Roberto Gedaly is a practicing transplant surgeon and clinician-scientist who has earned both national and international recognition for his work with infectious complications, including hepatitis and patients undergoing liver resection and liver transplantation. His research has focused on immunosuppressive strategies in liver transplantation. His currently seeks to define markers and prognostic indicators of hepatocellular carcinoma in an attempt to determine more effective therapies.
After receiving a medical degree from the Universidad Central de Venezuela in Caracas, Venezuela in 1990, Gedaly completed his general surgery residency at the University Hospital of Caracas. He then completed a two-year fellowship in hepatobiliary and transplantation service at Beth Israel Deaconess Medical Center through the Harvard Medical School in Boston; a one-year fellowship in liver and GI transplantation at the Jackson Memorial Hospital at the University of Miami School of Medicine in Miami, Fla.; and a two-year fellowship in transplantation at the Methodist Hospital at the University of Tennessee in Memphis. Gedaly joined the University of Kentucky in 2006. He is actively engaged in medical and surgical societies, is a frequently invited guest speaker at meetings worldwide and has authored numerous publications appearing in leading peer-review journals and text books.
Associate Professor of Surgery
Central University of Venezuela, Razetti School of Medicine, Caracas, Venezuela
University Hospital of Caracas, Central University of Venezuela, Caracas, Venezuela
Deaconess Hospital, Harvard University, Boston
Jackson Memorial Hospital, University of Miami, Fla.
Methodist Hospital, University of Tennessee, Memphis
Certifications or Special training
Member, American Association for the Study of Liver Diseases
Member, American Society of Transplant Surgeons
Member, American Society of Transplant Physicians
Member, International Liver Transplantation Society
Member, Venezuelan Surgical Society
Member, Kentucky Organ Donor Affiliates (KODA) Executive Board of Directors
Member, KODA Advisory Committee
Member, University of Kentucky Organ Transplant Evaluation Committees (liver, pancreas, kidney)
Pediatric Kidney Transplant
UK Transplant Center
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The Ras/Raf /MAPK, PI3K/AKT/mTOR and wnt/β-catenin signaling pathways are aberrantly activated in many hepatocellular carcinoma (HCC) patients. The wnt/β-catenin pathway is the most difficult to be blocked. The goal of this proposal is to apply sorafenib, PKI-587 (PF-05212384) and β-catenin inhibitor FH535 in single agent or in combination with sorafenib to inhibit HCC and LCSC. Drug combination effects will be tested in vitro and in xenograft animal model. The mechanisms of drug combination will be assayed by western-blot and by real-time RT-PCR. We will use FH535 derivatives (generated by our Co-I Dr. Watt) to inhibit HCC cell proliferation in vitro and tumorigenesis in xenograft in vivo model. The FH535 and its derivatives inhibition of β- catenin signaling will be assayed by dual luciferase assay in TOP-Flash Luc-reporter, in natural enhancer promoted Luc-reporter. These assays have not been done before for characterization of FH535 and its derivatives. The FH535 and its derivatives affected genes in the β-catenin signaling will assessed at mRNA and protein level by real time RT-PCR and Western-Blot experiments. The FH535 and its derivatives inhibition of tumorigenesis will be tested in a xenograft nude mice model. In our specific aim 3, we plan to do a pilot clinical trial of PKI-587 (PF-05212384) in patients with advanced stage HCC intolerant to sorafenib or with tumor progression under sorafenib treatment. Drug toxicity, pharmacokinetics, tumor recession and other outcomes will be evaluated. If the overall outcomes are good, we will in the future clinical trial apply for sorafenib and PKI-587 combination therapy in advanced stage HCC patients. I have strong background and motivation to study HCC markers and their impact on tumor recurrence and survival. I have done a study on predictors of relapse to alcohol and illicit drugs after liver transplantation for alcoholic liver disease; we have also reported the impact of obesity, diabetes, smoking and cancer on resource utilization in patients undergoing liver resection from a multicenter analysis of 1029 hepatectomies; and lately, our group reported the association of alpha-fetaprotein and tumor size with microvascular invasion in patients undergoing transplantation with hepatocellular carcinoma. I have extensive clinical expertise in the management of patients with hepatocellular carcinoma. I have had a long time interest and have been involved in basic science research. Recently, we have published three preclinical research papers studying PI3K/AKT/mTOR inhibitor PI-103 and PKI-587 as well as Ras/Raf/MAPK inhibitor sorafenib on inhibition of the two signaling pathways in HCC in in vitro and in animal xenograft in vivo model. We also accumulated some preliminary data in liver cancer stem cell (LCSC) studies including PKI-587 and sorafenib inhibition, β-catenin signaling and tumorigenesis of LCSC in SCID mice. We recently published a new article on Sorafenib and PKI-587 inhibition of liver cancer stem cells in Journal of Surgical Research this year. I am currently a PI in several multicenter clinical trials to study the role of new immunosuppression regimens. I have recently participated as PI in a phase I-II multicenter trial. A couple of these projects are studying different protocols using mTOR inhibitors such as Everolimus and Sirolimus in renal transplant patients. I am running an investigator initiated clinical trial sponsored by Novartis on the relationship bone disease and CAC in transplant patients. I am also running another investigator initiated trial in collaboration with the department of physiology on the study of sarcopenia in liver transplant recipients. Thus, I have demonstrated a record of successful and productive research in several different areas of liver diseases. We have had collaborations in different fields with Co investigators Dr. Evers (surgical oncology), Dr. Jones (Oncology), Dr. Spear (PhD working in liver disease), Dr. Watt (Biochemistry) and Dr. Liu (Biochemistry) from our institution. I am confident that working together with my Co-Investigators, we will have the ability to successfully accomplish this proposed project.
Roberto Gedaly, Roberto Galuppo, Yolanda Musgrave, Paul Angulo, Jonathan Hundley,
Malay Shah, Michael F. Daily, Changguo Chen, Donald A. Cohen, Brett T. Spear and B. Mark
Evers. PKI-587 and Sorafenib Alone and in Combination on Inhibition of Liver Cancer Stem
Cell Proliferation. J. Surg. Res 2013 E-Pub before Print
Gedaly R, Angulo P, Chen C, Creasy KT, Spear BT, Hundley J, et al. The Role of PI3K/mTOR
Inhibition in Combination with Sorafenib in Hepatocellular Carcinoma Treatment. Anticancer
Res 32:2531-2536, 2012
Gedaly R, Angulo P, Hundley J, Daily MF, Chen C, Evers BM. PKI-587 and Sorafenib Targeting
PI3K/AKT/mTOR and Ras/Raf/MAPK Pathways Synergistically Inhibit HCC Cell Proliferation. J
Surg Res 176: 542-548, 2012
Gedaly R, Angulo P, Hundley J, Daily MF, Chen C, Koch A, and Evers BM: PI-103 and
sorafenib inhibit hepatocellular carcinoma cell proliferation by blocking Ras/Raf/MAPK and
PI3K/AKT/mTOR pathways. Anticancer Res 30:4951-4958, 2010
Gedaly R, McHugh PP, Johnston TD, Jeon H, Koch A, Clifford TM, Ranjan D. Predictors
of relapse to alcohol and illicit drugs after liver transplantation for alcoholic liver disease.
Transplantation 86(8):1090-1095, 2008