Ana Gomes, PhD

  The Gomes Laboratory is interested in understanding how age-driven metabolic and epigenetic changes drive tumor progression and metastasis formation.  http://lab.moffitt.org/gomes  

Associations

• Gastrointestinal Oncology
• Molecular Oncology
• Cancer Biology & Evolution Program

Education & Training

Graduate:

• Harvard Medical School & University of Coimbra, PhD - Cell and Molecular Biology

Fellowship:

• Harvard Medical School - Aging Biology
• Weill Cornell Medicine - Cancer Biology

  The Gomes Laboratory is interested in understanding how age-driven metabolic and epigenetic changes drive tumor progression and metastasis formation.  Dr. Gomes will continue her transformative research by addressing three critical questions: (1) Are there age-induced factors that affect resistance to conventional anti-cancer therapies? (2) What are the age-driven changes that occur within a tissue that may aid the progression of tumors and resistance to anti-cancer therapies? (3) Are there ways to harness this knowledge to define biomarkers of responsiveness to therapies as well as design better therapeutic strategies that factor in aging? Answering these questions will allow for the discovery of novel pathways that regulate the tumorigenic process and the development of more efficacious therapeutic strategies for aggressive cancers.  

• Tejero J, Lazure F, Gomes AP. Methylmalonic acid in aging and disease. Trends Endocrinol Metab. 2024 Mar.35(3):188-200. Pubmedid: 38030482. Pmcid: PMC10939937.
• Wu Q, Hatse S, Kenis C, Fernández-García J, Altea-Manzano P, Billen J, Planque M, Vandekeere A, Lambrechts Y, Richard F, Punie K, Neven P, Smeets A, Nevelsteen I, Floris G, Desmedt C, Gomes AP, Fendt SM, Wildiers H. Serum methylmalonic acid concentrations at breast cancer diagnosis significantly correlate with clinical frailty. Geroscience. 2024 Apr.46(2):1489-1498. Pubmedid: 37632634. Pmcid: PMC10828366.
• Nowicka Z, Rentzeperis F, Beck R, Tagal V, Pinto AF, Scanu E, Veith T, Cole J, Ilter D, Viqueira WD, Teer JK, Maksin K, Pasetto S, Abdalah MA, Fiandaca G, Prabhakaran S, Schultz A, Ojwang M, Barnholtz-Sloan JS, Farinhas JM, Gomes AP, Katira P, Andor N. Interactions between ploidy and resource availability shape clonal interference at initiation and recurrence of glioblastoma. bioRxiv. 2023 Oct. Pubmedid: 37905142. Pmcid: PMC10614845.
• Ilter D, Drapela S, Schild T, Ward NP, Adhikari E, Low V, Asara J, Oskarsson T, Lau EK, DeNicola GM, McReynolds MR, Gomes AP. NADK-mediated de novo NADP(H) synthesis is a metabolic adaptation essential for breast cancer metastasis. Redox Biol. 2023 May.61:102627. Pubmedid: 36841051. Pmcid: PMC9982641.
• Drapela S, Gomes AP. The aging lung reawakens dormant tumor cells. Nat Cancer. 2023 Apr.4(4):442-443. Pubmedid: 37106111.
• Drapela S, Ilter D, Gomes AP. Metabolic reprogramming: a bridge between aging and tumorigenesis. Mol Oncol. 2022 Sep.16(18):3295-3318. Pubmedid: 35666002. Pmcid: PMC9490145.
• Andor N, Altrock PM, Jain N, Gomes AP. Tipping Cancer Cells Over the Edge: The Context-Dependent Cost of High Ploidy. Cancer Res. 2022 Mar.82(5):741-748. Pubmedid: 34785577. Pmcid: PMC8898264.
• Gomes AP, Ilter D, Low V, Drapela S, Schild T, Mullarky E, Han J, Elia I, Broekaert D, Rosenzweig A, Nagiec M, Nunes JB, Schaffer BE, Mutvei AP, Asara JM, Cantley LC, Fendt SM, Blenis J. Altered propionate metabolism contributes to tumour progression and aggressiveness. Nat Metab. 2022 Apr.4(4):435-443. Pubmedid: 35361954. Pmcid: PMC9050834.
• Schild T, McReynolds MR, Shea C, Low V, Schaffer BE, Asara JM, Piskounova E, Dephoure N, Rabinowitz JD, Gomes AP, Blenis J. NADK is activated by oncogenic signaling to sustain pancreatic ductal adenocarcinoma. Cell Rep. 2021 Jun.35(11):109238. Pubmedid: 34133937.
• Ilter D, Gomes AP. Age-induced metabolic reprogramming underlies cancer progression. Mol Cell Oncol. 2021 Feb.8(2):1876506. Pubmedid: 33860078. Pmcid: PMC8018342.
• Drapela S, Gomes AP. Metabolic requirements of the metastatic cascade. Curr Opin Syst Biol. 2021 Dec.28. Pubmedid: 34693082. Pmcid: PMC8535854.
• Gomes AP, Ilter D, Low V, Endress JE, Fernández-García J, Rosenzweig A, Schild T, Broekaert D, Ahmed A, Planque M, Elia I, Han J, Kinzig C, Mullarky E, Mutvei AP, Asara J, de Cabo R, Cantley LC, Dephoure N, Fendt SM, Blenis J. Age-induced accumulation of methylmalonic acid promotes tumour progression. Nature. 2020 Sep.585(7824):283-287. Pubmedid: 32814897. Pmcid: PMC7785256.
• Zon L, Gomes AP, Cance WG, Ribas A, Tuveson D, Postel-Vinay S, Massard C, Barlési F. Impact of COVID-19 Pandemic on Cancer Research. Cancer Cell. 2020 Nov.38(5):591-593. Pubmedid: 33086030. Pmcid: PMC7543995.
• Low V, Blenis J, Gomes AP. Targeting the premetastatic niche: epigenetic therapies in the spotlight. Signal Transduct Target Ther. 2020 May.5(1):68. Pubmedid: 32390001. Pmcid: PMC7211564.
• Ilter D, Blenis J, Gomes AP. Histone H3 variants at the root of metastasis. Mol Cell Oncol. 2020 Jan.7(2):1684128. Pubmedid: 32158911. Pmcid: PMC7051143.
• Gomes AP, Ilter D, Low V, Rosenzweig A, Shen ZJ, Schild T, Rivas MA, Er EE, McNally DR, Mutvei AP, Han J, Ou YH, Cavaliere P, Mullarky E, Nagiec M, Shin S, Yoon SO, Dephoure N, Massagué J, Melnick AM, Cantley LC, Tyler JK, Blenis J. Dynamic Incorporation of Histone H3 Variants into Chromatin Is Essential for Acquisition of Aggressive Traits and Metastatic Colonization. Cancer Cell. 2019 Oct.36(4):402-417.e13. Pubmedid: 31564638. Pmcid: PMC6801101.
• Schild T, Low V, Blenis J, Gomes AP. Unique Metabolic Adaptations Dictate Distal Organ-Specific Metastatic Colonization. Cancer Cell. 2018 Mar.33(3):347-354. Pubmedid: 29533780. Pmcid: PMC5889305.
• He L, Gomes AP, Wang X, Yoon SO, Lee G, Nagiec MJ, Cho S, Chavez A, Islam T, Yu Y, Asara JM, Kim BY, Blenis J. mTORC1 Promotes Metabolic Reprogramming by the Suppression of GSK3-Dependent Foxk1 Phosphorylation. Mol Cell. 2018 Jun.70(5):949-960.e4. Pubmedid: 29861159. Pmcid: PMC6591025.
• Costford SR, Brouwers B, Hopf ME, Sparks LM, Dispagna M, Gomes AP, Cornnell HH, Petucci C, Phelan P, Xie H, Yi F, Walter GA, Osborne TF, Sinclair DA, Mynatt RL, Ayala JE, Gardell SJ, Smith SR. Skeletal muscle overexpression of nicotinamide phosphoribosyl transferase in mice coupled with voluntary exercise augments exercise endurance. Mol Metab. 2018 Jan.7:1-11. Pubmedid: 29146412. Pmcid: PMC5784330.
• Rosenzweig A, Blenis J, Gomes AP. Beyond the Warburg Effect: How Do Cancer Cells Regulate One-Carbon Metabolism?. Front Cell Dev Biol. 2018 Aug.6:90. Pubmedid: 30159313. Pmcid: PMC6103474.
• Duarte FV, Amorim JA, Varela AT, Teodoro JS, Gomes AP, Cunha RA, Palmeira CM, Rolo AP. Adenosine receptors: regulatory players in the preservation of mitochondrial function induced by ischemic preconditioning of rat liver. Purinergic Signal. 2017 Jun.13(2):179-190. Pubmedid: 27848069. Pmcid: PMC5432478.
• Gomes AP, Schild T, Blenis J. Adding Polyamine Metabolism to the mTORC1 Toolkit in Cell Growth and Cancer. Dev Cell. 2017 Jul.42(2):112-114. Pubmedid: 28742999. Pmcid: PMC5705022.
• 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.
• Gomes AP, Sinclair DA. Measuring PGC-1α and its acetylation status in mouse primary myotubes. Methods Mol Biol. 2015 Jan.1241:49-57. Pubmedid: 25308487.
• Miranda MX, van Tits LJ, Lohmann C, Arsiwala T, Winnik S, Tailleux A, Stein S, Gomes AP, Suri V, Ellis JL, Lutz TA, Hottiger MO, Sinclair DA, Auwerx J, Schoonjans K, Staels B, Lüscher TF, Matter CM. The Sirt1 activator SRT3025 provides atheroprotection in Apoe-/- mice by reducing hepatic Pcsk9 secretion and enhancing Ldlr expression. Eur Heart J. 2015 Jan.36(1):51-59. Pubmedid: 24603306. Pmcid: PMC4286317.
• Gomes AP, Blenis J. A nexus for cellular homeostasis: the interplay between metabolic and signal transduction pathways. Curr Opin Biotechnol. 2015 Aug.34:110-117. Pubmedid: 25562138. Pmcid: PMC4490161.
• Mercken EM, Mitchell SJ, Martin-Montalvo A, Minor RK, Almeida M, Gomes AP, Scheibye-Knudsen M, Palacios HH, Licata JJ, Zhang Y, Becker KG, Khraiwesh H, González-Reyes JA, Villalba JM, Baur JA, Elliott P, Westphal C, Vlasuk GP, Ellis JL, Sinclair DA, Bernier M, de Cabo R. SRT2104 extends survival of male mice on a standard diet and preserves bone and muscle mass. Aging Cell. 2014 Oct.13(5):787-796. Pubmedid: 24931715. Pmcid: PMC4172519.
• Wu LE, Gomes AP, Sinclair DA. Geroncogenesis: metabolic changes during aging as a driver of tumorigenesis. Cancer Cell. 2014 Jan.25(1):12-19. Pubmedid: 24434207. Pmcid: PMC3970212.
• Teodoro JS, Zouhar P, Flachs P, Bardova K, Janovska P, Gomes AP, Duarte FV, Varela AT, Rolo AP, Palmeira CM, Kopecký J. Enhancement of brown fat thermogenesis using chenodeoxycholic acid in mice. Int J Obes (Lond). 2014 Aug.38(8):1027-1034. Pubmedid: 24310401.
• Teodoro JS, Duarte FV, Gomes AP, Varela AT, Peixoto FM, Rolo AP, Palmeira CM. Berberine reverts hepatic mitochondrial dysfunction in high-fat fed rats: a possible role for SirT3 activation. Mitochondrion. 2013 Nov.13(6):637-646. Pubmedid: 24041461.
• Hubbard BP, Gomes AP, Dai H, Li J, Case AW, Considine T, Riera TV, Lee JE, E SY, Lamming DW, Pentelute BL, Schuman ER, Stevens LA, Ling AJ, Armour SM, Michan S, Zhao H, Jiang Y, Sweitzer SM, Blum CA, Disch JS, Ng PY, Howitz KT, Rolo AP, Hamuro Y, Moss J, Perni RB, Ellis JL, Vlasuk GP, Sinclair DA. Evidence for a common mechanism of SIRT1 regulation by allosteric activators. Science. 2013 Mar.339(6124):1216-1219. Pubmedid: 23471411. Pmcid: PMC3799917.
• Martin-Montalvo A, Mercken EM, Mitchell SJ, Palacios HH, Mote PL, Scheibye-Knudsen M, Gomes AP, Ward TM, Minor RK, Blouin MJ, Schwab M, Pollak M, Zhang Y, Yu Y, Becker KG, Bohr VA, Ingram DK, Sinclair DA, Wolf NS, Spindler SR, Bernier M, de Cabo R. Metformin improves healthspan and lifespan in mice. Nat Commun. 2013 Jul.4:2192. Pubmedid: 23900241. Pmcid: PMC3736576.
• Hubbard BP, Loh C, Gomes AP, Li J, Lu Q, Doyle TL, Disch JS, Armour SM, Ellis JL, Vlasuk GP, Sinclair DA. Carboxamide SIRT1 inhibitors block DBC1 binding via an acetylation-independent mechanism. Cell Cycle. 2013 Jul.12(14):2233-2240. Pubmedid: 23892437. Pmcid: PMC3755073.
• Gomes AP, Price NL, Ling AJ, Moslehi JJ, Montgomery MK, Rajman L, White JP, Teodoro JS, Wrann CD, Hubbard BP, Mercken EM, Palmeira CM, de Cabo R, Rolo AP, Turner N, Bell EL, Sinclair DA. Declining NAD(+) induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell. 2013 Dec.155(7):1624-1638. Pubmedid: 24360282. Pmcid: PMC4076149.
• Duarte FV, Gomes AP, Teodoro JS, Varela AT, Moreno AJ, Rolo AP, Palmeira CM. Dibenzofuran-induced mitochondrial dysfunction: Interaction with ANT carrier. Toxicol In Vitro. 2013 Dec.27(8):2160-2168. Pubmedid: 24008156.
• Escande C, Nin V, Price NL, Capellini V, Gomes AP, Barbosa MT, O'Neil L, White TA, Sinclair DA, Chini EN. Flavonoid apigenin is an inhibitor of the NAD+ ase CD38: implications for cellular NAD+ metabolism, protein acetylation, and treatment of metabolic syndrome. Diabetes. 2013 Apr.62(4):1084-1093. Pubmedid: 23172919. Pmcid: PMC3609577.
• Teodoro JS, Gomes AP, Varela AT, Duarte FV, Rolo AP, Palmeira CM. Uncovering the beginning of diabetes: the cellular redox status and oxidative stress as starting players in hyperglycemic damage. Mol Cell Biochem. 2013 Apr.376(1-2):103-110. Pubmedid: 23292031.
• Price NL, Gomes AP, Ling AJ, Duarte FV, Martin-Montalvo A, North BJ, Agarwal B, Ye L, Ramadori G, Teodoro JS, Hubbard BP, Varela AT, Davis JG, Varamini B, Hafner A, Moaddel R, Rolo AP, Coppari R, Palmeira CM, de Cabo R, Baur JA, Sinclair DA. SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function. Cell Metab. 2012 May.15(5):675-690. Pubmedid: 22560220. Pmcid: PMC3545644.
• Gomes AP, Duarte FV, Nunes P, Hubbard BP, Teodoro JS, Varela AT, Jones JG, Sinclair DA, Palmeira CM, Rolo AP. Berberine protects against high fat diet-induced dysfunction in muscle mitochondria by inducing SIRT1-dependent mitochondrial biogenesis. Biochim Biophys Acta. 2012 Feb.1822(2):185-195. Pubmedid: 22027215. Pmcid: PMC3366688.
• Rolo AP, Gomes AP, Palmeira CM. Regulation of mitochondrial biogenesis in metabolic syndrome. Curr Drug Targets. 2011 Jun.12(6):872-878. Pubmedid: 21269264.
• Minor RK, Baur JA, Gomes AP, Ward TM, Csiszar A, Mercken EM, Abdelmohsen K, Shin YK, Canto C, Scheibye-Knudsen M, Krawczyk M, Irusta PM, Martín-Montalvo A, Hubbard BP, Zhang Y, Lehrmann E, White AA, Price NL, Swindell WR, Pearson KJ, Becker KG, Bohr VA, Gorospe M, Egan JM, Talan MI, Auwerx J, Westphal CH, Ellis JL, Ungvari Z, Vlasuk GP, Elliott PJ, Sinclair DA, de Cabo R. SRT1720 improves survival and healthspan of obese mice. Sci Rep. 2011 Aug.1:70. Pubmedid: 22355589. Pmcid: PMC3216557.
• Hafner AV, Dai J, Gomes AP, Xiao CY, Palmeira CM, Rosenzweig A, Sinclair DA. Regulation of the mPTP by SIRT3-mediated deacetylation of CypD at lysine 166 suppresses age-related cardiac hypertrophy. Aging (Albany NY). 2010 Dec.2(12):914-923. Pubmedid: 21212461. Pmcid: PMC3034180.
• Varela AT, Simões AM, Teodoro JS, Duarte FV, Gomes AP, Palmeira CM, Rolo AP. Indirubin-3'-oxime prevents hepatic I/R damage by inhibiting GSK-3beta and mitochondrial permeability transition. Mitochondrion. 2010 Aug.10(5):456-463. Pubmedid: 20433952.
• Varela AT, Gomes AP, Simões AM, Teodoro JS, Duarte FV, Rolo AP, Palmeira CM. Indirubin-3'-oxime impairs mitochondrial oxidative phosphorylation and prevents mitochondrial permeability transition induction. Toxicol Appl Pharm. 2008 Dec.233(2):179-185. Pubmedid: 18786556.

• Title: Adaptations of breast cancer metastasis to the aging lung
  Sponsor: Nat Institutes of Health
  PI: Gomes, A.
• Title: Metabolic vulnerabilities of dormant disseminated breast cancer cells
  Sponsor: METAvivor Research and Support, Inc.
  PI: Gomes, A.
• Title: Vitamin B12 supplementation as novel therapeutic strategy to improve cancer-associated outcomes
  Sponsor: Nat Institutes of Health
  PI: Gomes, A.
• Title: NAD+: A Missing Link Between Aging and Pancreatic Tumorigenesis
  Sponsor: Phi Beta Psi
  PI (Contact): Gomes, A.
• Title: How the aging tumor microenvironment affects development of leptomeningeal metastases
  Sponsor: Moffitt Cancer Center
  PI: Smalley, I., CO-PI: Gomes, A.
• Title: Aging as a selective pressure that drives tumor progression
  Sponsor: Nat Institutes of Health
  PI: Gomes, A.
• Title: Epigenetic mechanisms that underlie breast cancer dormancy
  Sponsor: Amer Cancer Society
  PI (Contact): Gomes, A.
• Title: Propionate metabolism as an essential metabolic adaptation for tumor progression
  Sponsor: Nat Institutes of Health
  PI: Gomes, A.
• Title: Pyridine Nucleotides: Missing Link between Aging and Lung Cancer
  Sponsor: Florida Biomedical Research Program (FBRP)
  PI: DeNicola, G., CO-PI: Gomes, A.