Institute Activities

Research in the laboratory of Prof. Eldad Tzahor has demonstrated that a transient state of senescence—a state in which cells cease to replicate, but do not die—is essential for tissue development and regeneration. Examining the first steps that take place after cardiac injuries in zebrafish and neonatal mice, Prof. Tzahor showed that agrin, a compound that promotes heart regeneration after heart attacks, orchestrates a repair process involving transient senescence in cardiac fibroblasts. This dynamic—conserved through evolution and observed from lower organisms to mammals—may have implications for improved understanding and clinical treatment of cardiac injury in humans.

Prof. Orly Reiner, a member of the Department of Molecular Genetics, has developed a platform for studying the migration of human embryonic stem cells in the developing brain.  The platform, called “Brain on a Chip,” has allowed Prof. Reiner (for the first time anywhere) to track the molecular interactions involved in the development of brain surface wrinkles. The technology provides a powerful model for the study of brain development, as well as developmental brain disorders like microcephaly, epilepsy, and schizophrenia. 

Prof. Jacob Hanna of the Department of Molecular Genetics recently attained a detailed profile of the molecular events associated with iPSCs—“induced” pluripotent stem cells, which are derived from adult cells, and which have the potential to differentiate into all adult cell types.

Working in collaboration with his departmental colleague Prof. Tzachi Pilpel, as well as Prof. Ido Amit of the Department of Immunology, Prof. Hanna identified two distinct and synergistic transcriptional modules that dominate successful reprogramming. The scientists’ findings show how these two molecular dynamics work together, creating the essential reconfiguration that marks fully differentiated adult cells for reprogramming, and drives them toward the “stemness” characteristic of iPSCs. 

Research conducted by Prof. Tsvee Lapidot of the Department of Immunology has demonstrated that stem cells retained in the marrow follow daily cycles of light and darkness.

This discovery, reported in Cell Stem Cell, suggests that adjusting the timing of stem cell harvesting to these daily cycles—or short pretreatment with the night hormone melatonin—may help increase the success of clinical bone marrow transplantation protocols. This research was conducted with Dr. Karin Golan, a consultant who is a member of the Lapidot team.

Prof. Steffen Jung of the Department of Immunology recently discovered that stem cell transplantation is associated with the generation of a distinct cell population in a specific area of the body: the brain and spinal cord.  In research published in Nature Communications, Prof. Jung demonstrated that offspring of transplanted stem cells could “seed” the brain, generating microglia—immune cells that scavenge the brain tissue for pathogens, plaques, and damaged neurons. However, the new graft-derived cells generated in this process were distinct from microglia native to the CNS, having a different gene expression pattern, chromosome structure, and functional immune response. Prof. Jung’s study could impact stem cell-based clinical therapies for diseases associated with pathological immune function in the central nervous system. 

Prof. Atan Gross of the Department of Biological Regulation, working with his departmental collague Dr. Ayelet Erez and Prof. Jacob Hanna of the Department of Immunology, has shown how cellular power plants called mitochondria—known to continuously change their shape by shrinking, expanding, elongating, and fusing—help regulate stem cell differentiation. The scientists found that in embryonic stem cells with an intact copy of the gene coding for MITCH2—a protein Prof. Gross discovered—adjacent mitochondria fused together at a high rate. This generated elongated mitochondrial structures capable of embarking on a path toward differentiation. In contrast, in MITCH2-lacking cells, mitochondria failed to elongate, and remained in their embryonic stem-cell state. Prof. Gross’s discovery opens up a new avenue for stem cell research, in which modification of mitochondrial size and shape might help drive cell fate.

Dr. Liran Shlush of the Department of Immunology, together with colleagues at the University of Toronto, has created a new cell line that will make it easier for scientists to study the molecular dynamics of acute myeloid leukemia (AML).

The novel cell line—based on stem cell-like connective tissue that expresses a genetic marker for pluripotency—is characterized both by the inv(3) genetic profile and the loss of chromosome 7. By establishing a platform for studying how inv(3) AML cells interact with other cell populations, Dr. Shlush’s new cell line could lead to the discovery of new strategies for AML treatment.

A number of year ago, Prof. Jacob Hanna of the Department of Molecular Cell Biology demonstrated that a reduction in the levels of a protein called Mbd3 improves the efficiency by which mature cells become iPSCs—“induced” pluripotent stem cells derived from adult cells.  He called this protein a “hand brake” because it normally protects cells from “sliding backwards” in development.

Recently, Prof. Hanna and his colleagues demonstrated that, by removing one particular conformation of the Mbd3 protein, it is possible to culture skin cells in which 100% of the cells revert from their mature, differentiated state, into iPSCs—in just eight days. A significant improvement on existing methods, Prof. Hanna’s new and highly efficient iPSC production platform will help advance research related to tissue engineering and regenerative medicine.