AG GUBA/KOLIOGIANNIS
Three Barriers, One Mission
Advancing Transplant Oncology, Immune Reprogramming, and Xenotransplantation
About Us
We are a translational research group within the Department of General, Visceral and Transplant Surgery at LMU University Hospital Munich. Under the direction of Prof. Dr. med. Markus Guba and Dr. med. Dionysios Koliogiannis, our team of clinician-scientists, biologists, and surgical residents addresses a central challenge in transplant medicine: How can we expand the donor organ pool, improve long-term graft and patient survival, and optimize transplantation outcomes for patients with complex oncologic disease?
Our research follows a bench-to-bedside approach. Each project originates from a clinical question encountered in daily surgical practice and is designed to generate findings with direct translational relevance. On the experimental side, we employ normothermic machine perfusion, molecular tissue profiling, deep-learning-based imaging, and preclinical xenotransplantation models. On the clinical side, we design and conduct investigator-initiated trials and participate in national and international multicenter studies. This integration of experimental discovery and rigorous clinical validation defines the methodological framework of our group.
Infrastructure
Research
Projects
Lead: M. Guba · D.T. Koch · Co-Investigators: S. Jacobi · M. Schirren
Liver transplantation remains the only curative treatment for selected patients with hepatocellular carcinoma (HCC), cholangiocarcinoma (CCC), and — in an evolving indication — colorectal liver metastases. Tumor recurrence following transplantation, however, continues to limit long-term survival. The interaction between post-transplant immunosuppression and residual tumor biology in this setting is incompletely understood.
Our group investigates the molecular and immunological mechanisms governing post-transplant tumor recurrence. Specific areas of focus include the identification of circulating and tissue-based biomarkers for recurrence risk stratification, the impact of pharmacologic immunosuppression on anti-tumor immune responses, and the development of individualized surveillance and treatment protocols.
Investigator-initiated studies:
- TRANSMIT — A compassionate-use exploratory study evaluating whether viable donor livers currently discarded due to the donor’s history of malignancy can be safely utilized for transplantation in patients with otherwise fatal liver tumors (CRC-LM, iCCC/phCCC, HCC) who are ineligible for standard organ allocation.
- RAPID-MUC — A study investigating living-donor partial liver transplantation (segments 2/3) combined with two-stage complete hepatectomy as a curative approach for selected patients with unresectable colorectal liver metastases.
National and international multicenter trials:
- PRODUCT-002 (national) — A pilot study assessing the rate of microscopic tumor clearance (R0) after liver transplantation for perihilar cholangiocarcinoma under strict patient selection criteria.
- LEOPARD (EU project) — Liver Electronic Offering Platform with Artificial Intelligence-based Devices — a European collaborative initiative developing AI-driven tools for optimized organ offering and allocation.
- HOPE 4 CANCER (multicenter trial)
Contact for TRANSMIT, RAPID-MUC and PRODUCT-002
Contact for LEOPARD
Lead: M. Guba · D. Koliogiannis · S. Jacobi · Co-Investigators: D.T. Koch · M. Schirren
Normothermic machine perfusion (NMP) has transformed organ preservation from passive cold storage into an active therapeutic platform. It enables sustained organ metabolism, real-time viability assessment, and the delivery of targeted interventions prior to implantation.
We utilize this therapeutic window to pursue a concept we term organ reprogramming: the immunological conditioning of a donor organ outside the body. Our objective is to modulate the graft’s antigen-presenting and endothelial cell compartments during perfusion, thereby inducing local immune tolerance. This approach aims to attenuate ischemia-reperfusion injury at the time of implantation and, over the longer term, to reduce the recipient’s dependence on systemic immunosuppression. This work is conducted in close collaboration with our Organ Assessment and Reconditioning Center.
Contact
Lead: D. Koliogiannis · M. Schirren · Co-Investigators: D.T. Koch · S. Jacobi · M. Guba
The disparity between organ demand and supply remains the principal limiting factor in transplant medicine. Xenotransplantation — the use of genetically engineered animal organs — represents a potential avenue toward substantially expanding the donor pool, though significant immunological and physiological barriers must be addressed.
Building on the pioneering contributions to cardiac xenotransplantation at the Munich site — notably the work of Bruno Reichart and Eckhard Wolf — our group extends this translational tradition to abdominal organ transplantation. Our experimental program focuses on large-animal preclinical testing of genetically modified organs and their conditioning via normothermic machine perfusion prior to transplantation. Key objectives include the prevention of hyperacute and delayed antibody-mediated rejection, improvement of physiological xenograft compatibility, and the establishment of perfusion-based protocols for real-time viability assessment and immunological preconditioning of xenogeneic organs.
Transplant Oncology — HCC, CCC, and Colorectal Liver Metastases
Walter KA, Moosburner S, Kreutz T, Gassner JM, Öllinger R, Krenzien F, Modest DP, Guba M, Pascher A, Pratschke J, Raschzok N. Requirements for a successful implementation of liver transplantation as a treatment option for non-resectable colorectal liver metastases into clinical routine — a narrative review. Langenbeck’s Arch Surg. 2026;411(1):107.
Koch DT, Schirren M, Jacobi S, Lange C, Werner J, Koliogiannis D, Guba M. TRANSMIT: Utilizing discarded livers from donors with a history of cancer for patients lacking access to standard allocation — A compassionate use exploratory study. Contemp Clin Trials Commun. 2025;44:101465.
Schindler P, von Beauvais P, Hoffmann E, et al. Combining radiomics and imaging biomarkers with clinical variables for the prediction of HCC recurrence after liver transplantation. Liver Transpl. 2025;31(10):1226–1237.
Settmacher U, Ali-Deeb A, Coubeau L, Cillo U, Line PD, Guba M, Nadalin S, Rauchfuß F. Auxilliary Liver Transplantation According to the RAPID Procedure in Noncirrhotic Patients: Technical Aspects and Early Outcomes. Ann Surg. 2023;277(2):305–312.
Drefs M, Schoenberg MB, Börner N, Koliogiannis D, Koch DT, Schirren MJ, Andrassy J, Bazhin AV, Werner J, Guba MO. Changes of long-term survival of resection and liver transplantation in hepatocellular carcinoma throughout the years: A meta-analysis. Eur J Surg Oncol. 2024;50(3):107952.
Ilmer M, Guba MO. Liver Transplant Oncology: Towards Dynamic Tumor-Biology-Oriented Patient Selection. Cancers. 2022;14(11):2662.
Schoenberg MB, Ehmer U, Umgelter A, et al. Liver transplantation versus watchful waiting in hepatocellular carcinoma patients with complete response to bridging therapy. Transpl Int. 2021;34:465–473.
Schoenberg MB, Bucher JN, Vater A, et al. Resection or Transplant in Early Hepatocellular Carcinoma. Dtsch Arztebl Int. 2017;114(31–32):519–526.
mTOR, Immunosuppression, and Cancer — Experimental and Clinical
Guba M, von Breitenbuch P, Steinbauer M, Koehl G, Flegel S, Hornung M, Bruns CJ, Zuelke C, Farkas S, Anthuber M, Jauch KW, Geissler EK. Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: involvement of vascular endothelial growth factor. Nat Med. 2002;8(2):128–135. — Landmark publication.
Guba M, Yezhelyev M, Eichhorn ME, et al. Rapamycin induces tumor-specific thrombosis via tissue factor in the presence of VEGF. Blood. 2005;105(11):4463–4469.
Koehl GE, Andrassy J, Guba M, et al. Rapamycin protects allografts from rejection while simultaneously attacking tumors in immunosuppressed mice. Transplantation. 2004;77(9):1319–1326.
Guba M, Graeb C, Jauch KW, Geissler EK. Pro- and anti-cancer effects of immunosuppressive agents used in organ transplantation. Transplantation. 2004;77(12):1777–1782.
Knoll GA, Kokolo MB, Mallick R, et al. Effect of sirolimus on malignancy and survival after kidney transplantation: systematic review and meta-analysis of individual patient data. BMJ. 2014;349:g6679.
Wolf S, Hoffmann VS, Habicht A, et al. Effects of mTOR-Is on malignancy and survival following renal transplantation: A systematic review and meta-analysis. PLoS One. 2018;13(4):e0194975.
Wimmer CD, Rentsch M, Crispin A, et al. The Janus Face of Immunosuppression — de novo malignancy after renal transplantation. Kidney Int. 2007;71:1271–1278.
Guba M, Pratschke J, Hugo C, et al. (SMART Study Group). Renal function, efficacy, and safety of sirolimus and mycophenolate mofetil after short-term calcineurin inhibitor-based quadruple therapy in de novo renal transplant patients. Transplantation. 2010;90:175–183.
Machine Perfusion and Organ Preservation
Eden J, Müller PC, Kuemmerli C, Bongini M, Albanesi F, Sposito C, et al. HCC recurrence in liver transplants treated with hypothermic oxygenated machine perfusion: An international matched cohort study. JHEP Rep. 2026;8(3):101732.
Eden J, Brüggenwirth IMA, Berlakovich G, Buchholz BM, Botea F, Camagni S, Cescon M, Cillo U, Colli F, Compagnon P, De Carlis LG, De Carlis R, Di Benedetto F, Dingfelder J, Diogo D, Dondossola D, Drefs M, Fronek J, Germinario G, Gringeri E, Györi G, Kocik M, Küçükerbil EH, Koliogiannis D, Lam HD, Lurje G, Magistri P, Monbaliu D, Moumni ME, Patrono D, Polak WG, Ravaioli M, Rayar M, Romagnoli R, Sörensen G, Uluk D, Schlegel A, Porte RJ, Dutkowski P, de Meijer VE. Long-term outcomes after hypothermic oxygenated machine perfusion and transplantation of 1,202 donor livers in a real-world setting (HOPE-REAL study). J Hepatol. 2025;82(1):97–106.
Eden J, Müller PC, Kuemmerli C, Aegerter N, Brüggenwirth IMA, Berlakovich G, et al. Life Expectancy of Transplanted Livers: HOPE Against Aging? Ann Surg. 2025;282(5):765–771.
Czigany Z, Uluk D, Pavicevic S, Lurje I, Froněk J, Keller T, Strnad P, Jiang D, Gevers T, Koliogiannis D, Guba M, et al. Improved outcomes after hypothermic oxygenated machine perfusion in liver transplantation — Long-term follow-up of a multicenter randomized controlled trial. Hepatol Commun. 2024;8(2):e0376.
Koch DT, Tamai M, Schirren M, et al. Mono-HOPE versus Dual-HOPE in Liver Transplantation: A Propensity Score-Matched Evaluation of Early Graft Outcome. Transpl Int. 2025;38:13891.
Koch DT, Schirren M, Jacobi S, et al. Impact of Hypothermic Oxygenated Machine Perfusion on Immune Cell Clearance in Liver Transplantation. J Clin Med. 2024;14(1):127.
Horné F, Drefs M, Schirren MJ, et al. Hypothermic Oxygenated Machine Perfusion (HOPE) Prior to Liver Transplantation Mitigates Post-Reperfusion Syndrome. J Clin Med. 2022;11(24):7381.
Czigany Z, Pratschke J, Froněk J, Guba M, et al. Hypothermic Oxygenated Machine Perfusion Reduces Early Allograft Injury and Improves Post-transplant Outcomes in Extended Criteria Donation Liver Transplantation (HOPE ECD-DBD). Ann Surg. 2021;274(5):705–712.
Deep Learning, AI, and Transplant Allocation
Koch DT, Hofmann FO, Trompoukis D, et al. Deep Learning-Based MRI Volumetry for Living Kidney Donor Assessment: A New Tool for Predicting Post-Donation Renal Function. Clin Transplant. 2025;39(10):e70338.
Börner N, Schoenberg MB, Pöschke P, et al. A Novel Deep Learning Model as a Donor-Recipient Matching Tool to Predict Survival after Liver Transplantation. J Clin Med. 2022;11(21):6422.
Börner N, Schoenberg MB, Pöllmann B, et al. Deep Learning-Adjusted Monitoring of In-Hospital Mortality after Liver Transplantation. J Clin Med. 2024;13(20):6046.
Tumor Biology, Angiogenesis, and Metastasis
Guba M, Cernaianu G, Koehl G, Geissler EK, Jauch KW, Anthuber M, Falk W, Steinbauer M. A primary tumor promotes dormancy of solitary tumor cells before inhibiting angiogenesis. Cancer Res. 2001;61(14):5575–5579.
Seeliger H, Guba M, Kleespies A, Jauch KW, Bruns CJ. Role of mTOR in solid tumor systems: a therapeutical target against primary tumor growth, metastases, and angiogenesis. Cancer Metastasis Rev. 2007;26(3–4):611–621.
Koch DT, Yu H, Beirith I, et al. Tigecycline causes loss of cell viability mediated by mitochondrial OXPHOS and RAC1 in hepatocellular carcinoma cells. J Transl Med. 2023;21(1):876.
Funding
Our research is supported by the Else Kröner-Fresenius Foundation, the German Cancer Aid (Deutsche Krebshilfe), and intramural research programs of the Faculty of Medicine at LMU Munich.
Join us
We welcome inquiries from motivated individuals interested in joining our team. Research opportunities are available for medical doctoral candidates (Dr. med.), natural science doctoral students (Dr. rer. nat.), and postdoctoral researchers with a background in immunology, molecular biology, or translational surgical science.
Prospective applicants are invited to contact us by e-mail with a brief statement of research interest and curriculum vitae, or to visit the department to discuss potential projects in person.
