John Melchior Email & Phone Number

Richland, Wa, Us

Richland, Washington, United States

I manage the Chemical Biology Team in the Biological Systems Science group at Pacific Northwest National Laboratories. Our team provides several services including synthesis of activity-based chemical probes for molecular profiling, generation of conformational-specific nanobodies to protein targets, and genetic code expansion. We complement these technologies with high-throughput structural proteomics platforms such as thermal proteome profiling and limited proteolysis to unravel molecular pathways that control phenotype across a broad range of biological systems. This includes human health (lipoproteins, host response, microbiome) and environmental systems (plants, soils, microbial communities). We interact with a variety of internal and external partners to pioneer novel workflows aimed at filling the gaps in our understanding of molecular pathways that underpin the biological processes essential to life.

Richland, Washington, United States

I manage a diverse project portfolio with a primary focus on lipoprotein biology and development of high-throughput molecular phenotyping technologies. To this end we recently engineered a fluorescent lipoprotein profiler to profile lipoprotein subspecies in plasma and cerebrospinal fluid with unprecedented sensitivity. This will open new avenues for understanding the role of these particles in neurodegenerative disorders which has dogged the field for decades. In addition to our molecular profiling approaches, we have developed workflows for obtaining high-resolution structural information on lipid-bound proteins using a combination of structure specific nanobodies and cryo-EM.I currently head multiple structural proteomics capabilities grounded in bottom-up, quantitative mass spectrometry. These include thermal proteome profiling, limited proteolysis, and chemical cross-linking. These complementary approaches allow us to map structural changes in the global proteome that occur due to metabolic perturbations or drug treatments. This allows us to comprehensively map biomolecular pathways and identify controllable molecular machinery that drives cellular function.

I hold a faculty joint appointment with the Department of Neurology in the School of Medicine at Oregon Health Sciences University. My research is focused on lipoproteins in the central nervous system and their role in neurodegenerative disorders such as Alzheimer's and Parkinson's Disease.

Cincinnati, Oh

I hold a faculty joint appointment in the Pathology and Laboratory Medicine Department at University of Cincinnati. Our team continues to collaborate with faculty to unravel the details of lipoprotein structure and function in cardiovascular disease and diabetes.

Cincinnati Area, Ky

As a postdoctoral fellow, I received conceptual and technical training in protein biochemistry under Dr. Sean Davidson, an expert in the structure/function relationships of protein moieties on lipoproteins. I mastered methodologies in protein expression and purification, size exclusion chromatography (SEC), immunoaffinify chromatography (IAC), chemical cross-linking, small-angle x-ray scattering (SAXS), and integrative protein modeling. I am an expert in mass spectrometry (MS) techniques; a technology that has emerged as the premier method in identifying and defining biomolecules. I have successfully exploited MS technology with cross-linking to define amino acid proximity and inter- vs intramolecular span between isotopically-labeled apoA-I molecules that reside on the surface of HDL.I successfully applied these methodologies to determine a "consensus" structure of lipid-free, human apoA-I in solution. The structure fits essentially all of the published structural data on apoA-I spanning nearly 4 decades. Moreover, our techniques and experimental approach have been featured in Nature Protocols. To complement the structural studies, I have speciated and defined distinct HDL populations with different functionalities from plasma. My work in Dr. Davidson's laboratory significantly bolstered our understanding of HDL structure and function.

Doctor Of Philosophy (Ph.D.), Molecular Pathology

During my tenure at Wake Forest, I received rigorous training in lipoprotein metabolism from the late Dr. Lawrence Rudel, a world expert.

Biology

B.S.E., Mechanical Engineering