Jennifer Chen, MD

Associate Professor

Hepatic fibrogenesis is the molecular process that leads to end-stage liver disease, and there are currently no FDA-approved therapies that target this process. During my clinical training in internal medicine and hepatology, I was struck by the lack of therapies available for my patients with chronic liver disease and by how the vast majority were unaware of their diagnosis of hepatic fibrosis. 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.
06/2016 - Fellowship in Gastroenterology and Hepatology, Massachusetts General Hospital
06/2012 - Residency in Internal Medicine, Brigham and Women's Hospital
MD, 06/2009 - Doctor of Medicine, Harvard Medical School
AB, 06/2003 - Government, Harvard College
  1. Yu A, Cable C, Sharma S, Shihan MH, Mattis AN, Mileva I, Hannun YA, Duwaerts CC, Chen JY. Targeting acid ceramidase ameliorates fibrosis in mouse models of non-alcoholic steatohepatitis. Frontiers in medicine 2022. PMID: 36275798

  2. Zhang P, Li X, Chen JY, Abate AR. Controlled fabrication of functional liver spheroids with microfluidic flow cytometric printing. Biofabrication 2022. PMID: 35917810

  3. Li W, Chen JY, Sun C, Sparks RP, Pantano L, Rahman RU, Moran SP, Pondick JV, Kirchner R, Wrobel D, Bieler M, Sauer A, Ho Sui SJ, Doerner JF, Rippmann JF, Mullen AC. Nanchangmycin regulates FYN, PTK2, and MAPK1/3 to control the fibrotic activity of human hepatic stellate cells. eLife 2022. PMID: 35617485

  4. Alsamman S, Christenson SA, Yu A, Ayad NME, Mooring MS, Segal JM, Hu JK, Schaub JR, Ho SS, Rao V, Marlow MM, Turner SM, Sedki M, Pantano L, Ghoshal S, Ferreira DDS, Ma HY, Duwaerts CC, Espanol-Suner R, Wei L, Newcomb B, Mileva I, Canals D, Hannun YA, Chung RT, Mattis AN, Fuchs BC, Tager AM, Yimlamai D, Weaver VM, Mullen AC, Sheppard D, Chen JY. Targeting acid ceramidase inhibits YAP/TAZ signaling to reduce fibrosis in mice. Science translational medicine 2020. PMID: 32817366

  5. Chen JY, Ren Y, Yan P, Belina ME, Chung RT, Butt AA. Tricyclic antidepressant use and the risk of fibrosis progression in hepatitis C-infected persons: Results from ERCHIVES. Journal of viral hepatitis 2018. PMID: 29478294

  6. Caniglia EC, Zash R, Jacobson DL, Diseko M, Mayondi G, Lockman S, Chen JY, Mmalane M, Makhema J, Hernán MA, Shapiro RL. Emulating a target trial of antiretroviral therapy regimens started before conception and risk of adverse birth outcomes. AIDS (London, England) 2018. PMID: 29112066

  7. Chen JY, Newcomb B, Zhou C, Pondick JV, Ghoshal S, York SR, Motola DL, Coant N, Yi JK, Mao C, Tanabe KK, Bronova I, Berdyshev EV, Fuchs BC, Hannun Y, Chung RT, Mullen AC. Tricyclic Antidepressants Promote Ceramide Accumulation to Regulate Collagen Production in Human Hepatic Stellate Cells. Scientific Reports 2017. PMID: 28322247

  8. Zash R, Souda S, Chen JY, Binda K, Dryden-Peterson S, Lockman S, Mmalane M, Makhema J, Essex M, Shapiro R. 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. PMID: 26379069

  9. Zhou C, York SR, Chen JY, Pondick JV, Motola DL, Chung RT, Mullen AC. Long noncoding RNAs expressed in human hepatic stellate cells form networks with extracellular matrix proteins. Genome medicine 2016. PMID: 27007663

  10. Dryden-Peterson S, Lockman S, Zash R, Lei Q, Chen JY, Souda S, Petlo C, Dintwa E, Lebelonyane R, Mmalane M, Shapiro RL. Initial programmatic implementation of WHO option B in Botswana associated with increased projected MTCT. Journal of acquired immune deficiency syndromes (1999) 2015. PMID: 25501611

  11. Kelly P, Saloojee H, Chen JY, Chung RT. Noncommunicable diseases in HIV infection in low- and middle-income countries: gastrointestinal, hepatic, and nutritional aspects. Journal of acquired immune deficiency syndromes (1999) 2014. PMID: 25117963

  12. Chen JY, Feeney ER, Chung RT. HCV and HIV co-infection: mechanisms and management. Nature reviews. Gastroenterology & hepatology 2014. PMID: 24535328

  13. Chen JY, Chung RT. Future classes of hepatitis C virus therapeutic agents. Infectious disease clinics of North America 2012. PMID: 23083826

  14. 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. Highly active antiretroviral therapy and adverse birth outcomes among HIV-infected women in Botswana. The Journal of infectious diseases 2012. PMID: 23066160

  15. Chung RT, Umbleja T, Chen JY, Andersen JW, Butt AA, Sherman KE. Extended therapy with pegylated interferon and weight-based ribavirin for HCV-HIV coinfected patients. HIV clinical trials 2012. PMID: 22510354

  16. Matthews LT, Ribaudo HJ, Parekh NK, Chen JY, Binda K, Ogwu A, Makhema J, Souda S, Lockman S, Essex M, Shapiro RL. 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. PMID: 22176889

  17. Zhang Y, Lu L, Li HQ, Liu W, Tang ZR, Fang H, Chen JY, Ma Y, Zhao Y, Chen RY, Zhang FJ. 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. PMID: 21740803

  18. Chen JY, Chung RT. Can we use the "C" word with confidence? Cure for chronic hepatitis C. Gastroenterology 2011. PMID: 21256845

  19. 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. Antiretroviral treatment initiation among HIV-infected pregnant women with low CD4(+) cell counts in Gaborone, Botswana. Journal of acquired immune deficiency syndromes (1999) 2010. PMID: 19864957

  20. Belkora JK, Loth MK, Chen DF, Chen JY, Volz S, Esserman LJ. Monitoring the implementation of Consultation Planning, Recording, and Summarizing in a breast care center. Patient education and counseling 2008. PMID: 18755564