Location: Salon Ville-Marie, Hotel Level

Michael Gelb, PhD University of Washington Michael H. Gelb is Professor of Chemistry and Barbara L. Weinstein Endowed Chair in Chemistry, Adjunct Professor of Biochemistry at the University of Washington. Major developments in the Gelb lab include discovery of protein prenylation, development of ICAT proteomic reagents, identification of phospholipases involved in lipid mediator generation, development of anti-parasite drugs, and development of mass spectrometry for newborn screening. Awards include: Repligen Award in Chemistry of Biological Processes (Amer. Chem. Soc.), Univ.of Washington Faculty Lecture Award, Gustavus John Esselen Award (Harvard Univ.), AAAS Fellow, NIH Merit Award, Medicines for Malaria Project of the Year Award, Pfizer Award in Enzyme Chemistry, ICI Pharmaceuticals Award for Excellence in Chemistry. The Gelb lab has published more than 500 papers and 100 patents in biological chemistry. The Gelb laboratory has developed mass spectrometry for worldwide newborn screening of lysosomal storage diseases (the latest expansion of newborn screening panels). Relevant Financial Disclosures (within past 24 months, reported on Jun 17, 2025) Not yet reported.

Targeted proteomics using complex biological fluids usually requires enrichment of signature peptides prior to tandem mass spectrometry. Anti-peptide antibodies are useful in this context but can be difficult to obtain in a timely fashion. We have recently developed a computational design platform that yields proteins capable of binding targeted peptides with high affinity (nanomolar to picomolar range). When applied to 30 targeted peptides, high affinity binders were obtained in 28 cases. In this talk we will illustrate the method for newborn screening and diagnosis of a rare lysosomal storage disease called cystinosis. Patients with this disease are deficient in a lysosomal cystine transporter. Trypsinization of proteins extracted from a 3 mm punch of a dried blood spot are treated with the designed peptide binder. After peptide capture and release, the signature peptide for the cystine transporter is readily detected by LC-MS/MS. Most cystinosis patients show a large decrease in the abundance of this target peptide. We also developed a peptide methylation scheme whereby peptides are methylated on amino groups by treatment with formaldehyde and sodium cyanoborohydride. Using heavy isotope forms of formaldehyde, we can combine 4 patient samples into a single LC-MS/MS run and thus decrease the time per sample by 4-fold. This method can be multiplexed to measure the abundance of several proteins in a single analysis. We will show data for Wilson disease and a panel of primary immunodeficiencies.