate Vice President for Research and Graduate Education and Dean of the Graduate School of Arts and Sciences at Columbia. He joined the faculty of the Division of Biology as Founding Dean in 2001, a position he held until 2006. He is the Director of the HHMI-supported Hughes Scholars Program at UCSD. He is also the editor-in-chief of Developmental Neurobiology and presently serves as president of the Academy of Neuroscience for Architecture.
Our laboratory is currently involved in three areas of basic neurobiological research. One area comprises studies of molecular pathways underlying the regulation of neuronal growth cone dynamics and interactions leading to neuronal arbor formation. In particular, we have focused on the mechanisms which receptors and signaling factors use to mediate self- and homologue-avoidance in the process of defining cell arbor boundaries, a phenomenon that is known as tiling and defines the topology of sensory and motor fields. Our model system is the medicinal leech nervous system, for which we have developed or adapted all the tools required for modulating the expression of specific genes in individual embryonic or adult neurons.
Figure 1. Bilateral Pair of Central Neurons in the Medicinal Leech
A second area consists of studies of the roles of gap junctions in the early differentiation of the central nervous system. We have cloned over one dozen leech innexins, several of which are expressed in nervous tissue. In one set of studies, we showed that innexins can not only form gap junctions but can also form functional hemi-channels that can be used in intercellular signaling via small molecules such as ATP - we are currently testing this signaling pathway in gangliogenesis. In another set of studies, we are assaying the role of innexins in interactions between segmental homologs that result in the retraction of some neuronal projections and the maintenance of others.
Figure 2. MALDI Imaging of Peptide Distributions in Leech Embryo Whole Mounts
The third area of current research consists of an international collaboration with several laboratories (in other UCSD departments as well as with colleagues in Lille, FRANCE) on the novel application of Imaging Mass Spectrometry (MALDI Imaging) to the mapping of peptides and proteins in leech embryos and adult nervous system sections. In order to study at a systems level the expression profiles, we are developing tools for molecular imaging using scanning MALDI-TOF MS/MS to obtain spectra in a raster analysis of whole-mount embryos and serially-sectioned adult ganglia, as well as software tools for the analysis of the enormous amount of data thus obtained. In particular, we are comparing gene expression in developing, regenerating and neuro-immune compromised nervous systems in order to analyze how the nervous system responds to various kinds of insults.
Figure 3. Pair of Live Medicinal Leech Embryos
Finally, we are also involved in a multidisciplinary project at the boundary of Neuroscience and Architecture. This project brings together human brain activity monitoring using portable high-definition EEG with cutting-edge Virtual Reality facilities on campus to assay human responses to the built environment, in particular, as the subjects attempt to navigate through a complex building. This project has exciting practical ramifications, for example, in providing evidence for the design of better healthcare and educational facilities, as well as testing therapies for improving the status of humans with neural impairment conditions.
Microtargeted gene silencing and ectopic expression in live embryos using biolistic delivery with a pneumatic capillary gun. Orit Shefi, Claire Simonnet, Michael W. Baker, James R. Glass, Eduardo R. Macagno and Alex Groisman. J. Neurosci. 26:6119-6123 (2006).
Proteome modifications of the medicinal leech nervous system under bacterial challenge. David Vergote, Eduardo Macagno, Michel Salzet, and Pierre-Eric Sauti?re. Proteomics 6:4817-4825 (2006).
In Vivo Imaging of Growth Cone and Filopodial Dynamics: Evidence for Contact-Mediated Retraction of Filopodia Leading to the Tiling of Sibling Processes. M.W. Baker and E.R. Macagno. J. Comp. Neurol. 500:850-862 (2007).
Innexins Form Two Types of Channels. L. Bao, S. Samuels, S. Locovei, E. R. Macagno, K. J. Muller, and G. Dahl. FEBS Letters 581:5703-5708 (2007).
Molecular MALDI Imaging: an Emerging Technology for Neuroscience Studies. I. Fournier, M. Wisztorski, D. Croix, E. Macagno and M. Salzet. Invited review, Special Issue on Dynamic Imaging, J. Glover, Guest Editor, Dev. Neurobiol. 68:845-858 (2008).
Microbial challenge promotes the regenerative process of the injured central nervous system of the medicinal leech by inducing the synthesis of antimicrobial peptides in neurons and microglia. D. Schikorski, V. Cuvillier Hot, M. Leippe, C. Wichlacz-Boidin, C. Slomianny, E. Macagno, M. Salzet and A. Tasiemski. J. Immunol. 181:1083-1095 (2008).
The Receptor Phosphatase HmLAR2 Sheds its Ectodomain and Collaborates with Focal Adhesion Proteins in Filopodial Tips to Control Growth Cone Morphology. M.W. Baker, S.M. Peterson and E.R. Macagno. Dev. Biol., 320:215-225 (2008).
MITICS (MALDI Imaging Team Imaging Computing System): a new open source mass spectrometry imaging software. Olivia Jardin-Math?, David Bonnel, Julien Franck, Maxence Wisztorski, Eduardo Macagno, Isabelle Fournier and Michel Salzet. J. Proteomics 71:332-345 (2008).
Recent Advances on Development, Regeneration and Immune Responses of the Leech Nervous System. M. Salzet and E. Macagno. Invited chapter in: Annelids as Models Systems in the Biological Sciences, Dan Shain, editor. In press (2008).