Noah Druckenbrod, Ph.D.
Meet the Researcher
Noah Druckenbrod, Ph.D. first did research on adrenergic receptor trafficking under Dr. Mike Sievert and Dr. Arnold Ruoho in the department of Pharmacology through an undergraduate honors thesis program in Neurobiology.
Later he received his Ph.D. working on the molecular and cellular biology of enteric nervous system development and disease with Dr. Miles Epstein at the University of Wisconsin in Madison. Dr. Druckenbrod is currently a postdoctoral research fellow with Dr. Lisa Goodrich’s laboratory in the department of Neurobiology at Harvard Medical School.
Dr. Druckenbrod's grant was generously funded by The Barbara Epstein Foundation, Inc.
The Research
Harvard University
Identifying roles for contact-dependent signaling between neurons and glia during axon guidance and synaptic targeting
The mature cochlea is a spiraled hollow chamber of bone that contains all the necessary components to transmit sound information to the brain. This feat is accomplished by the precise arrangement of hair cells and spiral ganglion neurons (SGNs). This arrangement requires SGNs extend peripheral projections and establish precise synaptic connections with hair cells. What signals guide these axons through the three-dimensional terrain of the cochlea? Most studies focus on the roles of classically described axon guidance cues, which act over long distances to attract or repel axons. However, mounting evidence from recent studies and our own preliminary data lead us to hypothesize that contact-dependent signaling between SGNs and Schwann cells (SCs) are required for normal development of inner ear neural architecture and hearing. The precise role of contact-dependent interactions between SGN axons and SCs on auditory circuit formation remains unknown. This is due in part to the obstacles towards gathering high-resolution, time-lapsed information on the spatial relationships between SGNs and SCs in situ. Therefore, we will genetically label and characterize live cellular interactions between these cells in their normal, and then abnormal, physiological environment. We will measure the extent to which each of these cell types rely on each other for normal migration, differentiation, proliferation and survival. Because we have identified a mutant in which SGN-Schwann cell interaction appears disrupted, these studies will also provide insight to our understanding of Schwannoma formation. Schwannomas are Schwann cell tumors commonly found in the inner-ear and are thought to arise from a disruption in reciprocal signaling between spiral ganglion neurons (SGNs) and Schwann cells. As these tumors grow they compress afferent vestibular and auditory nerves, usually causing hearing loss, tinnitus, and dizziness. Therefore, these studies will not only contribute to our understanding of auditory circuit formation but also provide insight into what can go wrong when SGN-Schwann cell interaction is disrupted.
Research Area: Hearing Loss, Tinnitus, Neuron-glia interaction, auditory circuit development and regeneration
Long-term goal: Currently very little is known the interaction between SGNs and glia during development and disease. Completion of the proposed experiments will be the first ever to show live interaction between neurites and peripheral glia during axon guidance and synaptic targeting in any mammalian system. Upon completion of the pilot experiments in this proposal, we will have determined whether SGN wiring is regulated by contact-dependent interactions with developing Schwann cells. Furthermore, it will determine whether disrupted interaction between these two cell types leads to disorganized auditory wiring (deafness), and abnormal Schwann cell proliferation or differentiation. It is my hope to eventually use the methods of this proposal as a platform to bridge the gap between the analysis provided by whole-organ time-lapse microscopy and the macroscopic phenotype of experimental animals, and, eventually, of neurological patients.