The University of Texas MD Anderson Cancer Center
Department of Epigenetics and Molecular Carcinogenesis
I have been studying spontaneous mouse mutations with skin phenotypes, trying to identify genes important for skin and hair follicle biology. As part of these positional cloning and phenotyping studies we have shown that one of these mutations (nackt) comprises a deletion in the cathepsin L (CTSL) gene, and found that CTSL is important for hair follicle morphogenesis and epidermal differentiation. Using this model, we found a paradoxical protective role of CTSL in mouse skin carcinogenesis. We obtained “in vivo” evidence that skin tumorigenesis is enhanced in the absence of CTSL. In addition, we have successfully identify the Luca Mutation (loss of hair and irritated skin) as a premature stop codon in the Zdhhc13 gene. This is the first animal model related with a defect in a protein palmitoyl acyltransferase. We have also recently identified another spontaneous recessive mutation (Barthez) that affects the Ass1 (argininosuccinate synthetase 1) gene. The phenotype of homozygous mice includes severe retardation in post-natal development, alopecia with scaly skin, ataxia and circling behavior, a complex phenotype that is virtually identical to the human Citrullinemia type I, a rare inherited disorder caused by deficiency of the ASS enzyme. Another new project deals with the development of a new genetically defined hairless inbred strain (SKHIN). This will represent a unique tool for the study of the underlying genetic basis of UV-induced skin carcinogenesis.
Education & Training
DVM, University of Buenos Aires, 1986
PhD, University of Buenos Aires, 1998
Director Laboratory Animal Genetic Services and Research Histology, Pathology and Imaging Core