About the Chen Lab

The body’s defense system is finely tuned to detect, destroy, or export endogenous or foreign toxic substances. While this system has obvious protective benefits, it can also contribute to treatment failure by decreasing drug efficacy and increasing drug resistance and toxicity. Our laboratory uses promiscuous xenobiotic nuclear receptors as a model to investigate the transcriptional regulation of response to therapeutics. Using small molecules to modulate these receptors, we are able to control their role in drug metabolism to help improve clinical intervention.

scientist in chen lab

Our research summary

By using both hypothesis-driven and technology-enabled approaches, our laboratory develops and uses small molecules targeting pregnane X receptor (PXR) and constitutive androstane receptor (CAR), xenobiotic receptors that detect toxic compounds and essentially act as switches of the garbage disposal in cells. PXR and CAR promiscuously bind to many toxic compounds and transcriptionally elevate the levels of enzymes [such as cytochrome P450 (CYP) CYP3A4 and CYP3A5] and transporters that destroy and export these toxic compounds. The ligand promiscuity and structural flexibility of PXR and CAR have historically hampered the development of chemical modulators, the lack of which has been critical barrier to investigating their transcriptional regulation. Our research aims to employ small molecules to inhibit and control PXR, CAR and their downstream targets CYP3A4 and CYP3A5 and, in turn, increase drug efficacy, decrease drug resistance and prevent toxicity.

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To tackle the challenging problem of controlling the transcription factor PXR, our laboratory integrates model systems and multidisciplinary approaches including cell biology, medicinal chemistry, structural biology and pharmacology as well as high-throughput technologies. These approaches led us to develop the first specific PXR antagonist/inverse agonist (SPA70), and its analogs and derivatives with varying cellular activities – activating, inhibiting, or blocking. These mechanistically characterized novel chemical modulators enable us to understand how to precisely control the transcriptional activity of PXR in regulating drug metabolism. SPA70 has been used to attenuate PXR-mediated liver injury in an animal model, supporting the feasibility of pharmacologic inhibition of PXR as a remedy for drug toxicity.

In addition, we have developed selective CAR inverse agonists (e.g., CINPA1), and discovered the first selective inhibitor of CYP3A5 (i.e., clobetasol propionate). CYP3A4 and CYP3A5 are highly homologous enzymes, but they also preferentially metabolize different drugs. Together they metabolize more than half of marketed drugs. The mechanism for selective inhibition of CYP3A5 is needed to distinguish its role from that of CYP3A4 and guide the development of potential therapeutics. Using clobetasol propionate as a tool compound, we discovered that the unique conformation of a surface loop of CYP3A5 enables the selective binding of the inhibitor. These efforts support the feasibility of selectively inhibiting the highly homologous CYP3A family members, and provide additional targets downstream of PXR/CAR to control therapeutic responses.

Selected publications


Journal cover feature

Unraveling the structural basis of selective inhibition of human cytochrome P450 3A5

Wang J, Buchman CD, Seetharaman J, Mller DJ, Huber AD, Wu J, Chai SC, Garcia-Maldonado E, Wright WC, Change J, Chen T.

J. Am. Chem. Soc. October 14 2021, 143, 44, 18467–18480. 

About Taosheng Chen

Dr. Taosheng Chen received his BS and MS degrees from Fudan University in Shanghai and his PhD from the University of Vermont guided by Janet Kurjan. He completed his post-doctoral training under Michael Weber at the University of Virginia. Having spent time in the pharmaceutical industry, Dr. Chen brings his expertise in drug discovery and development to St. Jude where he serves as Director of the High Throughput Bioscience Center. Dr. Chen has built a lab of chemists and biologists in order to answer questions about drug toxicity, drug resistance, and human disease.

Taosheng Chen

The team

Multidisciplinary team of biologists and chemists

Lab Alumni

Jude Chenge, PhD

  • Role: Postdoctoral Associate
  • Tenure: 10/2017 – 09/2019
  • Post-lab experience: Principal Consultant with Medical Device Companies
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Milu Cherian, PhD

  • Role: Postdoctoral Associate
  • Tenure: 09/2012 – 10/2017
  • Post-lab experience: Senior Analyst, Oncology, Putnam
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Hanqing Dong, PhD

  • Role: Postdoctoral Associate
  • Tenure: 02/2008 – 09/2009
  • Post-lab experience: Research Fellow, Mount Sinai School of Medicine
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Ayesha Elias, PhD

  • Role: Postdoctoral Associate
  • Tenure: 02/2010 – 05/2015
  • Post-lab experience: Manager, Global Medical Information, Eli Lilly and Company
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Asli Goktug, MS

  • Role: Senior HTS Automation Technologist
  • Tenure: 05/2010 – 05/2016
  • Post-lab experience: Sr. Automation Engineer II, AbbVie
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Lingling Liu, PhD

  • Role: Postdoctoral Associate
  • Tenure: 03/2008 – 08/2012
  • Post-lab experience: Research Scientist, Nationwide Children’s Hospital
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Wenwei Lin, PhD

  • Role: Postdoctoral Associate
  • Tenure: 11/2006 – 01/2008
  • Post-lab experience: Lead Scientist, St. Jude Children’s Research Hospital
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Delira Robbins, PhD

  • Role: Postdoctoral Associate
  • Tenure: 06/2012 – 03/2016
  • Post-lab experience: Preclinical Project Manager - Neurobiology & Brain Tumor Program, St. Jude Children’s Research Hospital
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William (Charlie) Wright, PhD

  • Role: Graduate Student
  • Tenure: 01/2017 – 06/2020
  • Post-lab experience: Bioinformatics Research Scientist, St. Jude Children’s Research Hospital
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Yue-Ming Wang, PhD

  • Role: Postdoctoral Associate
  • Tenure: 10/2010 – 05/2013
  • Post-lab experience: Principal Scientist, Pfizer Inc.
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Fu-Yue Zeng, PhD

  • Role: Principal HTS Scientist
  • Tenure: 01/2007 – 07/2009
  • Post-lab experience: Associate Director, HTS & Compound Management, Sanford-Burnham Medical Research Institute
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Satyanarayana Pondugula, PhD

  • Role: Postdoctoral Associate
  • Tenure: 11/2006 – 06/2010
  • Post-lab experience: Associate Professor, Auburn University
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Monimoy Banerjee, PhD

  • Role: Postdoctoral Associate
  • Tenure: 08/2011 – 04/2015
  • Post-lab experience: Principal Scientist 2, Charles River Laboratories
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Monicah Bwayi, PhD

  • Role: Postdoctoral Associate
  • Tenure: 02/2017 – 12/2021
  • Post-lab experience: Sr Scientist, St. Jude Children’s Research Hospital
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Jordan Beard, PhD

  • Role: Graduate Student
  • Tenure: 04/2010 – 03/2016
  • Post-lab experience: Postdoctoral Associate, St. Jude Children’s Research Hospital
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David Bouck, PhD

  • Role: Postdoctoral Associate
  • Tenure: 06/2007 – 10/2009
  • Post-lab experience: Head of HTS Operations, Ginkgo Bioworks, Inc.
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Jesse Bakke, PhD

  • Role: Postdoctoral Associate
  • Tenure: 08/2014 – 03/2018
  • Post-lab experience: Assistant Professor, Central Michigan University College of Medicine
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Cameron Buchman, PhD

  • Role: Postdoctoral Associate
  • Tenure: 06/2017 – 11/2021
  • Post-lab experience: Staff Scientist at Vanderbilt University Medical Center
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Su Sien Ong, PhD

  • Role: Postdoctoral Associate
  • Tenure: 02/2010 – 01/2013
  • Post-lab experience: Principal Scientist, EMD Serono, Inc.
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Alexa (Tenga) Farmer, PhD

  • Role: Graduate Student
  • Tenure: 05/2012 – 07/2016
  • Post-lab experience: Postdoctoral Associate, University of Arizona
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Explore career opportunities in the Chen Lab

We are currently recruiting!

Contact us

Taosheng Chen, PhD, PMP

Chemical Biology & Therapeutics
MS 1000, Room E9054
St. Jude Children’s Research Hospital

262 Danny Thomas Place
Memphis, TN, 38105-3678 USA
901-595-5937 taosheng.chen@stjude.org
262 Danny Thomas Place
Memphis, TN, 38105-3678 USA
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