Jennifer Chen, MD

Title(s)Associate Professor, Medicine
SchoolSchool of Medicine
Address513 Parnassus Avenue, HSE, #1424
San Francisco CA 94143
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    Harvard College, Cambridge, MAAB06/2003Government
    Harvard Medical School, Boston, MAMD06/2009Doctor of Medicine
    Brigham and Women's Hospital, Boston, MA06/2012Residency in Internal Medicine
    Massachusetts General Hospital, Boston, MA06/2016Fellowship in Gastroenterology and Hepatology

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    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.
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    Targeting Acid Ceramidase for Hepatic Fibrogenesis
    NIDDK 1R01DK137892-01Dec 15, 2023 - Nov 30, 2028
    Role: Co-Investigator
    Dissecting the Acid Ceramidase Pathway in Hepatic Fibrogenesis
    NIH R01DK134723Aug 15, 2023 - May 31, 2028
    Role: Principal Investigator
    Targeting Acid Ceramidase to Reverse NASH FIbrosis
    Harrington Discovery Institute Aug 1, 2021 - Jul 30, 2023
    Role: Principal Investigator
    Precision Gene Signatures for NASH Fibrogenesis
    Merck SEEDS Program Jul 1, 2021 - Jun 30, 2022
    Role: Principal Investigator
    Targeting Acid Ceramidase for the Treatment of NASH and HCC
    InVent FundMar 1, 2020 - Feb 28, 2022
    Role: Principal Investigator
    Dissecting the Role of YAP and TAZ in Hepatic Stellate Activation and Liver Fibrosis
    P30DK026743Jun 1, 2018 - May 31, 2019
    Role: Principal Investigator
    Role of Ceramide in Hepatic Stellate Cell Activation and Liver Fibrosis
    NIH K08DK114548Sep 1, 2017 - Apr 30, 2023
    Role: Principal Investigator
    Tricyclic Antidepressants Induce Hepatic Stellate Cell Quiescence: Identification of Mechanisms to Halt Hepatic Fibrosis
    NIH F32DK107197Sep 15, 2015 - Sep 14, 2016
    Role: Principal Investigator

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    Collapse Publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help. to make corrections and additions.
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    Altmetrics Details PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. Targeting acid ceramidase ameliorates fibrosis in mouse models of non-alcoholic steatohepatitis. Front Med (Lausanne). 2022; 9:881848. Yu A, Cable C, Sharma S, Shihan MH, Mattis AN, Mileva I, Hannun YA, Duwaerts CC, Chen JY. PMID: 36275798; PMCID: PMC9582277.
      View in: PubMed   Mentions: 1  
    2. Controlled fabrication of functional liver spheroids with microfluidic flow cytometric printing. Biofabrication. 2022 08 23; 14(4). Zhang P, Li X, Chen JY, Abate AR. PMID: 35917810.
      View in: PubMed   Mentions: 2     Fields:    Translation:Cells
    3. Nanchangmycin regulates FYN, PTK2, and MAPK1/3 to control the fibrotic activity of human hepatic stellate cells. Elife. 2022 05 26; 11. 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. PMID: 35617485; PMCID: PMC9135407.
      View in: PubMed   Mentions: 3     Fields:    Translation:HumansCells
    4. Targeting acid ceramidase inhibits YAP/TAZ signaling to reduce fibrosis in mice. Sci Transl Med. 2020 08 19; 12(557). 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. PMID: 32817366; PMCID: PMC7976849.
      View in: PubMed   Mentions: 39     Fields:    Translation:HumansAnimalsCells
    5. Tricyclic antidepressant use and the risk of fibrosis progression in hepatitis C-infected persons: Results from ERCHIVES. J Viral Hepat. 2018 07; 25(7):825-833. Chen JY, Ren Y, Yan P, Belina ME, Chung RT, Butt AA. PMID: 29478294; PMCID: PMC6019114.
      View in: PubMed   Mentions: 3     Fields:    Translation:Humans
    6. Emulating a target trial of antiretroviral therapy regimens started before conception and risk of adverse birth outcomes. AIDS. 2018 Jan 02; 32(1):113-120. Caniglia EC, Zash R, Jacobson DL, Diseko M, Mayondi G, Lockman S, Chen JY, Mmalane M, Makhema J, Hernán MA, Shapiro RL. PMID: 29112066; PMCID: PMC5718935.
      View in: PubMed   Mentions: 17     Fields:    Translation:Humans
    7. Tricyclic Antidepressants Promote Ceramide Accumulation to Regulate Collagen Production in Human Hepatic Stellate Cells. Sci Rep. 2017 03 21; 7:44867. 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. PMID: 28322247; PMCID: PMC5359599.
      View in: PubMed   Mentions: 14     Fields:    Translation:HumansCells
    8. Reassuring Birth Outcomes With Tenofovir/Emtricitabine/Efavirenz Used for Prevention of Mother-to-Child Transmission of HIV in Botswana. J Acquir Immune Defic Syndr. 2016 Apr 01; 71(4):428-36. Zash R, Souda S, Chen JY, Binda K, Dryden-Peterson S, Lockman S, Mmalane M, Makhema J, Essex M, Shapiro R. PMID: 26379069; PMCID: PMC4767604.
      View in: PubMed   Mentions: 48     Fields:    Translation:HumansPHPublic Health
    9. Long noncoding RNAs expressed in human hepatic stellate cells form networks with extracellular matrix proteins. Genome Med. 2016 Mar 23; 8(1):31. Zhou C, York SR, Chen JY, Pondick JV, Motola DL, Chung RT, Mullen AC. PMID: 27007663; PMCID: PMC4804564.
      View in: PubMed   Mentions: 31     Fields:    Translation:HumansCells
    10. Initial programmatic implementation of WHO option B in Botswana associated with increased projected MTCT. J Acquir Immune Defic Syndr. 2015 Mar 01; 68(3):245-9. Dryden-Peterson S, Lockman S, Zash R, Lei Q, Chen JY, Souda S, Petlo C, Dintwa E, Lebelonyane R, Mmalane M, Shapiro RL. PMID: 25501611; PMCID: PMC4326565.
      View in: PubMed   Mentions: 13     Fields:    Translation:HumansPHPublic Health
    11. Noncommunicable diseases in HIV infection in low- and middle-income countries: gastrointestinal, hepatic, and nutritional aspects. J Acquir Immune Defic Syndr. 2014 Sep 01; 67 Suppl 1:S79-86. Kelly P, Saloojee H, Chen JY, Chung RT. PMID: 25117963; PMCID: PMC4159720.
      View in: PubMed   Mentions: 9     Fields:    Translation:Humans
    12. HCV and HIV co-infection: mechanisms and management. Nat Rev Gastroenterol Hepatol. 2014 Jun; 11(6):362-71. Chen JY, Feeney ER, Chung RT. PMID: 24535328; PMCID: PMC4330991.
      View in: PubMed   Mentions: 78     Fields:    Translation:Humans
    13. Future classes of hepatitis C virus therapeutic agents. Infect Dis Clin North Am. 2012 Dec; 26(4):949-66. Chen JY, Chung RT. PMID: 23083826; PMCID: PMC4624290.
      View in: PubMed   Mentions:    Fields:    Translation:HumansCells
    14. Highly active antiretroviral therapy and adverse birth outcomes among HIV-infected women in Botswana. J Infect Dis. 2012 Dec 01; 206(11):1695-705. 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. PMID: 23066160; PMCID: PMC3488194.
      View in: PubMed   Mentions: 175     Fields:    Translation:Humans
    15. Extended therapy with pegylated interferon and weight-based ribavirin for HCV-HIV coinfected patients. HIV Clin Trials. 2012 Mar-Apr; 13(2):70-82. Chung RT, Umbleja T, Chen JY, Andersen JW, Butt AA, Sherman KE, Actg A5178 Study Team. PMID: 22510354; PMCID: PMC3367320.
      View in: PubMed   Mentions: 5     Fields:    Translation:HumansCTClinical Trials
    16. 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 Pediatr. 2011 Dec 16; 11:115. Matthews LT, Ribaudo HJ, Parekh NK, Chen JY, Binda K, Ogwu A, Makhema J, Souda S, Lockman S, Essex M, Shapiro RL. PMID: 22176889; PMCID: PMC3271964.
      View in: PubMed   Mentions: 11     Fields:    Translation:HumansCells
    17. Engaging HIV-infected patients in antiretroviral therapy services: CD4 cell count testing after HIV diagnosis from 2005 to 2009 in Yunnan and Guangxi, China. Chin Med J (Engl). 2011 May; 124(10):1488-92. Zhang Y, Lu L, Li HQ, Liu W, Tang ZR, Fang H, Chen JY, Ma Y, Zhao Y, Chen RY, Zhang FJ. PMID: 21740803.
      View in: PubMed   Mentions: 10     Fields:    Translation:Humans
    18. Can we use the "C" word with confidence? Cure for chronic hepatitis C. Gastroenterology. 2011 Mar; 140(3):766-8. Chen JY, Chung RT. PMID: 21256845.
      View in: PubMed   Mentions: 1     Fields:    Translation:HumansCells
    19. Antiretroviral treatment initiation among HIV-infected pregnant women with low CD4(+) cell counts in Gaborone, Botswana. J Acquir Immune Defic Syndr. 2010 May 01; 54(1):102-6. 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. PMID: 19864957.
      View in: PubMed   Mentions: 10     Fields:    Translation:Humans
    20. Monitoring the implementation of Consultation Planning, Recording, and Summarizing in a breast care center. Patient Educ Couns. 2008 Dec; 73(3):536-43. Belkora JK, Loth MK, Chen DF, Chen JY, Volz S, Esserman LJ. PMID: 18755564; PMCID: PMC2622737.
      View in: PubMed   Mentions: 24     Fields:    Translation:Humans
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