Research in the Gelb lab is in the area of medicinal enzymology. Research is not based on a single approach, but rather a variety of modern experimental techniques are used to solve research problems. Because the areas of expertise of lab members are diverse, the lab provides an ideal forum for students and postdocs to learn new experimental approaches. This is accomplished not only by “hands-on” research experiences but also by the variety of scientific discussions that occur in various formats.
The facilities in the newly constructed labs together with on-campus equipment centers provide all of the necessary tools for meeting research goals. The lab has received strong funding from the National Institutes of Health and a number of pharmaceutical companies which allows graduate students to devote most of their time to research.
Lysosomal storage diseases are caused by deficiency in the activity of enzymes in the lysosome that are required for the degradation of cellular components. Many of these diseases have become treatable either by enzyme replacement therapy or by bone marrow transplantation. Halting the disease progression is most dramatic when treatment is started early in life. Thus, it makes sense to expand newborn screening programs to include lysosomal storage diseases.
The Gelb laboratory is developing the use of tandem mass spectrometry for the direct assay of several lysosomal enzymes. The advantage of mass spectrometry is that many enzymes can be analyzed in a single infusion. The technique is exquisitely sensitive and rapid, and it is made quantitative by the use of internal standards. The Gelb lab is the leading lab in the world in this area. The technology for newborn screening of lysosomal storage diseases has advanced to an FDA-approved kit, and reagents are used by numerous newborn screening labs worldwide.
Current efforts are aimed at expanind the genetic conditions that can be screened by mass spectrometry. The key is to consolidate all assays into a single-multiplex assay to save time and money.
The work is supported by two grants from the National Institutes of Health and several grants from Disease Foundations and the Pharmaceutical Industry.
Above: Top panel shows our tandem mass spectrometry assay for Hurler syndrome. The bottom panel shows assay results using dried blood spots from Hurler patients, Hurler carriers and non-Hurler patients.
Drugs are desperately needed for Malaria, African sleeping sickness and Chagas’ disease, which effect millions of people worldwide. Lack of financial interest for development of drugs for diseases that are endemic in developing countries has necessitated the development of these drugs in academic institutions.
The Gelb lab works closely with the lab of Fred Buckner in the Dept. of Medicine at UW. The Buckner lab test drug candidates on parasites in vitro and in animal models.
The Gelb lab carries out hit-to-lead medicinal chemistry and pharmacokinetic studies. The Gelb and Buckner labs work together to determine the mode of action of novel anti-parasite lead compounds.
The work is supported by a grant from the National Institutes of Health.