Dr. UTIBE-ABASI Sunday Udoh Profile

Current Research Work

My current research focuses on unveiling the molecular mechanisms/signaling pathways that underpin the development and progression of Non-alcoholic steatohepatitis (NASH) related Hepatocellular Carcinoma (HCC) and how such pathways/mechanisms could be targeted for NASH related HCC therapy. Specifically, I am investigating the molecular mechanism that underpin the tumor suppressor function of the  Na/K-ATPase-α1- Src signalosome in the liver and how a dysregulation of this signaling complex in pathological states (such as in NASH) works in tandem with survivin (anti-apoptotic protein) and SMAC/Diablo (a proapoptotic protein) to create an oncogenic apoptotic switch that drives the progression of NASH to hepatocellular carcinoma (HCC) in cells, murine models and Human subjects. This study also involved a therapeutic normalization of the dysregulation of the complex using a novel peptide (pNaKtide) to restore cell function back to normal. The results from this study raised the possibility that pNaKtide may be a useful therapeutic agent for the treatment of NASH-related HCC and other forms of cancer. I am also involved in a study to develop a liquid biopsy for early detection of HCC as well as assessing the role of autophagy and epigenetic modifications in NASH- related HCC.

Past Research work

Effects of Adenosine Monophosphate Activated Protein Kinase (AMPK) deletion on the response to Hypoxia. The  study involved the exposure of AMPK transgenic mice (AMPKα1/α2-/- mice, AMPKα2-/- mice) and their floxed counterparts (AMPKα1/α2fl/fl) to a period of hypoxic challenge with the aim of examining their ventilatory responses via whole body plethysmograph as well as elucidating the activation of their brainstem catecholaminegic respiratory neurons during the period of hypoxia using c-Fos/tyrosine hydroxylase (TH) double immunofluorescence staining and microscopy techniques. The results from this work identified for the first time that A2 noradrenergic neurons in the SubP region of the Solitary Tract Nucleus as well adrenergic neurons in the C2 region of the brainstem are the central oxygen sensors that control breathing during hypoxia, and they mediate this action via AMPK activation while synergising the inputs from the carotid bodies. The findings from this work point to the possible cause of apnoeas in certain breathing disorders such as non-obstructive sleep apnoeas. Interestingly, this work offers in longer term opportunities to develop therapeutic interventions in managing such disorders. Furthermore, the results from this study also raised the possibility that AMPK may be a useful therapeutic tool for disease conditions whose etiology is based on cellular proliferation, such as various forms of cancer and even atherosclerosis; this was based on the observation of widespread hyperplasia of catecholaminergic cells in the mice brainstem following AMPK deletion. (Link to published paper  http://dx.doi.org/10.1164/rccm.201508-1667OC).

Publications

•  Udoh, U.-A. S., Rajan, P. K., Nakafuku, Y., Finley, R., & Sanabria, J. R. (2022). Cell Autophagy in NASH and NASH-Related Hepatocellular Carcinoma. International Journal of Molecular Sciences, 23(14), 7734.https://doi.org/10.3390/ijms23147734
• Udoh, U. S., Banerjee, M., Rajan, P. K., Sanabria, J. D., Smith, G., Schade, M., Sanabria, J. A., Nakafuku, Y., Sodhi, K., Pierre, S. V., Shapiro, J. I., & Sanabria, J. R. (2022). Tumor-Suppressor Role of the α1-Na/K-ATPase Signalosome in NASH Related Hepatocellular Carcinoma. International journal of molecular sciences, 23(13), 7359. https://doi.org/10.3390/ijms23137359
• Schade, M.; Sanabria, J.A.; Mallick, A.; Aguilar, R.; Andryka, M.; Schlatzer, D.; Li, X.; Hazlett, F.E.; Kachman, M.; Raskind, A.; Udoh, U.; Rajan, P.K.; Sanabria, J.D.; Brunengraber, H.; Sodhi, K.; Pierre, S.; Xie, Z.; Shapiro, J.I.; Sanabria, J. Normalization of the α1-Na/K-ATPase/Src Signalosome Restored Microbiota Communities and Rescinded NASH Progression in the Mouse. Preprints 2021, 2021090023 (doi: 10.20944/preprints202109.0023.v2).
• Udoh, U.-A., Sanabria, J. D., Rajan, P. K., Banerjee, M., Schade, M., Sanabria, J. A., Smith, G., Udoh, G., Sodhi, K., Pierre, S., Shapiro, J. I., & Sanabria, J. R. (2021). Non-Alcoholic Fatty Liver Disease Progression to Non-Alcoholic Steatohepatitis-Related Primary Liver Cancer. In C. M. Sergi (Ed.), Liver Cancer. Exon Publications. https://doi.org/10.36255/exonpublications.livercancer.2021.ch3.
• Rajan, P. K., Udoh, U.-A., Sanabria, J. D., Banerjee, M., Smith, G., Schade, M. S., Sanabria, J., Sodhi, K., Pierre, S., Xie, Z., Shapiro, J. I., & Sanabria, J. (2020). The Role of Histone Acetylation-/Methylation-Mediated Apoptotic Gene Regulation in Hepatocellular Carcinoma. International journal of molecular sciences, 21(23), 8894. https://doi.org/10.3390/ijms21238894
• Udoh, U., Sanabria, J. D., Smith, G., Schade, M., Sanabria, J.A., Mallick, A., et al (2020) 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 Surgical Res 3: 1232 https://www.surgeryresearchjournal.com/open-access/the-role-of-src-phosphorylation-at-the-alpha1-nak-atpase-at-7387.pdf.
• Babalola, T., Udoh, U. S. (2018) Effects of exercise on plasma lactic acid and body temperature in man, following a standardized meal. Bangladash Journal of Medical Science 17 (2), 270.
• Mahmoud, A. D., Lewis S., Juričić, L., Udoh, U-A., Hartmann, S., Jansen, M. A., Ogunbayo, O.A., Puggioni, P., Navarro-Dorado , J.M., Holmes, A.P., Kumar, P., Foretz, M., Viollet, , B., Dutia, M.B., Marshall, I., Evans. A. M.(2016) AMPK deficiency blocks the hypoxic ventilatory response and thus precipitates hypoventilation and apnea. American Journal of Respiratory and Critical Care Medicine, 193, 1032-1043. http://dx.doi.org/10.1164/rccm.201508-1667OC.
• Ige, S.F., Olaleye, S.B., Akhigbe, R.E., Akanbi,T.A., Oyekunle O.A , Udoh, U.S.(2012) Testicular toxicity and sperm quality following cadmium exposure in rats. Ameliorative potentials of Allium cepa. Journal of Human Reproductive Sciences 5, 37-42.
•  Oyekunle O.A., Udoh U.S., Obadire M.O (2012) Deleterious effects of chronic administration of ethanolic extract of Rauwolfla vomittoria root bark on testicular function in Wister rats. International journal of Advance Pharmaceutical and Biological Sciences 2, 64-69.
• Oyekunle O.A., Okoje A.K., Udoh U.S (2010) Analgesic and Anti-inflammatory Effects of Fadogia agrestis in  Neurophysiology 42, 124-129.
•  Udoh U.S., Oyekunle O.A., Ige S.F, Okoje A.K., Ogunwale E.B. (2009) Effect of oral Administration of Aqueous kola Nut Extract (kola nitida) on Reproductive hormones in Male Sprague dawley rats. Journal of Scientific and Industrial Studies 7, 42-44.
•  Oyekunle, O.A., Ibironke G.F., Ige S.F., Udoh, U.S. and Okojie A.K (2009) Relationship between the plasma testosterone level and pain reaction times in male rats. Neurophysiology 41, 231-234.
•  Oyadeyi, A.S. Ajao, F.O., Afolabi, A.O. Udoh, U.S and Azeez, M.O (2007) The formalin test in African toad (Bufo regularis): A novel pain model in amphibians. American-Eurasian journal of Scientific Research 2, 24-28.
•  Oyadeyi, A.S., Adebiyi, O.O., Afolabi, A.O., Udoh, U.S. Ajao F.O., Ige, S.F., Ibironke G.F. and Oyewopo, A.O. (2007) Analgesic and anti-inflammatory activities of crude extract of Icacina trichantha leaves. International journal of Pharmacology 1(1).
•  Oyadeyi, A.S., Ajao, F.O., Afolabi, A.O, Azeez, O.M., and Udoh, U.S. (2006) The Formalin Test: Effect of Different injection Sites on the Pattern of Nociceptive Responses. Nigerian journal of Health and Biomedical Sciences 5, 48-50.
•  Oyadeyi A.S., Ajao, F.O., Afolabi A.O., Udoh, U.S. and Ibironke G.F: (2005): Chronic vitamin C administration induces thermal hyperalgesia in male rats. Nigerian journal of Health and Biomedical Sciences 4 (2), 153-155.
•  Adekunle, A.S., Ifabunmi, O.S., and Udoh, U.S. (2004). Insulin Response to Glucose Load in first degree relatives of type II Diabetic patients. Science Focus 6, 6-8.
• Raji, Y, Udoh, U.S and Ojo, O. (2003): Gastric ulcerogenic activities of piper guineense extract in rats. Nigerian journal of Physiological Sciences 18, 27-30.
•  Raji Y., Udoh U.S., Mewoyeka O.O. and Bolarinwa, A.B (2003) Implication of reproductive Endocrine malfunction in male antifertility efficacy of Azadirachata Indica extract in rats. African journal of Medicine and Medical Sciences 32,159-165.
• Raji Y., Udoh U.S., Oluwadara, O.O., Akinsomisoye, O.S., Awobajo, O. Adeshoga, K. (2002) Anti-inflammatory and analgesic properties of the rhizome extract zingiber officinale. African Journal of Biomedical Research,5,121 – 124.
• Rajan, P.K.; Udoh, U.-A.S.; Nakafuku, Y.; Pierre, S.V.; Sanabria, J. Normalization of the ATP1A1 Signalosome Rescinds Epigenetic Modifications and Induces Cell Autophagy in Hepatocellular Carcinoma. Cells 2023, 12, 2367. https://doi.org/10.3390/cells12192367
• Ugonabo, O.; Udoh, U.-A.S.; Rajan, P.K.; Reeves, H.; Arcand, C.; Nakafuku, Y.; Joshi, T.; Finley, R.; Pierre, S.V.; Sanabria, J.R. (2023). The Current Status of the Liver Liquid Biopsy in MASH Related HCC: Overview and Future Directions. Biomolecules, 13, 1369. https://doi.org/10.3390/biom13091369

Professional Membership

• Member, Physiological Society, United Kingdom (2011-2014)
• Member, British Neuroscience Association (BNA) (2014-2019)
• Member, Federation of European Neuroscience Societies (2015-2019)
• Member, Society of Endocrinology, United Kingdom (2013-2015)
• Member, International Society for Neurochemistry (2017- 2017)
• Member, Nigerian Society for Experimental Biology (NSEB)(2002-)
• Member, Physiological Society of Nigeria (PSN) (2001-)
• Member, American Association for Cancer Research (2021-)
• Member, American Association for the Study of Liver Diseases (2021-)

Awards/Scholarships

• Charles Darwin Postgraduate Research Scholarship, College of Medicine & Veterinary Medicine, University of Edinburgh, UK (May 2011).
• NIH/NIDDK Translational Science Research Award- NMRI 2023 Annual Workshop, Bethesda, MD.

Previous Positions

• Post- Doctoral Research Fellow/ Research Scholar, Marshall Institute for Interdisciplinary Research /Dept. of Surgery, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA.
• Teaching Assistant, University of Edinburgh, United Kingdom
• Lecturer/Researcher in Physiology, Ladoke Akintola University of Technology, Nigeria.