David L. Gasser
Emeritus Professor of Genetics
Department: Genetics
Contact information
575 Clinical Research Building
415 Curie Boulevard
Philadelphia, PA 19104-6145
415 Curie Boulevard
Philadelphia, PA 19104-6145
Office: 215-898-5175
Fax: 215-573-5892
Fax: 215-573-5892
Email:
GASSERD@MAIL.MED.UPENN.EDU
GASSERD@MAIL.MED.UPENN.EDU
Publications
Links
Search PubMed for articles
Cell and Molecular Biology graduate group faculty webpage.
Immunology graduate group faculty webpage.
Search PubMed for articles
Cell and Molecular Biology graduate group faculty webpage.
Immunology graduate group faculty webpage.
Education:
B.S. (Biology)
University of Akron, 1964.
M.S. (Zoology)
University of Michigan, 1966.
Ph.D. (Zoology)
University of Michigan, 1970.
B.S. (Biology)
University of Akron, 1964.
M.S. (Zoology)
University of Michigan, 1966.
Ph.D. (Zoology)
University of Michigan, 1970.
Post-Graduate Training
U.S.P.H.S. Postdoctoral Fellow, Department of Medical Genetics, University of Pennsylvania, with Dr. W.K. Silvers, 1970-1972.
Sabbatical leave with Dr. J.G. Seidman, Department of Genetics, Harvard Medical School, 1983-1984.
Sabbatical leave with Dr. David D. Chaplin, Department of Medicine, Washington University School of Medicine, St. Louis, 1990-1990.
Sabbatical leave with Dr. Noel Rose, Department of Pathology, Johns Hopkins University School of Medicine, 1998-1998.
Permanent linkU.S.P.H.S. Postdoctoral Fellow, Department of Medical Genetics, University of Pennsylvania, with Dr. W.K. Silvers, 1970-1972.
Sabbatical leave with Dr. J.G. Seidman, Department of Genetics, Harvard Medical School, 1983-1984.
Sabbatical leave with Dr. David D. Chaplin, Department of Medicine, Washington University School of Medicine, St. Louis, 1990-1990.
Sabbatical leave with Dr. Noel Rose, Department of Pathology, Johns Hopkins University School of Medicine, 1998-1998.
Description of Research Expertise
Research InterestsMouse models of human disease
Key words: kidney, autoimmune disease, mitochondria
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. We have cloned the relevant gene, and have found that it codes for a mitochondrial protein similar to trans-prenyltransferase. This enzyme is needed for isoprenylation of coenzyme Q (CoQ), and is now known as prenyl diphosphate synthase subunit 2 (Pdss2). The mutant mice have defective mitochondria, as demonstrated by ultrastructural analysis, and we believe that this defect leads to the death of glomerular podocytes. This in turn leads to an autoimmune response which involves both the tubular interstitium and the glomeruli. The kidney disease can be prevented to some extent by CoQ supplementation, and to an even greater extent by probucol.
In collaboration with Dr. Julie Blendy, Dr. Harry Ischiropoulos, and their students, we have demonstrated that these mutant mice also have neuromuscular defects that resemble Parkinson’s disease.
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 in collaboration with a group at the NIH, we have obtained evidence that PDSS2 is one of the genes that is involved in this susceptibility.
Lab Personnel:
Min Peng, MD,PhD, Research Specialist
Description of Itmat Expertise
We are working with a mouse mutant which develops a lethal kidney disease. This disease can be prevented, and even ameliorated after the disease begins, by probucol (Falk et al., EMBO Molecular Medicine 3: 1-18, 2011).Selected Publications
Gasser, D. L., Winkler, C. A., Peng, M., An, P., McKenzie, L. M., Kirk, G. D., Shi, Y., Xie, L. X., Marbois, B. N., Clarke, C. F., Kopp, J. B.: Focal segmental glomerulosclerosis is associated with a PDSS2 haplotype and, independently, with a decreased content of coenzyme Q10. American journal of physiology. Renal physiology 305(8): F1228-38, 2013.Ziegler, Carly G. K., Peng, Min, Falk, Marni J., Polyak, Erzsebet, Tsika, Elpida, Ischiropoulos, Harry, Bakalar, Dana, Blendy, Julie A., Gasser, David L.: Parkinson''s disease-like neuromuscular defects occur in prenyl diphosphate synthase subunit 2 (Pdss2) mutant mice. Mitochondrion 12(2): 248-257, 2012.
Falk, M. J., Polyak, E., Zhang, Z., Peng, M., King, R., Maltzman, J. S., Okwuego, E., Horyn, O., Nakamaru-Ogiso, E., Ostrovsky, J., Xie, L. X., Chen, J. Y., Marbois, B., Nissim, I., Clarke, C. F., Gasser, D. L.: Probucol ameliorates renal and metabolic sequelae of primary CoQ deficiency in Pdss2 mutant mice. EMBO Mol Med 3(7): 410-27, 2011.
Peng, M., Falk, M. J., Haase, V. H., King, R., Polyak, E., Selak, M., Yudkoff, M., Hancock, W. W., Meade, R., Saiki, R., Lunceford, A. L., Clarke, C. F., and Gasser, D, L.: Primary coenzyme Q deficiency in Pdss2 mutant mice causes isolated renal disease. PLoS Genetics 4(4): e1000061, 2008.
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.
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.
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.
Hancock WW, T-L Tsai, MP Madaio, and DL Gasser: Cutting edge: Multiple autoimmune pathways in kdkd mice. Journal of Immunology 171: 2778-81, 2003.
Dell, K.M., Li, Y.X., Peng, M., Nielson, E.G., and Gasser, D.L.: Localization of the mouse kidney disease (kd) gene to a YAC/BAC contig on mouse chromosome 10. Mammalian Genome 11: 967-971, 2000.