Department of Biological Regulation

Nava Dekel, 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 and (iv) mechanisms of angiogenesis and oncogenesis. 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

L. Gilboa

Soma - germ line interactions and germ line stem cell establishment in Drosophila melanogaster

1.  Formation of the somatic niche for germ line stem cells.

2.  Establishment of germ line stem cells from primordial germ cells.

3.  Understanding how somatic cells determine the number of germ line stem cells.

4.  Uncovering new genes that affect germ line stem cell maintenance and differentiation.

A. Gross

Mitochondria in apoptosis: Mechanisms of action of the BCL-2 family members

Mitochondria Carrier Homolog 2: role and function in embryogenesis, apoptosis and cancer

The response of cells to DNA damage: The role of ATM-mediated BID phosphorylation

M. Neeman

Targeted imaging of angiogenesis
M. Neeman, Helena Sheikhet Migalovich, Sefi Addadi

Multimodality imaging
M. Neeman, Alon Harmelin, Inbal Biton, Vyacheslav Kalchenko

Angiogenesis in ovarian cancer
M. Neeman, Gila Meir, Sefi Addadi, Yael Tzuman, Helena Sheikhet Migalovich

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

3.  Development of a contrast material for MR mapping hyaluronidase activity

Regulation of lymphangiogenesis.
M. Neeman, Batya Cohen, Gila Meir, Stav Sapoznik

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

1.  Ferritin expression in endothelial cells

2.  Ferritin expression in liver hepatocytes

Imaging of apoptosis
M. Neeman, Atan Gross, Natalie Yivgi-Ohana, Michal Eifer

Y. Salomon

Anti-cancer treatments :

1.  Development of novel bacteriochlorophyll-based drugs for photochemotherapy.

2.  Boron neutron capture therapy.

Reactive oxygen species, their generation by bacteriochlorophyll and light, their role in signal transduction and mechanisms of cell and tumor destruction.

Vascular biology and vascular destruction.

R. Seger

MAPK signaling in proliferation and oncogenic transformation

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

2.  The role of non-alpha Importins in regulating nuclear effects of MAPKs.

3.  Structure-function relationships of ERK and MEK.

4.  The effect of calcium on the ERK1/2 and ERK5 signaling cascades.

5.  Protein-protein interaction in the MAPK cascades.

6.  Alternative splicing in determining signaling specificity of ERKs.

Apoptotic MAPK and PKB signaling

1.  Mechanism of PKB inactivation upon stimulation.

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

3.  Scaffold proteins in the PKB cascade.

4.  Mechanism of GPCR signaling to MAPKs and PKB.

PEDF phosphorylation: role in angiogenesis and cancer.
R. Seger, Teva

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.

E. Tzahor

Head muscle patterning and differentiation

1.  Characterization of head muscle derived satellite cells

2.  Dissecting the myogenic programs in head muscle progenitors

3.  Involvement of p53 in cranial myogenesis

Cardiac and skeletal muscle progenitors during vertebrate embryogenesis

1.  Studying the crosstalk between BMP and FGF signaling pathways in cardiac progenitors

2.  Regulation of Islet1 gene expression using novel imaging techniques in live embryos

3.  The origin of the heart endocardium: Focus on the role of endothelial cells in cardiogenesis

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 EGFR and HER2 in carcinoma development, resistance to conventional therapy and potential for future drug development.

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.