Neurofibromatosis 1:
The major project in the Wallace laboratory is the molecular study of neurofibromatosis type 1, which is a common dominant tumor condition characterized by localized overgrowth of neural crest tissues. This condition is caused by mutations in the NF1 gene, a large complex gene whose protein is not well understood. We are using genetic and cell biology approaches to study this condition, using a large set of patient samples. In particular we are focusing on neurofibromas-benign Schwann cell tumors that can form on any peripheral nerve (including the gut), with some patients developing thousands. Some neurofibromas become massive and undergo malignant transformation. Some specific genes (in addition to NF1) are under study at the germline and somatic levels, and we are using differential display and cDNA array studies to observe transcript level changes between normal and tumor-derived Schwann cells. This is leading to discovery of novel genes and study of known genes that are implicated in tumor development. Other NF1 work planned or underway with collaborators involves understanding the protein-level result of various mutations, attempting to use human tumor cells to develop a mouse model, use of antisense approaches to mimic NF1 knockout in cultured cells, searching for epigenetic effects at the NF1 and other loci, and investigating the role of steroid hormones in tumorigenesis.
Heart Defects
The laboratory has projects to map and clone genes responsible for hereditary heart defects and cardiomyopathy, as well as study known genes and candidate genes for cardiomyopathy and structural defects. We are studying patient samples from a number of conditions (e.g. dominant cardiomyopathy, Pompe disease, SVAS), attempting to identify underlying genetic contributions and pathogenetic mechanisms in these conditions. A future goal is to employ cDNA array technology to understand global transcript changes in cardiomyopathy, to identify therapeutic targets.
Multifactorial Disorders:
The laboratory is also studying conditions which do not always show Mendelian inheritance but have a genetic component. We are searching for genetic polymorphisms which contribute susceptibility to traits such as vitiligo, pain, and variations in taste.
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