Prof. Daniel Segal
Ph.D.: 1981, Hebrew University
Phone: (Office) +972-3-640-9835
(Fax) +972-3-640-9407
E-mail: dsegal@post.tau.ac.il
Room#: Green 207
Member's portrait
  Personal Information
  Research Interests
  Selected Publications

Personal Information

Education

1970-73 B.Sc. Hebrew University, Biology
1974-75/
1977-81
Ph.D. Hebrew University, Genetics
1-9/1976 Univ. Utrecht, Developmental Biology


Academic Positions

1974-1981 Teaching Assistant, Department of Genetics, Hebrew University
4-10/1981 Post doc, Leiden University, Drosophila development
1981-1984 Post doc, Harvard University, Drosophila, developmental genetics
1984-1987 Scientist, Weizmann Institute of Science, Drosophila oncogene homologs, Drosophila neurogenetics
1987-1992 Lecturer, Tel-Aviv University, Drosophila, developmental genetics, Drosophila neuroendocrinology
1992-1996 Senior lecturer, Tel-Aviv University, Drosophila, developmental genetics, Drosophila neuroendocrinology
1993-1994 Visiting Professor, Indiana University, Molecular genetics of cultured cells
1996-1999 Head of the Department, Tel-Aviv University
1997-2008 Associate Professor, Department of Molecular Microbiology and Biotechnology, Tel-Aviv University
2008-ongoing Professor, Department of Molecular Microbiology and Biotechnology, Tel-Aviv University

Research Interests

'Conformational diseases' are diseases caused by misfolding of a protein, often as a result of a missense mutation that does not necessarily disrupt the active site of the protein. As a result, the protein may lose its function, and often the misfolded monomers self-assemble to form cytotoxic aggregates. We study the structural causes of such protein misfolding in conditions ranging from neurodegenerative diseases to certain cancers.

In various cases such misfolding can be reversible under experimental conditions. Thus, drugs that will cause refolding of the misfolded protein may restore its function and prevent its harmful aggregation. Research methods: In vitro and bacterial assays of protein folding and aggregation (in collaboration with Prof. Ehud Gazit, Dept. Biotechnology), cytotoxcisity assays in cell culture, genetics and molecular biology of transgenics (Drosophila, mice), immunohistochemistry, behavioral and cognitive assays (mouse work - in collaboration with Dr. Dan Frenkel, Dept. Neurobiology).

Main projects in the lab include:

1. Develop and screen in vivo novel small molecules as amyloid-beta and tau inhibitors in Alzheimer’s disease.

2. Develop and screen natural plant compounds as amyloid-beta and tau inhibitors in Alzheimer’s disease.

3. Develop and screen in vivo novel small molecules as alpha-synuclein inhibitors in Parkinson’s disease

4. Develop and screen in vivo novel small molecules as TDP-43 inhibitors in ALS.

5. Examine the mechanism of spreading of TDP-43 in ALS.

6. Examine the role of protein glycosylation in the aging and neurodegenerative brain.

7. Study misfolding of the tumor suppressor proteins p53 and VHL and develop small molecules for restoring their folding and function.

Tel: 03-6409835; email: dsegal@post.tau.ac.il

Selected Publications

 

Selected publications:

Frydman-Marom, A., Levin, A., Farfara, D., Benromano, T., Scherzer-Attali, R., Peled, S., Vassar, R., Segal, D., Gazit, E., Frenkel, D., and Ovadia, M. (2011). Orally administrated cinnamon extract reduces beta-amyloid oligomerization and corrects cognitive impairment in Alzheimer's disease animal models. PLoS One, 6(1): e16564.


Frydman-Marom, A., Convertino, M., Pellarin, R., Lampel, A., Shaltiel-Karyo, R., Segal, D., Caflisch, A., Shalev , D.E., and Gazit, E. (2011). Structural basis for inhibiting beta-Amyloid oligomerization by a non-coded beta-breaker substituted endomorphin analogue. ACS Chemical Biology, 6(11):1265-76.

Scherzer -Attali, R., Farfara, D., Ben-Romano, T., Trudler, D., Vientrov, M., Shaltiel-Karyo, R., Shalev, D.E., Gazit, E., Segal, D., and Frenkel, D. (2012). Naphthoquinone-tryptophan reduces neurotoxic A-beta*56 level and improves cognition in Alzheimer's disease animal model. Neurobiology of Disease 46(3): 663–672.


Scherzer-Attali, R., Shaltiel-Karyo, R., Adalist, Y., Segal, D., and Gazit, E. (2012). Generic inhibition of amyloidogenic proteins by two naphthoquinone-tryptophan hybrid molecules. Proteins, 80(8):1962-73.


Shaltiel-Karyo, R., Davidi, D., Menuchin, Y., Frenkel-Pinter, M., Marcus-Kalish, M., Ringo, J., Gazit, E. and Segal, D. (2012). A novel, sensitive assay for behavioral defects in Parkinson’s disease model Drosophila. Parkinson's Disease (697564, Epub 2012 Jul 25).


Shaltiel-Karyo, R., Davidi, D., Frenkel-Pinter, M., Ovadia, M., Segal, D., and Gazit, E. (2012). Differential inhibition of alpha-synuclein oligomeric and fibrillar assembly by cinnamon extract. Biochimica et Biophysica Acta 1820: 1628–1635.


Herzog, G., Joerger, A.C., Shmueli, M., Fersht, A.R., Gazit, E. and Segal, D. (2012) Evaluating Drosophila p53 as a model system for studying cancer mutations. J Biol Chem, 287(53):44330-7


Scherzer-Attali, R., Convertino, M., Pellarin, R., Gazit , E., Segal, D., and Caflisch, A. (2013). Methylations of tryptophan modified naphtoquinone affect its inhibitory potential towards A-beta aggregation. J. Phys Chem B 117:1780-9.


Shaltiel-Karyo, R., Frenkel-Pinter, M., Matia, N., Patrick, C., Rockenstein, E., Masliah, E., Segal, D., and Gazit, E. (2013). A BBB disrupter is also a potent α-synuclein aggregation inhibitor: A novel dual mechanism of Mannitol for the treatment of Parkinson's disease. J Biol Chem, 288(24):17579-88.


Shmueli, M.D., Schnaider, L., Rosenblum, D., Herzog, G., Gazit, E., and Segal, D. (2013). Structural Insights into the Folding Defects of Oncogenic pVHL Lead to Correction of Its Function In Vitro. PLoS ONE, 8: e66333.


Maor, G., Rencus-Lazar, S., Filocamo, M., Steller, H., Segal, D. and Horowitz. M. (2013). The unfolded protein response in Gaucher disease: from human to Drosophila. Orphanet J of Rare Diseases 11;8(1):140.


Saad, Y. Segal, D. and Ayali, A. (2014). Enhanced neurite outgrowth and branching precede increased A-beta-induced neuronal apoptosis in an in-vitro Alzheimer's model. J. Alzheimer's Disease (in press).


Shmueli, MD., Schnaider, L., Herzog, G., Gazit, E., and Segal, D. (2014). Computational and experimental characterization of dVHL establish a Drosophila model of VHL syndrome. PLOS ONE (in press).

 

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