Jennifer Chen, MD
Associate Professor
Medicine
School of Medicine

As a physician-scientist trained in hepatology, my research program is focused on developing a precision approach for the diagnosis and treatment of hepatic fibrogenesis to improve the care of my patients with chronic liver disease.

We previously performed a small molecule screen to identify mechanisms that inactivate hepatic stellate cells (HSCs), the primary cell type responsible for hepatic fibrosis. We identified several targets, including the enzyme acid ceramidase (aCDase). Our studies uncovered a novel signaling network through which aCDase inhibition regulates phosphorylation and degradation of YAP/TAZ, key effectors of the Hippo signaling pathway. We validated aCDase as an antifibrotic target using conditional genetic knockout and pharmacologic approaches, and demonstrated that targeting aCDase inhibits YAP/TAZ activity, decreases matrix stiffness, and reduces fibrosis development and promotes fibrosis regression using multiple mouse models of fibrosis. Our data also show that aCDase inhibition reduces fibrogenesis in fibrotic rat and human liver tissues ex vivo. We also developed a gene signature score, the ceramide responsiveness score, which is significantly increased in NASH patients with advanced fibrosis.

Current projects in our research laboratory include identification of the upstream and downstream targets of the acid ceramidase-YAP/TAZ pathway; the development of novel aCDase inhibitors in partnership with medicinal chemists William DeGrado and Hyunil Jo for the treatment of hepatic fibrosis and hepatocellular carcinoma; and the refinement and validation of gene signature scores as biomarkers for hepatic fibrogenesis. We are also pursuing additional novel antifibrotic targets.

• Controlled fabrication of functional liver spheroids with microfluidic flow cytometric printing.
  Biofabrication 2022 Zhang P, Li X, Chen JY, Abate AR
• Emulating a target trial of antiretroviral therapy regimens started before conception and risk of adverse birth outcomes.
  AIDS (London, England) 2018 Caniglia EC, Zash R, Jacobson DL, Diseko M, Mayondi G, Lockman S, Chen JY, Mmalane M, Makhema J, Hernán MA, Shapiro RL
• Reassuring Birth Outcomes With Tenofovir/Emtricitabine/Efavirenz Used for Prevention of Mother-to-Child Transmission of HIV in Botswana.
  Journal of acquired immune deficiency syndromes (1999) 2016 Zash R, Souda S, Chen JY, Binda K, Dryden-Peterson S, Lockman S, Mmalane M, Makhema J, Essex M, Shapiro R
• Initial programmatic implementation of WHO option B in Botswana associated with increased projected MTCT.
  Journal of acquired immune deficiency syndromes (1999) 2015 Dryden-Peterson S, Lockman S, Zash R, Lei Q, Chen JY, Souda S, Petlo C, Dintwa E, Lebelonyane R, Mmalane M, Shapiro RL
• Noncommunicable diseases in HIV infection in low- and middle-income countries: gastrointestinal, hepatic, and nutritional aspects.
  Journal of acquired immune deficiency syndromes (1999) 2014 Kelly P, Saloojee H, Chen JY, Chung RT
• HCV and HIV co-infection: mechanisms and management.
  Nature reviews. Gastroenterology & hepatology 2014 Chen JY, Feeney ER, Chung RT
• Future classes of hepatitis C virus therapeutic agents.
  Infectious disease clinics of North America 2012 Chen JY, Chung RT
• Highly active antiretroviral therapy and adverse birth outcomes among HIV-infected women in Botswana.
  The Journal of infectious diseases 2012 Chen JY, Ribaudo HJ, Souda S, Parekh N, Ogwu A, Lockman S, Powis K, Dryden-Peterson S, Creek T, Jimbo W, Madidimalo T, Makhema J, Essex M, Shapiro RL
• Extended therapy with pegylated interferon and weight-based ribavirin for HCV-HIV coinfected patients.
  HIV clinical trials 2012 Chung RT, Umbleja T, Chen JY, Andersen JW, Butt AA, Sherman KE, Actg A5178 Study Team
• Birth weight for gestational age norms for a large cohort of infants born to HIV-negative women in Botswana compared with norms for U.S.-born black infants.
  BMC pediatrics 2011 Matthews LT, Ribaudo HJ, Parekh NK, Chen JY, Binda K, Ogwu A, Makhema J, Souda S, Lockman S, Essex M, Shapiro RL
• Engaging HIV-infected patients in antiretroviral therapy services: CD4 cell count testing after HIV diagnosis from 2005 to 2009 in Yunnan and Guangxi, China.
  Chinese medical journal 2011 Zhang Y, Lu L, Li HQ, Liu W, Tang ZR, Fang H, Chen JY, Ma Y, Zhao Y, Chen RY, Zhang FJ
• Can we use the "C" word with confidence? Cure for chronic hepatitis C.
  Gastroenterology 2011 Chen JY, Chung RT
• Antiretroviral treatment initiation among HIV-infected pregnant women with low CD4(+) cell counts in Gaborone, Botswana.
  Journal of acquired immune deficiency syndromes (1999) 2010 Chen JY, Ogwu AC, Svab P, Lockman S, Moffat HJ, Gaolathe T, Moilwa S, Størdal K, Dryden-Peterson S, Moffat C, Makhema J, Essex M, Shapiro RL
• Monitoring the implementation of Consultation Planning, Recording, and Summarizing in a breast care center.
  Patient education and counseling 2008 Belkora JK, Loth MK, Chen DF, Chen JY, Volz S, Esserman LJ