Brian Pierchala, PhD
Sherry Sonneborn Professor of ALS Research
Professor of Anatomy, Cell Biology & Physiology
- brpierch@iu.edu
- Phone
- 317-278-4865
- Address
-
NB 214F
ANAT
IN
Indianapolis, IN
Bio
The Pierchala laboratory investigates the development and regenerative capacity of peripheral axons, such as motor axons, with a focus on motor neuron degeneration and death due to amyotrophic lateral sclerosis (ALS).Key Publications
C.R. Donnelly, N.A. Gabreski, M. Chowdhury, E.B. Suh and B.A. Pierchala. 2018. Non-canonical Ret signaling augments p75-mediated cell death in developing sympathetic neurons. J. Cell Biology. 217: 3237-3253.
J.L. Shadrach and B.A. Pierchala. 2018. Semaphorin3A signaling is dispensible for motor axon reinnervation of the adult neuromuscular junction. eNeuro. 5: 0155-17.
C.R. Donnelly, A. Shah, C.M. Mistretta, R.M. Bradley and B.A. Pierchala. 2018. Biphasic functions for the GDNF-Ret signaling pathway in chemosensory neuron development and diversification. Proc. Natl. Acad. Sci. USA (PNAS). 115: E516-E525.
Z. Chen*, C.R. Donnelly*, B. Dominguez, Y. Harada, W. Lin, A.S. Halim, B.A. Pierchala#and K.-F. Lee#. 2017. P75 is required for the establishment of postnatal sensory neuron diversity by potentiating Ret signaling. Cell Reports. 21: 707-720. *Authors contributed equally; #Co-corresponding authors.
A.B. Wehner*, H. Abdesselem*, T.L. Dickendesher, R.J. Giger and B.A. Pierchala. 2016. Semaphorin 3A is a retrograde cell death signal in developing sympathetic neurons. Development. 143: 1560-1570. *Authors contributed equally.
C.C. Tsui, N.A. Gabreski, S.J. Hein and B.A. Pierchala. 2015. Lipid rafts are physiologic membrane microdomains necessary for the morphogenic and developmental functions of GDNF in vivo. J. Neurosci. 35: 13233-13243.
| Year | Degree | Institution |
|---|---|---|
| 1998 | PhD | Johns Hopkins University |
| 1994 | BS | Oakland University |
During development of the nervous system, peripheral neurons and their axonal projections are supported by target-derived neuroptrophic factors, such as the neurotrophins and the glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs). During this period of target innervation, neurons often make excessive projections into their targets that are later pruned back. In addition to target-derived survival factors, competing neurons release “competition factors” that actively “push out” weaker axonal connections, and subsequently induce the apoptotic death of these less successful neurons. 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 mechanisms responsible for survival promotion, apoptosis and regeneration of peripheral neurons.
The neuromuscular junction (NMJ) is a specialized synapse that allows for communication between spinal motor neurons and muscle fibers. Maintenance of motor-muscle connectively at the NMJ is critical for the preservation of muscle strength and coordinated motor function. Although motor neurons have some regenerative capacity in response to injury, severe acute trauma or chronic denervation from underlying neurodegenerative disease can have a profound effect on neuromuscular activity and function. We utilize ribosomal profiling to identify motor neuron specific translational responses to acute trauma and ALS neurodegeneration in order to uncover underlying mechanisms of degeneration and regeneration. This analysis has identified genes that are differentially upregulated during the progression of a mouse model of ALS, as well as genes upregulated during axonal regeneration after a nerve crush injury. We anticipate that the analysis of these genetic pathways will lead to unique insights on the mechanisms that lie at the interface between regeneration and degeneration.