Jennifer Chen, MD

Assistant 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.
Education
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
Websites
Publications
  1. 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. 2020. PMID: 32817366


  2. 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. 2018. PMID: 29112066


  3. 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. 2017. PMID: 28322247


  4. 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. 2016. PMID: 26379069


  5. 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. 2016. PMID: 27007663


  6. 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. 2015. PMID: 25501611


  7. Chen JY, Feeney ER, Chung RT. HCV and HIV co-infection: mechanisms and management. 2014. PMID: 24535328


  8. Chen JY, Chung RT. Future classes of hepatitis C virus therapeutic agents. 2012. PMID: 23083826


  9. 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. 2012. PMID: 23066160


  10. 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. 2012. PMID: 22510354


  11. 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. 2011. PMID: 22176889


  12. 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. 2011. PMID: 21740803


  13. 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. 2010. PMID: 19864957


  14. 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. 2008. PMID: 18755564