Marto, Jarrod A
Primary Appointment
Professor, Biochemistry and Molecular Genetics
Education
- B.S., Centre College
- Ph.D., The Ohio State University
Contact Information
Email: jam9n@virginia.edu
Research Disciplines
Biochemistry, Biotechnology, Cancer Biology
Research Interests
Leveraging Chemoproteomic Tools to Drive Discovery in Chemical Biology
Research Description
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.