David L. Gasser
Professor, Dept of Genetics

Genetics and Gene Regulation Program

Address

575 Clinical Research Building
415 Curie Boulevard
Philadelphia, Pennsylvania 19104-6145

Office tel.: 215 898-5175
Lab tel.: 215 898-5575
Fax: 215 573-5892
E-mail: gasserd@mail.med.upenn.edu

Link(s)

Dr. Gasser at the Dept of Genetics

Dr. Gasser at the Imun Grad Group


Education

University of Akron: BS (Biology), 1964.

University of Michigan: MS (Zoology), 1966.

University of Michigan: Ph.D. (Zoology, Genetics), 1970.

Research Interests

• Genes that affect the immune response

Key words: kidney, autoimmune disease.

Search PubMed for articles

Description of Research

We are studying a mutant gene which when homozygous leads to a lethal kidney disease in mice. These mice undergo a spontaneous autoimmune reaction which involves multiple immune pathways. Effector T cells are involved, as well as natural killer (NK) cells. We have reason to believe that regulatory NKT cells also participate.

We have cloned the relevant gene, and have found that it codes for a mitochondrial protein similar to trans-prenyltransferase. In other organisms, this enzyme is needed for isoprenylation of coenzyme Q. The mutant mice have defective mitochondria, as demonstrated by ultrastructural analysis, and we believe that this defect leads to apoptosis in both renal tubular epithelial cells and glomerular podocytes. This in turn leads to an autoimmune response which involves both the tubular interstitium and the glomeruli.

The human disease with the greatest similarity to this phenotype is focal segmental glomerular sclerosis, or FSGS. It is well known that there is a significant genetic component to FSGS susceptibility, and we are exploring the possibility that the human counterpart of this prenyltransferase-like mitochondrial protein (PLMP) is one of the genes that is involved in this susceptibility.

Recent Publications

Dell KM, Y-X Li, M Peng, EG Nielson and DL Gasser. Localization of the mouse kidney disease (kd) gene to a YAC/BAC contig on Chromosome 10. Mammalian Genome 11: 967-971, 2000.

Hancock WW, T-L Tsai, MP Madaio, and DL Gasser. Cutting edge: Multiple autoimmune pathways in kdkd mice. Journal of Immunology 171: 2778-2781, 2003.

Peng M, Jarett L, Meade R, Madaio MP, Hancock WW, George AL, Neilson EG and Gasser DL. Mutant prenyltransferase-like mitochondrial protein (PLMP) and mitochondrial abnormalities in kd/kd mice. Kidney International 66: 20-28, 2004.

Madaio, M. P., Ahima, R.S., Meade, R., Rader D.J., Mendoza, A., Peng, M., Tomaszewski, J. E., Hancock, W. W. and Gasser, D. L.: Glomerular and tubular epithelial defects in kd/kd mice lead to progressive renal failure. Am. J. Nephrol. 25: 604-610, 2005.

Hallman, T.M., Peng, M., Meade, R., Hancock, W.W., Madaio, M.P. and Gasser, D.L.: The mitochondrial and kidney disease phenotypes of kd/kd mice under germfree conditions. Journal of Autoimmunity 26: 1-6, 2006.

Lab

Rotation Projects

1. Investigation of NK effector cells and NKT regulatory cells by immunohistochemistry, fluorescence-activated cell sorting, and genetic crosses with strains that are deficient in those functions.

Min Peng, MD,PhD, Research Specialist
Zhaohui Wang, M.D. Visiting Scientist

last updated 3/2006