Program Official

Principal Investigator

Awardee Organization

Baylor College Of Medicine
United States

Fiscal Year
Activity Code
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date

Identify the DNA Adduct and Associated Metabolic Alterations in Bladder Cancer of Smokers

Smoking is a major risk factor for bladder cancer (BCa). Patients with current or past history of smoking have a three times higher likelihood of developing BCa. Smoking is also known to have a potential dose-dependent effect on the grade and stage of BCa, with high-dose smokers having more aggressive disease. In addition, smokers with BCa have a higher likelihood of failing chemotherapy. Currently, markers that can stratify smokers based on their risk of developing BCa are lacking. Furthermore, predictive markers for aggressive BCa among high-dose smokers are also lacking. The central goal of this application is to characterize the DNA adducts and biochemical alterations observed in smoking-associated BCa and use this information to develop metabolite-based predictive markers and therapeutic strategies for this deadly disease. Cigarette smoke contains a number of xenobiotic compounds that include arylamines, methylated metabolites, Nicotinederived nitrosamine ketone (NNK), Benzo[a]pyrene (BaP), nicotine etc which are usually metabolized by the xenobiotic metabolism and excreted in the urine. Our strong preliminary data demonstrates altered DNA adducts and reprogramming of xenobiotic metabolism in BCa smokers. This effect is exaggerated by components of cigarette smoke including nicotine. Using a novel metabolomics approach, we had earlier shown that BCa was associated with a unique metabolic signature. From the patients perspective it is important to be able to measure these markers non-invasively in body fluids like urine. Intriguingly, metabolites are the end products of overall cellular metabolism. These are small molecules that could be easily monitored in body fluids to interrogate disease phenotype in question. Quiet provocatively, our group is being established to utilize metabolites to further monitor tumors. Thus, our current proposal aims to identify DNA adducts and associated metabolites in BCa smokers and use the information to develop markers for early identification of patients who are at risk for developing aggressive bladder cancer. Further will enable clinicians to take an informed decision about more appropriate therapeutic strategies towards personalized medicine.


  • Piyarathna DWB, Balasubramanian A, Arnold JM, Lloyd SM, Karanam B, Castro P, Ittmann MM, Putluri N, Navone N, Jones JA, Yu W, Sandulache VC, Sikora AG, Michailidis G, Sreekumar A. ERR1 and PGC1α associated mitochondrial alterations correlate with pan-cancer disparity in African Americans. The Journal of clinical investigation. 2019 Mar 28;129(6):2351-2356. PMID: 30920960
  • Vantaku V, Putluri V, Bader DA, Maity S, Ma J, Arnold JM, Rajapakshe K, Donepudi SR, von Rundstedt FC, Devarakonda V, Dubrulle J, Karanam B, McGuire SE, Stossi F, Jain AK, Coarfa C, Cao Q, Sikora AG, Villanueva H, Kavuri SM, Lotan Y, Sreekumar A, Putluri N. Epigenetic loss of AOX1 expression via EZH2 leads to metabolic deregulations and promotes bladder cancer progression. Oncogene. 2020 Oct;39(40):6265-6285. Epub 2019 Aug 5. PMID: 31383940
  • Vantaku V, Dong J, Ambati CR, Perera D, Donepudi SR, Amara CS, Putluri V, Ravi SS, Robertson MJ, Piyarathna DWB, Villanueva M, von Rundstedt FC, Karanam B, Ballester LY, Terris MK, Bollag RJ, Lerner SP, Apolo AB, Villanueva H, Lee M, Sikora AG, Lotan Y, Sreekumar A, Coarfa C, Putluri N. Multi-omics Integration Analysis Robustly Predicts High-Grade Patient Survival and Identifies CPT1B Effect on Fatty Acid Metabolism in Bladder Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research. 2019 Jun 15;25(12):3689-3701. Epub 2019 Mar 7. PMID: 30846479
  • Suter MA, Aagaard KM, Coarfa C, Robertson M, Zhou G, Jackson BP, Thompson D, Putluri V, Putluri N, Hagan J, Wang L, Jiang W, Lingappan K, Moorthy B. Association between elevated placental polycyclic aromatic hydrocarbons (PAHs) and PAH-DNA adducts from Superfund sites in Harris County, and increased risk of preterm birth (PTB). Biochemical and biophysical research communications. 2019 Aug 20;516(2):344-349. Epub 2019 Jun 14. PMID: 31208719
  • Tang W, Putluri V, Ambati CR, Dorsey TH, Putluri N, Ambs S. Liver- and Microbiome-derived Bile Acids Accumulate in Human Breast Tumors and Inhibit Growth and Improve Patient Survival. Clinical cancer research : an official journal of the American Association for Cancer Research. 2019 Oct 1;25(19):5972-5983. Epub 2019 Jul 11. PMID: 31296531
  • Xing Z, Zhang Y, Liang K, Yan L, Xiang Y, Li C, Hu Q, Jin F, Putluri V, Putluri N, Coarfa C, Sreekumar A, Park PK, Nguyen TK, Wang S, Zhou J, Zhou Y, Marks JR, Hawke DH, Hung MC, Yang L, Han L, Ying H, Lin C. Expression of Long Noncoding RNA YIYA Promotes Glycolysis in Breast Cancer. Cancer research. 2018 Aug 15;78(16):4524-4532. Epub 2018 Jul 2. PMID: 29967256
  • Amara CS, Ambati CR, Vantaku V, Badrajee Piyarathna DW, Donepudi SR, Ravi SS, Arnold JM, Putluri V, Chatta G, Guru KA, Badr H, Terris MK, Bollag RJ, Sreekumar A, Apolo AB, Putluri N. Serum Metabolic Profiling Identified a Distinct Metabolic Signature in Bladder Cancer Smokers: A Key Metabolic Enzyme Associated with Patient Survival. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2019 Apr;28(4):770-781. Epub 2019 Jan 14. PMID: 30642841
  • Muthuswamy R, McGray AR, Battaglia S, He W, Miliotto A, Eppolito C, Matsuzaki J, Takemasa T, Koya R, Chodon T, Lichty BD, Shrikant P, Odunsi K. CXCR6 by increasing retention of memory CD8+ T cells in the ovarian tumor microenvironment promotes immunosurveillance and control of ovarian cancer. Journal for immunotherapy of cancer. 2021 Oct;9. (10). PMID: 34607898
  • Thaiparambil J, Dong L, Jasso D, Huang JA, El-Zein RA. Mitotic Spindle Apparatus Abnormalities in Chronic Obstructive Pulmonary Disease Cells: A Potential Pathway to Lung Cancer. Cancer prevention research (Philadelphia, Pa.). 2020 Nov;13(11):923-934. Epub 2020 Jul 12. PMID: 32655004
  • Kami Reddy KR, Piyarathna DWB, Kamal AHM, Putluri V, Ravi SS, Bollag RJ, Terris MK, Lotan Y, Putluri N. Lipidomic Profiling Identifies a Novel Lipid Signature Associated with Ethnicity-Specific Disparity of Bladder Cancer. Metabolites. 2022 Jun 14;12. (6). PMID: 35736477
  • Li Y, Tan Z, Zhang Y, Zhang Z, Hu Q, Liang K, Jun Y, Ye Y, Li YC, Li C, Liao L, Xu J, Xing Z, Pan Y, Chatterjee SS, Nguyen TK, Hsiao H, Egranov SD, Putluri N, Coarfa C, Hawke DH, Gunaratne PH, Tsai KL, Han L, Hung MC, Calin GA, Namour F, Guéant JL, Muntau AC, Blau N, Sutton VR, Schiff M, Feillet F, Zhang S, Lin C, Yang L. A noncoding RNA modulator potentiates phenylalanine metabolism in mice. Science (New York, N.Y.). 2021 Aug 6;373(6555):662-673. PMID: 34353949
  • Tao L, Mohammad MA, Milazzo G, Moreno-Smith M, Patel TD, Zorman B, Badachhape A, Hernandez BE, Wolf AB, Zeng Z, Foster JH, Aloisi S, Sumazin P, Zu Y, Hicks J, Ghaghada KB, Putluri N, Perini G, Coarfa C, Barbieri E. MYCN-driven fatty acid uptake is a metabolic vulnerability in neuroblastoma. Nature communications. 2022 Jun 28;13(1):3728. PMID: 35764645
  • Becker W, Alrafas HR, Busbee PB, Walla MD, Wilson K, Miranda K, Cai G, Putluri V, Putluri N, Nagarkatti M, Nagarkatti PS. Cannabinoid Receptor Activation on Haematopoietic Cells and Enterocytes Protects against Colitis. Journal of Crohn's & colitis. 2021 Jun 22;15(6):1032-1048. PMID: 33331878
  • Tao L, Moreno-Smith M, Ibarra-García-Padilla R, Milazzo G, Drolet NA, Hernandez BE, Oh YS, Patel I, Kim JJ, Zorman B, Patel T, Kamal AHM, Zhao Y, Hicks J, Vasudevan SA, Putluri N, Coarfa C, Sumazin P, Perini G, Parchem RJ, Uribe RA, Barbieri E. CHAF1A Blocks Neuronal Differentiation and Promotes Neuroblastoma Oncogenesis via Metabolic Reprogramming. Advanced science (Weinheim, Baden-Wurttemberg, Germany). 2021 Oct;8(19):e2005047. Epub 2021 Aug 8. PMID: 34365742
  • Odunsi K, Qian F, Lugade AA, Yu H, Geller MA, Fling SP, Kaiser JC, Lacroix AM, D'Amico L, Ramchurren N, Morishima C, Disis ML, Dennis L, Danaher P, Warren S, Nguyen VA, Ravi S, Tsuji T, Rosario S, Zha W, Hutson A, Liu S, Lele S, Zsiros E, McGray AJR, Chiello J, Koya R, Chodon T, Morrison CD, Putluri V, Putluri N, Mager DE, Gunawan R, Cheever MA, Battaglia S, Matsuzaki J. Metabolic adaptation of ovarian tumors in patients treated with an IDO1 inhibitor constrains antitumor immune responses. Science translational medicine. 2022 Mar 16;14(636):eabg8402. Epub 2022 Mar 16. PMID: 35294258
  • Gastelum G, Jiang W, Wang L, Zhou G, Borkar R, Putluri N, Moorthy B. Polycyclic Aromatic Hydrocarbon-induced Pulmonary Carcinogenesis in Cytochrome P450 (CYP)1A1- and 1A2-Null Mice: Roles of CYP1A1 and CYP1A2. Toxicological sciences : an official journal of the Society of Toxicology. 2020 Oct 1;177(2):347-361. PMID: 32726451
  • Arnold JM, Gu F, Ambati CR, Rasaily U, Ramirez-Pena E, Joseph R, Manikkam M, Martin RS, Charles C, Pan Y, Chatterjee SS, Den Hollander P, Zhang W, Nagi C, Sikora AG, Rowley D, Putluri N, Zhang XH, Karanam B, Mani SA, Sreekumar A. Correction: UDP-glucose 6-dehydrogenase regulates hyaluronic acid production and promotes breast cancer progression. Oncogene. 2020 Apr;39(15):3226-3228. PMID: 32214199
  • Karunanithi S, Liu R, Hou Y, Gonzalez G, Oldford N, Roe AJ, Idipilly N, Gupta K, Amara CS, Putluri S, Lee GK, Valentin-Goyco J, Stetson L, Moreton SA, Putluri V, Kavuri SM, Saunthararajah Y, de Lima M, Tochtrop GP, Putluri N, Wald DN. Thioredoxin reductase is a major regulator of metabolism in leukemia cells. Oncogene. 2021 Aug;40(33):5236-5246. Epub 2021 Jul 8. PMID: 34239044
  • Vantaku V, Amara CS, Piyarathna DWB, Donepudi SR, Ambati CR, Putluri V, Tang W, Rajapakshe K, Estecio MR, Terris MK, Castro PD, Ittmann MM, Williams SB, Lerner SP, Sreekumar A, Bollag R, Coarfa C, Kornberg MD, Lotan Y, Ambs S, Putluri N. DNA methylation patterns in bladder tumors of African American patients point to distinct alterations in xenobiotic metabolism. Carcinogenesis. 2019 Nov 25;40(11):1332-1340. PMID: 31284295
  • Vantaku V, Donepudi SR, Piyarathna DWB, Amara CS, Ambati CR, Tang W, Putluri V, Chandrashekar DS, Varambally S, Terris MK, Davies K, Ambs S, Bollag R, Apolo AB, Sreekumar A, Putluri N. Large-scale profiling of serum metabolites in African American and European American patients with bladder cancer reveals metabolic pathways associated with patient survival. Cancer. 2019 Mar 15;125(6):921-932. Epub 2019 Jan 2. PMID: 30602056
  • Fischer GM, Jalali A, Kircher DA, Lee WC, McQuade JL, Haydu LE, Joon AY, Reuben A, de Macedo MP, Carapeto FCL, Yang C, Srivastava A, Ambati CR, Sreekumar A, Hudgens CW, Knighton B, Deng W, Ferguson SD, Tawbi HA, Glitza IC, Gershenwald JE, Vashisht Gopal YN, Hwu P, Huse JT, Wargo JA, Futreal PA, Putluri N, Lazar AJ, DeBerardinis RJ, Marszalek JR, Zhang J, Holmen SL, Tetzlaff MT, Davies MA. Molecular Profiling Reveals Unique Immune and Metabolic Features of Melanoma Brain Metastases. Cancer discovery. 2019 May;9(5):628-645. Epub 2019 Feb 20. PMID: 30787016
  • Moye LM, Liu Y, Coarfa C, Putluri N, Rhoads JM. Plasma Urea Cycle Metabolites May Be Useful Biomarkers in Children With Eosinophilic Esophagitis. Frontiers in pediatrics. 2019 Jan 10;6:423. doi: 10.3389/fped.2018.00423. eCollection 2018. PMID: 30687688
  • Amara CS, Vantaku V, Lotan Y, Putluri N. Recent advances in the metabolomic study of bladder cancer. Expert review of proteomics. 2019 Apr;16(4):315-324. Epub 2019 Feb 26. PMID: 30773067
  • Amobi-McCloud A, Muthuswamy R, Battaglia S, Yu H, Liu T, Wang J, Putluri V, Singh PK, Qian F, Huang RY, Putluri N, Tsuji T, Lugade AA, Liu S, Odunsi K. IDO1 Expression in Ovarian Cancer Induces PD-1 in T Cells via Aryl Hydrocarbon Receptor Activation. Frontiers in immunology. 2021 Apr 16;12:678999. doi: 10.3389/fimmu.2021.678999. eCollection 2021. PMID: 34025677
  • Li Y, Hu Q, Li C, Liang K, Xiang Y, Hsiao H, Nguyen TK, Park PK, Egranov SD, Ambati CR, Putluri N, Hawke DH, Han L, Hung MC, Danesh FR, Yang L, Lin C. PTEN-induced partial epithelial-mesenchymal transition drives diabetic kidney disease. The Journal of clinical investigation. 2019 Mar 1;129(3):1129-1151. Epub 2019 Feb 11. PMID: 30741721
  • Kornberg MD, Bhargava P, Kim PM, Putluri V, Snowman AM, Putluri N, Calabresi PA, Snyder SH. Dimethyl fumarate targets GAPDH and aerobic glycolysis to modulate immunity. Science (New York, N.Y.). 2018 Apr 27;360(6387):449-453. Epub 2018 Mar 29. PMID: 29599194
  • Hu Q, Ye Y, Chan LC, Li Y, Liang K, Lin A, Egranov SD, Zhang Y, Xia W, Gong J, Pan Y, Chatterjee SS, Yao J, Evans KW, Nguyen TK, Park PK, Liu J, Coarfa C, Donepudi SR, Putluri V, Putluri N, Sreekumar A, Ambati CR, Hawke DH, Marks JR, Gunaratne PH, Caudle AS, Sahin AA, Hortobagyi GN, Meric-Bernstam F, Chen L, Yu D, Hung MC, Curran MA, Han L, Lin C, Yang L. Oncogenic lncRNA downregulates cancer cell antigen presentation and intrinsic tumor suppression. Nature immunology. 2019 Jul;20(7):835-851. Epub 2019 Jun 3. PMID: 31160797
  • Meng H, Gonzales NM, Jung SY, Lu Y, Putluri N, Zhu B, Dacso CC, Lonard DM, O'Malley BW. Defining the mammalian coactivation of hepatic 12-h clock and lipid metabolism. Cell reports. 2022 Mar 8;38(10):110491. PMID: 35263593
  • Moreno-Smith M, Milazzo G, Tao L, Fekry B, Zhu B, Mohammad MA, Di Giacomo S, Borkar R, Reddy KRK, Capasso M, Vasudevan SA, Sumazin P, Hicks J, Putluri N, Perini G, Eckel-Mahan K, Burris TP, Barbieri E. Restoration of the molecular clock is tumor suppressive in neuroblastoma. Nature communications. 2021 Jun 28;12(1):4006. PMID: 34183658
  • Ambati CR, Vantaku V, Donepudi SR, Amara CS, Ravi SS, Mandalapu A, Perla M, Putluri V, Sreekumar A, Putluri N. Measurement of methylated metabolites using Liquid Chromatography-Mass Spectrometry and its biological application. Analytical methods : advancing methods and applications. 2019 Jan 7;11(1):49-57. Epub 2018 Nov 15. PMID: 31762797
  • El Saie A, Fu C, Grimm SL, Robertson MJ, Hoffman K, Putluri V, Ambati CSR, Putluri N, Shivanna B, Coarfa C, Pammi M. Metabolome and microbiome multi-omics integration from a murine lung inflammation model of bronchopulmonary dysplasia. Pediatric research. 2022 Dec;92(6):1580-1589. Epub 2022 Mar 25. PMID: 35338351
  • Jaggupilli A, Ly S, Nguyen K, Anand V, Yuan B, El-Dana F, Yan Y, Arvanitis Z, Piyarathna DWB, Putluri N, Piwnica-Worms H, Manning HC, Andreeff M, Battula VL. Metabolic stress induces GD2+ cancer stem cell-like phenotype in triple-negative breast cancer. British journal of cancer. 2022 Mar;126(4):615-627. Epub 2021 Nov 22. PMID: 34811508
  • Alam H, Tang M, Maitituoheti M, Dhar SS, Kumar M, Han CY, Ambati CR, Amin SB, Gu B, Chen TY, Lin YH, Chen J, Muller FL, Putluri N, Flores ER, DeMayo FJ, Baseler L, Rai K, Lee MG. KMT2D Deficiency Impairs Super-Enhancers to Confer a Glycolytic Vulnerability in Lung Cancer. Cancer cell. 2020 Apr 13;37(4):599-617.e7. Epub 2020 Apr 2. PMID: 32243837
  • Lovisa S, Fletcher-Sananikone E, Sugimoto H, Hensel J, Lahiri S, Hertig A, Taduri G, Lawson E, Dewar R, Revuelta I, Kato N, Wu CJ, Bassett RL Jr, Putluri N, Zeisberg M, Zeisberg EM, LeBleu VS, Kalluri R. Endothelial-to-mesenchymal transition compromises vascular integrity to induce Myc-mediated metabolic reprogramming in kidney fibrosis. Science signaling. 2020 Jun 9;13. (635). PMID: 32518142
  • Thaiparambil J, Amara CS, Sen S, Putluri N, El-Zein R. Cigarette smoke condensate induces centrosome clustering in normal lung epithelial cells. Cancer medicine. 2023 Apr;12(7):8499-8509. Epub 2023 Jan 9. PMID: 36621828
  • Fujita Y, Nunez-Rubiano L, Dono A, Bellman A, Shah M, Rodriguez JC, Putluri V, Kamal AHM, Putluri N, Riascos RF, Zhu JJ, Esquenazi Y, Ballester LY. IDH1 p.R132H ctDNA and D-2-hydroxyglutarate as CSF biomarkers in patients with IDH-mutant gliomas. Journal of neuro-oncology. 2022 Sep;159(2):261-270. Epub 2022 Jul 11. PMID: 35816267