Rose Goodchild, Ph.D.

Research Statement

Several human hereditary diseases are caused by genetic mutations affecting proteins of the nuclear envelope. The nuclear envelope is the region of endoplasmic reticulum that surrounds the nucleus. It contains its own distinctive collection of proteins, which appear to perform diverse functions within a cell. However, these functions, and their cellular importance, are poorly understood compared with other subcellular organelles. We study the cellular roles of nuclear envelope proteins and aim to explain why their dysfunction causes human disease.

We are particularly interested in the recent recognition that nuclear envelope proteins connect the nucleus with the cellular cytoskeleton. We hypothesize that these connections are important for the cell movements that occur during mammalian development, perhaps especially so in the developing central nervous system (CNS). We will also examine their importance for maintenance of cells in a developed animal and determine whether their impairment can explain why some select cell types degenerate in certain nuclear envelope diseases.

Our nuclear envelope focus is continued by a long running project that investigates another human disease causing protein. A single amino acid deletion in torsinA causes DYT1 dystonia. This is a neurological disease with the core symptom of abnormal, involuntary twisting movements. Neither the cellular dysfunction, nor the neurobiological abnormalities that cause these abnormal movements are understood. TorsinA is unusual in that it can localize to either the main endoplasmic reticulum or the nuclear envelope. Nevertheless, previous work showed that its nuclear envelope function has particular importance for neurons. Since the CNS is specifically affected in DYT1 dystonia, we hypothesize that impairment of the nuclear envelope function of torsinA causes this disease. We investigate many aspects of torsinA function and dysfunction. This includes studying its cellular roles and those of its binding partners. We also ask why its nuclear envelope function is particularly important for neurons and how CNS functioning is disrupted to cause the symptoms of DYT1 dystonia.

We approach these problems using a variety of different experimental techniques. We use biochemical approaches to identify protein-protein interactions; mammalian cell culture to investigate protein behavior and assess the importance of proteins in individual cells; and mouse genetic mutants to look at how a protein is important for functioning or development of a whole animal.

Selected Publications

Goodchild, R.E., Kim, C.E., Dauer, W.T. Disease mutant torsinA selectively disrupts the neuronal nuclear envelope. Neuron 2005 Dec 22;48(6):923-32

Goodchild, R.E., Dauer, W.T. The disease associated AAA+ protein, torsinA, interacts with homologous proteins in the nuclear envelope and endoplasmic reticulum lumen. Journal of Cell Biology. 2005 168(6): 855-62 

Goodchild R.E., Dauer, W.T. Mislocalization to the Nuclear Envelope: A Novel Effect of the Dystonia-Causing TorsinA Mutation. PNAS. 2004 20;101(3):847-52. 

Contact Information

Office:
Room F-221
Walters Life Sciences
Phone: (865) 974-3089

Lab:
Room B208
Walters Life Sciences
Phone: (865) 974-3980

Email: rgoodchi@utk.edu