Assistant Professor of Chemistry
Ph.D. University of Cambridge, 2011
(Analytical and Biological Chemistry, Biomedical Science & Engineering)
The Theberge group studies the chemical mechanisms underlying diseases such as bladder infections, prostate cancer, benign prostatic hyperplasia, and asthma. We develop analytical chemistry tools to advance medicine, including biomimetic microfluidic systems for integrated cell culture and small molecule isolation. We collaborate closely with clinicians who treat patients with the diseases that we study and utilize complimentary methods, such as in vivo models, to better understand how chemical processes are linked to patient symptoms.
Metabolomics of infections
Small molecule signals, such as oxylipin immune mediators and microbial secondary metabolites, play an important role in infections. We aim to understand how these signals contribute to bacterial infections in the bladder and fungal infections in the lung. Advanced culture models are required to recreate the salient features of these complex multikingdom systems, incorporating human epithelial cells, immune cells, and microbial pathogens. We combine these organotypic culture models with microscale methods for small molecule isolation and advances in mass spectrometry to study the metabolomics of human diseases.
Steroid synthesis in development
Steroidogenesis, the synthesis of steroids, is a critical driver of normal development. Many toxins and toxicants (synthetic compounds) have been found to inhibit or hijack steroidogenic pathways, resulting in birth defects or increased risk for steroid-responsive cancers, including prostate and breast cancer. We develop in vitro microscale assays to identify and study compounds that interfere with steroidogenesis. One of our goals is to determine how the action of these compounds is affected by microenvironment, such as extracellular matrix composition and supporting cell types cocultured with steroidogenic cells.
Establishing links between small molecule production and biological function
We develop functional readouts within our engineered in vitro microenvironments to better understand the effects of small molecules on biological processes. For example, angiogenesis (the formation of blood vessels from existing blood vessels) plays an important role in development, wound healing, and many diseases. We have developed a microscale cell-based assay that responds to complex pro- and anti-angiogenic factors with an in vitro readout for vessel formation. We are incorporating this angiogenesis assay with microscale metabolomics methods to identify the chemical factors regulating blood vessel formation in prostate disease.
Barkal, L. J.*; Theberge, A. B.*; Guo, C. J.*; Spraker, J.; Rappert, L.; Berthier, J.; Brakke, K. A.; Wang, C. C.; Beebe, D. J.; Keller, N. P.; Berthier, E. "Microbial metabolomics in open microscale platforms." Nature Commun. 2016, 7:10610. DOI: 10.1038/ncomms10610.
Theberge, A. B.*; Yu, J.*; Young, E. W. K.; Ricke, W. A.; Bushman, W.; Beebe, D. J. "Microfluidic multiculture assay to analyze biomolecular signaling in angiogenesis." Anal. Chem. 2015, 87, 3239.
Carney, C. M.; Muszynski, J. L.; Strotman, L. N.; Lewis, S. R.; O’Connell, R. L.; Beebe, D. J.; Theberge, A. B.*; Jorgensen, J. S.* "Cellular microenvironment dictates androgen production by murine fetal Leydig cells in primary culture." Biol. Reprod. 2014, 91, Article 85.
Casavant, B. P.; Berthier, E.; Theberge, A. B.; Berthier, J.; Montanez-Sauri, S. I.; Bischel, L. L.; Brakke, K.; Hedman, C. J.; Bushman, W.; Keller, N. P.; Beebe, D. J. "Suspended microfluidics." Proc. Natl. Acad. Sci. U.S.A. 2013, 110, 10111.
Theberge, A. B.; Courtois, F.; Schaerli, Y.; Fischlechner, M.; Abell, C.; Hollfelder, F.; Huck, W. T. S. "Microdroplets in microfluidics: An evolving platform for discoveries in chemistry and biology." Angew. Chem., Int. Ed. 2010, 49, 5846.