Powered By Bing

Taosheng Chen Lab: About Us

Welcome to the lab of Taosheng Chen, PhD, PMP

We study the broad cellular function of two nuclear receptors—human pregnane X receptor (hPXR) and constitutive androstane receptor (hCAR)—and drug–metabolizing enzymes within the cytochrome P4503A (CYP3A) subfamily. We are particularly interested in the roles that hPXR, hCAR, and CYP3A play in human diseases, with a current focus on cancer drug resistance, tumorigenesis, and drug-induced liver toxicity (see “Research”).

The laboratory consists of graduate students, postdoctoral fellows, and research staff with training in biology, pharmacology, structural biology, and medicinal chemistry. Our alumni frequently acquire positions either in the pharmaceutical industry or at academic institutions (see “People”). We use a multidisciplinary approach in our research (i.e., biology, chemistry, and structural biology), develop novel chemical probes/therapeutic leads, and apply these unique tools to interrogate or modulate the cellular function of hPXR, hCAR, and CYP3A. Our research outputs provide not only a broader comprehension of the regulation of hPXR, hCAR and CYP3A and how they control the human body’s response to xenobiotics and endobiotics but also novel chemical entities which can be used as leads for therapies to prevent or overcome drug toxicity and drug resistance (see “Publications” such as Lin et al, Nat Commun. 8:741, 2017 and Figure 1).

In addition to cellular, molecular, biochemical, genomic, and proteomic techniques and animal models, we also capitalize on our unique technology platforms for small molecules (> 800,000 compounds) and RNA interference/gene editing (whole genome), facilitated by laboratory automation and high-throughput and high-content screening, to accelerate our research (see “HTB Center”).

If you are interested in joining us, please contact us (see “Contact Chen Lab”)!

Figure 1. Compounds SJB7 (agonist, left) and SPA70 (antagonist, right) are structurally similar analogs but modulate hPXR in opposing ways.
(Left) Model based on crystal structure depicting agonist SJB7 interacting with the activation function 2 (AF-2) helix residues M425, L428, and F429 of hPXR. The sphere indicates the methoxy group that contacts the L428 and F429 pair.
(Right) The antagonist SPA70 docked in the ligand-binding site, showing the missing interactions with L428 and F429. Color code for stick representations of compounds: blue, nitrogen; magenta, oxygen; yellow, sulfur.