Since 2000 I am an independent principal investigator at Hadassah Medical Center. Previously I developed novel functional MRI methodologies to assess vascular responses to physiological stimuli - hypercapnia and hyperoxia. During the last twelve years, I have chosen to focus my research on the liver, a multi-functional organ with its unique role and blood supply system. Currently I am a Senior Lecturer at the Hebrew University of Jerusalem. I was recently selected to be the chairman and to establish the Wohl National Center for Translational Medicine at the Hadassah Hebrew University Medical Center. I run a research lab that focuses on studying tissue interactions that modulate primary and metastatic liver cancer progression, combing various methodologies including mouse models, imaging and molecular biology. Additional project in the lab focus on understanding the process of liver regeneration following partial hepatectomy.
- Elucidating the effect of chronic liver inflammation on colorectal cancer metastatic dissemination and progression
- Liver regenerative process alterations as a consequence of bleeding and transfusion of red blood cells with different storage time: fresh vs. "aged"
- Establishment of an fMRI method for liver and kidney hemodynamic assessment
- Assessment of anti-angiogenic therapies on multiple tumor models using MRI
- The effect of partial hepatectomy in a chronic inflamed liver on regeneration and carcinogenesis
- The Liver Response to Hemorrhagic Shock and Subsequent Resuscitation
- Elucidating new drugs for NAFLD (nonalcoholic fatty liver disease)
Elucidating the effect of chronic liver inflammation on colorectal cancer metastatic dissemination
Outgrowths of disseminated metastases remain the primary cause of mortality in cancer patients; however, molecular and cellular mechanisms regulating metastatic spread remain partially elusive. It is estimated that approximately 50% of colorectal cancer (CRC) patients develop liver metastases. Recently published clinical studies have shown that colorectal liver metastasis (CRLM) is less frequent in patients with fatty liver, hepatic cirrhosis or chronic hepatitis B and C virus infection. The proposed research is designed to take a different perspective on this complicated process and to elucidate the pre-existing heterogeneous biological microenvironment in which the liver is less permissive to support metastases establishment and the factors which play a role in this. By using Mdr2-ko mice with our already established CRLM model we will be able to shed light on these complex molecular and cellular interactions. Our preliminary data demonstrates that the existence of a chronic hepatic inflammatory background in mice proactively obstructs CRLM dissemination at the age of two month while proactively mediates CRLM at the age of five months. Our central hypothesis is that the pre-existing hepatic microenvironment can alter liver metastatic seeding. The proposed research is designed to elucidate the unexplored aspects of the variable hepatic environments in facilitating or arresting metastatic disease. In order to address this complex issue, a multidisciplinary approach is undertaken involving analyses of liver samples from the different pre-existing hepatic scenarios (RNA sequencing, cytokine array etc.), cell analysis, intravital imaging and cell population manipulations.
Liver regenerative process alterations as a consequence of bleeding and transfusion of red blood cells with different storage time: fresh vs. "aged"
Liver regeneration, a process that rapidly compensates for the acute loss of liver parenchyma, plays a critical role in patients requiring large liver resections. These operations are frequently associated with massive blood loss with subsequent blood transfusion. Concerns have been raised about the safety and efficacy of transfusing stored blood. Previously, in a rat model of acute bleeding followed by blood resuscitation we found that whereas the transfusion of fresh blood improved liver outcome, transfusion of blood stored for 7 days exacerbated liver injury (Crit Care Med, 2013). Thus avoiding further liver injury induced by the transfusion of aged blood in liver surgeries is of paramount clinical importance. Our currently ongoing study, in a rat model of PHx, revealed that acute bleeding during PHx delays and attenuates liver regeneration. Moreover, with bleeding the mode of liver regeneration is altered from hepatocytes proliferation to hypertrophy (FASEB J, 2017). Furthermore, our preliminary results demonstrate that transfusion with fresh RBCs restored liver regeneration capacity following PHx and bleeding, while stored RBCs administration impedes the process and alters the pattern of liver regeneration causing further liver injury. Our current research goal is to further elucidate the underlining molecular pathways involved in the altered regenerative process due to "aged" blood transfusion. The results of this study may lead to better understanding of the liver regeneration process under pathological conditions.
- Nathalie Nachmansson Abudi
- Tal Asraf
- Dr. Shira Yanovsky-Dagan
- Eyal Yehezkel
- Ariel Weil
- Adi Yehezkel
- Dr. Hila Barash
- Dr. Yifat Edrei
- Dr. Shlomi Laufer
- Elia Dery
- Zohar Milman
- Chani Komar
- Omri Duev
- Esther Goldlist
- Prof. Eithan Galun, Hadassah Hebrew University Hospital
- Prof. Idit Matot, Sourasky Medical Center
- Dr. Stilla Frede, University Hospital Bonn, Germany
- Prof. Yehuda Ginosar, Hadassah Hebrew University Hospital
- Prof. Marta Weinstock-Rosin, Institute for Drug Research, Hebrew University
- Ministry of Health