The Fornelli lab focuses on the development of new mass spectrometry methods for the characterization of intact protein forms, or proteoforms. Specifically, our main interest is in the validation of the “proteoform hypothesis”, which posits that molecularly defined forms of proteins (with individual sets of genetic and chemical modifications) are ultimately responsible for observable phenotypes.
Our interdisciplinary research team advances analytical technology which is later used to implement new proteomic applications.
Research directions include the analysis of biotherapeutics, the investigation of large proteoforms from complex samples, the evaluation of proteoform dynamics in clinically relevant biofluids to identify molecular mechanisms of human diseases, and the characterization of proteoform complexes.
Kline JT, Belford MW, Boeser CL, Huguet R, Fellers RT, Greer JB, Greer SM, Horn DM, Durbin KR, Dunyach JJ, Ahsan N, Fornelli L. Orbitrap mass spectrometry and high-field asymmetric waveform ion mobility spectrometry (FAIMS) enable the in-depth analysis of human serum proteoforms. J Proteome Res (2023), 22 (11), 3418-3426. Doi: 10.1021/acs.jproteome.3c00488
Kline JT, Melani RD, Fornelli L. Mass spectrometry characterization of antibodies at the intact and subunit levels: from targeted to large-scale analysis. Int J Mass Spectrom (2023), 492, 117117. Doi: 10.1016/j.ijms.2023.117117
Kline JT, Belford MW, Huang J, Greer JB, Bergen D, Fellers RT, Greer SM, Horn DM, Zabrouskov V, Huguet R, Boeser CL, Durbin KR, Fornelli L. Improved label-free quantification of intact proteoforms using field asymmetric ion mobility spectrometry. Anal Chem (2023), 95 (23), 9090–9096. Doi: 10.1021/acs.analchem.3c01534
Fornelli L, Toby TK. Characterization of large intact protein ions by mass spectrometry: What directions should we follow? BBA-Proteins and proteomics (2022), 1870 (4), 140758. Doi: 10.1016/j.bbapap.2022.140758
Huguet R, Mullen C, Srzentić K, Greer JB, Fellers RT, Zabrouskov V, Syka JEP, Kelleher NL, Fornelli L. Proton Transfer Charge Reduction Enables High-Throughput Top-Down Analysis of Large Proteoforms. Anal Chem (2019), 91 (24), 15732-15739.
Doi: 10.1021/acs.analchem.9b03925
