Defining the tumor suppressor properties of the α1-Na/K-ATPase signalosome in Fatty Liver Disease progression to malignancy
How does signaling at the Na/K-ATPase pump not only regulates cellular metabolism but determine cell apoptotic and autophagy activities?
The integrity of Na+/K+-ATPase protein complexes at the cell membrane is critical for the maintenance of ion homeostasis. It is also key to adequate initiation and transduction of signaling by cardiotonic steroids and subsequent developmental, physiological, and pharmacological effects.
We utilize genetic approaches and preclinical animal models, as well as human cell lines to understand the molecular mechanisms of Na+/K+-ATPase receptor function and develop novel approaches for therapeutic interventions in nonalcoholic fatty liver disease (NAFL) to prevent its progression to nonalcoholic steato-hepatitis (NASH), and end stage liver disease (cirrhosis), the main risk factor for the development of primary liver malignancy or hepatocellular carcinoma (HCC).
- Professor of Surgery, Marshall University School of Medicine (MUSOM)
- Associate Dean for Clinical Trials, MUSOM
- Scientific Director Comprehensive Cancer Center
- Vice-Chair for Quality Assessment & Assurance
- GBD Cancer Collaborators. The global burden of cancer attributable to risk factors, 2010–2019: a systematic analysis for the Global Burden of Disease Study 2019. Submitted to JAMA, 2022.
- U-A S Udoh, M Banerjee, PK Rajan,JD Sanabria, G Smith, Y Nakafuku, K Sodhi, SV Pierre, Z Xie, JI. Shapiro, and JR Sanabria. Tumor-Suppressor Role of the Caveolar α1-Na/K-ATPase Signalosome in NASH related Hepatocellular Carcinoma. Submitted to Cancer Research, 2022.
- Global Burden of Disease 2019 Colorectal Cancer Collaborators. Global, Regional and National Burden of Colorectal Cancer and its risk factors, 1990-2019: A systematic examination for Global Burden of Disease 2019. Submitted to The Lancet, GI & Hepatology 2021.
- GBD 2019 Hepatitis B Collaborators. Global, regional, and national burden of hepatitis B, 1990–2019: a systematic analysis of the Global Burden of Disease Study 2019. Submitted to The Lancet, GI & Hepatology 2022.
- GBD Collaborators 2019. Tracking development assistance for health and for COVID-19: a review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990–2050. Submitted to The Lancet 2021. \
- GBD 2019 Adolescent and Young Adult Cancer Collaborators. The global burden of adolescent and young adult cancer in 2019: An analysis of the Global Burden of Disease Study 2019. Submitted to The Lancet Oncology, 2021.
- GBD Cancer Collaborators 2019. Cancer Incidence, Mortality, Years of Life Lost, Years Lived with Disability, and Disability-Adjusted Life Years for 29 Cancer Groups from 2010 to 2019: A Systematic Analysis of Cancer Burden Globally, Nationally, and by Socio-Demographic Index for the Global Burden of Disease Study 2019. JAMA Oncology, doi:10.1001/jamaoncol.2021.6987.
- IHPBA Research Committee Collaborators. Liver Transplantation for Colorectal Liver Metastasis; the International Hepato-Pancreato Biliary Association consensus guidelines. Accepted for publication The Lancet Oncology, 2021.
- Banerjee M, Li Z, Gao Y, Lai F, Huang M, Zhang Z, Cai L, Sanabria J, Gao T, Xie Z, Pierre SV. Inverse agonism at the Na/K-ATPase receptor reverses EMT in prostate cancer cells. Prostate. 2021 Jul;81(10):667-682. doi: 10.1002/pros.24144. Epub 2021 May 6. PubMed PMID: 33956349.
- Udoh U1, Sanabria JD1, Smith G1, Schade M, Sanabria JA, Mallick A, Rajan PK, Beltran N, Banerjee M, Udoh G, Sodhi K, Pierre S, Xie Z, Shapiro J and Sanabria J. The Role of Src-Phosphorylation at the α1-Na/K-ATPase at Caveola in the Pathogenesis and Treatment of NASH Related Hepatocellular Carcinoma: Overview of Published Literature. World J Surg Res 2020: 3; 1232-42.
- Rajan PK, Udoh UA, Sanabria JD, Banerjee M, Smith G, Schade M, Sanabria JA, Sodhi K, Pierre S, Xie Z, Shapiro J and Sanabria J. The Role of Histone Acetylation/Methylation Mediated Apoptotic Gene Regulation in Hepatocellular Carcinoma. J. Mol. Sci. 2020, 21, 8894; doi:10.3390/ijms21238894
- Sodhi K, Denvir J, Liu J, Sanabria J, Chen Y, Silverstein R, Xie Z, Abraham NG, and Shapiro JI. Oxidant Alterations in Adipocyte mRNA Expression: Role of the Na,K-ATPase Oxidant Amplification Loop. Intl J Mol Scien, 2020.
- Khitan Z, Jacob AD, Balentine C, Jacob AN, Sanabria JR, Shapiro JI. Predicting adverse outcomes in end stage renal disease: machine learning applied to the United States Renal Data System. Accepted in Marshall Journal of Medicine, 2020.
- GBD Diabetes Collaborators 2019. Burden of diabetes mellitus and hyperglycemia in adults in the Americas, 1990-2017: GBD 2017 study. Re-submitted to JAMA, 2022.
- SodhiK, Wang X, Chaudhary MA, Lakhani HV, Zehra M, Pratt R, Nawab A, Cottrill CL, Snoad B, Bai F, Denvir J, Liu J, Sanabria JR, Xie Z, Abraham NG, and Shapiro Central Role for Adipocyte Na/K-ATPase Oxidant Amplification Loop in the Pathogenesis of Experimental Uremic Cardiomyopathy. Accepted for publication Am J Nephro, 2020.
- Crank M, Abdelmasseh M, Iqbal A, Levowitz Y, Griswold M, Alsharedi, and Sanabria J. Complete Response to Stage IV Colorectal Adenocarcinoma with free disease survival at 12 months: Case report and overview of the literature. Accepted for publication Marshall Journal of Medicine, 2020.
- Udoh U, Sanabria JD, Smith G, Schade M, Sanabria JA, Mallick A, Rajan PK, Beltran N, Banerjee M, Sodhi K, Pierre S, Xie Z, Shapiro Jand Sanabria J.The Role of Src-phosphorylation at the α1-Na/K-ATPase at Caveola in the Pathogenesis and Treatment of NASH related Hepatocellular Carcinoma: Overview of Published Literature. Accepted for publication International Surgical Research,
- Mohammed I, Nagisetty C, Jamil M, Abdelmasseh M, Iqbal. A, Griswold D, and Sanabria J. Eradication of Stage IV gastric cancer: case report. Accepted for publication, Marshall Journal of Medicine, 2020.
- GBD Collaborators 2019. The global, regional, and national burden of stomach cancer in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease study 2017. Submitted to the Lancet, Gastroenterology and Hepatology, 2019.
- Pratt R, Brickman C, Nawab A, Cottrill C, Snoad B, Lakhani HV, Jelcick A, Henderson B, Bhardwaj N, Sanabria J, Liu J, Xie Z, Abraham, Shapiro J, Sodhi K. The Adipocyte Na/K-ATPase Oxidant Amplification Loop is the Central Regulator of Western Diet-Induced Obesity and Associated Comorbidities. Accepted for publication, Nature Scientific Reports, 2019.
- Nakamoto K, Weaver A, Griswold D, Sanabria J. Large-Cell Neuroendocrine Carcinoma of the Gallbladder: A Rare Case. American Surgeon. July 20192 Vol. 85, 2019.
- GBD 2019 Pancreatic Cancer Collaborator. The global, regional, and national burden of pancreatic cancer in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease study 2017. Submitted to LancetGastroenterology & Hepatology, 2019.
- GBD 2019 Collaborator. The global, regional, and national burden of colorectal cancer in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease study 2017. Submitted to LancetGastroenterology & Hepatology, 2019.
- GBD Cancer Collaborators 2017. Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived with Disability-Adjusted Life years for 29 Cancer Groups, 1990 to 2017: A Systematic Analysis for the Global Burden of Disease Study. Submitted to JAMA Oncology, 2019.
- GBD Collaborators 2017. The under-recognized burden of diarrhea among adults: a systematic analysis for the Global Burden of Disease Study 2017. Submitted to The Lancet Infectious Disease, 2018.
- GBD Cancer Collaborators. Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived with Disability, and Disability-Adjusted Life Years for 29 Cancer Groups, 2006 to 2016: A Systematic Analysis for the Global Burden of Disease Study. Submitted to JAMA Oncology, 2018.
- Global Burden of Disease Cancer Collaboration. The Burden of primary liver cancer and underlying etiologies from 1990 to 2015 at the Global, regional and national level: results from the Global Burden of Disease Study 2015. JAMA Oncol, 2017, DOI: 10.1001/jamaoncol.2017.3055
- SodhiK, Nichols A, Mallick A,Wang X, Klug R, Yan Y, Liu J, Srikanthan K, Goguet-Rubio P, Nawab A, Martin R, Lilly M, Sanabria J, Xie Z, Abraham N, and Shapiro J. The Na/K-ATPase Oxidant Amplification Loop Regulates Aging. Accepted to Nature Scientific Reports, 2018.
- Schade M, Sanabria JA, Aguilar R, Modarresi M, Gillon B, Hunter Z, Fannin J, Mallick A, Brunengraber H, Sanabria J. Cellular Senescence and their Role in Liver Metabolism in Health and Disease: Overview and Future Directions. Intl J Surg & Res
- GBD 2016 Occupational carcinogens Collaborators. Global and regional burden of cancer in 2016 arising from occupational exposure to selected carcinogens: a systematic analysis for the Global Burden of Disease Study 2016. BMJ Occupational & Environmental Medicine, 2019: 77: (3). http://dx.doi.org/10.1136/oemed-2019-106012
- GBD Liver Cancer Collaborators 2015. Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived with Disability, and Disability-Adjusted Life-years for 32 Cancer Groups, 1990 to 2015: A Systematic Analysis for the Global Burden of Disease Study. JAMA Oncol, 2017; 3:524-548. https://www.ncbi.nlm.nih.gov/pubmed/27918777
- GBD Obesity risk factors collaborator. Health Effects of Overweight and Obesity in 195 Countries over 25 Years. N Eng J Med, 2017: 377; 13-27. https://www.ncbi.nlm.nih.gov/pubmed/28604169
- Sanabria J, Kombu R, Zhang G-F, Sandlers Y, Ai J, Ibarra R, Abbas R, Goyal K, Brunengraber H. Glutathione species and Metabolomic Prints in Subjects with Liver Disease as Biological Markers for the detection of Hepatocellular Carcinoma. HPB, 2016. 18(12): 979–990. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5144552
- Stanaway, J. D., Flaxman, A. D., Naghavi, M., Fitzmaurice, C., Vos, T., Abubakar, I., Abu-Raddad, L. J., Assadi, R., Bhala, N., Cowie, B., Forouzanfour, M. H., Groeger, J., Hanafiah, K. M., Jacobsen, K. H., James, S. L., MacLachlan, J., Malekzadeh, R., Martin, N. K., Mokdad, A. A., Mokdad, A. H., Murray, C. J., Plass, D., Rana, S., Rein, D. B., Richardus, J. H., Sanabria, J., Saylan, M., Shahraz, S., So, S., Vlassov, V. V., Weiderpass, E., Wiersma, S. T., Younis, M., Yu, C., El Sayed Zaki, M., Cooke, G. S. The global burden of viral hepatitis from 1990 to 2013: findings from the Global Burden of Disease Study 2013. Lancet, 2016: 388; 1081-1088. http://www.ncbi.nlm.nih.gov/pubmed/27394647
- Global Health Institute for Health Metric and Evaluation with the GBD cancer collaborators. Global Burden of Cancer. JAMA Oncology, 2015;4:505-27. http://www.ncbi.nlm.nih.gov/pubmed/26181261
- Y Zhang, A Desai, S Y Yang, K B Bae, M I Antczak, S Fink, S Tiwari, J E Willis, G Larusch, N Williams, D Dawson, W-D Chen, L He, A J Dannenberg, F Cominelli, L Di Martino, G Milne, M Chance, J Sanabria, C Dealwis, L Kasturi, D Mikkola, J Naidoo, S Wei, H-H Tai, S Gerson, J Ready, B Posner, J K V Willson, S D Genetic and Chemical Inhibition of 15-PGDH Potentiates Tissue Regeneration in Multiple Organs. Science, 2015; 348: 2340. http://www.ncbi.nlm.nih.gov/pubmed/26068857
- Galal ElGazzaz, Rafael Ibarra, Juan Sanabria, Narayanan Menon, Bejan Eghtesad, Koji Hashimoto, Cristiano Quintini, Charles Miller, John Fung, Federico Aucejo. Radiologic- Histological Correlation of Hepatocellular Carcinoma (HCC) Treated Via Pre- Liver Transplant (LT). Hepatobiliary Pancreat Dis Int. 2013; 12:34. http://www.ncbi.nlm.nih.gov/pubmed/23392796
- Betul Berber, M.D., Juan R. Sanabria MD, MSc, Kelly Braun, M.Sc., Min Yao, D., Ph.D., Rodney J. Ellis, M.D. Charles A. Kunos, M.D., Ph.D., Jason Sohn, Ph.D, Mitchell Machtay, M.D., Bin S. Teh, M.D., Zhibin Huang, Ph.D., Nina A. Mayr, M.D., Simon S. Lo, M.D. Emerging role of stereotactic body radiation therapy (SBRT) in the treatment of pancreatic cancer. Expert Rev Anticancer Therapy. 2013; 13:481. http://www.ncbi.nlm.nih.gov/pubmed/23560842
- R Ibarra MD, Y Sandlers PhD, R Abbas MD, R Kombu PhD, G Zhang PhD, J Dazard PhD, H Brunengraber MD PhD and J Sanabria MD MSc. Metabolomic analysis of liver tissue samples from the VX2 Rabbit model of Secondary Liver Tumors using Gas Chromatography-Mass Spectrometry. HPB Surgery, 2014: 310372. http://www.ncbi.nlm.nih.gov/pubmed/24723740
- B Berber, R Ibarra, L Snyder, M Yao, J Fabien, MT Milano, AW Katz, K Goodman, K Stephans, G El-Gazzaz, F Aucejo, C Miller, J Fung, S Lo, M Machtay, J Sanabria. Multicenter results of Stereotactic Body Radiotherapy (SBRT) for secondary non-resectable liver tumors. HPB. 2013. http://www.ncbi.nlm.nih.gov/pubmed/23458468
- Cherian S, Djemil T, Abdel-Wahab M, Greskovich J, Fung J, Aucejo F, Miller C, Sanabria J, Menon N and Stephan K. Stereotactic Radiation (SBRT) for primary liver malignancies. Intl J Rad Oncol Biol Phys 84: S338-S339,
- R Ibarra, D Rojas, L Snyder, M Yao, J Fabien, M T Milano, A W Katz, K Goodman, K Stephans, G El-Gazzaz, F Aucejo, C Miller, J Fung, S S Lo, M Machtay and J Sanabria. Multicenter Results of Stereotactic Body Radiotherapy (SBRT) for Non-resectable Primary Liver Tumors. Acta Oncologica, 2012; 51: 575-83. http://www.ncbi.nlm.nih.gov/pubmed/22263926
- A Sourianarayanane, G El-Gazzaz, JR Sanabria, N Menon, C Quantini, K Hashimoto, D Kelly, B Eghtesad, C Miller, J Fung, F Aucejo. Locoregional Therapy in patients with Milan Criteria-complaint Hepatocellular Carcinoma and short waitlist time to transplant: an outcome analysis. HPB. 2012; 14:325. http://www.ncbi.nlm.nih.gov/pubmed/22487070
- Goyal MD, D Einstein MD PhD, RA Ibarra MD, M Yao MD PhD, C Kunos MD PhD, R Ellis MD, J Brindle PhD, D Singh MD, J Hardacre MD, Y Zhang MS, J Fabien MS, G Funkhouser RTT, M Machtay MD PhD and JR Sanabria MD MSc. Stereotactic body radiation therapy for non-resectable tumors of the pancreas. J Surg Res. 2012; 174:319. http://www.ncbi.nlm.nih.gov/pubmed/21937061
- RA Ibarra MD, R Abbas MD, RS Kombu PhD, GF Zhang PhD, G Jacobs MD, Z Lee PhD, H Brunengraber MD PhD and JR Sanabria MD MSc. Disturbances in the glutathione/ ophthalmate redox buffer system in the woodchuck model of hepatitis virus-induced hepatocellular carcinoma. HPB, 2011; 789323. http://www.ncbi.nlm.nih.gov/pubmed/21941408
- Abbas, R., Ibarra R., Kombu R., Yana S., Brunengraber H, Sanabria J. The dynamics of glutathione species and ophthalmate concentrations in plasma from the VX2 rabbit model of secondary liver tumors. HPB Surg, 2011; 709052. http://www.ncbi.nlm.nih.gov/pubmed/21350723
- Goyal KK, Einstein DB, Kunos C, Siegel C, Singh D, Brindle J, Zhang Y, Williams J, Stulberg J, and Sanabria JR. Cyberknife Radiosurgery for non-resectable Tumors of the Liver: Preliminary Results. HPB Surg, http://www.ncbi.nlm.nih.gov/pubmed/20689733
- Jin J; Williams CP; Soltanian H; Smith MK; Pearl J; Sanabria J; Rosen MJ. Use of abdominal wall allotransplantation as an alternative for the management of end stage abdominal wall failure in a porcine model. J Surg Res, 162:314-20, http://www.ncbi.nlm.nih.gov/pubmed/19560162
- Kombu RJ, Zhang G, Abbas R, Mieyal JJ, Anderson VE, Kelleher JK, Sanabria JR, Brunengraber H. Dynamics of glutathione and ophthalmate traced with 2H- enriched body water in rats and humans. Am J Physiol Endocrinol Metab; 297(1): E260-9, http://www.ncbi.nlm.nih.gov/pubmed/19401458
- Abbas R, Kombu RJ, Dingam D, Gumming W, Stulberg J, Brunengraber H, and Sanabria Polyethylene Glycol Albumin enhances the cold preservation properties of University of Wisconsin solution in rat liver and a hepatocyte cell line. J Surg Res. 2010:164;95. http://www.ncbi.nlm.nih.gov/pubmed/19577257
- Abbas R, Adam S, Kim J, Counter C, and Sanabria J. (2008). The development of a swine model of secondary liver tumors from a genetically induced swine fibroblasts cell HPB, 2008, 10(3): 204–210. http://www.ncbi.nlm.nih.gov/pubmed/18773055
- Messick C, Hardacre JM, McGee MF, Siegel CT, Stellato TA, Sanabria JR, Kinsella TJ, and Schulak JA. Early Experience with Intraoperative Radiotherapy in Resected Pancreatic Adenocarcinoma. Am J Surg, 2008, 195(3):308-11. http://www.ncbi.nlm.nih.gov/pubmed/18207129
- Kinsella TJ, Seo Y, Willis J, Stellato TA, Siegel CT, Harpp D, Willson JK, Brell J, Gibbons J, Krishnamurthi SA, Sanabria JR, Hardacre JM, and Schulak The impact of resection margin status and post-operative CA19-9 levels on survival and patterns of recurrence following post-operative high-dose radiotherapy with 5FU-based concurrent chemotherapy for resectable pancreatic cancer. Am J Clin Oncol 2008. 31(5):446-453. http://www.ncbi.nlm.nih.gov/pubmed/18838880
- Abbas R, Willis J, Kinsella T, Siegel C, and Sanabria JR. 2008. Primary Squamous Cell Carcinoma of the Main Hepatic Bile Ducts: A Case Report and Review of the current literature. Can J Surg; 2008: 51(4): E85-6.
- Sanabria J, T Hiruki, D Szalay, V Tandan and S Gallinger. Postoperative Superior mesenteric vein thrombosis after the Whipple procedure: an aggressive, combine approach. Can J Surg, 40: 467-70. http://www.ncbi.nlm.nih.gov/pubmed/9416259
Education and Training
UNIVERSITY Colegio Mayor Ntra Sra del Rosario School of Medicine Degree: MD and Surgeon
INTERNSHIP Andes Medical Center – Andes University
Clinical Associate, Dpt. of Surgery
Andes Medical Center. Andes University
Institute of Medical Sciences, U Toronto
Degree: Master in Surgical Sciences
MD International Medical Graduate
U Toronto School of Medicine
Degree: MD IMG U Toronto
Epidemiology Unit Research Fellow
UHN Outcomes and Ontario Cancer Registry
Resident Academic Surgery
The Gallie Program
Designation: FRCSC Royal College of Surgeons
Abdominal Transplantation & HPB Surgery
Toronto General Hospital
Degree: Transplant & HPB Surgeon
ASTS/AST & AHPBA/IHPBA member
ECFMG & America Board of Surgery
Designation: FACS American College of Surgeons
Fellow in Health Policy Making
Fellow in Liver Diseases
San Francisco, CA
SOCIETY MEMBERSHIP & SERVICE RANK
FRCSC: Fellow of the Royal College of Physicians and Surgeons of Canada #494832
CAGS: Canadian Association of General Surgeons
CATS: Canadian Association of Transplant Surgeons
CMPA: Canadian Medical Protective Association
CPSO: College of Physicians and Surgeons of Ontario #67929
OAGS: Ontario Association of General Surgeons
OMA: Ontario Medical Association University of Toronto Alumni Association
FACS: Fellow American College of Surgeons #03069482
SSAT: The Society for the Surgery of the Alimentary Tract, Leadership role
AAS: Association for Academic Surgery
SUS: Society of University Surgeons, Leadership role
ASTS: American Society of Transplant Surgeons, Leadership role
AASLD: American Association for the Study of Liver Diseases #1845, Leadership role
AHPBA: American Hepato-Pancreatic and Biliary Association, Leadership role
CSA: Central Surgical Association #1667
SAGES: The Society of American Gastrointestinal and Endoscopic Surgeons
NHMA: National Hispanic Medical Association
ISDS: International Society for Digestive Surgery
IASG: International Association of Surgeons and Gastroenterologist (and Oncologist)
IHPB: International Hepato-Pancreatic and Biliary Association, Leadership role
ESSLD: European Society for the Study of Liver Diseases, Leadership role
ILCA: International Liver Cancer Association #100298
ILTS: International Liver Transplantation Society
OCACS: Ohio Chapter American College of Surgeons
OSOTC: Ohio Solid Organ Transplant Consortium
OSMA: Ohio State Medical Association
WVACS: West Virginia Chapter American College of Surgeons
The Cleveland Surgical Society
The Toledo Surgical Society
The Academy of Medicine of Toledo and Lucas County
The West Virginia Medical Society
The Cabell County Medical Society
SERVICE UNITED STATES ARM FORCES
United States of America Navy Officer USN-SR Commander (O5) DoD # 1505698297
BuMed DET L Great Lakes (2014-2017)
BuMed DET G Bethesda (2017 to 2018)
Marine Corps 4th Surgical Battalion DET 1 BuMed Jacksonville (2018 to present)
BuMed Executive Voting Member, Navy Bureau of Medicine Jacksonville (2019 – present)
Officer in Command (OIC) Det 1 4th Btn SCoA MLG (2019-2021)
Gotham COVID19 Operation, New York City Deployment (2020)