Department of Biological Regulation

Rony Seger, Head


The research in the department of Biological Regulation is concentrated on molecular, cellular and physiological studies of processes that collectively control the action of cells, tissues, organs and the entire body. Extensive efforts are directed to the elucidation of the regulators and pathways of the transmission and translation of signals evoked by hormones, as well as growth and death signaling factors. These studies include: (i) characterization of interactions between growth factors, hormones and extra cellular matrix components with specific receptors; (ii) induction and mechanisms of action of programmed cell death, necrosis and cell survival; (iii) mediation of intracellular signaling via second messengers protein kinase cascades or through lipid mediators (iv) mechanisms of angiogenesis and oncogenesis and (v) role of proteases and protein degradation in cellular regulation. The results of these investigations advance our basic understanding of phenomena related to reproduction as well as tumor and vascular biology. In addition, it enables us to develop useful applications that intend to improve patient management.

A diversity of experimental methodologies is used in these projects. In particular unique non invasive methodologies of Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS) are being developed in this department. The research groups include students from life sciences and chemistry, residents, physicians, and guest researchers from Israel and abroad. Several projects have already incorporated clinical assessment of experimental drugs and new diagnostic methods.


H. Degani

Estrogen regulation of angiogenesis and perfusion of breast cancer; from molecular mechanisms to functional MRI of the microvascular physiology

Hyperpolarized magnetic resonance spectroscopy and imaging of cancer metabolism; searching for novel metabolic markers of cancer
H. Degani, Professor Lucio Frydman, Weizmann Institute

Renal function through sodium grandients; Non-invasive, high resolution sodium MRI.
H. Degani, Dr. Edna Haran, Weizmann Institute

Mechanisms of lymphatic metastasis in breast cancer; In vivo fluorescence and magnetic resonanc imaging

Advanced non invasive MRI methods for breast cancer detection and diagnosis ; clinical investigations
H. Degani, Dr. Myra Shapiro, Meir medical Center

  1.  3D Tracking of the mammary tree using diffusion tensor magnetic resonance imaging

  2.  Advanced methods for analysis of dynamic contrast enhanced MRI based on a combined model free and model based method.

Molecular magnetic resonance imaging of the estrogen receptor
H. Degani, Professors David Milstein and Joel Sussman, Weizmann Institute

  1.  Synthesis of new, high affinity ligands of the estrogen receptor as probes for molecular imaging

  2.  Structuaral studies (x-ray crystalography and NMR) of the estrogen receptor - targeted ligands complex

  3.  Functional activities and molecular imaging of the new targeted ligands in estrogen receptor positive huaman breast cancer cells

Perfusion and angiogensis in lung cancer: The role of the bronchial and pulmonary vascular network using Fluorescence and magnetic resonance imaging methods


N. Dekel

Regulation of the meiotic cell cycle: use of rodent oocytes as a model system.

Cell-to-cell communication: regulation of expression, posttranslational modification, degradation and function of the gap junction proteins, Cx43 and Cx37.

Mechanisms involved in successful implantation.

Molecular characterization of the ovulatory cascade


A. Gross

Establishing the role of MTCH2/MIMP in mitochondrial metabolism and apoptosis

Establishing the role of the ATM-BID pathway in regulating the quiescence of haematopoietic stem cells


M. Neeman

Cardiac MRI
M. Neeman, Katrien Vandoorne, Moriel Vandesburger

Vascular remodeling during pregnancy and development
M. Neeman, Tal Raz, Katrien Vandoorne, Reut Avni,

Angiogenesis in ovarian cancer
M. Neeman, Gila Meir, Sefi Addadi, Hagit Dafni, Roni Oren, Michal Weiler

  1.  The role of fibroblasts and myofibroblasts in tumor growth, angiogenesis, vascular permeability and vascular maturation

  2.  MR labeling and tracking of cell migration during angiogenesis

Regulation of lymphangiogenesis.
M. Neeman, Batya Cohen, Gila Meir, Sefi Addadi

  1.  The role of VEGF-A and Akt/PKB in interstitial convection and lymphatic drain

  2.  In vivo imaging of lymphatic drain and lymph node metastasis

  3.  The role of VEGF family members and microenvironmental stress in tumor lymphangiogenesis

Development of a reporter gene for MRI
M. Neeman, Batya Cohen, Moriel Vandsburger, Marina Radoul

  1.  Ferritin expression in tumor cells

  2.  Ferritin expression in fibroblasts


I. Sagi

Structural -Dynamic studies of Metalloenzymes and Protein-Nucleic Acid Interactions.

Our research covers a wide range of areas with the common themes of dynamic structure-function investigations. The principle areas of investigation are mechanism of action of metalloenzymes and protein-nucleic acid interactions. Our objective is to study


R. Seger

MAPK and PKB signaling in proliferation and oncogenic transformation

  1.  The nuclear translocation of MAPKs - characterization and molecular mechanisms.

  2.  Inter-relationship between the PKB, JNK and ERK cascades.

  3.  Mechanisms of GPCR signaling to MAPKs and PKB.

  4.  Alternative splicing in determining signaling specificity of ERKs.

  5.  Role of calcium in MAPK-protein interactions

Alterantive nuclear translocation mechanisms of signaling proteins

  1.  Characterization of nuclear translocation of MAPKs and other signaling proteins.

  2.  Molecular mechanisms of the nuclear translocation of MAPKs.

  3.  Inhibition of nuclear shuttling as anti-oncogenic therapy

PEDF phosphorylation: role in angiogenesis and cancer.

  1.  Development of the phospho-mimetic mutants of PEDF as anti angiogenic drugs.

  2.  Signaling by PEDF and its phospho-mimetic mutants.

  3.  Study the phosphorylation of PEDF as a model for extracellular phosphorylation.


A. Tsafriri

Molecular regulation of ovulatory changes in mammals.
A. Tsafriri, Helena Ashkenazi, Shmulik Motola, Xiumei Cao, Malka Popliker, Seymour Pomerantz, Marco Conti, Stanford

  1.  The roles of gonadotropins and EGF-like factors in triggering ovulation.

  2.  The resumption of meiosis and its regulation.

  3.  Ovulation as a tissue remodeling process.

The development and demise of ovarian follicles in vivo and in vitro: the role of apoptosis.
A. Tsafriri, Atan Gross, KerenYacobi


I. Ulitsky

Roles of long noncoding RNAs in gene regulation

  1.  Functions of long noncoding RNAs in establishing cell identify

  2.  Sequence determinants in long noncoding RNAs

  3.  Evolution of intergenic regions in vertebrates

  4.  Subcellular localization determinants in long RNAs


Y. Yarden

Roles for growth factors in cancer progression, focusing on epithelial cell migration and metastasis.

Feedback regulation of growth factor signaling, concentrating on receptor phosphorylation, ubiquitination, and endocytosis. Transcription-mediated control is studied at the level of mRNA and microRNA.

Molecular targeted therapy of cancer, including monoclonal anti-receptor antibodies, kinase inhibtors, soluble receptors and emerging technologies.

Roles for microRNAs and other non-coding RNAs in signal transduction and tumor progression

Research on biomarkers based on detailed characterization of signal transduction and feedback regulation.

Brain tumors, pancreatic, breast and other types of cancer: molecular mechanisms underlying aggressiveness and resistance to therapies.