M.D.: Tel-Aviv University, Israel
Ph.D.: Weizmann Institute of Science, Israel
Residency in Pediatrics: Sheba Medical Center, Israel
Post-doctorate: National Institutes of Health, USA
Position: Head, Genetics Institute
Soroka University Medical Center
The Sraga Segal Department of Microbiology, Immunology and Genetics
Faculty of Health Sciences
E-mail: obirk@bgu.ac.il
Webpage: http://fohs.bgu.ac.il/hmglab/


Identification and characterization of genes associated with human diseases: Unraveling of novel drug targets, developing tools for diagnosis of genetic diseases






  • Background

Genetic studies of unique inbred consanguineous populations in southern Israel enable unraveling of the molecular basis of hereditary diseases. The laboratory focuses on the identification and characterization of genes associated with human diseases. The research being conducted is of importance to three areas:

Medicine: Allowing for molecular diagnosis of hereditary human diseases, enabling carrier detection and prenatal diagnosis.

Science: Discovery of the molecular basis for human diseases and of normal molecular developmental pathways.

Biotechnology: Discovery of novel drug targets for hereditary disorders, as well as developing diagnostic tools for genetic diseases.


  • Current research

Studies being performed rely on:

- Linkage analysis studies of large inbred families, mostly from Bedouin communities of southern Israel.

- Molecular analysis of chromosomal aberrations associated with specific human disorders.

- Microarray analysis of disease vs. normal tissues.

- Functional genomics analysis (in vitro and in vivo) of disease-associated genes uncovered in 1-3 above.

Once disease-associated genes are identified, studies of these genes ensue – from biochemical and structural analysis of the encoded proteins, to cellular studies of mutated cells and to the generation and analysis of animal models of the diseases. We have thus far identified the molecular basis of 15 human diseases, including myopia, short stature, a variant of seborrheic dermatitis and psoriasis and other rare and common diseases, including 6 severe neurodegenrative diseases in the Bedouin and the Jewish population. The findings are of both scientific and medical interest and are immediately implemented in massive carrier testing and prenatal diagnosis.

Potential for joint ventures with the pharmaceutical industry.

Identifying and characterizing novel disease-associated genes to serve as drug targets to be subsequently marketed to big pharmaceutical companies.

Generation of genetic carrier / prenatal diagnosis for the Arab/Bedouin population worldwide. This could evolve as a testing plant in Beer-Sheva, or an operation for generation of lab kits.

Establishing a service lab for testing mutations in various common diseases – competitive prices, using local existing equipment and well-trained people (DHPLC, Affymetrix set-up, etc.)

We are affiliated with the Soroka University Medical Center, and thus have direct access to the largest health services supplier in Israel.


  • Selected publications

Birk O.S., Casiano D.E., Wassif C.A., Cogliati T., Zhao L., Zhao Y., Grinberg A., Huang S., Kreidberg J.A., Parker K.L., Porter F.D. and Westpha H. (2000). The LIM homeobox gene Lhx9 is essential for mouse gonad formation. Nature, 403:909-913.

Birnbaum R.Y., Zvulunov A., Hallel-Halevy D., Cagnano E., Finer G., Ofir R., Geiger D., Silberstein E., Feferman Y. and Birk O.S. (2006). Seborrhea-like dermatitis with psoriasiform elements caused by a mutation in ZNF750, encoding a putative C2H2 zinc finger protein. Nature Genetics, 38:749-751.

Agamy O., Ben Zeev B., Lev D., Marcus B., Fine D., Su D., Narkis G., Ofir R., Hoffmann C., Leshinsky-Silver E., Flusser H., Sivan S., Söll D., Lerman-Sagie T. and Birk O.S.(2010). Mutations disrupting selenocysteine formation cause progressive cerebello-cerebral atrophy. Am. J. Hum. Genet. 87(4):538-44.

Narkis G, Ofir R., Manor E., Landau D., Elbedour K., Birk O.S (2007). Lethal congenital contractural syndrome type 2 (LCCS2) is caused by a mutation in ERBB3 (Her3), a modulator of the phosphatidylinositol-3-kinase/Akt pathway. Am. J. Hum. Genet. 81:589-595.

Narkis G, Ofir R., Landau D., Manor E., Volokita M., Hershkowitz T., Elbedour K., Birk O.S (2007). Lethal contractural syndrome type 3 (LCCS3) is caused by a mutation in PIP5K1C, which encodes PIPKI gamma of the phophatidylinsitol pathway. Am J Hum Genet. 81:530-9.

Barel O., Shorer Z., Flusser H., Ofir R., Narkis G., Shalev H., Nasasra A., Saada A., Birk O.S. (2008). Mitochondrial complex III deficiency associated with a homozygous mutation in UQCRQ. Am. J. Hum. Genet. 82:1211-1216.

Barel O.,  Shalev S.A., Ofir R., Cohen A., Zlotogora J., Shorer Z., Mazor G., Finer G., Khateeb S., Zilberberg N.,  Birk O.S. (2008). Maternally inherited Birk Barel mental retardation dysmorphism syndrome caused by a mutation in the genomically imprinted potassium channel KCNK9. Am J Hum Genet 83(2):193-199.