John Bixby, Ph.D.

Associate Dean for Graduate Studies
Director of the Neuroscience Center
Primary Appointment: Molecular and Cellular Pharmacology
Secondary Appointment: The Miami Project to Cure Paralysis

Our lab is trying to achieve a molecular understanding of the ways in which specific neural connections are formed and maintained. To this end, we have studied two aspects of nerve cell differentiation: axon growth and synapse formation. Recently, we have focused on the regulation of axon growth and guidance by protein tyrosine phosphatases (PTPs). These proteins help to control the signaling state of a large variety of other proteins inside the cell, and thus are part of a master regulatory system. Many PTPs are transmembrane proteins with large extracellular domains like those of signaling receptors; these "receptor protein tyrosine phosphatases" (RPTPs) seem particularly important for axon growth and guidance. Our studies concern ligand/receptor interactions, signal transduction mechanisms, and biological functions of these RPTPs.

Accumulating evidence suggests that receptor-type tyrosine phosphatases (RPTPs) play key roles in the signaling processes underlying axon growth. Several classes of RPTP possess extracellular domains (ECDs) that are structurally similar to those of cell adhesion molecules (CAMs). Our overall hypothesis is that these CAM-like RPTPs, which are expressed on the surfaces of developing neurons, are involved both as regulatory ligands and as neuronal receptors in the regulation of vertebrate axon growth. Our lab has established that 2 vertebrate RPTPs, PTP-δ and PTPRO, are likely to be involved in axon growth regulation. We are currently working on a number of projects to build on these observations. These include: characterization of the ligand/receptor interactions for PTP-δ and PTPRO, identification of physiological substrates for PTPRO and PTP-δ , and examination of the biological roles of PTPRO, PTP-δ and other RPTPs in the regulation of vertebrate axon growth and guidance. We are particularly excited by our recent identification of a novel substrate for PTPRO whose function appears to be required for axon growth, at least in vitro.

Most recently, we have become interested in the extent to which the kinds of signals we study during development are relevant to regeneration after injury. New projects include the development of in vitro assays to study regeneration efficiency, and the assessment of gene changes occurring in neurons that are growing axons and forming synapses.

I grew up in N.J., and earned a B.A. in Biology from Cornell University in 1975. Although this was early days for neuroscience, Cornell already had a bunch of neurobiologists on the faculty, and my degree included a concentration in neurobiology. As an undergraduate, I worked on a project to study the effects of auditory stimulation on development and hatching of Japanese quail. I have worked on neural development ever since. After graduation, I moved to California, where I stayed until 1988. I went to graduate school in Pasadena at Caltech, where I studied with David Van Essen. At Caltech I worked on the mechanisms underlying synapse elimination at the neuromuscular junction, as well as the anatomy and physiology of extrastriate visual cortex in monkeys.

In 1980 I moved down the coast to UCSD, where I did postdoctoral work with Nick Spitzer. My major interest here was in the early differentiation of Xenopus spinal neurons. Among other things, we showed that these spinal neurons can grow and thrive in the complete absence of extracellular calcium, and that calcium removal increases the rate of axon growth in these cells. Up to this point, I was a dyed-in-the-wool electrophysiologist, but I was becoming more and more interested in the nascent field of molecular neuroscience. In 1983, I decided to try to learn this new field, and I moved back up the coast, to Lou Reichardt's lab at UCSF. I stayed at UCSF for 5 years, where I not only learned a lot about molecular biology and biochemistry, but also managed to make some novel observations on the regulation of axon growth by extracellular matrix proteins and cell adhesion molecules. I finally got a real job in 1988, when I moved to the Dept. of Molecular & Cellular Pharmacology at the University of Miami. Our work here has focused on axon growth regulation by cell adhesion molecules and related proteins, as well as the control of synapse formation at neuromuscular junctions.

In 2003, we managed to recruit Dr. Vance Lemmon from Case Western to the University of Miami. Vance and I decided to work together, and I was fortunate to be able to join the Miami Project to Cure Paralysis at this time. It is a great opportunity to start applying what we learn about the basic processes of axon growth and guidance during development to the incredibly challenging problem of spinal cord regeneration after injury. My lab is merged with Vance Lemmon's lab, and we share equipment, lab space, lab meetings, and ideas.
Copyright Dr. Vance Lemmon and Dr. John Bixby. All Rights Reserved