Dr. Niv Pencovich, MD, PhD

Email: niv.pencovich@sheba.health.gov.il, niv.pencovich1@gmail.com

Phone: Israel 03-5307022, 052-736-0036,
International +972-3-530-7022 +972-52-736-0036

Position:

Attending Surgeon, Department of Surgery and Transplantation

Primary Investigator, Molecular Biology Lab, Department of Surgery and Transplantation, Sheba Medical Center

Areas of Expertise:

Molecular genetics, Immune suppression, Angiogenesis, Liver regeneration, Cancer biology, Transplant Immunology

Transplant surgery, Hepato-Pancreato-Biliary surgery

Education:

MD studies, Tel-Aviv University, Tel Aviv, Israel

PhD and Post-doctoral studies, The Weizmann Institute of Science, Rehovot, Israel

Residencies and Further Training:

Residency, General surgery, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel

Fellowship, Abdominal transplant surgery, Mayo Clinic, Rochester Minnesota, USA

Research Interests:

Immature Myeloid Cells (IMCs) in tumor development and progression: 

IMCs and specifically CD11b⁺Gr1⁺ (Ly6G/C) Myeloid Derived Suppressor Cells (MDSCs) were shown to play role in the escape from tumor dormancy, and we have demonstrated that the preferential recruitment of these cells into angiogenic versus dormant tumors was associated with unique genome wide expression patterns.  Moreover, we showed that the proangiogenic transcriptional response of MDSCs in malignant tumors was similar to that demonstrated in other proangiogenic developmental processes such as placenta formation and endometriosis. In a recent study we have shown that the transcriptional profile of circulating MDSCs correlates with tumor development and progression in mouse. Unique transcriptional fingerprints correlated with different stages of tumor growth in mouse, and key MDSC genes and canonical signaling pathways were activated along tumor progression. This phenomenon was demonstrated in two cancer models, and a consensus set of genes, involved in MDSC recruitment and angiogenesis, was identified. This data suggest that the transcriptional signatures of circulating MDSCs may serve as markers for tumor progression (Studies are currently held in patients), as well as providing potential targets for future therapies. These ongoing studies were supported by the Israeli Cancer Research Fund (ICRF) and Israeli Cancer Association (ICA), and the data achieved so far was published in the manuscripts in the link below.

Immune Suppression and Myeloid Derived Suppressor Cells in liver regeneration:

Liver regeneration depends on sequential activation of pathways and cells involving the remaining organ in recovery of mass.  Proliferation of parenchyma is dependent on angiogenesis. Understanding liver regeneration associated neovascularization may be useful for development of clinical interventions aiming to enhance resectability for patients with liver malignancies. Myeloid Derived Suppressor Cells (MDSCs) promote tumor angiogenesis, and play a role in developmental processes that necessitate rapid vascularization. We have demonstrated that following partial hepatectomy, MDSCs were enriched within regenerating livers, and their depletion led to increased liver injury and post-operative mortality, reduced liver weights, decreased hepatic vascularization, reduced hepatocyte hypertrophy and proliferation, and to aberrant liver function. Gene expression profiling of regenerating liver-derived MDSCs demonstrated a large-scale transcriptional response, involving key pathways related to angiogenesis and immune suppression. Functionally, enhanced reactive oxygen species production and angiogenic capacities of regenerating liver-derived MDSCs were confirmed. A comparative analysis revealed that the transcriptional response of MDSCs during liver regeneration resembled that of peripheral blood MDSCs during progression of abdominal tumors, suggesting a common MDSC gene expression profile promoting angiogenesis and immune suppression. This study showed that MDSCs contribute to early stages of liver regeneration possibly by exerting pro-angiogenic and immune suppressive functions using a unique transcriptional program. Further studies will examine the complex interaction of MDSCs with the immune milieu within the regenerating liver, and the possibility to enhance the regenerative capacity by modulating the function of MDSCs and their counterparts.  This study is supported by the Israeli Science Foundation (ISF) and the data so far was published in the manuscripts in the link below.

Clinical studies in general surgery:

We are interested in studies regarding decision making and outcomes of various surgical procedures, mainly related to hepatobiliary surgery. Numerous studies were published during the recent years as can be found in the link below.

Publications:

Here is a link to the list of publications of Dr. Pencovich in PubMed. PubMed is a database of scientific articles in the fields of medicine and life sciences.

Research Grants and Awards: