Principal Investigator

Lopa Mishra

Awardee Organization

Feinstein Institute For Medical Research
United States

Fiscal Year

2022

Activity Code

U01

Early Stage Investigator Grants (ESI)

Not Applicable

Project End Date

8/31/2024

NIH RePORTER

For more information, see NIH RePORTER Project 7U01CA230690-06

Pathway Specific Functional Biomarkers for the Early Detection of Liver Cancer

Here, we propose to validate tissue and blood-based combinatorial biomarker panels, derived from functional pathway-specific studies, to improve the early detection of liver cancer [hepatocellular carcinoma (HCC)] and stratify populations according to their risk for developing HCC. In its early stages, HCC is curable; once advanced, HCC is associated with high mortality. Most early HCCs are undetected, demonstrating the challenge in predicting and diagnosing early HCC. Through preclinical studies that integrate analysis of human genomic data from The Cancer Genome Atlas (TCGA), mouse models, and human tissue/cell line studies, we determined that specific high-risk populations may be identified through alterations in the following biomarkers: EpCAM, Osteopontin (OPN), the polo-like kinase 1 (PLK1) the TGF-β and DNA repair members. We have established a multi-center consortium of 4 Translational Research Centers (TRCs): Johns Hopkins University (TRC1), George Washington University (TRC2), University of Texas MD Anderson Cancer Center (TRC3), University of Hawaii (TRC4). These 4 TRCs will work in collaboration with NCI to implement a multi-institutional framework to collect the highest quality biospecimens from patients with various well-defined liver pathologies and conduct specific biomarker validation studies for early detection of HCC and risk stratification of patients with cirrhosis. The central hypothesis, based upon our functional preclinical models and pilot studies in human liver disease samples, is that alterations in the above markers lead to HCC, and that aberrant expression of these can lead to early detection of HCC, as well as risk stratification. Specifically, the following biomarker panels will be assessed (a) Tissue EpCAM, OPN, PLK1 levels (Panel 1, Project 1, TRC1), (b) Tissue levels of TBR2, SPTBN1, FancD2 and Sirt6 (Panel 2, Project 2 TRC2). (c) Serum markers (Panel 3, EpCAM, OPN, TGF-β) will be tested in TRC1 and 2; (d) In circulating tumor cells (CTCs), mutational analyses (Panel 4, Smad4 and SPTBN1, Project 2, TRC2) and surface vimentin (CSV) (Panel 5, Project 3, TRC3) will be performed. Validation of candidate biomarkers (Project 4, TRC4) will also be done at TRC4, and also with collaborations in NCI, China and external cohorts, that include EDRN samples. The 4 projects will collectively address: Aim 1: EDRN Phase 2 studies (to find markers of current HCCs) in tissue only using panels 1 and 2. All samples are retrospective, collected in patients (cases) and controls. Aim 2: EDRN Phase 2 studies in blood only on panels 3, 4 and 5. Here, all samples are retrospective, collected in current cases and current controls. Aim 3: EDRN Phase 3 studies (Panel 3 markers that predict future development of HCC) in blood using longitudinal data (both retrospective and prospective). Data are collected before participants develop HCC, and they are followed over time to see who develops HCC, and multiple time points of marker data are collected and stored over time prior to tumor onset. In addition, we will maintain and share a biorepository, and collaborate with other Centers in the Translational Research Network for Liver Cancer.

Publications

Bhowmick K, Yang X, Mohammad T, Xiang X, Molmenti CL, Mishra B, Dasarathy S, Krainer AR, Hassan MI, Crandall KA, Mishra L. Microbial metabolite ammonia disrupts TGF-β signaling to promote colon cancer. The Journal of biological chemistry. 2025 Jun;301(6):108559. Epub 2025 Apr 29. PMID: 40311681
Ohshiro K, Chen J, Srivastav J, Mishra L, Mishra B. Alterations in TGF-β signaling leads to high HMGA2 levels potentially through modulation of PJA1/SMAD3 in HCC cells. Genes & cancer. 2020;11(1-2):43-52. PMID: 32577156
Xiang X, Ohshiro K, Zaidi S, Yang X, Bhowmick K, Vegesna AK, Bernstein D, Crawford JM, Mishra B, Latham PS, Gough NR, Rao S, Mishra L. Impaired reciprocal regulation between SIRT6 and TGF-β signaling in fatty liver. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2022 Jun;36(6):e22335. PMID: 35506565
Mitra A, Yan J, Zhang L, Li S. A small molecule Hedgehog agonist HhAg1.5 mediated reprogramming breaks the quiescence of noninjured liver stem cells for rescuing liver failure. Translational research : the journal of laboratory and clinical medicine. 2019 Mar;205:44-50. Epub 2018 Oct 19. PMID: 30399369
Wang H, Tsung A, Mishra L, Huang H. Regulatory T cell: a double-edged sword from metabolic-dysfunction-associated steatohepatitis to hepatocellular carcinoma. EBioMedicine. 2024 Mar;101:105031. Epub 2024 Feb 23. PMID: 38401419
Zaidi S, Amdur R, Xiang X, Yu H, Wong LL, Rao S, He AR, Amin K, Zaheer D, Narayan RK, Satapathy SK, Latham PS, Shetty K, Guha C, Gough NR, Mishra L. Using quantitative immunohistochemistry in patients at high risk for hepatocellular cancer. Genes & cancer. 2022 Jun 6;13:9-20. doi: 10.18632/genesandcancer.220. eCollection 2022. PMID: 35677836
Xiang X, Shetty K, Yu H, Mishra B, Wong LL, Zhou XJ, Satapathy SK, Crawford JM, Latham PS, Han SH, Mathew B, Dagher NN, Lau L, Cacaj F, Vegesna AK, Dasarathy S, He AR, Huang H, Amdur RL, Mishra L. Serum Proteomic Profile Based on the TGF-β Pathway Stratifies Risk of Hepatocellular Carcinoma. Liver international : official journal of the International Association for the Study of the Liver. 2025 Oct;45(10):e70325. PMID: 40919824
Wong LL. Surveillance of hepatocellular cancer-why can't we do better? Hepatobiliary surgery and nutrition. 2019 Dec;8(6):662-663. PMID: 31930002
Korkut A, Zaidi S, Kanchi RS, Rao S, Gough NR, Schultz A, Li X, Lorenzi PL, Berger AC, Robertson G, Kwong LN, Datto M, Roszik J, Ling S, Ravikumar V, Manyam G, Rao A, Shelley S, Liu Y, Ju Z, Hansel D, de Velasco G, Pennathur A, Andersen JB, O'Rourke CJ, Ohshiro K, Jogunoori W, Nguyen BN, Li S, Osmanbeyoglu HU, Ajani JA, Mani SA, Houseman A, Wiznerowicz M, Chen J, Gu S, Ma W, Zhang J, Tong P, Cherniack AD, Deng C, Resar L, Cancer Genome Atlas Research Network, Weinstein JN, Mishra L, Akbani R, Caesar-Johnson SJ, Demchok JA, Felau I, Kasapi M, Ferguson ML, Hutter CM, Sofia HJ, Tarnuzzer R, Wang Z, Yang L, Zenklusen JC, Zhang JJ, Chudamani S, Liu J, Lolla L, Naresh R, Pihl T, Sun Q, Wan Y, Wu Y, Cho J, DeFreitas T, Frazer S, Gehlenborg N, Getz G, Heiman DI, Kim J, Lawrence MS, Lin P, Meier S, Noble MS, Saksena G, Voet D, Zhang H, Bernard B, Chambwe N, Dhankani V, Knijnenburg T, Kramer R, Leinonen K, Liu Y, Miller M, Reynolds S, Shmulevich I, Thorsson V, Zhang W, Akbani R, Broom BM, Hegde AM, Ju Z, Kanchi RS, Korkut A, Li J, Liang H, Ling S, Liu W, Lu Y, Mills GB, Ng KS, Rao A, Ryan M, Wang J, Weinstein JN, Zhang J, Abeshouse A, Armenia J, Chakravarty D, Chatila WK, de Bruijn I, Gao J, Gross BE, Heins ZJ, Kundra R, La K, Ladanyi M, Luna A, Nissan MG, Ochoa A, Phillips SM, Reznik E, Sanchez-Vega F, Sander C, Schultz N, Sheridan R, Sumer SO, Sun Y, Taylor BS, Wang J, Zhang H, Anur P, Peto M, Spellman P, Benz C, Stuart JM, Wong CK, Yau C, Hayes DN, Parker JS, Wilkerson MD, Ally A, Balasundaram M, Bowlby R, Brooks D, Carlsen R, Chuah E, Dhalla N, Holt R, Jones SJM, Kasaian K, Lee D, Ma Y, Marra MA, Mayo M, Moore RA, Mungall AJ, Mungall K, Robertson AG, Sadeghi S, Schein JE, Sipahimalani P, Tam A, Thiessen N, Tse K, Wong T, Berger AC, Beroukhim R, Cherniack AD, Cibulskis C, Gabriel SB, Gao GF, Ha G, Meyerson M, Schumacher SE, Shih J, Kucherlapati MH, Kucherlapati RS, Baylin S, Cope L, Danilova L, Bootwalla MS, Lai PH, Maglinte DT, Van Den Berg DJ, Weisenberger DJ, Auman JT, Balu S, Bodenheimer T, Fan C, Hoadley KA, Hoyle AP, Jefferys SR, Jones CD, Meng S, Mieczkowski PA, Mose LE, Perou AH, Perou CM, Roach J, Shi Y, Simons JV, Skelly T, Soloway MG, Tan D, Veluvolu U, Fan H, Hinoue T, Laird PW, Shen H, Zhou W, Bellair M, Chang K, Covington K, Creighton CJ, Dinh H, Doddapaneni H, Donehower LA, Drummond J, Gibbs RA, Glenn R, Hale W, Han Y, Hu J, Korchina V, Lee S, Lewis L, Li W, Liu X, Morgan M, Morton D, Muzny D, Santibanez J, Sheth M, Shinbrot E, Wang L, Wang M, Wheeler DA, Xi L, Zhao F, Hess J, Appelbaum EL, Bailey M, Cordes MG, Ding L, Fronick CC, Fulton LA, Fulton RS, Kandoth C, Mardis ER, McLellan MD, Miller CA, Schmidt HK, Wilson RK, Crain D, Curley E, Gardner J, Lau K, Mallery D, Morris S, Paulauskis J, Penny R, Shelton C, Shelton T, Sherman M, Thompson E, Yena P, Bowen J, Gastier-Foster JM, Gerken M, Leraas KM, Lichtenberg TM, Ramirez NC, Wise L, Zmuda E, Corcoran N, Costello T, Hovens C, Carvalho AL, de Carvalho AC, Fregnani JH, Longatto-Filho A, Reis RM, Scapulatempo-Neto C, Silveira HCS, Vidal DO, Burnette A, Eschbacher J, Hermes B, Noss A, Singh R, Anderson ML, Castro PD, Ittmann M, Huntsman D, Kohl B, Le X, Thorp R, Andry C, Duffy ER, Lyadov V, Paklina O, Setdikova G, Shabunin A, Tavobilov M, McPherson C, Warnick R, Berkowitz R, Cramer D, Feltmate C, Horowitz N, Kibel A, Muto M, Raut CP, Malykh A, Barnholtz-Sloan JS, Barrett W, Devine K, Fulop J, Ostrom QT, Shimmel K, Wolinsky Y, Sloan AE, De Rose A, Giuliante F, Goodman M, Karlan BY, Hagedorn CH, Eckman J, Harr J, Myers J, Tucker K, Zach LA, Deyarmin B, Hu H, Kvecher L, Larson C, Mural RJ, Somiari S, Vicha A, Zelinka T, Bennett J, Iacocca M, Rabeno B, Swanson P, Latour M, Lacombe L, Têtu B, Bergeron A, McGraw M, Staugaitis SM, Chabot J, Hibshoosh H, Sepulveda A, Su T, Wang T, Potapova O, Voronina O, Desjardins L, Mariani O, Roman-Roman S, Sastre X, Stern MH, Cheng F, Signoretti S, Berchuck A, Bigner D, Lipp E, Marks J, McCall S, McLendon R, Secord A, Sharp A, Behera M, Brat DJ, Chen A, Delman K, Force S, Khuri F, Magliocca K, Maithel S, Olson JJ, Owonikoko T, Pickens A, Ramalingam S, Shin DM, Sica G, Van Meir EG, Zhang H, Eijckenboom W, Gillis A, Korpershoek E, Looijenga L, Oosterhuis W, Stoop H, van Kessel KE, Zwarthoff EC, Calatozzolo C, Cuppini L, Cuzzubbo S, DiMeco F, Finocchiaro G, Mattei L, Perin A, Pollo B, Chen C, Houck J, Lohavanichbutr P, Hartmann A, Stoehr C, Stoehr R, Taubert H, Wach S, Wullich B, Kycler W, Murawa D, Wiznerowicz M, Chung K, Edenfield WJ, Martin J, Baudin E, Bubley G, Bueno R, De Rienzo A, Richards WG, Kalkanis S, Mikkelsen T, Noushmehr H, Scarpace L, Girard N, Aymerich M, Campo E, Giné E, Guillermo AL, Van Bang N, Hanh PT, Phu BD, Tang Y, Colman H, Evason K, Dottino PR, Martignetti JA, Gabra H, Juhl H, Akeredolu T, Stepa S, Hoon D, Ahn K, Kang KJ, Beuschlein F, Breggia A, Birrer M, Bell D, Borad M, Bryce AH, Castle E, Chandan V, Cheville J, Copland JA, Farnell M, Flotte T, Giama N, Ho T, Kendrick M, Kocher JP, Kopp K, Moser C, Nagorney D, O'Brien D, O'Neill BP, Patel T, Petersen G, Que F, Rivera M, Roberts L, Smallridge R, Smyrk T, Stanton M, Thompson RH, Torbenson M, Yang JD, Zhang L, Brimo F, Ajani JA, Angulo Gonzalez AM, Behrens C, Bondaruk J, Broaddus R, Czerniak B, Esmaeli B, Fujimoto J, Gershenwald J, Guo C, Lazar AJ, Logothetis C, Meric-Bernstam F, Moran C, Ramondetta L, Rice D, Sood A, Tamboli P, Thompson T, Troncoso P, Tsao A, Wistuba I, Carter C, Haydu L, Hersey P, Jakrot V, Kakavand H, Kefford R, Lee K, Long G, Mann G, Quinn M, Saw R, Scolyer R, Shannon K, Spillane A, Stretch J, Synott M, Thompson J, Wilmott J, Al-Ahmadie H, Chan TA, Ghossein R, Gopalan A, Levine DA, Reuter V, Singer S, Singh B, Tien NV, Broudy T, Mirsaidi C, Nair P, Drwiega P, Miller J, Smith J, Zaren H, Park JW, Hung NP, Kebebew E, Linehan WM, Metwalli AR, Pacak K, Pinto PA, Schiffman M, Schmidt LS, Vocke CD, Wentzensen N, Worrell R, Yang H, Moncrieff M, Goparaju C, Melamed J, Pass H, Botnariuc N, Caraman I, Cernat M, Chemencedji I, Clipca A, Doruc S, Gorincioi G, Mura S, Pirtac M, Stancul I, Tcaciuc D, Albert M, Alexopoulou I, Arnaout A, Bartlett J, Engel J, Gilbert S, Parfitt J, Sekhon H, Thomas G, Rassl DM, Rintoul RC, Bifulco C, Tamakawa R, Urba W, Hayward N, Timmers H, Antenucci A, Facciolo F, Grazi G, Marino M, Merola R, de Krijger R, Gimenez-Roqueplo AP, Piché A, Chevalier S, McKercher G, Birsoy K, Barnett G, Brewer C, Farver C, Naska T, Pennell NA, Raymond D, Schilero C, Smolenski K, Williams F, Morrison C, Borgia JA, Liptay MJ, Pool M, Seder CW, Junker K, Omberg L, Dinkin M, Manikhas G, Alvaro D, Bragazzi MC, Cardinale V, Carpino G, Gaudio E, Chesla D, Cottingham S, Dubina M, Moiseenko F, Dhanasekaran R, Becker KF, Janssen KP, Slotta-Huspenina J, Abdel-Rahman MH, Aziz D, Bell S, Cebulla CM, Davis A, Duell R, Elder JB, Hilty J, Kumar B, Lang J, Lehman NL, Mandt R, Nguyen P, Pilarski R, Rai K, Schoenfield L, Senecal K, Wakely P, Hansen P, Lechan R, Powers J, Tischler A, Grizzle WE, Sexton KC, Kastl A, Henderson J, Porten S, Waldmann J, Fassnacht M, Asa SL, Schadendorf D, Couce M, Graefen M, Huland H, Sauter G, Schlomm T, Simon R, Tennstedt P, Olabode O, Nelson M, Bathe O, Carroll PR, Chan JM, Disaia P, Glenn P, Kelley RK, Landen CN, Phillips J, Prados M, Simko J, Smith-McCune K, VandenBerg S, Roggin K, Fehrenbach A, Kendler A, Sifri S, Steele R, Jimeno A, Carey F, Forgie I, Mannelli M, Carney M, Hernandez B, Campos B, Herold-Mende C, Jungk C, Unterberg A, von Deimling A, Bossler A, Galbraith J, Jacobus L, Knudson M, Knutson T, Ma D, Milhem M, Sigmund R, Godwin AK, Madan R, Rosenthal HG, Adebamowo C, Adebamowo SN, Boussioutas A, Beer D, Giordano T, Mes-Masson AM, Saad F, Bocklage T, Landrum L, Mannel R, Moore K, Moxley K, Postier R, Walker J, Zuna R, Feldman M, Valdivieso F, Dhir R, Luketich J, Mora Pinero EM, Quintero-Aguilo M, Carlotti CG Jr, Dos Santos JS, Kemp R, Sankarankuty A, Tirapelli D, Catto J, Agnew K, Swisher E, Creaney J, Robinson B, Shelley CS, Godwin EM, Kendall S, Shipman C, Bradford C, Carey T, Haddad A, Moyer J, Peterson L, Prince M, Rozek L, Wolf G, Bowman R, Fong KM, Yang I, Korst R, Rathmell WK, Fantacone-Campbell JL, Hooke JA, Kovatich AJ, Shriver CD, DiPersio J, Drake B, Govindan R, Heath S, Ley T, Van Tine B, Westervelt P, Rubin MA, Lee JI, Aredes ND, Mariamidze A. A Pan-Cancer Analysis Reveals High-Frequency Genetic Alterations in Mediators of Signaling by the TGF-β Superfamily. Cell systems. 2018 Oct 24;7(4):422-437.e7. Epub 2018 Sep 26. PMID: 30268436
Wang Z, Hopson LM, Singleton SS, Yang X, Jogunoori W, Mazumder R, Obias V, Lin P, Nguyen BN, Yao M, Miller L, White J, Rao S, Mishra L. Mice with dysfunctional TGF-β signaling develop altered intestinal microbiome and colorectal cancer resistant to 5FU. Biochimica et biophysica acta. Molecular basis of disease. 2021 Oct 1;1867(10):166179. Epub 2021 May 31. PMID: 34082069
Saberi B, Garonzik-Wang J, Ma M, Ajayi T, Kim A, Luu H, Jakhete N, Pustavoitau A, Anders RA, Georgiades C, Kamel I, Ottmann S, Philosophe B, Cameron AM, Gurakar A. Accuracy of Milan, University of California San Francisco, and Up-To-7 Criteria in Predicting Tumor Recurrence Following Deceased-Donor Liver Transplant in Patients With Hepatocellular Carcinoma. Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation. 2020 Aug;18(4):463-469. Epub 2018 Aug 6. PMID: 30084757
Sempokuya T, Wong LL. Ten-year survival and recurrence of hepatocellular cancer. Hepatoma research. 2019;5. Epub 2019 Oct 13. PMID: 31701016
Batth IS, Mitra A, Rood S, Kopetz S, Menter D, Li S. CTC analysis: an update on technological progress. Translational research : the journal of laboratory and clinical medicine. 2019 Oct;212:14-25. Epub 2019 Jul 11. PMID: 31348892
King CH, Desai H, Sylvetsky AC, LoTempio J, Ayanyan S, Carrie J, Crandall KA, Fochtman BC, Gasparyan L, Gulzar N, Howell P, Issa N, Krampis K, Mishra L, Morizono H, Pisegna JR, Rao S, Ren Y, Simonyan V, Smith K, VedBrat S, Yao MD, Mazumder R. Baseline human gut microbiota profile in healthy people and standard reporting template. PloS one. 2019 Sep 11;14(9):e0206484. doi: 10.1371/journal.pone.0206484. eCollection 2019. PMID: 31509535
Rao S, Mishra L. Targeting Transforming Growth Factor Beta Signaling in Liver Cancer. Hepatology (Baltimore, Md.). 2019 Apr;69(4):1375-1378. Epub 2019 Mar 5. PMID: 30549280
Lominadze Z, Shaik MR, Choi D, Zaffar D, Mishra L, Shetty K. Hepatocellular Carcinoma Genetic Classification. Cancer journal (Sudbury, Mass.). 2023 Sep-Oct 1;29(5):249-258. PMID: 37796642
Shen Y, Risch H, Lu L, Ma X, Irwin ML, Lim JK, Taddei T, Pawlish K, Stroup A, Brown R, Wang Z, Jia W, Wong L, Mayne ST, Yu H. Risk factors for hepatocellular carcinoma (HCC) in the northeast of the United States: results of a case-control study. Cancer causes & control : CCC. 2020 Apr;31(4):321-332. Epub 2020 Feb 14. PMID: 32060838
Sempokuya T, Wong LL. Do we really need a standardized approach to spontaneously ruptured hepatocellular carcinoma? Hepatobiliary surgery and nutrition. 2024 Feb 1;13(1):191-193. Epub 2024 Jan 12. PMID: 38322214
Gough NR, Xiang X, Mishra L. TGF-β Signaling in Liver, Pancreas, and Gastrointestinal Diseases and Cancer. Gastroenterology. 2021 Aug;161(2):434-452.e15. Epub 2021 Apr 30. PMID: 33940008
Wu EM, Hernandez BY, Wong LL. Hepatocellular carcinoma in Micronesians, a growing Pacific Islander population in the U.S. Open journal of gastroenterology. 2018;8. (6). Epub 2018 Jun 29. PMID: 30079276
John S, Bhowmick K, Park A, Huang H, Yang X, Mishra L. Recent advances in targeting obesity, with a focus on TGF-β signaling and vagus nerve innervation. Bioelectronic medicine. 2025 Apr 30;11(1):10. PMID: 40301996
Lominadze Z, Hill K, Shaik MR, Canakis JP, Bourmaf M, Adams-Mardi C, Abutaleb A, Mishra L, Shetty K. Immunotherapy for Hepatocellular Carcinoma in the Setting of Liver Transplantation: A Review. International journal of molecular sciences. 2023 Jan 25;24. (3). PMID: 36768686
Xiang X, Bhowmick K, Shetty K, Ohshiro K, Yang X, Wong LL, Yu H, Latham PS, Satapathy SK, Brennan C, Dima RJ, Chambwe N, Sharifova G, Cacaj F, John S, Crawford JM, Huang H, Dasarathy S, Krainer AR, He AR, Amdur RL, Mishra L. Mechanistically based blood proteomic markers in the TGF-β pathway stratify risk of hepatocellular cancer in patients with cirrhosis. Genes & cancer. 2024 Feb 1;15:1-14. doi: 10.18632/genesandcancer.234. eCollection 2024. PMID: 38323119
Yokoo T, Masaki N, Parikh ND, Lane BF, Feng Z, Mendiratta-Lala M, Lee CH, Khatri G, Marsh TL, Shetty K, Dunn CT, Al-Jarrah T, Aslam A, Davenport MS, Gopal P, Rich NE, Lok AS, Singal AG. Multicenter Validation of Abbreviated MRI for Detecting Early-Stage Hepatocellular Carcinoma. Radiology. 2023 Apr;307(2):e220917. Epub 2023 Jan 24. PMID: 36692401
Serper M, Parikh ND, Thiele G, Ovchinsky N, Mehta S, Kuo A, Ho C, Kanwal F, Volk M, Asrani SK, Ghabril MS, Lake JR, Merriman RB, Morgan TR, Tapper EB. Patient-reported outcomes in HCC: A scoping review by the Practice Metrics Committee of the American Association for the Study of Liver Diseases. Hepatology (Baltimore, Md.). 2022 Jul;76(1):251-274. Epub 2022 Jan 22. PMID: 34990516
Yee SK, Hernandez BY, Kwee S, Wong LL. Hepatocellular carcinoma in Pacific Islanders: comparison of Pacific Island-born vs. US-born. Hepatoma research. 2023;9. Epub 2023 Mar 17. PMID: 37035453
Benhammou JN, Rich NE, Cholankeril G, Zhang P, Zeng W, Rao S, Tayob N, National Cancer Institute’s Translational Liver Consortium Early-Career Working Group, Li W, Wu X, Feng S, Fujiwara N, Meng X, Zhu S, Zaidi S. DETECT: Development of Technologies for Early HCC Detection. Gastroenterology. 2022 Jul;163(1):21-27. Epub 2022 Mar 23. PMID: 35339460
Da BL, Suchman KI, Lau L, Rabiee A, He AR, Shetty K, Yu H, Wong LL, Amdur RL, Crawford JM, Fox SS, Grimaldi GM, Shah PK, Weinstein J, Bernstein D, Satapathy SK, Chambwe N, Xiang X, Mishra L. Pathogenesis to management of hepatocellular carcinoma. Genes & cancer. 2022 Dec 13;13:72-87. doi: 10.18632/genesandcancer.226. eCollection 2022. PMID: 36533190
Mishra L. STRAP: A Bridge Between Mutant APC and Wnt/ß-Catenin Signaling in Intestinal Cancer. Gastroenterology. 2022 Jan;162(1):44-46. Epub 2021 Oct 19. PMID: 34678214
Singal AG, Parikh ND, Shetty K, Han SH, Xie C, Ning J, Rinaudo JA, Arvind A, Lok AS, Kanwal F, Translational Liver Cancer Investigators. Natural History of Indeterminate Liver Nodules in Patients With Advanced Liver Disease: A Multicenter Retrospective Cohort Study. The American journal of gastroenterology. 2024 Nov 1;119(11):2251-2258. Epub 2024 Apr 30. PMID: 38686922
Yang X, Bhowmick K, Rao S, Xiang X, Ohshiro K, Amdur RL, Hassan MI, Mohammad T, Crandall K, Cifani P, Shetty K, Lyons SK, Merrill JR, Vegesna AK, John S, Latham PS, Crawford JM, Mishra B, Dasarathy S, Wang XW, Yu H, Wang Z, Huang H, Krainer AR, Mishra L. Aldehydes alter TGF-β signaling and induce obesity and cancer. Cell reports. 2024 Sep 24;43(9):114676. Epub 2024 Aug 31. PMID: 39217614
Simsek C, Kim A, Ma M, Danis N, Gurakar M, Cameron AM, Philosophe B, Garonzik-Wang J, Ottmann S, Gurakar A, Saberi B. Recurrence of hepatocellular carcinoma following deceased donor liver transplantation: case series. Hepatoma research. 2020;6. Epub 2020 Mar 20. PMID: 32582866
Rao S, Yang X, Ohshiro K, Zaidi S, Wang Z, Shetty K, Xiang X, Hassan MI, Mohammad T, Latham PS, Nguyen BN, Wong L, Yu H, Al-Abed Y, Mishra B, Vacca M, Guenigault G, Allison MED, Vidal-Puig A, Benhammou JN, Alvarez M, Pajukanta P, Pisegna JR, Mishra L. β2-spectrin (SPTBN1) as a therapeutic target for diet-induced liver disease and preventing cancer development. Science translational medicine. 2021 Dec 15;13(624):eabk2267. Epub 2021 Dec 15. PMID: 34910547
Yoneoka G, Bozhilov K, Wong LL. Prognostic ability of inflammation-based markers in radioembolization for hepatocellular carcinoma. Hepatoma research. 2020;6. Epub 2020 Oct 12. PMID: 33134551
Malta TM, Sokolov A, Gentles AJ, Burzykowski T, Poisson L, Weinstein JN, Kamińska B, Huelsken J, Omberg L, Gevaert O, Colaprico A, Czerwińska P, Mazurek S, Mishra L, Heyn H, Krasnitz A, Godwin AK, Lazar AJ, Cancer Genome Atlas Research Network, Stuart JM, Hoadley KA, Laird PW, Noushmehr H, Wiznerowicz M, Caesar-Johnson SJ, Demchok JA, Felau I, Kasapi M, Ferguson ML, Hutter CM, Sofia HJ, Tarnuzzer R, Wang Z, Yang L, Zenklusen JC, Zhang JJ, Chudamani S, Liu J, Lolla L, Naresh R, Pihl T, Sun Q, Wan Y, Wu Y, Cho J, DeFreitas T, Frazer S, Gehlenborg N, Getz G, Heiman DI, Kim J, Lawrence MS, Lin P, Meier S, Noble MS, Saksena G, Voet D, Zhang H, Bernard B, Chambwe N, Dhankani V, Knijnenburg T, Kramer R, Leinonen K, Liu Y, Miller M, Reynolds S, Shmulevich I, Thorsson V, Zhang W, Akbani R, Broom BM, Hegde AM, Ju Z, Kanchi RS, Korkut A, Li J, Liang H, Ling S, Liu W, Lu Y, Mills GB, Ng KS, Rao A, Ryan M, Wang J, Weinstein JN, Zhang J, Abeshouse A, Armenia J, Chakravarty D, Chatila WK, de Bruijn I, Gao J, Gross BE, Heins ZJ, Kundra R, La K, Ladanyi M, Luna A, Nissan MG, Ochoa A, Phillips SM, Reznik E, Sanchez-Vega F, Sander C, Schultz N, Sheridan R, Sumer SO, Sun Y, Taylor BS, Wang J, Zhang H, Anur P, Peto M, Spellman P, Benz C, Stuart JM, Wong CK, Yau C, Hayes DN, Parker JS, Wilkerson MD, Ally A, Balasundaram M, Bowlby R, Brooks D, Carlsen R, Chuah E, Dhalla N, Holt R, Jones SJM, Kasaian K, Lee D, Ma Y, Marra MA, Mayo M, Moore RA, Mungall AJ, Mungall K, Robertson AG, Sadeghi S, Schein JE, Sipahimalani P, Tam A, Thiessen N, Tse K, Wong T, Berger AC, Beroukhim R, Cherniack AD, Cibulskis C, Gabriel SB, Gao GF, Ha G, Meyerson M, Schumacher SE, Shih J, Kucherlapati MH, Kucherlapati RS, Baylin S, Cope L, Danilova L, Bootwalla MS, Lai PH, Maglinte DT, Van Den Berg DJ, Weisenberger DJ, Auman JT, Balu S, Bodenheimer T, Fan C, Hoadley KA, Hoyle AP, Jefferys SR, Jones CD, Meng S, Mieczkowski PA, Mose LE, Perou AH, Perou CM, Roach J, Shi Y, Simons JV, Skelly T, Soloway MG, Tan D, Veluvolu U, Fan H, Hinoue T, Laird PW, Shen H, Zhou W, Bellair M, Chang K, Covington K, Creighton CJ, Dinh H, Doddapaneni H, Donehower LA, Drummond J, Gibbs RA, Glenn R, Hale W, Han Y, Hu J, Korchina V, Lee S, Lewis L, Li W, Liu X, Morgan M, Morton D, Muzny D, Santibanez J, Sheth M, Shinbrot E, Wang L, Wang M, Wheeler DA, Xi L, Zhao F, Hess J, Appelbaum EL, Bailey M, Cordes MG, Ding L, Fronick CC, Fulton LA, Fulton RS, Kandoth C, Mardis ER, McLellan MD, Miller CA, Schmidt HK, Wilson RK, Crain D, Curley E, Gardner J, Lau K, Mallery D, Morris S, Paulauskis J, Penny R, Shelton C, Shelton T, Sherman M, Thompson E, Yena P, Bowen J, Gastier-Foster JM, Gerken M, Leraas KM, Lichtenberg TM, Ramirez NC, Wise L, Zmuda E, Corcoran N, Costello T, Hovens C, Carvalho AL, de Carvalho AC, Fregnani JH, Longatto-Filho A, Reis RM, Scapulatempo-Neto C, Silveira HCS, Vidal DO, Burnette A, Eschbacher J, Hermes B, Noss A, Singh R, Anderson ML, Castro PD, Ittmann M, Huntsman D, Kohl B, Le X, Thorp R, Andry C, Duffy ER, Lyadov V, Paklina O, Setdikova G, Shabunin A, Tavobilov M, McPherson C, Warnick R, Berkowitz R, Cramer D, Feltmate C, Horowitz N, Kibel A, Muto M, Raut CP, Malykh A, Barnholtz-Sloan JS, Barrett W, Devine K, Fulop J, Ostrom QT, Shimmel K, Wolinsky Y, Sloan AE, De Rose A, Giuliante F, Goodman M, Karlan BY, Hagedorn CH, Eckman J, Harr J, Myers J, Tucker K, Zach LA, Deyarmin B, Hu H, Kvecher L, Larson C, Mural RJ, Somiari S, Vicha A, Zelinka T, Bennett J, Iacocca M, Rabeno B, Swanson P, Latour M, Lacombe L, Têtu B, Bergeron A, McGraw M, Staugaitis SM, Chabot J, Hibshoosh H, Sepulveda A, Su T, Wang T, Potapova O, Voronina O, Desjardins L, Mariani O, Roman-Roman S, Sastre X, Stern MH, Cheng F, Signoretti S, Berchuck A, Bigner D, Lipp E, Marks J, McCall S, McLendon R, Secord A, Sharp A, Behera M, Brat DJ, Chen A, Delman K, Force S, Khuri F, Magliocca K, Maithel S, Olson JJ, Owonikoko T, Pickens A, Ramalingam S, Shin DM, Sica G, Van Meir EG, Zhang H, Eijckenboom W, Gillis A, Korpershoek E, Looijenga L, Oosterhuis W, Stoop H, van Kessel KE, Zwarthoff EC, Calatozzolo C, Cuppini L, Cuzzubbo S, DiMeco F, Finocchiaro G, Mattei L, Perin A, Pollo B, Chen C, Houck J, Lohavanichbutr P, Hartmann A, Stoehr C, Stoehr R, Taubert H, Wach S, Wullich B, Kycler W, Murawa D, Wiznerowicz M, Chung K, Edenfield WJ, Martin J, Baudin E, Bubley G, Bueno R, De Rienzo A, Richards WG, Kalkanis S, Mikkelsen T, Noushmehr H, Scarpace L, Girard N, Aymerich M, Campo E, Giné E, Guillermo AL, Van Bang N, Hanh PT, Phu BD, Tang Y, Colman H, Evason K, Dottino PR, Martignetti JA, Gabra H, Juhl H, Akeredolu T, Stepa S, Hoon D, Ahn K, Kang KJ, Beuschlein F, Breggia A, Birrer M, Bell D, Borad M, Bryce AH, Castle E, Chandan V, Cheville J, Copland JA, Farnell M, Flotte T, Giama N, Ho T, Kendrick M, Kocher JP, Kopp K, Moser C, Nagorney D, O'Brien D, O'Neill BP, Patel T, Petersen G, Que F, Rivera M, Roberts L, Smallridge R, Smyrk T, Stanton M, Thompson RH, Torbenson M, Yang JD, Zhang L, Brimo F, Ajani JA, Gonzalez AMA, Behrens C, Bondaruk J, Broaddus R, Czerniak B, Esmaeli B, Fujimoto J, Gershenwald J, Guo C, Lazar AJ, Logothetis C, Meric-Bernstam F, Moran C, Ramondetta L, Rice D, Sood A, Tamboli P, Thompson T, Troncoso P, Tsao A, Wistuba I, Carter C, Haydu L, Hersey P, Jakrot V, Kakavand H, Kefford R, Lee K, Long G, Mann G, Quinn M, Saw R, Scolyer R, Shannon K, Spillane A, Stretch J, Synott M, Thompson J, Wilmott J, Al-Ahmadie H, Chan TA, Ghossein R, Gopalan A, Levine DA, Reuter V, Singer S, Singh B, Tien NV, Broudy T, Mirsaidi C, Nair P, Drwiega P, Miller J, Smith J, Zaren H, Park JW, Hung NP, Kebebew E, Linehan WM, Metwalli AR, Pacak K, Pinto PA, Schiffman M, Schmidt LS, Vocke CD, Wentzensen N, Worrell R, Yang H, Moncrieff M, Goparaju C, Melamed J, Pass H, Botnariuc N, Caraman I, Cernat M, Chemencedji I, Clipca A, Doruc S, Gorincioi G, Mura S, Pirtac M, Stancul I, Tcaciuc D, Albert M, Alexopoulou I, Arnaout A, Bartlett J, Engel J, Gilbert S, Parfitt J, Sekhon H, Thomas G, Rassl DM, Rintoul RC, Bifulco C, Tamakawa R, Urba W, Hayward N, Timmers H, Antenucci A, Facciolo F, Grazi G, Marino M, Merola R, de Krijger R, Gimenez-Roqueplo AP, Piché A, Chevalier S, McKercher G, Birsoy K, Barnett G, Brewer C, Farver C, Naska T, Pennell NA, Raymond D, Schilero C, Smolenski K, Williams F, Morrison C, Borgia JA, Liptay MJ, Pool M, Seder CW, Junker K, Omberg L, Dinkin M, Manikhas G, Alvaro D, Bragazzi MC, Cardinale V, Carpino G, Gaudio E, Chesla D, Cottingham S, Dubina M, Moiseenko F, Dhanasekaran R, Becker KF, Janssen KP, Slotta-Huspenina J, Abdel-Rahman MH, Aziz D, Bell S, Cebulla CM, Davis A, Duell R, Elder JB, Hilty J, Kumar B, Lang J, Lehman NL, Mandt R, Nguyen P, Pilarski R, Rai K, Schoenfield L, Senecal K, Wakely P, Hansen P, Lechan R, Powers J, Tischler A, Grizzle WE, Sexton KC, Kastl A, Henderson J, Porten S, Waldmann J, Fassnacht M, Asa SL, Schadendorf D, Couce M, Graefen M, Huland H, Sauter G, Schlomm T, Simon R, Tennstedt P, Olabode O, Nelson M, Bathe O, Carroll PR, Chan JM, Disaia P, Glenn P, Kelley RK, Landen CN, Phillips J, Prados M, Simko J, Smith-McCune K, VandenBerg S, Roggin K, Fehrenbach A, Kendler A, Sifri S, Steele R, Jimeno A, Carey F, Forgie I, Mannelli M, Carney M, Hernandez B, Campos B, Herold-Mende C, Jungk C, Unterberg A, von Deimling A, Bossler A, Galbraith J, Jacobus L, Knudson M, Knutson T, Ma D, Milhem M, Sigmund R, Godwin AK, Madan R, Rosenthal HG, Adebamowo C, Adebamowo SN, Boussioutas A, Beer D, Giordano T, Mes-Masson AM, Saad F, Bocklage T, Landrum L, Mannel R, Moore K, Moxley K, Postier R, Walker J, Zuna R, Feldman M, Valdivieso F, Dhir R, Luketich J, Pinero EMM, Quintero-Aguilo M, Carlotti CG Jr, Dos Santos JS, Kemp R, Sankarankuty A, Tirapelli D, Catto J, Agnew K, Swisher E, Creaney J, Robinson B, Shelley CS, Godwin EM, Kendall S, Shipman C, Bradford C, Carey T, Haddad A, Moyer J, Peterson L, Prince M, Rozek L, Wolf G, Bowman R, Fong KM, Yang I, Korst R, Rathmell WK, Fantacone-Campbell JL, Hooke JA, Kovatich AJ, Shriver CD, DiPersio J, Drake B, Govindan R, Heath S, Ley T, Van Tine B, Westervelt P, Rubin MA, Lee JI, Aredes ND, Mariamidze A. Machine Learning Identifies Stemness Features Associated with Oncogenic Dedifferentiation. Cell. 2018 Apr 5;173(2):338-354.e15. PMID: 29625051
Zaidi S, Rao S, Mishra L. Reply. Gastroenterology. 2020 Jul;159(1):398-399. Epub 2020 Apr 11. PMID: 32289371
Chianchiano P, Pezhouh MK, Kim A, Luchini C, Cameron A, Weiss MJ, He J, Voltaggio L, Oshima K, Anders RA, Wood LD. Distinction of intrahepatic metastasis from multicentric carcinogenesis in multifocal hepatocellular carcinoma using molecular alterations. Human pathology. 2018 Feb;72:127-134. Epub 2017 Nov 24. PMID: 29180252
Hernaez R, Karvellas CJ, Liu Y, Sacleux SC, Khemichian S, Stein LL, Shetty K, Lindenmeyer CC, Boike JR, Simonetto DA, Rahimi RS, Jalal PK, Izzy M, Kriss MS, Im GY, Lin MV, Jou JH, Fortune BE, Cholankeril G, Kuo A, Mahmud N, Kanwal F, Saliba F, Sundaram V, Artzner T, Jalan R, Multi-Organ Dysfunction and Evaluation for Liver Transplantation (MODEL) Consortium, Al Attar A, Kosari K, Garcia R, Salmastyan G, Cranford W, Patel P, Xue P, Mishra S, Parks M, Flocco G, Gao J, Wu T, Thanneeru P, Reddy V, Gao J, Hurtado M, Mohamed I, Vyhmeister R, Lopez CR, Campbell B, Winters AC, Simpson MA, Ying X. The novel SALT-M score predicts 1-year post-transplant mortality in patients with severe acute-on-chronic liver failure. Journal of hepatology. 2023 Sep;79(3):717-727. Epub 2023 Jun 12. PMID: 37315809
Gu S, Zaidi S, Hassan MI, Mohammad T, Malta TM, Noushmehr H, Nguyen B, Crandall KA, Srivastav J, Obias V, Lin P, Nguyen BN, Yao M, Yao R, King CH, Mazumder R, Mishra B, Rao S, Mishra L. Mutated CEACAMs Disrupt Transforming Growth Factor Beta Signaling and Alter the Intestinal Microbiome to Promote Colorectal Carcinogenesis. Gastroenterology. 2020 Jan;158(1):238-252. Epub 2019 Oct 1. PMID: 31585122
Luk BT, Jiang Y, Copp JA, Hu CJ, Krishnan N, Gao W, Li S, Fang RH, Zhang L. Biomimetic Targeting of Nanoparticles to Immune Cell Subsets via Cognate Antigen Interactions. Molecular pharmaceutics. 2018 Sep 4;15(9):3723-3728. Epub 2018 Mar 16. PMID: 29533668
Zaidi S, Gough NR, Mishra L. Mechanisms and clinical significance of TGF-β in hepatocellular cancer progression. Advances in cancer research. 2022;156:227-248. Epub 2022 Mar 16. PMID: 35961701
Hernandez BY, Zhu X, Risch HA, Lu L, Ma X, Irwin ML, Lim JK, Taddei TH, Pawlish KS, Stroup AM, Brown R, Wang Z, Wong LL, Yu H. Oral Cyanobacteria and Hepatocellular Carcinoma. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2022 Jan;31(1):221-229. Epub 2021 Oct 25. PMID: 34697061
Block TM, Alter H, Brown N, Brownstein A, Brosgart C, Chang KM, Chen PJ, Cohen C, El-Serag H, Feld J, Gish R, Glenn J, Greten TF, Guo JT, Hoshida Y, Kowdley KV, Li W, Lok AS, McMahon B, Mehta A, Perrillo R, Rice CM, Rinaudo J, Schinazi RF, Shetty K. Research priorities for the discovery of a cure for chronic hepatitis B: Report of a workshop. Antiviral research. 2018 Feb;150:93-100. Epub 2017 Dec 14. PMID: 29248746
Wong L, Bozhilov K, Hernandez B, Kwee S, Chan O, Ellis L, LeMarchand L. Underlying liver disease and advanced stage liver cancer are associated with elevated neutrophil-lymphocyte ratio. Clinical and molecular hepatology. 2019 Sep;25(3):305-316. Epub 2019 Apr 19. PMID: 31001964
Alter H, Block T, Brown N, Brownstein A, Brosgart C, Chang KM, Chen PJ, Chisari FV, Cohen C, El-Serag H, Feld J, Gish R, Glenn J, Greten T, Guo H, Guo JT, Hoshida Y, Hu J, Kowdley KV, Li W, Liang J, Locarnini S, Lok AS, Mason W, McMahon B, Mehta A, Perrillo R, Revill P, Rice CM, Rinaudo J, Schinazi R, Seeger C, Shetty K, Tavis J, Zoulim F. A research agenda for curing chronic hepatitis B virus infection. Hepatology (Baltimore, Md.). 2018 Mar;67(3):1127-1131. Epub 2018 Jan 24. PMID: 28877549
Wong LL, Landsittel DP, Kwee SA. Liver Transplantation vs Partial Hepatectomy for Stage T2 Multifocal Hepatocellular Carcinoma <3 cm Without Vascular Invasion: A Propensity Score-Matched Survival Analysis. Journal of the American College of Surgeons. 2023 Sep 1;237(3):568-577. Epub 2023 Apr 27. PMID: 37102575
Chaudhari P, Tian L, Kim A, Zhu Q, Anders R, Schwarz KB, Sharkis S, Ye Z, Jang YY. Transient c-Src Suppression During Endodermal Commitment of Human Induced Pluripotent Stem Cells Results in Abnormal Profibrotic Cholangiocyte-Like Cells. Stem cells (Dayton, Ohio). 2019 Mar;37(3):306-317. Epub 2018 Dec 17. PMID: 30471152
Batth IS, Mitra A, Manier S, Ghobrial IM, Menter D, Kopetz S, Li S. Circulating tumor markers: harmonizing the yin and yang of CTCs and ctDNA for precision medicine. Annals of oncology : official journal of the European Society for Medical Oncology. 2017 Mar 1;28(3):468-477. PMID: 27998963
Li K, Mathew B, Saldanha E, Ghosh P, Krainer AR, Dasarathy S, Huang H, Xiang X, Mishra L. New insights into biomarkers and risk stratification to predict hepatocellular cancer. Molecular medicine (Cambridge, Mass.). 2025 Apr 23;31(1):152. PMID: 40269686
Chen J, Mitra A, Li S, Song S, Nguyen BN, Chen JS, Shin JH, Gough NR, Lin P, Obias V, He AR, Yao Z, Malta TM, Noushmehr H, Latham PS, Su X, Rashid A, Mishra B, Wu RC, Mishra L. Targeting the E3 Ubiquitin Ligase PJA1 Enhances Tumor-Suppressing TGFβ Signaling. Cancer research. 2020 May 1;80(9):1819-1832. Epub 2020 Mar 3. PMID: 32127355
Wang Z, Budhu AS, Shen Y, Wong LL, Hernandez BY, Tiirikainen M, Ma X, Irwin ML, Lu L, Zhao H, Lim JK, Taddei T, Mishra L, Pawlish K, Stroup A, Brown R, Nguyen MH, Koshiol J, Hernandez MO, Forgues M, Yang HI, Lee MH, Huang YH, Iwasaki M, Goto A, Suzuki S, Matsuda K, Tanikawa C, Kamatani Y, Mann D, Guarnera M, Shetty K, Thomas CE, Yuan JM, Khor CC, Koh WP, Risch H, Wang XW, Yu H. Genetic susceptibility to hepatocellular carcinoma in chromosome 22q13.31, findings of a genome-wide association study. JGH open : an open access journal of gastroenterology and hepatology. 2021 Nov 27;5(12):1363-1372. doi: 10.1002/jgh3.12682. eCollection 2021 Dec. PMID: 34950780