Molecular neurobiology
Molecular neurobiology
Our laboratory explores the cellular and molecular processes that regulate the crosstalk between neurons and their tissue microenvironment during development of neural circuits and in response to damage. We employ mouse models, transcriptomics, cellular assays, biochemistry, and imaging to study the assembly, homeostasis, and repair of neuronal connectivity in the vertebrate nervous system. We are motivated by a strong interest in fundamental aspects of cell signaling, axon guidance and tissue morphogenesis. At the same time, we seek to leverage this knowledge to open new therapeutic avenues for motor neuron disease and nerve repair.
Research Activity
How neurovascular crosstalk shapes circuit development
Neurons are energy-demanding, as reflected in the expansive vascularization of the nervous system and precise alignment of nerves and blood vessels. What remains unclear is how this neurovascular link is established so that the vascular network matches the functional requirements of specific neuronal populations. We have shown that molecular cues from axons pattern blood vessels to ensure a tight association, yet preventing interference with circuit assembly. Our current interest is on the neurovascular signals that coordinate these complex interactions crucial for the development and maintenance of neuronal connectivity
Unlocking the secrets of nerve regeneration
Peripheral nerves display a remarkable ability to regenerate after injury but this capacity gradually diminishes with aging or in conditions such as diabetes, and is absent in the central nervous system (CNS; brain and spinal cord). We seek to decipher the rules of peripheral nerve repair and utilize them to promote nerve regeneration. The current focus is on understanding the reparative role of blood vessels in healing injured nerves. We have found that neovessels play a critical role in creating a microenvironment conducive to nerve fiber regrowth, and we are identifying the molecular basis of this repair process.
Motor neuron degeneration from mechanisms to new biomarkers
Motor neurons are susceptible to disease, influenced by both intrinsic factors and features of surrounding cells. Our research investigates changes in cell-cell communication networks and phenotypes within the spinal cord and peripheral nerves of ALS mouse models. In collaboration with clinicians, we relate these changes to alterations in tissues and biofluids from patients, with the goal of uncovering new biomarkers that offer potential paths for diagnostics and therapeutic solutions for motor neuron disease.
Amin ND, Bai G, Klug JR, Bonanomi D, Pankratz MT, Gifford WD, Hinckley CA, Sternfeld MJ, Driscoll SP, Dominguez B, Lee KF, Jin X, Pfaff SL. Loss of motoneuron-specific microRNA-218 causes systemic neuromuscular failure. Science 2015 Dec 18;350(6267):1525-9.
Wang L, Mongera A, Bonanomi D, Cyganek L, Pfaff SL, Nüsslein-Volhard C, Marquardt T. A conserved axon type hierarchy governing peripheral nerve assembly. Development 2014 May;141(9):1875-83.
Macfarlan TS, Gifford WD, Driscoll S, Lettieri K, Rowe HM, Bonanomi D, Firth A, Singer O, Trono D, Pfaff SL. Embryonic stem cell potency fluctuates with endogenous retrovirus activity. Nature 2012 Jul 5;487(7405):57-63.
Bonanomi D, Chivatakarn O, Bai G, Abdesselem H, Lettieri K, Marquardt T, Pierchala BA, Pfaff SL. Ret is a multifunctional coreceptor that integrates diffusible- and contact-axon guidance signals. Cell. 2012 Feb 3;148(3):568-82.
Bai G, Chivatakarn O, Bonanomi D, Lettieri K, Franco L, Xia C, Stein E, Ma L, Lewcock JW, Pfaff SL. Presenilin-dependent receptor processing is required for axon guidance. Cell 2011 Jan 7;144(1):106-18.
Bonanomi D, Pfaff SL. Motor axon pathfinding. Cold Spring Harb Perspect Biol. 2010 Mar; 2(3): a001735.
Gallarda BW, Bonanomi D, Muller D, Brown A, Alaynick WA, Andrews SE, Lemke G, Pfaff SL, Marquardt T. Segregation of axial motor and sensory pathways via heterotypic trans-axonal signaling. Science 2008 Apr 11;320(5873):233-6.
Bonanomi D, Fornasiero EF, Valdez G, Halegoua S, Benfenati F, Menegon A, Valtorta F. Identification of a developmentally regulated pathway of membrane retrieval in neuronal growth cones. J Cell Sci. 2008 Nov 15;121(Pt 22):3757-69.
Bonanomi D, Menegon A, Miccio A, Ferrari G, Corradi A, Kao HT, Benfenati F, Valtorta F. Phosphorylation of synapsin I by cAMP-dependent protein kinase controls synaptic vesicle dynamics in developing neurons. J Neurosci. 2005 Aug 10;25(32):7299-308.