Assistant Professor of Chemistry
Adjunct Assistant Professor of Urology
Ph.D. University of Cambridge, 2012
(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 complementary methods, such as in vivo models, to better understand how chemical processes are linked to patient symptoms. A related emerging area of research within our group centers on developing culture models and molecular isolation tools to study microbial signaling in the environment and agriculture.
Metabolomics across biological kingdoms
Multikingdom signaling—such as signaling between fungi, bacteria, and plants—plays a key role in the environment and agriculture; symbiotic microbes significantly boost crop yields, and pathogenic microbes can infect or contaminate entire batches of crops. Similarly, signals such as oxylipin immune mediators and microbial secondary metabolites contribute significantly to human health and infections. Advanced culture models are required to recreate the salient features of these complex multikingdom systems, and novel sample preparation methods are required to isolate key effector molecules from the chemical milieu. We combine environmental and organotypic culture models with novel methods for small molecule isolation and advances in mass spectrometry to study the metabolomics of signaling in diverse microbiomes.
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 disease.
Yu, J.; Berthier, E.; Craig, A.; de Groot, T. E.; Sparks, S.; Ingram, P. N.; Jarrard, D. F.; Huang, W.; Beebe, D. J.; Theberge, A. B. Reconfigurable open microfluidics for studying the spatiotemporal dynamics of paracrine signalling. Nat. Biomed. Eng. 2019, in press.
Zhang, T.; Day, J. H.; Su, X.; Guadarrama, A. G.; Sandbo, N. K.; Esnault, S.; Denlinger, L. C.; Berthier, E.; Theberge, A. B. Investigating fibroblast-induced collagen gel contraction using a dynamic microscale platform. Front. Bioeng. Biotechnol. 2019, 7, 196.
Millik, S. C.; Dostie, A. M.; Karis, D. G.; Smith, P. T.; McKenna, M.; Chan, N.; Curtis, C. D.; Nance, E.; Theberge, A. B.; Nelson, A. 3D printed coaxial nozzles for the extrusion of hydrogel tubes toward modeling vascular endothelium. Biofabrication 2019, 11, 045009.
Berthier, E.; Dostie, A. M.; Lee, U. N.; Berthier, J.; Theberge, A. B. Open microfluidic capillary systems. Anal. Chem. 2019, 91, 8739.
Lee, J. J.; Berthier, J.; Brakke, K. A.; Dostie, A. M.; Theberge, A. B.; Berthier, E. Droplet behavior in open biphasic microfluidics. Langmuir 2018, 18, 5358.
Lee, U. N.; Su, X.; Guckenberger, D. J.; Dostie, A. M.; Zhang, T.; Berthier, E.; Theberge, A. B. Fundamentals of rapid injection molding for microfluidic cell-based assays. Lab Chip 2018, 18, 196.
Berry, S. B.; Zhang, T.; Day, J. H.; Su, X.; Wilson, I. Z.; Berthier, E.; Theberge, A. B. Upgrading well plates using open microfluidic patterning. Lab Chip 2017, 17, 4253.
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. Nat. Commun. 2016, 7:10610.
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.