Luca Fornelli

Associate Professor of Biology

Research Areas: Mass Spectrometry, Proteomics
Email: luca.fornelli@ou.edu
Phone: (405) 325-1483
Office: SLSRC 1590, RH 411b

Education:
B.S., 2005, University of Padova, Italy
M.S., 2005, University of Padova, Italy
Ph.D., 2014, École Polytechnique Fédérale de Lausanne, Switzerland
Postdoc, 2014-2018, Northwestern University, Evanston, Illinois

Research projects where top-down proteomics is applied to biology and translational sciences:

Cancer biology: quantitative analysis of proteoforms distinguishing healthy tissues vs tumors, with specific focus on key oncogenes and their modifications, which have important implications in the onset and progression of disease;
Development of a systems biology platform centered on the concept of proteoform to investigate biological processes at the molecular level in model organisms (e.g., budding yeast);
Improvement of mass spectrometry-based solutions for the characterization of large proteins and protein complexes: the proteomes of mammals consist primarily of proteins with molecular weight between 30 and 60 kDa, and often their biological functions are carried out in multi-proteoforms complexes whose stoichiometry and bioactivity can be modulated by post-translational modifications and binding with small molecules (ligands); hence the importance of mass spectrometry tools specifically designed to analyze large biomolecules.

“Protein” is a concept, “proteoform” a molecule.

Cells and tissue function thanks to the action of molecularly defined versions of gene products that we call protein forms, or proteoforms. Each proteoform carries a specific set of genetic and chemical variations. It is estimated that more than a million different proteoforms can be simultaneously present in a human cell.

Mass spectrometry-based top-down proteomics.

Our research focuses on the study of the proteins present in an organism, or proteomics, using high resolution mass spectrometry. Traditionally, proteomics is carried out by enzymatically digesting the original proteins into short peptides, which are easier to analyze – a process similar to the “shotgun” approach normally used in genomics. This approach, known as bottom-up proteomics, fails to reconstruct the original complexity of individual proteoforms, as the correlation between sources of variation present on different parts of the amino acid sequence is lost and cannot be inferred starting from proteolytic peptides, which may be shared among multiple proteoforms.

Our research group develops top-down proteomics, an approach based on the direct analysis of undigested proteoforms. We use top-down proteomics to study the specific modification patterns of proteoforms differentially localized in various sub-cellular compartments, or how different proteoforms derived from the same gene can distinguish between healthy and aberrant phenotypes.