Associate Professor of Pathology
NRB-858B, HMS | Pathology
77 Avenue Louis Pasteur
Boston, MA 02115
PH: 617-432-4104
FX: 617-432-4101
azad_bonni@hms.harvard.edu

Lab Website

Research Interests

 Our research is focused on elucidation of the signaling mechanisms regulating neuronal morphogenesis and connectivity in the brain. We are also interested in determining how abnormalities of brain developmental signaling pathways contribute to neurologic disorders. We employ in our studies a combination of molecular and cell biological, biochemical, and genetic approaches and use neurons from the rat or mouse brain in culture or in vivo.
 
 We have identified a function for the ubiquitin ligase, Cdh1-anaphase promoting complex (Cdh1-APC), in the control of axonal growth and patterning. We have also defined the CaMKII-NeuroD signaling pathway as a mechanism specifying dendritic morphogenesis. In a recent study, we have found that sumoylation of the transcription factor MEF2 coordinates postsynaptic dendritic differentiation. Our findings have raised many questions that we are pursuing with the goal of elucidating the cell-intrinsic mechanisms that control axonal and dendritic development, including those intimately linked to synaptic connectivity.
 
 In addition to neuronal morphogenesis, neuronal apoptosis ensures the proper wiring of the brain during normal development. In our investigations of the mechanisms of neuronal cell death, we have identified the Cdc2-BAD pathway as a cell cycle-based mechanism of apoptosis in postmitotic neurons. We have also defined a mechanism by which the stress-activated protein kinase JNK activates the mitochondrial cell death machinery specifically in neural cells.
 
 As the molecular underpinnings of brain development are unraveled, the more opportunities we are likely to have to gain novel insights in the pathogenesis of neurologic disorders. As part of this approach, we are carrying out studies of brain tumors based on our understanding of mechanisms controlling cell differentiation in the developing brain.

Publications

1. Konishi Y, Stegmüller J, Matsuda T, Bonni S, Bonni A. Cdh1-APC controls axonal growth and patterning in the mammalian brain. Science, 2004, 303:1026-30.

 2. Shalizi A*, Gaudillière B*, Yuan Z, Shirogane T, Stegmüller J, Ge Q, Tan Y, Schulman B, Harper JW, Bonni A. (*equal contribution). A calcium-regulated MEF2 sumoylation switch controls postsynaptic dendritic differentiation. Science, 2006, 311:1012-1017.

 3. Becker E, Bonni A. Pin1 mediates neural-specific activation of the mitochondrial apoptotic machinery. Neuron, 2006, 49: 655-662.