Friderici, Karen H.
Department of Microbiology and Molecular Genetics
Department of Pediatrics and Human Development
Ph.D., 1988, Michigan State University
Research in my laboratory centers on the molecular pathology of genetic disease. Our focus is primarily on human disease. The understanding of normal function of organs or proteins can be better understood when we observe the effects of mutation. One study in the laboratory focuses on a specific protein, beta-mannosidase, and how it is affected by various naturally occurring mutations. Another thrust of the laboratory is identification and characterization of genes that are involved in the hearing process.
To study the effects of mutations on the function of the lysosomal enzyme beta-mannosidase, we are identifying the mutations that cause human beta-mannosidosis, a lysosomal storage disease. When we identify a sequence alteration that may affect function we examine the effect of these mutations on beta-mannosidase mRNA and protein metabolism by introducing the mutations into eukaryotic expression vectors. Possible tissue-specific regulation of expression of this enzyme is being studied by introducing the beta-mannosidase human and bovine promoters into luciferase reporter vectors.
At present the process by which we hear is very incompletely understood at the molecular level. Approximately 100 genes are predicted to be involved in hearing and mutations in these genes can cause deafness with no other symptoms. In collaboration with Dr. Rachel Fisher (Department of Pediatrics & Human Development) we are investigating the genetics of hearing. To approach this problem we have identified families from the Mid-Michigan area that have genetic hearing loss. Several of the families are now being studied in detail. In one of the families we have found the location of a gene that has not been previously described to be involved in the hearing process. We are using the resources of the Human Genome Project to identify the gene and we intend to pursue studies of its function once the gene has been identified. In another very large family we are studying the genes for recessive hearing loss. One of the mutated genes has been identified but at least one other defective gene causes deafness in this family. We are in the process of identifying the second gene by linkage analysis. We will be studying the possible effect of these recessive genes on hearing and age related hearing loss in heterozygous carriers of the mutation.
I am also collaborating in studies that examine the role candidate genes may play in the etiology of multifactorial disease by correlating common polymorphisms in selected genes with disease risk. We are examining genes potentially involved in Attention Deficit Hyperactivity Disorder (with Dr. Joel Nigg, Department of Psychology) and in Prematurity (with Dr. Claudia Holtzman, Epidemiology).