Education and Biography

B.S. Centre College, 1990

Ph.D. The Ohio State University, 1995

Postdoctoral Fellow, University of Virginia, 1995-2000

Senior Scientist, MDS Proteomics, 2000-2004

Principal Investigator and Associate Professor, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Harvard Medical School, 2004-2025

Director, Blais Proteomics Center (Dana-Farber Cancer Institute), 2006-2025

Co-Director, Center for Emergent Drug Targets (Dana-Farber Cancer Institute), 2022-2025

Research Program

Despite tremendous progress in cataloging the human genome, we have much to learn about the tightly choreographed dance between proteins, nucleotides, and metabolites in cells and tissues. These data provide a molecular roadmap for the genotype-phenotype relationships that control normal development and physiology as well as a testable framework to understand how disruptions in these networks lead to human disease. Conversely, we can interrogate these data for vulnerabilities that may be harnessed for therapeutic benefit via traditional and new pharmacologic modalities.

My laboratory develops and uses mass spectrometry, chemical, and genetic tools to understand how DNA alterations or other pathological insults manifest in cellular biochemical and signaling networks or other compartments in the functional proteome. We leverage these quantitative data, comprising protein expression, isoform regulation, biochemical interactions, and post-translational modifications, to explore molecular mechanisms in human disease, identify new therapeutic entry points, or to develop molecular ‘QR codes’ that may be clinically actionable for early detection, disease prognosis, or patient stratification.

We also use these analytical tools as screening platforms to identify new chemical starting points for probes against disease-associated protein targets with an emphasis on covalent pharmacology. We use similar approaches to characterize drugs or early-stage lead compounds to understand how they modulate the activity of their cellular targets to arrest progression of established disease or thwart the onset of nascent disease. These studies span validated and emergent drug targets, mechanistically related target-classes, as well as ligand-target discovery performed directly in complex proteomes.

In pursuit of these goals, we develop numerous analytical, chemical, and software tools paired with automated methods to support generation of reproducible, proteome-scale data in cell line or genetic models of human disease as well as primary clinical tissues. We are also exploring single cell approaches to support geospatial proteome analysis as well as context-specific small molecule screening campaigns. Our approach to science is multidisciplinary and deeply collaborative. We enjoy productive synergies with colleagues in synthetic and medicinal chemistry, structural and chemical biology, functional genomics, computational bioinformatics, advanced instrumentation, and device engineering.

Representative Publications:

1. Ficarro SB, Kothiwal D, Bae HJ, Tavares I, Giordano G. Buratowski S, Marto JA. Leveraging hilic/erlic separations for online nanoscale lc-ms/ms analysis of phosphopeptide isoforms from rna polymerase ii c-terminal domain. J Chrom B Analyt Technol Biomed Life Sci 2025;1257:124560.
2. Beddows I, Djirackor S, Omran D, Jung E, Shih N, Roy R, Hechmer A, Olshen A, Adelmant G, Tom A, Morrison J, Adams M, Rohrer D, Schwartz L, Pearce CL, Auman H, Marto JA, Drescher CW, Drapkin R, Shen H. Impact of brca mutations, age, surgical indication, and hormone status on the molecular phenotype of the human fallopian tube. Nat Commun 2025;16:2981.
3. Ficarro SB, Marto ZH, Girardi NM, Deng D, Maisonet IJ, Adelmant G, Fleming LE, Sharafi M, Tavares I, Zhao A, Kim HJ, Seo HS, Dhe-Paganon S, Buhrlage SJ, Marto JA. Open-source electrophilic fragment screening platform to identify chemical starting points for uchl1 covalent inhibitors. SLAS Disc 2024;29:100198.
4. Siriwongsup S, Schmoker AM, Ficarro SB, Marto JA, Kim J. Bioorthogonal activated reactive species for target identification. Chem 2024;10:1306-15.
5. Li Z, Jiang J, Ficarro SB, Beyett TS, To C, Tavares I, Zhu Y, Li J, Eck MJ, Janne PA, Marto JA, Zhang T, Che J, Gray NS. Molecular bidents with two electrophilic warheads as a new pharmacological modality. ACS Central Science 2024;10:1156-66.
6. Chan WC, Liu X, Magin RS, Girardi NM, Ficarro SB, Hu W, Starnbach CA, Felix A, Adelmant G, Varca AC, Hu B, Bratt AS, DaSilva E, Schauer NJ, Maisonet IJ, Dolen EK, Ayala AX, Marto JA, Buhrlage SJ. Accelerating Inhibitor Discovery for Deubiquitinating Enzymes. Nat Commun 2023;14:686.
7. Zhu H, Mellors JS, Chan WC, Thompson JW, Ficarro SB, Tavares I, Bratt AS, Decker J, Krause M, Kruppa G, Buhrlage SJ, Marto JA. On-chip preconcentration microchip capillary electrophoresis based ce-prm-live for high-throughput selectivity profiling of deubiquitinase inhibitors. Anal Chem 2022;94:9508-13.
8. Zhu H, Ficarro SB, Alexander WM, Fleming LE, Adelmant G, Zhang T, Willetts M, Decker J, Brehmer S, Krause M, East MP, Gray NS, Johnson GL, Kruppa G, Marto JA. PRM-LIVE with trapped ion mobility spectrometry and its application in selectivity profiling of kinase inhibitors. Anal Chem 2021;93:13791-99.

9. Browne CM, Jiang B, Ficarro SB, Doctor ZM, Johnson JL, Card JD, Sivakumaren SC, Alexander WM, Yaron TM, Murphy CJ, Kwiatkowski NP, Zhang T, Cantley LC, Gray NS, Marto JA. A chemoproteomic strategy for direct and proteome-wide covalent inhibitor target-site identification. J Am Chem Soc 2019;141:191-203.

    

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