John Gordan, MD, PhD
Associate Professor
Medicine
School of Medicine

My laboratory applies proteomic methods to identify novel targets and improve the application of existing therapeutics for liver cancers including hepatocellular carcinoma, cholangiocarcinoma and fibrolamellar liver cancer. We have three major areas of investigation: 1. Mapping oncogenic kinase signaling and its response to targeted therapeutics to define biomarkers and combination treatments for clinically relevant agents 2. Characterizing the impact of hepatitis viruses on liver cancer and its response to treatment 3. Developing small molecule strategies to target Hippo pathway dysregulation

• DNAJB1-PRKACA fusion protein-regulated LINC00473 promotes tumor growth and alters mitochondrial fitness in fibrolamellar carcinoma.
  PLoS genetics 2024 Ma RK, Tsai PY, Farghli AR, Shumway A, Kanke M, Gordan JD, Gujral TS, Vakili K, Nukaya M, Noetzli L, Ronnekleiv-Kelly S, Broom W, Barrow J, Sethupathy P
• Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline Update.
  Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2024 Gordan JD, Kennedy EB, Abou-Alfa GK, Beal E, Finn RS, Gade TP, Goff L, Gupta S, Guy J, Hoang HT, Iyer R, Jaiyesimi I, Jhawer M, Karippot A, Kaseb AO, Kelley RK, Kortmansky J, Leaf A, Remak WM, Sohal …
• Recruitment of BAG2 to DNAJ-PKAc scaffolds promotes cell survival and resistance to drug-induced apoptosis in fibrolamellar carcinoma.
  Cell reports 2024 Lauer SM, Omar MH, Golkowski MG, Kenerson HL, Lee KS, Pascual BC, Lim HC, Forbush K, Smith FD, Gordan JD, Ong SE, Yeung RS, Scott JD
• Preclinical evidence for anaplastic lymphoma kinase inhibitors as novel therapeutic treatments for cholangiocarcinoma.
  Frontiers in oncology 2023 Myint KZ, Sueca-Comes M, Collier P, Balasubramanian B, Venkatraman S, Gordan J, Zaitoun AM, Mukherjee A, Arora A, Larbcharoensub N, Suriyonplengsaeng C, Wongprasert K, Janvilisri T, Gomez D, Grabowska…
• New Opportunities to Individualize Frontline Therapy in Advanced Stages of Hepatocellular Carcinoma.
  Drugs 2023 Gordan JD, Keenan BP, Lim HC, Yarchoan M, Kelley RK
• Recruitment of BAG2 to DNAJ-PKAc scaffolds promotes cell survival and resistance to drug-induced apoptosis in fibrolamellar carcinoma.
  bioRxiv : the preprint server for biology 2023 Lauer SM, Omar MH, Golkowski MG, Kenerson HL, Pascual BC, Forbush K, Smith FD, Gordan J, Ong SE, Yeung RS, Scott JD
• Defining incidence and complications of fibrolamellar liver cancer through tiered computational analysis of clinical data.
  NPJ precision oncology 2023 Zack T, Losert KP, Maisel SM, Wild J, Yaqubie A, Herman M, Knox JJ, Mayer RJ, Venook AP, Butte A, O'Neill AF, Abou-Alfa GK, Gordan JD
• Oncogenic PKA signaling increases c-MYC protein expression through multiple targetable mechanisms.
  eLife 2023 Chan GKL, Maisel S, Hwang YC, Pascual BC, Wolber RRB, Vu P, Patra KC, Bouhaddou M, Kenerson HL, Lim HC, Long D, Yeung RS, Sethupathy P, Swaney DL, Krogan NJ, Turnham RE, Riehle KJ, Scott JD, Bardeesy …
• EGFR Inhibition Potentiates FGFR Inhibitor Therapy and Overcomes Resistance in FGFR2 Fusion-Positive Cholangiocarcinoma.
  Cancer discovery 2022 Wu Q, Zhen Y, Shi L, Vu P, Greninger P, Adil R, Merritt J, Egan R, Wu MJ, Yin X, Ferrone CR, Deshpande V, Baiev I, Pinto CJ, McLoughlin DE, Walmsley CS, Stone JR, Gordan JD, Zhu AX, Juric D, Goyal L, …
• Methods to assess small molecule allosteric modulators of the STRAD pseudokinase.
  Methods in enzymology 2022 Qing T, Liu J, Liu F, Mitchell DC, Beresis RT, Gordan JD
• A framework for fibrolamellar carcinoma research and clinical trials.
  Nature reviews. Gastroenterology & hepatology 2022 Dinh TA, Utria AF, Barry KC, Ma R, Abou-Alfa GK, Gordan JD, Jaffee EM, Scott JD, Zucman-Rossi J, O'Neill AF, Furth ME, Sethupathy P
• Targeting a splicing-mediated drug resistance mechanism in prostate cancer by inhibiting transcriptional regulation by PKCβ1.
  Oncogene 2022 Melnyk JE, Steri V, Nguyen HG, Hwang YC, Gordan JD, Hann B, Feng FY, Shokat KM
• A protein interaction landscape of breast cancer.
  Science (New York, N.Y.) 2021 Kim M, Park J, Bouhaddou M, Kim K, Rojc A, Modak M, Soucheray M, McGregor MJ, O'Leary P, Wolf D, Stevenson E, Foo TK, Mitchell D, Herrington KA, Muñoz DP, Tutuncuoglu B, Chen KH, Zheng F, Kreisberg JF…
• Phase II Trial of the Combination of Temsirolimus and Sorafenib in Advanced Hepatocellular Carcinoma with Tumor Mutation Profiling.
  Liver cancer 2021 Kelley RK, Joseph NM, Nimeiri HS, Hwang J, Kulik LM, Ngo Z, Behr SC, Onodera C, Zhang K, Bocobo AG, Benson AB, Venook AP, Gordan JD
• STRAD-binding agents and uses thereof
  STRAD-binding agents and uses thereof. 2021 Gordan JD, Mitchell DC, Beresis RT, Adler M
• A Multicenter Randomized Three-Arm Phase II Study of (1) Everolimus, (2) Estrogen Deprivation Therapy (EDT) with Leuprolide + Letrozole, and (3) Everolimus + EDT in Patients with Unresectable Fibrolamellar Carcinoma.
  The oncologist 2020 El Dika I, Mayer RJ, Venook AP, Capanu M, LaQuaglia MP, Kobos R, O'Neill AF, Chou JF, Ly M, Ang C, O'Reilly EM, Gordan JD, Abou-Alfa GK
• Checkpoint Inhibitors for the Treatment of Advanced Hepatocellular Carcinoma.
  Clinical liver disease 2020 Huppert LA, Gordan JD, Kelley RK
• Phase II Multicenter, Open-Label Study of Oral ENMD-2076 for the Treatment of Patients with Advanced Fibrolamellar Carcinoma.
  The oncologist 2020 Abou-Alfa GK, Mayer R, Venook AP, O'Neill AF, Beg MS, LaQuaglia M, Kingham PT, Kobos R, Basturk O, Brennan C, Yopp A, Harding JJ, Leong S, Crown J, Hoti E, Leonard G, Ly M, Bradley M, Valentino E, …
• A single H/ACA small nucleolar RNA mediates tumor suppression downstream of oncogenic RAS.
  eLife 2019 McMahon M, Contreras A, Holm M, Uechi T, Forester CM, Pang X, Jackson C, Calvert ME, Chen B, Quigley DA, Luk JM, Kelley RK, Gordan JD, Gill RM, Blanchard SC, Ruggero D
• Loss of Fbxw7 synergizes with activated Akt signaling to promote c-Myc dependent cholangiocarcinogenesis.
  Journal of hepatology 2019 Wang J, Wang H, Peters M, Ding N, Ribback S, Utpatel K, Cigliano A, Dombrowski F, Xu M, Chen X, Song X, Che L, Evert M, Cossu A, Gordan J, Zeng Y, Chen X, Calvisi DF
• Nivolumab in patients with advanced hepatocellular carcinoma and Child-Pugh class B cirrhosis: Safety and clinical outcomes in a retrospective case series.
  Cancer 2019 Kambhampati S, Bauer KE, Bracci PM, Keenan BP, Behr SC, Gordan JD, Kelley RK
• MEK inhibition suppresses K-Ras wild-type cholangiocarcinoma in vitro and in vivo via inhibiting cell proliferation and modulating tumor microenvironment.
  Cell death & disease 2019 Wang P, Song X, Utpatel K, Shang R, Yang YM, Xu M, Zhang J, Che L, Gordan J, Cigliano A, Seki E, Evert M, Calvisi DF, Hu X, Chen X
• Road map for fibrolamellar carcinoma: progress and goals of a diversified approach.
  Journal of hepatocellular carcinoma 2019 Kastenhuber ER, Craig J, Ramsey J, Sullivan KM, Sage J, de Oliveira S, Riehle KJ, Scott JD, Gordan JD, Bardeesy N, Abou-Alfa GK
• Translation control of the immune checkpoint in cancer and its therapeutic targeting.
  Nature medicine 2019 Xu Y, Poggio M, Jin HY, Shi Z, Forester CM, Wang Y, Stumpf CR, Xue L, Devericks E, So L, Nguyen HG, Griselin A, Gordan JD, Umetsu SE, Reich SH, Worland ST, Asthana S, Barna M, Webster KR, Cunningham …
• Overexpression-mediated activation of MET in the Golgi promotes HER3/ERBB3 phosphorylation.
  Oncogene 2018 Frazier NM, Brand T, Gordan JD, Grandis J, Jura N
• Combined CDK4/6 and Pan-mTOR Inhibition Is Synergistic Against Intrahepatic Cholangiocarcinoma.
  Clinical cancer research : an official journal of the American Association for Cancer Research 2018 Song X, Liu X, Wang H, Wang J, Qiao Y, Cigliano A, Utpatel K, Ribback S, Pilo MG, Serra M, Gordan JD, Che L, Zhang S, Cossu A, Porcu A, Pascale RM, Dombrowski F, Hu H, Calvisi DF, Evert M, Chen X
• Hybrid Capture-Based Tumor Sequencing and Copy Number Analysis to Confirm Origin of Metachronous Metastases in BRCA1-Mutant Cholangiocarcinoma Harboring a Novel YWHAZ-BRAF Fusion.
  The oncologist 2018 Lim HC, Montesion M, Botton T, Collisson EA, Umetsu SE, Behr SC, Gordan JD, Stephens PJ, Kelley RK
• Notch2 controls hepatocyte-derived cholangiocarcinoma formation in mice.
  Oncogene 2018 Wang J, Dong M, Xu Z, Song X, Zhang S, Qiao Y, Che L, Gordan J, Hu K, Liu Y, Calvisi DF, Chen X
• Efficacy of MEK inhibition in a K-Ras-driven cholangiocarcinoma preclinical model.
  Cell death & disease 2018 Dong M, Liu X, Evert K, Utpatel K, Peters M, Zhang S, Xu Z, Che L, Cigliano A, Ribback S, Dombrowski F, Cossu A, Gordan J, Calvisi DF, Evert M, Liu Y, Chen X
• Sampling strategies to capture single-cell heterogeneity.
  Nature methods 2017 Rajaram S, Heinrich LE, Gordan JD, Avva J, Bonness KM, Witkiewicz AK, Malter JS, Atreya CE, Warren RS, Wu LF, Altschuler SJ
• Pan-mTOR inhibitor MLN0128 is effective against intrahepatic cholangiocarcinoma in mice.
  Journal of hepatology 2017 Zhang S, Song X, Cao D, Xu Z, Fan B, Che L, Hu J, Chen B, Dong M, Pilo MG, Cigliano A, Evert K, Ribback S, Dombrowski F, Pascale RM, Cossu A, Vidili G, Porcu A, Simile MM, Pes GM, Giannelli G, Gordan …
• An Optimized Chromatographic Strategy for Multiplexing In Parallel Reaction Monitoring Mass Spectrometry: Insights from Quantitation of Activated Kinases.
  Molecular & cellular proteomics : MCP 2016 Urisman A, Levin RS, Gordan JD, Webber JT, Hernandez H, Ishihama Y, Shokat KM, Burlingame AL
• Synthetic Lethal Targeting of ARID1A-Mutant Ovarian Clear Cell Tumors with Dasatinib.
  Molecular cancer therapeutics 2016 Miller RE, Brough R, Bajrami I, Williamson CT, McDade S, Campbell J, Kigozi A, Rafiq R, Pemberton H, Natrajan R, Joel J, Astley H, Mahoney C, Moore JD, Torrance C, Gordan JD, Webber JT, Levin RS, …
• Isocitrate Dehydrogenase Mutations Confer Dasatinib Hypersensitivity and SRC Dependence in Intrahepatic Cholangiocarcinoma.
  Cancer discovery 2016 Saha SK, Gordan JD, Kleinstiver BP, Vu P, Najem MS, Yeo JC, Shi L, Kato Y, Levin RS, Webber JT, Damon LJ, Egan RK, Greninger P, McDermott U, Garnett MJ, Jenkins RL, Rieger-Christ KM, Sullivan TB, …
• Identification of Chemical Inhibitors of β-Catenin-Driven Liver Tumorigenesis in Zebrafish.
  PLoS genetics 2015 Evason KJ, Francisco MT, Juric V, Balakrishnan S, Lopez Pazmino Mdel P, Gordan JD, Kakar S, Spitsbergen J, Goga A, Stainier DY
• Linking tumor mutations to drug responses via a quantitative chemical-genetic interaction map.
  Cancer discovery 2014 Martins MM, Zhou AY, Corella A, Horiuchi D, Yau C, Rakhshandehroo T, Gordan JD, Levin RS, Johnson J, Jascur J, Shales M, Sorrentino A, Cheah J, Clemons PA, Shamji AF, Schreiber SL, Krogan NJ, Shokat …
• Oncogene mimicry as a mechanism of primary resistance to BRAF inhibitors.
  Cell reports 2014 Sos ML, Levin RS, Gordan JD, Oses-Prieto JA, Webber JT, Salt M, Hann B, Burlingame AL, McCormick F, Bandyopadhyay S, Shokat KM
• Integrative genomic analyses of sporadic clear cell renal cell carcinoma define disease subtypes and potential new therapeutic targets.
  Cancer research 2011 Dondeti VR, Wubbenhorst B, Lal P, Gordan JD, D'Andrea K, Attiyeh EF, Simon MC, Nathanson KL
• "And what other medications are you taking?".
  Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2011 Gordan JD, Chay WY, Kelley RK, Ko AH, Choo SP, Venook AP
• HIF2alpha inhibition promotes p53 pathway activity, tumor cell death, and radiation responses.
  Proceedings of the National Academy of Sciences of the United States of America 2009 Bertout JA, Majmundar AJ, Gordan JD, Lam JC, Ditsworth D, Keith B, Brown EJ, Nathanson KL, Simon MC
• Ror2, a developmentally regulated kinase, promotes tumor growth potential in renal cell carcinoma.
  Oncogene 2009 Wright TM, Brannon AR, Gordan JD, Mikels AJ, Mitchell C, Chen S, Espinosa I, van de Rijn M, Pruthi R, Wallen E, Edwards L, Nusse R, Rathmell WK
• HIF-alpha effects on c-Myc distinguish two subtypes of sporadic VHL-deficient clear cell renal carcinoma.
  Cancer cell 2008 Gordan JD, Lal P, Dondeti VR, Letrero R, Parekh KN, Oquendo CE, Greenberg RA, Flaherty KT, Rathmell WK, Keith B, Simon MC, Nathanson KL
• Hypoxia-mediated selective mRNA translation by an internal ribosome entry site-independent mechanism.
  The Journal of biological chemistry 2008 Young RM, Wang SJ, Gordan JD, Ji X, Liebhaber SA, Simon MC
• HIF and c-Myc: sibling rivals for control of cancer cell metabolism and proliferation.
  Cancer cell 2007 Gordan JD, Thompson CB, Simon MC
• The transcription factor HIF-1alpha plays a critical role in the growth factor-dependent regulation of both aerobic and anaerobic glycolysis.
  Genes & development 2007 Lum JJ, Bui T, Gruber M, Gordan JD, DeBerardinis RJ, Covello KL, Simon MC, Thompson CB
• HIF-2alpha promotes hypoxic cell proliferation by enhancing c-myc transcriptional activity.
  Cancer cell 2007 Gordan JD, Bertout JA, Hu CJ, Diehl JA, Simon MC
• Hypoxia-inducible factors: central regulators of the tumor phenotype.
  Current opinion in genetics & development 2007 Gordan JD, Simon MC
• Ribosomal stress couples the unfolded protein response to p53-dependent cell cycle arrest.
  The Journal of biological chemistry 2006 Zhang F, Hamanaka RB, Bobrovnikova-Marjon E, Gordan JD, Dai MS, Lu H, Simon MC, Diehl JA
• HIF-2alpha regulates Oct-4: effects of hypoxia on stem cell function, embryonic development, and tumor growth.
  Genes & development 2006 Covello KL, Kehler J, Yu H, Gordan JD, Arsham AM, Hu CJ, Labosky PA, Simon MC, Keith B
• ADAP-SLP-76 binding differentially regulates supramolecular activation cluster (SMAC) formation relative to T cell-APC conjugation.
  The Journal of experimental medicine 2004 Wang H, McCann FE, Gordan JD, Wu X, Raab M, Malik TH, Davis DM, Rudd CE
• The Keap1-BTB protein is an adaptor that bridges Nrf2 to a Cul3-based E3 ligase: oxidative stress sensing by a Cul3-Keap1 ligase.
  Molecular and cellular biology 2004 Cullinan SB, Gordan JD, Jin J, Harper JW, Diehl JA
• Antigens recognized by autologous antibody in patients with renal-cell carcinoma.
  International journal of cancer 1999 Scanlan MJ, Gordan JD, Williamson B, Stockert E, Bander NH, Jongeneel V, Gure AO, Jäger D, Jäger E, Knuth A, Chen YT, Old LJ
• Isoforms of the human PDZ-73 protein exhibit differential tissue expression.
  Biochimica et biophysica acta 1999 Scanlan MJ, Williamson B, Jungbluth A, Stockert E, Arden KC, Viars CS, Gure AO, Gordan JD, Chen YT, Old LJ
• Aspects of GnRH neurobiology conserved across vertebrate forms.
  General and comparative endocrinology 1998 Dellovade T, Schwanzel-Fukuda M, Gordan J, Pfaff D
• Characterization of human colon cancer antigens recognized by autologous antibodies.
  International journal of cancer 1998 Scanlan MJ, Chen YT, Williamson B, Gure AO, Stockert E, Gordan JD, Türeci O, Sahin U, Pfreundschuh M, Old LJ
• Mathematical exploration of pulsatility in cultured gonadotropin-releasing hormone neurons.
  Neuroendocrinology 1998 Gordan JD, Attardi BJ, Pfaff DW
• Reproductive functions illustrating direct and indirect effects of genes on behavior.
  Hormones and behavior 1996 Ogawa S, Gordan JD, Taylor J, Lubahn D, Korach K, Pfaff DW
• Initial preparation of the periodontally advanced dentition.
  Journal of the California Dental Association 1989 Yang LR, Gordan J