During development of the nervous system, axonal projections and synaptic contacts are supported by target-derived neuroptrophic factors, such as the neurotrophins and the glial cell line-derived (GDNF) family ligands (GFLs). During this period of target innervation, neurons often make excessive projections into their targets that are later pruned back. Development of the neuromuscular junction (NMJ), for example, undergoes a process in which NMJs are initially innervated by several axons, known as polyneuronal innervation. Then, through a process known as synaptic elimination, weaker connections are eliminated resulting in a 1:1 pairing between the presynaptic motor neuron and the postsynaptic receptor clusters in the muscle. This competitive “pushing out” of weaker axonal connections occurs by the release of inhibitory factors by the successful axons. The delicate balance between growth and survival-promoting neurotrophic factors, and inhibitory competitive factors, is thought to ultimately sculpt the architecture of mature circuits. My laboratory is interested in understanding the ligand and receptor mechanisms responsible for growth and survival promotion, synaptic elimination and apoptosis, and regeneration of peripheral neurons. We utilize biochemical and cell biological methods for the analysis of transgenic mice in which these receptors and ligands are deleted at specific developmental times. The determination of these mechanisms of survival, cell death and circuit maintenance will enable a more rational approach for the development of therapeutic strategies for diseases and injuries of the nervous system.
Brian Pierchala received his B.S. in Biochemistry from Oakland University in Michigan and obtained a Ph.D. in Neuroscience from the Johns Hopkins University School of Medicine. In the laboratory of David D. Ginty, his doctoral research investigated the ability of Nerve Growth Factor, a potent survival factor for sensory and sympathetic neurons, to support neuronal function when only activating receptors on axon terminals. His work on “retrograde” NGF signaling influenced the most widely accepted view of the field, namely that stable ligand-receptor complexes are trafficked in neurons over long distances to regulate biochemical events in the cell body necessary for survival, growth, and differentiation. Dr. Pierchala conducted his postdoctoral training in the laboratory of Eugene M. Johnson, Jr. at Washington University School of Medicine in Saint Louis. There, he investigated a newly discovered family of neuronal growth factors, the Glial Cell Line-derived Neurotrophic Factor (GDNF) Family Ligands (GFLs) and made several contributions to the understanding of how the GDNF receptor complex signals survival and differentiation. He continued his investigation of GDNF receptor signal transduction as an Assistant Professor at the State University of New York at Buffalo prior to his arrival to the Department of Biologic and Materials Sciences. His laboratory investigates the mechanisms of action of neurotrophic factors and proapoptotic factors in the development, maintenance and regeneration of the peripheral nervous system.
Dr. Pierchala is a Principal Investigator on research projects funded by the NIH and CHDI. He has instructed undergraduate students, Ph.D. graduate students and dental students in neurobiology, signal transduction, and cell biology. Dr. Pierchala serves as a reviewer for multiple journals including The Journal of Neuroscience, Nature and Science, and has served as a reviewer on NIH study sections.
The most recent publications are reported below.
A p75-Ret Signaling Complex Mediates Neuronal Survival and Death in the Developing Peripheral Nervous