Research Interests

  • Development of Bioinformatics Methods, Databases, and Web Tools

    Our lab develops scalable and user-friendly computational tools to support research. We build informatics platforms that enable researchers to navigate, analyze, and interpret complex omics datasets across human and preclinical models.

    Projects and tools include:

    • Lung Cancer Autochthonous Model Gene Expression Database (LCAMGDB): A web app for transcriptomic data from over 1,300 samples across > 50 labs, enabling cross-model comparisons.

    • Lung Cancer Explorer (LCE): An open web portal for survival and co-expression analysis across > 6,700 lung cancer patients in 56 studies.

    • Functional Data Consistency Explorer (FDCE): A web app evaluating consistency across drug and CRISPR/RNAi screens.

    • CoMut: A co-mutation analysis tool using AACR Project GENIE pan-cancer patient data.

    • NEcalc: A web tool for developing a generalized neuroendocrine (NE) score for classifying tumors with NE features.

    • Genomic Regression Analysis of Co-Expression (GRACE): A web app facilitating co-expression analysis using denoised TCGA RNA-seq data (adjusted for DNA copy number).

    • Gazdar Neuroendocrine Transdifferentiation Explorer (GSNE): A web tool for small cell lung cancer and neuroblastoma transcriptomic comparisons in patient and preclinical model datasets.

    • NSCLC Cell Line Metabolic Diversity: A web tool to facilitate exploration of 13C glucose and glutamine labeling patterns in 81 NSCLC cell lines

    Under Development (feedback and data contribution welcomed):

    • Lung Cancer Cell Line Explorer (LCCL): A web tool to explorer multi-omics lung cancer cell line data.

    • Lung Model Pathology Viewer (LUMP): An access-controlled pathology image archive of in vivo lung cancer preclinical model pathology images.

  • Cancer Metabolism and Multi-Omics Integration

    We investigates metabolic heterogeneity and genotype-specific programs in cancer and rare disease. In collaboration with the DeBerardinis lab(https://cri.utsw.edu/faculty/ralph-deberardinis/), we integrate metabolomics, isotope tracing, transcriptomics, and imaging to uncover key metabolic dependencies, identify biomarkers of tumor aggressiveness, and support translational tool development.

    Selected publication:

    Lung Cancer

    • Cai L, Hammond NG, Tasdogan A, Alsamraae M, Yang C, Cameron RB, Quan P, Solmonson A, Gu W, Pachnis P, Kaur M, Chang BK, Zhou Q, Hensley CT, Do QN, Martins Nascentes Melo L, Ubellacker JM, Kaushik A, Clare MG, Alcazar IN, Kurylowicz K, Marcuccilli JD, Allies G, Kutritz A, Klode J, Ramesh V, Rogers TJ, Rao AD, Crentsil HE, Li H, Brister F, McDaniel P, Xu X, Evers BM, Zacharias LG, Sudderth J, Xu J, Mathews TP, Oliver D, Minna JD, Waters J, Morrison SJ, Kernstine KH, Faubert B, DeBerardinis RJ. High Glucose Contribution to the TCA Cycle Is a Feature of Aggressive Non-Small Cell Lung Cancer in Patients. Cancer Discov. 2025 Apr 2;15(4):702-716. doi: 10.1158/2159-8290.CD-23-1319. PubMed PMID: 39960461; PubMed Central PMCID: PMC11962397.
    • Huang F, Huffman KE, Wang Z, Wang X, Li K, Cai F, Yang C, Cai L, Shih TS, Zacharias LG, Chung A, Yang Q, Chalishazar MD, Ireland AS, Stewart CA, Cargill K, Girard L, Liu Y, Ni M, Xu J, Wu X, Zhu H, Drapkin B, Byers LA, Oliver TG, Gazdar AF, Minna JD, DeBerardinis RJ. Guanosine triphosphate links MYC-dependent metabolic and ribosome programs in small-cell lung cancer. J Clin Invest. 2021 Jan 4;131(1). doi: 10.1172/JCI139929. PubMed PMID: 33079728; PubMed Central PMCID: PMC7773395.
    • Kim J, Lee HM, Cai F, Ko B, Yang C, Lieu EL, Muhammad N, Rhyne S, Li K, Haloul M, Gu W, Faubert B, Kaushik AK, Cai L, Kasiri S, Marriam U, Nham K, Girard L, Wang H, Sun X, Kim J, Minna JD, Unsal-Kacmaz K, DeBerardinis RJ. The hexosamine biosynthesis pathway is a targetable liability in KRAS/LKB1 mutant lung cancer. Nat Metab. 2020 Dec;2(12):1401-1412. doi: 10.1038/s42255-020-00316-0. Epub 2020 Nov 30. PubMed PMID: 33257855; PubMed Central PMCID: PMC7744327.
    • Faubert B, Li KY, Cai L, Hensley CT, Kim J, Zacharias LG, Yang C, Do QN, Doucette S, Burguete D, Li H, Huet G, Yuan Q, Wigal T, Butt Y, Ni M, Torrealba J, Oliver D, Lenkinski RE, Malloy CR, Wachsmann JW, Young JD, Kernstine K, DeBerardinis RJ. Lactate Metabolism in Human Lung Tumors. Cell. 2017 Oct 5;171(2):358-371.e9. doi: 10.1016/j.cell.2017.09.019. PubMed PMID: 28985563; PubMed Central PMCID: PMC5684706.
    • Kim J, Hu Z, Cai L, Li K, Choi E, Faubert B, Bezwada D, Rodriguez-Canales J, Villalobos P, Lin YF, Ni M, Huffman KE, Girard L, Byers LA, Unsal-Kacmaz K, Peña CG, Heymach JV, Wauters E, Vansteenkiste J, Castrillon DH, Chen BPC, Wistuba I, Lambrechts D, Xu J, Minna JD, DeBerardinis RJ. CPS1 maintains pyrimidine pools and DNA synthesis in KRAS/LKB1-mutant lung cancer cells. Nature. 2017 Jun 1;546(7656):168-172. doi: 10.1038/nature22359. Epub 2017 May 24. PubMed PMID: 28538732; PubMed Central PMCID: PMC5472349.

    Kidney Cancer

    • Bezwada D, Perelli L, Lesner NP, Cai L, Brooks B, Wu Z, Vu HS, Sondhi V, Cassidy DL, Kasitinon S, Kelekar S, Cai F, Aurora AB, Patrick M, Leach A, Ghandour R, Zhang Y, Do D, McDaniel P, Sudderth J, Dumesnil D, House S, Rosales T, Poole AM, Lotan Y, Woldu S, Bagrodia A, Meng X, Cadeddu JA, Mishra P, Garcia-Bermudez J, Pedrosa I, Kapur P, Courtney KD, Malloy CR, Genovese G, Margulis V, DeBerardinis RJ. Mitochondrial complex I promotes kidney cancer metastasis. Nature. 2024 Sep;633(8031):923-931. doi: 10.1038/s41586-024-07812-3. Epub 2024 Aug 14. PubMed PMID: 39143213; PubMed Central PMCID: PMC11424252.
    • Zhang Y, Udayakumar D, Cai L, Hu Z, Kapur P, Kho EY, Pavía-Jiménez A, Fulkerson M, de Leon AD, Yuan Q, Dimitrov IE, Yokoo T, Ye J, Mitsche MA, Kim H, McDonald JG, Xi Y, Madhuranthakam AJ, Dwivedi DK, Lenkinski RE, Cadeddu JA, Margulis V, Brugarolas J, DeBerardinis RJ, Pedrosa I. Addressing metabolic heterogeneity in clear cell renal cell carcinoma with quantitative Dixon MRI. JCI Insight. 2017 Aug 3;2(15). doi: 10.1172/jci.insight.94278. eCollection 2017 Aug 3. PubMed PMID: 28768909; PubMed Central PMCID: PMC5543910.

    Tool Development

    • Cai L, Vu HS, Gu W, Chen H, Franklin J, Haidar LA, Wu Z, Pan C, Cai F, Nguyen P, Ko B, Yang C, Zacharias LG, Sudderth J, Montgomery S, Uhles C, Fisher H, Hudnall J, Hornbuckle C, Quinn C, Michel D, Umaña L, Scheuerle A, McNutt MC, Gotway GK, Afroze B, Ni M, DeBerardinis R. An interactive web application for exploring human plasma and fibroblast metabolomics data from patients with inborn errors of metabolism. bioRxiv. 2023 Dec 12;. doi: 10.1101/2023.12.11.571124. PubMed PMID: 38168314; PubMed Central PMCID: PMC10760037.
    • Cai F, Bezwada D, Cai L, Mahar R, Wu Z, Chang MC, Pachnis P, Yang C, Kelekar S, Gu W, Brooks B, Ko B, Vu HS, Mathews TP, Zacharias LG, Martin-Sandoval M, Do D, Oaxaca KC, Jin ES, Margulis V, Malloy CR, Merritt ME, DeBerardinis RJ. Comprehensive isotopomer analysis of glutamate and aspartate in small tissue samples. Cell Metab. 2023 Oct 3;35(10):1830-1843.e5. doi: 10.1016/j.cmet.2023.07.013. Epub 2023 Aug 22. PubMed PMID: 37611583; PubMed Central PMCID: PMC10732579.

  • Small Cell Lung Cancer (SCLC) and Neuroendocrine Plasticity

    In collaboration with SCLC investigators, we explored neuroendocrine (NE) transdifferentiation and its implications for immune evasion and molecular reclassification. Our work revealed parallels between SCLC and neuroblastoma, informed NE scoring systems, and helped reclassify YAP1⁺ SCLC lines as SMARCA4-deficient malignancies.

    Selected publication:

    • Cai L, Liu H, Huang F, Fujimoto J, Girard L, Chen J, Li Y, Zhang YA, Deb D, Stastny V, Pozo K, Kuo CS, Jia G, Yang C, Zou W, Alomar A, Huffman K, Papari-Zareei M, Yang L, Drapkin B, Akbay EA, Shames DS, Wistuba II, Wang T, Johnson JE, Xiao G, DeBerardinis RJ, Minna JD, Xie Y, Gazdar AF. Cell-autonomous immune gene expression is repressed in pulmonary neuroendocrine cells and small cell lung cancer. Commun Biol. 2021 Mar 9;4(1):314. doi: 10.1038/s42003-021-01842-7. PubMed PMID: 33750914; PubMed Central PMCID: PMC7943563.
    • Cai L, DeBerardinis RJ, Xie Y, Minna JD, Xiao G. A Comparative Study of Neuroendocrine Heterogeneity in Small Cell Lung Cancer and Neuroblastoma. Mol Cancer Res. 2023 Aug 1;21(8):795-807. doi: 10.1158/1541-7786.MCR-23-0002. PubMed PMID: 37255415; PubMed Central PMCID: PMC10390888.
    • Ng J, Cai L, Girard L, Prall OWJ, Rajan N, Khoo C, Batrouney A, Byrne DJ, Boyd DK, Kersbergen AJ, Christie M, Minna JD, Burr ML, Sutherland KD. Molecular and Pathologic Characterization of YAP1-Expressing Small Cell Lung Cancer Cell Lines Leads to Reclassification as SMARCA4-Deficient Malignancies. Clin Cancer Res. 2024 May 1;30(9):1846-1858. doi: 10.1158/1078-0432.CCR-23-2360. PubMed PMID: 38180245; PubMed Central PMCID: PMC11061608.

  • Non-Small Cell Lung Cancer (NSCLC) Data Mining

    We have leveraged public and institutional NSCLC datasets to generate integrative analyses and provide insights for collaborating investigators.

    Selected publication:

    • Cai L, Xiao G, Gerber D, D Minna J, Xie Y. Lung Cancer Computational Biology and Resources. Cold Spring Harb Perspect Med. 2022 Feb 1;12(2). doi: 10.1101/cshperspect.a038273. Review. PubMed PMID: 34751162; PubMed Central PMCID: PMC8805643.
    • Chiang JC, Shang Z, Rosales T, Cai L, Chen WM, Cai F, Vu H, Minna JD, Ni M, Davis AJ, Timmerman RD, DeBerardinis RJ, Zhang Y. Lipoylation inhibition enhances radiation control of lung cancer by suppressing homologous recombination DNA damage repair. Sci Adv. 2025 Mar 14;11(11):eadt1241. doi: 10.1126/sciadv.adt1241. Epub 2025 Mar 12. PubMed PMID: 40073141; PubMed Central PMCID: PMC11900879.
    • Lee HM, Muhammad N, Lieu EL, Cai F, Mu J, Ha YS, Cao G, Suchors C, Joves K, Chronis C, Li K, Ducker GS, Olszewski K, Cai L, Allison DB, Bachert SE, Ewing WR, Wong H, Seo H, Kim IY, Faubert B, Kim J, Kim J. Concurrent loss of LKB1 and KEAP1 enhances SHMT-mediated antioxidant defence in KRAS-mutant lung cancer. Nat Metab. 2024 Jul;6(7):1310-1328. doi: 10.1038/s42255-024-01066-z. Epub 2024 Jun 14. PubMed PMID: 38877143; PubMed Central PMCID: PMC11809267.
    • Park JV, Chandra R, Cai L, Ganguly D, Li H, Toombs JE, Girard L, Brekken RA, Minna JD. Tumor Cells Modulate Macrophage Phenotype in a Novel In Vitro Co-Culture Model of the NSCLC Tumor Microenvironment. J Thorac Oncol. 2022 Oct;17(10):1178-1191. doi: 10.1016/j.jtho.2022.06.011. Epub 2022 Jul 5. PubMed PMID: 35798240; PubMed Central PMCID: PMC9529910.
    • Wang S, Rong R, Yang DM, Fujimoto J, Bishop JA, Yan S, Cai L, Behrens C, Berry LD, Wilhelm C, Aisner D, Sholl L, Johnson BE, Kwiatkowski DJ, Wistuba II, Bunn PA Jr, Minna J, Xiao G, Kris MG, Xie Y. Features of tumor-microenvironment images predict targeted therapy survival benefit in patients with EGFR-mutant lung cancer. J Clin Invest. 2023 Jan 17;133(2). doi: 10.1172/JCI160330. PubMed PMID: 36647832; PubMed Central PMCID: PMC9843059.
    • Ci B, Yang DM, Cai L, Yang L, Girard L, Fujimoto J, Wistuba II, Xie Y, Minna JD, Travis W, Xiao G. Molecular differences across invasive lung adenocarcinoma morphological subgroups. Transl Lung Cancer Res. 2020 Aug;9(4):1029-1040. doi: 10.21037/tlcr-19-321. PubMed PMID: 32953482; PubMed Central PMCID: PMC7481608.
    • Wang S, Chen A, Yang L, Cai L, Xie Y, Fujimoto J, Gazdar A, Xiao G. Comprehensive analysis of lung cancer pathology images to discover tumor shape and boundary features that predict survival outcome. Sci Rep. 2018 Jul 10;8(1):10393. doi: 10.1038/s41598-018-27707-4. PubMed PMID: 29991684; PubMed Central PMCID: PMC6039531.