The Reznik Lab studies metabolic and mitochondrial dysfunction in cancer through analysis of multimodal genetic, metabolomic, and clinical data. We use computational tools to address a basic question: how do tumors adapt their metabolism, the process by which they obtain energy and nutrition from the extracellular environment, to sustain malignancy? Our research draws on data from basic science and clinical practice to understand how metabolic adaptations confer selective advantages to tumors, serve as biomarkers of response and resistance to therapy, and poise tumors for effective targeted intervention.
The lab’s research is equal parts machine learning, data science, and bioinformatics, and is conducted by a multidisciplinary group of quantitative scientists and translationally-minded physicians. We study metabolism in many disease contexts, but also have a unique translational focus on kidney cancer.
View available career opportunities in the lab here.
Benedetti E, Liu EM, Tang C, Kuo F, Buyukozkan M, Park T, Park J, Correa F, Hakimi AA, Intlekofer AM, Krumsiek J, Reznik E. A multimodal atlas of tumour metabolism reveals the architecture of gene-metabolite covariation. Nat Metab. 2023 Jun;5(6):1029-1044. doi: 10.1038/s42255-023-00817-8. Epub 2023 Jun 19. PMID: 37337120; PMCID: PMC10290959.
Posada Calderon L, Eismann L, Reese SW, Reznik E, Hakimi AA. Advances in Imaging-Based Biomarkers in Renal Cell Carcinoma: A Critical Analysis of the Current Literature. Cancers (Basel). 2023 Jan 5;15(2):354. doi: 10.3390/cancers15020354. PMID: 36672304; PMCID: PMC9856305.
Golkaram M, Kuo F, Gupta S, Carlo MI, Salmans ML, Vijayaraghavan R, Tang C, Makarov V, Rappold P, Blum KA, Zhao C, Mehio R, Zhang S, Godsey J, Pawlowski T, DiNatale RG, Morris LGT, Durack J, Russo P, Kotecha RR, Coleman J, Chen YB, Reuter VE, Motzer RJ, Voss MH, Liu L, Reznik E, Chan TA, Hakimi AA. Spatiotemporal evolution of the clear cell renal cell carcinoma microenvironment links intra-tumoral heterogeneity to immune escape. Genome Med. 2022 Dec 19;14(1):143. doi: 10.1186/s13073-022-01146-3. PMID: 36536472; PMCID: PMC9762114.
Freeman BA, Jaro S, Park T, Keene S, Tansey W, Reznik E. MIRTH: Metabolite Imputation via Rank-Transformation and Harmonization. Genome Biol. 2022 Sep 1;23(1):184. doi: 10.1186/s13059-022-02738-3. PMID: 36050754; PMCID: PMC9438248.
Ganly I, Liu EM, Kuo F, Makarov V, Dong Y, Park J, Gong Y, Gorelick AN, Knauf JA, Benedetti E, Tait-Mulder J, Morris LGT, Fagin JA, Intlekofer AM, Krumsiek J, Gammage PA, Ghossein R, Xu B, Chan TA, Reznik E. Mitonuclear genotype remodels the metabolic and microenvironmental landscape of Hürthle cell carcinoma. Sci Adv. 2022 Jun 24;8(25):eabn9699. doi: 10.1126/sciadv.abn9699. Epub 2022 Jun 22. PMID: 35731870; PMCID: PMC9216518.
Lee CH, Voss MH, Carlo MI, Chen YB, Zucker M, Knezevic A, Lefkowitz RA, Shapnik N, Dadoun C, Reznik E, Shah NJ, Owens CN, McHugh DJ, Aggen DH, Laccetti AL, Kotecha R, Feldman DR, Motzer RJ. Phase II Trial of Cabozantinib Plus Nivolumab in Patients With Non-Clear-Cell Renal Cell Carcinoma and Genomic Correlates. J Clin Oncol. 2022 Jul 20;40(21):2333-2341. doi: 10.1200/JCO.21.01944. Epub 2022 Mar 17. PMID: 35298296; PMCID: PMC9287282.
Tourigny DS, Zucker M, Kim M, Russo P, Coleman J, Lee CH, Carlo MI, Chen YB, Hakimi AA, Kotecha RR, Reznik E. Molecular Characterization of the Tumor Microenvironment in Renal Medullary Carcinoma. Front Oncol. 2022 Jun 28;12:910147. doi: 10.3389/fonc.2022.910147. PMID: 35837094; PMCID: PMC9275834.
Yoo A, Tang C, Zucker M, Fitzgerald K, DiNatale RG et al. Reznik E. Genomic and Metabolic Hallmarks of SDH- and FH-deficient Renal Cell Carcinomas. Eur Urol Focus. 2022 Mar 11;S2405-4569(21)00312-6. doi: 10.1016/j.euf.2021.12.002. PMID: 35288096
Nguyen B, Fong C, Luthra A, Smith SA, DiNatale RG, Nandakumar S, Walch H, Chatila WK, Madupuri R, Kundra R, Bielski CM, Mastrogiacomo B, Donoghue MTA, Boire A, Chandarlapaty S, Ganesh K, Harding JJ, Iacobuzio-Donahue CA, Razavi P, Reznik E, ……, Shah SP, Massague J, Gao J, Zehir A, Berger MF, Solit DB, Bakhoum SF, Sanchez-Vega F, Schultz N. Genomic characterization of metastatic patterns from prospective clinical sequencing of 25,000 patients. Cell. 2022 Feb 3;185(3):563-575.e11. doi: 10.1016/j.cell.2022.01.003. PMID: 35120664; PMCID: PMC9147702.
Attalla K, DiNatale RG, Rappold PM, Fong CJ, Sanchez-Vega F, Silagy AW, Weng S, Coleman J, Lee CH, Carlo MI, Durack JC, Solomon SB, Reuter VE, Russo P, Chan TA, Motzer RJ, Schultz ND, Reznik E, Voss MH, Hakimi AA. Prevalence and Landscape of Actionable Genomic Alterations in Renal Cell Carcinoma. Clin Cancer Res. 2021 Oct 15;27(20):5595-5606. doi: 10.1158/1078-0432.CCR-20-4058. Epub 2021 Jul 14. PMID: 34261695; PMCID: PMC8530915.
DiNatale RG, Mano R, Makarov V, Rusk N, Drill E, et al., Reznik E, Hakimi AA. Resource-efficient pooled sequencing expands translational impact in solid tumors. Kidney Cancer J. 2021;19(2):18-23.
Gorelick AN, Kim M, Chatila WK, La K, Hakimi AA, Berger MF, Taylor BS, Gammage PA, Reznik E. Respiratory complex and tissue lineage drive recurrent mutations in tumour mtDNA. Nat Metab. 2021;3(4):558-70.
Reznik E, Jiang H, Hakimi AA. Chemerin Tips the Scales in ccRCC to Evade Ferroptosis. Cancer Discov. 2021;11(8):1879-80.
DiNatale RG, Mano R, Makarov V, Rusk N, Drill E, Winer A. et al. Reznik E. and Hakimi AA. Resource-efficient pooled sequencing expands translational impact in solid tumors Kidney Cancer J. 2021 Jun;19(2):18-23. doi: 10.52733/KCJ18n2.a1. PMID: 34316321
Attalla K, DiNatale RG, Rappold PM, Fong CJ, Sanchez-Vega F et al. Reznik E, Voss MH, Hakimi AA. Prevalence and Landscape of Actionable Genomic Alterations in Renal Cell Carcinoma Clin Cancer Res. 2021 Oct 15;27(20):5595-5606. doi: 10.1158/1078-0432.CCR-20-4058. PMID: 34261695
Gorelick AN, Sánchez-Rivera FJ, …, Reznik E*, Taylor BS*. Phase and context shape the function of composite oncogenic mutations. Nature. 2020;582(7810):100-103. doi:10.1038/s41586-020-2315-8
Xu J, Reznik E, et al. Abnormal oxidative metabolism in a quiet genomic background underlies clear cell papillary renal cell carcinoma. Elife. 2019 Apr 1;8. pii: e38986. doi: 10.7554/eLife.38986. PubMed PMID: 30924768; PubMed Central PMCID: PMC6459676.
Reznik E, et al. A Landscape of Metabolic Variation across Tumor Types. Cell Syst. 2018 Mar 28;6(3):301-313.e3. doi: 10.1016/j.cels.2017.12.014. Epub 2018 Jan 27. PubMed PMID: 29396322; PubMed Central PMCID: PMC5876114.
Reznik E, et al. Genome-Scale Architecture of Small Molecule Regulatory Networks and the Fundamental Trade-Off between Regulation and Enzymatic Activity. Cell Rep. 2017 Sep 12;20(11):2666-2677. doi: 10.1016/j.celrep.2017.08.066. PubMed PMID: 28903046; PubMed Central PMCID: PMC5600504.
Metabolic Determinants of the Tumor Microenvironment – How does metabolism dictate the composition of the tumor microenvironment?
Function and Evolution of Mitochondrial DNA Mutations – How do mutations to the mitochondrial genome arise in tumors, and what selective advantage do they confer?
Genotype to Metabolic Phenotype – What are the metabolic adaptations and vulnerabilities associated with the acquisition of a particular genetic lesion?
The Multimodal Metabolism Map – Tumors are made of heterogeneous mixtures of different cell types with distinct modes of metabolism. Our research group is developing the Multimodal Metabolism Map, a harmonized dataset of hundreds of matched metabolomic and transcriptomic measurements across hundreds of tumor and normal tissue specimens covering numerous cancer types. Using the MMM, we are deconvolving the individual metabolic phenotypes of malignant, stromal, and immune cell types, and studying how each of them individually contribute to translationally meaningful metabolic phenotypes in tumors.
Please visit Dr. Reznik’s faculty page, PubMed or Google Scholar for publications from the Reznik lab
