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Molecular Biomarkers for Neurodegeneration

Dr. Rivka Dikstein of the Department of Biomolecular Sciences is investigating the “checks and balances” that control how our genetic code is transformed into functional proteins. While fascinating from the point of view of basic science, Dr. Dikstein’s research also has practical, biomedical significance. Among her recent accomplishments, she has positively identified 150 compounds with clinical potential for preventing the binding of molecular factors associated with the onset of neurodegeneration. This work has significance for the development of future treatments for three currently incurable neurodegenerative diseases: Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD).

A new model for rheumatoid arthritis

When the immune system activates its defenses against a foreign invader, cells called T-lymphocytes migrate to the peripheral lymphatic nodes (LNs). Occasionally, however, the entry and subsequent response of T-lymphocytes in these LN sites leads to severe inflammation. This is what happens in rheumatoid arthritis, and this is the focus of research being conducted by Prof. Idit Shachar from the Department of Immunology. 

Prof. Shachar has identified how a protein called CD151 mediates T-cell migration. To directly inhibit CD151 function, Prof. Shachar and her team generated a truncated CD151 peptide fragment mimicking a segment of the CD151 extra cellular loop. This engineered protein managed to inhibit T-cell migration in vitro and in animal models. This preclinical experimentation identified a strategy that may be used, in the future, for the development of novel drugs for combatting rheumatoid arthritis.

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MS biomarkers

Autoimmune disorders such as multiple sclerosis (MS) are likely caused by a complex combination of genetic and environmental factors. In particular, autoimmunity can often arise as a result of errors in cellular protein levels. Dr. Yifat Merbl of the Department of Immunology is working to map the changes that occur as a result of post-translational modifications (PTMs), and which are implicated in autoimmunity and MS. Her ultimate goal is to discover biomarkers for diagnosis and treatment.

Dr. Merbl uses PTM profiling—a system which she established during her postdoctoral studies at Harvard Medical School, developed further in her Weizmann lab, and has already been used to uncover PTM signatures and targets of relevance to malignant tumors and Alzheimer’s disease. PTM profiling enables Dr. Merbl to conduct quantitative and tractable high-throughput monitoring of multiple modifications of thousands of proteins in parallel, under conditions that are relatively close to those of the complex cellular environment.

She is also using a second method recently developed in her lab, called mass spectrometry analysis of proteolytic peptides (MAPP), in order to generate patient-specific signatures of protein breakdown in cells and tissues. By identifying peptides as they are generated by the proteasome, MAPP is poised to reveal new insights into MS and other autoimmune diseases.

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