Image Place holder

Gina DeNicola, PhD

Academic Rank: Assistant Member

View Lab Page



    • Thoracic Oncology
    • Cancer Physiology
    • Cancer Biology and Evolution Program
    • Lung Cancer Center of Excellence

Education & Training


  • University of Pennsylvania & Cancer Research UK Cambridge, PhD - Cell and Molecular Biology
  • Beth Israel Deaconess Medical Center & Weill Cornell Medical Collage, Fellow -

Cells have energetic and anabolic needs for growth and proliferation. Dr. DeNicola's research is focused on understanding how cells meet these needs and the mechanisms governing the regulation of tumor metabolism in vivo. While cell culture systems are useful for querying the activity of metabolic pathways, many factors in vivo likely play a major role in the regulation of cellular metabolism, including tumor/stroma interactions, contact with the extracellular matrix, local hypoxia and nutrient availability and nutrient intake by the host. The DeNicola laboratory investigates the influence of both genomic alterations and the microenvironment on cellular metabolism in vivo. Mutations in KEAP1 and NRF2, which lead to NRF2 hyperactivation, are commonly found in cancers and lead to metabolic deregulation. Despite the identification of the first KEAP1 mutations in 2006, the precise mechanisms by which NRF2 promotes tumorigenesis are unclear owing to the lack of genetically engineered KEAP1 and NRF2 mutant mouse models that recapitulate the human disease. Dr. DeNicola and others, have identified that NRF2 activation leads to profound deregulation of cellular metabolism, including the promotion of serine biosynthesis, which is critical for the proliferation of KEAP1 and NRF2 mutant cells. However, the activity of these pathways in KEAP1/NRF2 mutant lung tumors in vivo is not established. A major research focus of her lab is investigating how NRF2 promotes tumorigenesis and metabolic deregulation in vivo using genetically engineered mouse model systems. The DeNicola laboratory also focuses on how the microenvironment affects metabolic dependencies. Much of the understanding of tumor metabolism comes from cell culture experiments in which other cell types typically found in tumors, such as fibroblasts and immune cells, are absent. However, these cells have the potential to significantly affect tumor metabolism in vivo by both providing and/or competing for metabolites that the tumor cells require. Her laboratory is examining how the metabolic interaction between epithelial tumor cells with fibroblasts and immune cells affects the metabolism and growth of these compartments.


  • Kang YP, Mockabee-Macias A, Jiang C, Falzone A, Prieto-Farigua N, Stone E, Harris IS, DeNicola GM. Non-canonical Glutamate-Cysteine Ligase Activity Protects against Ferroptosis. Cell Metab. 2021 Jan.33(1):174-189.e7. Pubmedid: 33357455. Pmcid: PMC7839835.
  • Beato F, Reverón D, Dezsi KB, Ortiz A, Johnson JO, Chen DT, Ali K, Yoder SJ, Jeong D, Malafa M, Hodul P, Jiang K, Centeno BA, Abdalah MA, Balasi JA, Tassielli AF, Sarcar B, Teer JK, DeNicola GM, Permuth JB, Fleming JB. Establishing a living biobank of patient-derived organoids of intraductal papillary mucinous neoplasms of the pancreas. Lab Invest. 2021 Feb.101(2):204-217. Pubmedid: 33037322. Pmcid: PMC7855435.
  • Combs JA, DeNicola GM. The smell of death and deCYStiny: polyamines play the hero. Nat Metab. 2020 Oct.2(10):995-996. Pubmedid: 32747795.
  • Combs JA, DeNicola GM. Publisher Correction: The smell of death and deCYStiny: polyamines play the hero. Nat Metab. 2020 Oct.2(10):1180. Pubmedid: 32973367.
  • DeBlasi JM, DeNicola GM. Dissecting the Crosstalk between NRF2 Signaling and Metabolic Processes in Cancer. Cancers (Basel). 2020 Oct.12(10). Pubmedid: 33080927. Pmcid: PMC7603127.
  • Ward NP, Kang YP, Falzone A, Boyle TA, DeNicola GM. Nicotinamide nucleotide transhydrogenase regulates mitochondrial metabolism in NSCLC through maintenance of Fe-S protein function. J Exp Med. 2020 Jun.217(6). Pubmedid: 32196080.
  • Harris IS, DeNicola GM. The Complex Interplay between Antioxidants and ROS in Cancer. Trends Cell Biol. 2020 Jun.30(6):440-451. Pubmedid: 32303435.
  • Ward NP, DeNicola GM. The Golgi: Keeping It Unapologetically Basic. Cancer Discov. 2020 Jun.10(6):768-770. Pubmedid: 32482665.
  • Kang YP, Falzone A, Liu M, González-Sánchez P, Choi BH, Coloff JL, Saller JJ, Karreth FA, DeNicola GM. PHGDH supports liver ceramide synthesis and sustains lipid homeostasis. Cancer Metab. 2020 Jun.8:6. Pubmedid: 32549981. Pmcid: PMC7294658.
  • Cheung EC, DeNicola GM, Nixon C, Blyth K, Labuschagne CF, Tuveson DA, Vousden KH. Dynamic ROS Control by TIGAR Regulates the Initiation and Progression of Pancreatic Cancer. Cancer Cell. 2020 Feb.37(2):168-182.e4. Pubmedid: 31983610. Pmcid: PMC7008247.
  • Torrente L, Prieto-Farigua N, Falzone A, Elkins CM, Boothman DA, Haura EB, DeNicola GM. Inhibition of TXNRD or SOD1 overcomes NRF2-mediated resistance to β-lapachone. Redox Biol. 2020 Feb.30:101440. Pubmedid: 32007910. Pmcid: PMC6997906.
  • Humpton TJ, Alagesan B, DeNicola GM, Lu D, Yordanov GN, Leonhardt CS, Yao MA, Alagesan P, Zaatari MN, Park Y, Skepper JN, Macleod KF, Perez-Mancera PA, Murphy MP, Evan GI, Vousden KH, Tuveson DA. Oncogenic KRAS Induces NIX-Mediated Mitophagy to Promote Pancreatic Cancer. Cancer Discov. 2019 Sep.9(9):1268-1287. Pubmedid: 31263025. Pmcid: PMC6726540.
  • Kang YP, Torrente L, Falzone A, Elkins CM, Liu M, Asara JM, Dibble CC, DeNicola G. Correction: Cysteine dioxygenase 1 is a metabolic liability for non-small cell lung cancer. Elife. 2019 Oct.8. Pubmedid: 31625908. Pmcid: PMC6799999.
  • Harris IS, Endress JE, Coloff JL, Selfors LM, McBrayer SK, Rosenbluth JM, Takahashi N, Dhakal S, Koduri V, Oser MG, Schauer NJ, Doherty LM, Hong AL, Kang YP, Younger ST, Doench JG, Hahn WC, Buhrlage SJ, DeNicola GM, Kaelin WG, Brugge JS. Deubiquitinases Maintain Protein Homeostasis and Survival of Cancer Cells upon Glutathione Depletion. Cell Metab. 2019 May.29(5):1166-1181.e6. Pubmedid: 30799286. Pmcid: PMC6506399.
  • Combs JA, DeNicola GM. The Non-Essential Amino Acid Cysteine Becomes Essential for Tumor Proliferation and Survival. Cancers (Basel). 2019 May.11(5). Pubmedid: 31100816. Pmcid: PMC6562400.
  • Kang YP, Torrente L, Falzone A, Elkins CM, Liu M, Asara JM, Dibble CC, DeNicola G. Cysteine dioxygenase 1 is a metabolic liability for non-small cell lung cancer. Elife. 2019 May.8. Pubmedid: 31107239. Pmcid: PMC6584702.
  • Stewart PA, Welsh EA, Slebos RJC, Fang B, Izumi V, Chambers M, Zhang G, Cen L, Pettersson F, Zhang Y, Chen Z, Cheng CH, Thapa R, Thompson Z, Fellows KM, Francis JM, Saller JJ, Mesa T, Zhang C, Yoder S, DeNicola GM, Beg AA, Boyle TA, Teer JK, Ann Chen Y, Koomen JM, Eschrich SA, Haura EB. Proteogenomic landscape of squamous cell lung cancer. Nat Commun. 2019 Aug.10(1):3578. Pubmedid: 31395880. Pmcid: PMC6687710.
  • Ward NP, DeNicola GM. Sulfur metabolism and its contribution to malignancy. Int Rev Cell Mol Biol. 2019 Aug.347:39-103. Pubmedid: 31451216.
  • Lee SB, Sellers B, DeNicola G. The Regulation of NRF2 by Nutrient-Responsive Signaling and Its Role in Anabolic Cancer Metabolism. Antioxid Redox Signal. 2018 Dec.29(17):1774-1791. Pubmedid: 28899208.
  • Kang YP, Ward NP, DeNicola GM. Recent advances in cancer metabolism: a technological perspective. Exp Mol Med. 2018 Apr.50(4):1-16. Pubmedid: 29657324. Pmcid: PMC5938018.
  • Permuth JB, Choi JW, Chen DT, Jiang K, DeNicola G, Li JN, Coppola D, Centeno BA, Magliocco A, Balagurunathan Y, Merchant N, Trevino JG, Jeong D. A pilot study of radiologic measures of abdominal adiposity: weighty contributors to early pancreatic carcinogenesis worth evaluating?. Cancer Biol Med. 2017 Feb.14(1):66-73. Pubmedid: 28443205. Pmcid: PMC5365183.
  • Torrente L, DeNicola GM. Stressing Out PanIN: NRF2 Pushes over the Edge. Cancer Cell. 2017 Dec.32(6):723-725. Pubmedid: 29232549.
  • Moon JS, Nakahira K, Chung KP, DeNicola GM, Koo MJ, Pabón MA, Rooney KT, Yoon JH, Ryter SW, Stout-Delgado H, Choi AM. NOX4-dependent fatty acid oxidation promotes NLRP3 inflammasome activation in macrophages. Nat Med. 2016 Sep.22(9):1002-1012. Pubmedid: 27455510. Pmcid: PMC5204248.
  • Mullarky E, Lucki NC, Beheshti Zavareh R, Anglin JL, Gomes AP, Nicolay BN, Wong JC, Christen S, Takahashi H, Singh PK, Blenis J, Warren JD, Fendt SM, Asara JM, DeNicola GM, Lyssiotis CA, Lairson LL, Cantley LC. Identification of a small molecule inhibitor of 3-phosphoglycerate dehydrogenase to target serine biosynthesis in cancers. Proc Natl Acad Sci U S A. 2016 Feb.113(7):1778-1783. Pubmedid: 26831078. Pmcid: PMC4763784.
  • DeNicola GM, Harris IS. Making sense of reAKTive oxygen species. Cell Death Differ. 2016 Aug.23(8):1269-1270. Pubmedid: 27315299. Pmcid: PMC4947676.
  • Chio II, Jafarnejad SM, Ponz-Sarvise M, Park Y, Rivera K, Palm W, Wilson J, Sangar V, Hao Y, Öhlund D, Wright K, Filippini D, Lee EJ, Da Silva B, Schoepfer C, Wilkinson JE, Buscaglia JM, DeNicola GM, Tiriac H, Hammell M, Crawford HC, Schmidt EE, Thompson CB, Pappin DJ, Sonenberg N, Tuveson DA. NRF2 Promotes Tumor Maintenance by Modulating mRNA Translation in Pancreatic Cancer. Cell. 2016 Aug.166(4):963-976. Pubmedid: 27477511. Pmcid: PMC5234705.
  • DeNicola GM, Chen PH, Mullarky E, Sudderth JA, Hu Z, Wu D, Tang H, Xie Y, Asara JM, Huffman KE, Wistuba II, Minna JD, DeBerardinis RJ, Cantley LC. Erratum: NRF2 regulates serine biosynthesis in non-small cell lung cancer. Nat Genetics. 2016 Apr.48(4):473. Pubmedid: 27023779.
  • DeNicola GM, Karreth FA, Adams DJ, Wong CC. The utility of transposon mutagenesis for cancer studies in the era of genome editing. Genome Biol. 2015 Oct.16:229. Pubmedid: 26481584. Pmcid: PMC4612416.
  • DeNicola GM, Cantley LC. Cancer's Fuel Choice: New Flavors for a Picky Eater. Mol Cell. 2015 Nov.60(4):514-523. Pubmedid: 26590711. Pmcid: PMC4676726.
  • Moon JS, Hisata S, Park MA, DeNicola GM, Ryter SW, Nakahira K, Choi AM. mTORC1-Induced HK1-Dependent Glycolysis Regulates NLRP3 Inflammasome Activation. Cell Rep. 2015 Jul.12(1):102-115. Pubmedid: 26119735. Pmcid: PMC4858438.
  • DeNicola GM, Chen PH, Mullarky E, Sudderth JA, Hu Z, Wu D, Tang H, Xie Y, Asara JM, Huffman KE, Wistuba II, Minna JD, DeBerardinis RJ, Cantley LC. NRF2 regulates serine biosynthesis in non-small cell lung cancer. Nat Genetics. 2015 Dec.47(12):1475-1481. Pubmedid: 26482881. Pmcid: PMC4721512.
  • Emerling BM, Hurov JB, Poulogiannis G, Tsukazawa KS, Choo-Wing R, Wulf GM, Bell EL, Shim HS, Lamia KA, Rameh LE, Bellinger G, Sasaki AT, Asara JM, Yuan X, Bullock A, Denicola GM, Song J, Brown V, Signoretti S, Cantley LC. Depletion of a putatively druggable class of phosphatidylinositol kinases inhibits growth of p53-null tumors. Cell. 2013 Nov.155(4):844-857. Pubmedid: 24209622. Pmcid: PMC4070383.
  • Caldwell ME, DeNicola GM, Martins CP, Jacobetz MA, Maitra A, Hruban RH, Tuveson DA. Cellular features of senescence during the evolution of human and murine ductal pancreatic cancer. Oncogene. 2012 Mar.31(12):1599-1608. Pubmedid: 21860420. Pmcid: PMC3397306.
  • Gopinathan A, Denicola GM, Frese KK, Cook N, Karreth FA, Mayerle J, Lerch MM, Reinheckel T, Tuveson DA. Cathepsin B promotes the progression of pancreatic ductal adenocarcinoma in mice. Gut. 2012 Jun.61(6):877-884. Pubmedid: 22157328.
  • Karreth FA, Tay Y, Perna D, Ala U, Tan SM, Rust AG, DeNicola G, Webster KA, Weiss D, Perez-Mancera PA, Krauthammer M, Halaban R, Provero P, Adams DJ, Tuveson DA, Pandolfi PP. In vivo identification of tumor- suppressive PTEN ceRNAs in an oncogenic BRAF-induced mouse model of melanoma. Cell. 2011 Oct.147(2):382-395. Pubmedid: 22000016. Pmcid: PMC3236086.
  • Massie CE, Lynch A, Ramos-Montoya A, Boren J, Stark R, Fazli L, Warren A, Scott H, Madhu B, Sharma N, Bon H, Zecchini V, Smith DM, Denicola GM, Mathews N, Osborne M, Hadfield J, Macarthur S, Adryan B, Lyons SK, Brindle KM, Griffiths J, Gleave ME, Rennie PS, Neal DE, Mills IG. The androgen receptor fuels prostate cancer by regulating central metabolism and biosynthesis. Embo J. 2011 May.30(13):2719-2733. Pubmedid: 21602788. Pmcid: PMC3155295.
  • Karreth FA, Frese KK, DeNicola GM, Baccarini M, Tuveson DA. C-Raf is required for the initiation of lung cancer by K-Ras(G12D). Cancer Discov. 2011 Jul.1(2):128-136. Pubmedid: 22043453. Pmcid: PMC3203527.
  • DeNicola GM, Karreth FA, Humpton TJ, Gopinathan A, Wei C, Frese K, Mangal D, Yu KH, Yeo CJ, Calhoun ES, Scrimieri F, Winter JM, Hruban RH, Iacobuzio-Donahue C, Kern SE, Blair IA, Tuveson DA. Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis. Nature. 2011 Jul.475(7354):106-109. Pubmedid: 21734707. Pmcid: PMC3404470.
  • DeNicola GM, Tuveson DA. RAS in cellular transformation and senescence. Eur J Cancer. 2009 Sep.45 Suppl 1:211-216. Pubmedid: 19775620.
  • Karreth FA, DeNicola GM, Winter SP, Tuveson DA. C-Raf inhibits MAPK activation and transformation by B-Raf(V600E). Mol Cell. 2009 Nov.36(3):477-486. Pubmedid: 19917255.
  • Olive KP, Jacobetz MA, Davidson CJ, Gopinathan A, McIntyre D, Honess D, Madhu B, Goldgraben MA, Caldwell ME, Allard D, Frese KK, Denicola G, Feig C, Combs C, Winter SP, Ireland-Zecchini H, Reichelt S, Howat WJ, Chang A, Dhara M, Wang L, Rückert F, Grützmann R, Pilarsky C, Izeradjene K, Hingorani SR, Huang P, Davies SE, Plunkett W, Egorin M, Hruban RH, Whitebread N, McGovern K, Adams J, Iacobuzio-Donahue C, Griffiths J, Tuveson DA. Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Science. 2009 Jun.324(5933):1457-1461. Pubmedid: 19460966. Pmcid: PMC2998180.
  • Denicola G, Tuveson DA. VAV1: a new target in pancreatic cancer?. Cancer Biol Ther. 2005 May.4(5):509-511. Pubmedid: 15970675.