My academic interests involve the inter-related areas of fetal development, mechanisms of disease, and animal models of human genetic diseases. I have worked in academic environments as a research-oriented clinician since receiving my veterinary medical degree. I completed a residency in veterinary medical genetics, then obtained a Ph.D. studying in utero transplantation in a mouse model of a human genetic disease (mucopolysaccharidosis type VII). I obtained further training in murine hematopoeisis before starting my assistant professorship. My immediate goal for further mentored research training is to expand my knowledge in the field of cell and molecular biology. With the additional specialized training, the further investigation of the model proposed in this grant application and characterization of three more models of genetic skin disorders I have found in the last several months, I expect to submit an application for an RO1 grant. My residency, graduate, and postgraduate training have provided the opportunity to characterize and publish the mode of inheritance, principles of disease processes, and treatment modalities of several genetic diseases. Over the past nine years, I have been able to establish a colony of dogs with clinical, pathologic, and genetic features of X-linked ectodermal dysplasia (HED) characterized by hypoplasia of hair and sweat glands, and missing and malformed teeth. As in human patients with HED, the affected dogs are at increased risk for pulmonary disorders, but I have also found an increased susceptibilty to other, usually benign, rarely fatal, non-pulmonary infectious diseases. Thus, there is the possibility that the dogs have the canine equivalent to the newly described HED associated with immune deficiency in humans, caused by a defect in the NEMO gene which is also X-linked. My hypothesis is that the HED dogs have a defect in ED1, the gene responsible for X-linked ectodermal dysplasia in man and that the pulmonary disorders are due to specific defects in local immunity. The genetic defect in the HED dogs will be studied by sequencing both the ED1 and the NEMO gene, determining the mutation, and performing expression studies to provide proof of principle and to understand the basis of disease during development. Furthermore, the HED dogs will be examined to demonstrate that a specific immune deficiency is responsible for pulmonary disease rather than the previously thought lack of respiratory mucoid glands.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01AR049817-02
Application #
6755196
Study Section
Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee (AMS)
Program Officer
Tyree, Bernadette
Project Start
2003-06-01
Project End
2008-05-31
Budget Start
2004-06-15
Budget End
2005-05-31
Support Year
2
Fiscal Year
2004
Total Cost
$124,794
Indirect Cost
Name
University of Pennsylvania
Department
Other Clinical Sciences
Type
Schools of Veterinary Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Lewis, J R; Reiter, A M; Mauldin, E A et al. (2010) Dental abnormalities associated with X-linked hypohidrotic ectodermal dysplasia in dogs. Orthod Craniofac Res 13:40-7
Mauldin, Elizabeth A; Gaide, Olivier; Schneider, Pascal et al. (2009) Neonatal treatment with recombinant ectodysplasin prevents respiratory disease in dogs with X-linked ectodermal dysplasia. Am J Med Genet A 149A:2045-9
Casal, Margret L; Lewis, John R; Mauldin, Elizabeth A et al. (2007) Significant correction of disease after postnatal administration of recombinant ectodysplasin A in canine X-linked ectodermal dysplasia. Am J Hum Genet 81:1050-6
Casal, Margret L; Scheidt, Jennifer L; Rhodes, James L et al. (2005) Mutation identification in a canine model of X-linked ectodermal dysplasia. Mamm Genome 16:524-31
Casal, Margret L; Mauldin, Elizabeth A; Ryan, Sara et al. (2005) Frequent respiratory tract infections in the canine model of X-linked ectodermal dysplasia are not caused by an immune deficiency. Vet Immunol Immunopathol 107:95-104