Prof. Uri Nir is Director of the Nano Medicine Center at the Institute of Nanotechnology and Advanced Materials (BINA) and Dean of The Mina and Everard Goodman Faculty of Life Sciences.
Having revealed a “trio” of proteins that appear to play a pivotal role in the onset of various cancers, Nir is now dedicated to the development of novel anti-cancer drugs that will target these key regulators.
Nir uses nanosized vehicles to deliver cancer-fighting drugs directly to malignant cells. Working together with Dr. Yoav Paas, Nir’s techniques may make it possible to achieve better results with lower doses, leading to a reduction in chemotherapy-related side effects.
One of the key questions in modern biology is what governs the normal proliferation and life span of mammalian cells and what “goes wrong” in cancer cells. Unraveling these molecular events should lead to a better understanding of the malignant process and ultimately to the rational development of novel cancer-therapy approaches.
Nir’s lab studies the involvement of stress response circuits in the adaptation of cells to stress insults, and in the growth of cancer cells.
Three intracellular proteins which “cross-talk” with each other are currently being studied in Nir’s lab.
The tyrosine kinase Fer is an enzyme residing in both the cytoplasm and nucleus of cells that supports the resistance of cells to various stress cues such as oxidation and nutrient deprivation. Nir’s team has recently discovered a previously unknown oncogenic form of Fer which is solely expressed in malignant cells. Specific knock-down of this oncogenic form led to the apoptotic death of the treated cancer cells.
Thus, the oncogenic Fer is a novel target for cancer intervention. To translate these findings into the development of a new anti-cancer drug, they developed a yeast-based high-throughput screening assay performed in an advanced robotic system. This enabled the development of a highly potent and selective Fer inhibitor that induces apoptotic death selectively in malignant cells, paving the way for the development of a new anti-cancer drug.
TRNP, a nuclear protein that associates with chromatin and is highly expressed in neuronal brain cells, is a transcription regulator that supports the survival of these cells under defined stress conditions.
The malfunctioning of TRNP may, therefore, contribute to the onset of neuronal cell death and consequent neurodegenerative diseases. Nir’s lab is currently examining the functioning of TRNP in mice models under normal and pathological conditions.
TMF, a Golgi-associated protein, is translocated under stress, and dispersed in the cytoplasm, where it directs key transcription regulators to degradation.
Recently, Nir’s group characterized TMF as a master regulator which modulates the response of cells to stress insults and thus plays a key role in the acquired resistance of cancer cells to chemotherapeutic agents. They are currently devising molecular approaches for manipulating the TMF system and, thereby, restoring the sensitivity of cancer cells to chemotherapeutic treatments.
The future scientific goals of Nir’s group include further exploration of the role of Fer in cancer and inflammatory diseases, and identification of low molecular weight compounds that would affect Fer and attenuate the progression of cancer and inflammatory diseases.
In addition, they hope to identify and characterize substrates of the meiotic Fer tyrosine kinase and elucidate its spermatogenic function. Lastly, they would like to investigate the tumor suppressive activity of TMF using modified TMF genes, for the purpose of developing novel anti-cancer gene therapy approaches.