Research Groups | The Laboratory for Molecular Genetics and Pharmacogenetics

The Laboratory for Molecular Genetics and Pharmacogenetics was established in 2001 by Dr. Dani Bercovich and focuses on finding new genetic variations that are compatible with attractive phenotypes in human, animals, plants and bacteria, and how genetic variations determine an individual’s response to a given drug. This research has captured the attention of pharmaceutical companies, which see it as potentially leading to:

• Faster drug development at reduced costs
• Higher predictability of response to drug therapy
• Less frequent and less severe adverse drug effects
• Individualized drug dosing
• Improvement in the overall health of patients

The rapid and sensitive identification of a DNA sequence variation is one of the key steps in pharmacogenomic analysis. A relatively new addition to such DNA scanning methods utilized by the Bercovich laboratory is denaturing high performance liquid chromatography (DHPLC).
Scanning for mutations or polymorphism by DHPLC involves the comparison of native homozygous DNA strand samples and mutative samples. The elution profiles for such samples are distinct from those having a homozygous sequence. This makes the identification of samples harboring polymorphism’s or mutations a straightforward procedure.
The unique contexture of DNA in Israel with its many founder effects due to the proximity of ethnic groupings, enables us to screen DNA samples with higher frequency of alterations then that exist in the general world population, so it is feasible to screen a lesser number of samples, and yet to find new mutations and unique SNP’s.

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Research team :

• Dr. Dani Bercovich | head of team | cv
• Dr. Sigal Korem, Post-doc | cv

Our Lab is seeking for funding of the on going genetic projects in the pharmacogenetic area:

A dverse effect of Statin in lowering cholesterol;
Design of molecular platform on the basis of pharmacogenetic studies of candidate genes associated with clinical tolerance,
Efficacy and development of adverse effects of psychotropic drug treatment, directed at the three major psychiatric disorders including schizophrenia, bipolar disorder and major depression.
We are interested in finding new genetic Bio-markers for disease like familial Arthritis with eyes diseases, Keratoconus which is a noninflammatory corneal thinning disorder. Progressive thinning and protrusion of the cornea and loss of acuity are the clinical characteristics. It is a major indication for cornea transplantation in the Western world, and more projects in this field, because of our accesses to the unique DNA composition in Israel.

Activates:

The laboratory is conducting joint R&D projects with medical experts from major hospitals. These include:

Development of genetic diagnostic method for the identification of poor and high response to HMG CoA reductase inhibitors (statins’ therapy) in FH patients (Familial Hypercholesterolemia - high plasma LDL cholesterol).

Genetic screening of patient population is an important approach to upgrade drug therapy. The present project is aimed to utilize a unique genetic variation screening technology DHPLC (Denaturing High Performance Liquid Chromatography) for identifying candidate genes that are responsible for the variability in response to HMG CoA reductase inhibitors (statins).
These drugs are currently the leading antihypercholesterolemic agents. Elevated cholesterol level is a major health problem in the western world causing high rates of morbidity and mortality.
The research will analyze the responsiveness of familial hypercholesterolemic patients to statins and correlate it to their genetic properties (genotype).
The patients are known from previous studies of our group to vary in their response to statins. The study will differentiate between major determinants of drug response variability: genetic, pharmacokinetic and patient compliance.

Partners:

• Prof. Leidersdorf & Dr. Vardiela Minner, Hadassah Hospital, Israel
• Prof. Amnon Hoffman, school of pharmacy, Hadassah Hospital
  The HPBM company.
• A Grant from the Industrial and Trade ministry funds this project together with the HPBM Company.

Screening for candidate genes associated with different responses to anticoagulation agents and treatment with anticoagulants in recurrent miscarriages.

The aim of the project is to test the hypothesis by screening with the denaturing high performance liquid chromatography (DHPLC) apparatus (see below), DNA from pregnant women’s after gestation vascular complications (GVC), who were treated with anticoagulant drug, low molecular weight heparin (LMWH) enoxaparin and had a live or a dead fetus, for variance in DNA of specific genes. Our target genes in the initial stage of this study are the Human Tissue Factor Pathway Inhibitor (TFPI), Anti Thrombin, Factor X and Factor II.

Partners:

• Prof. Brenner, Rambam Medical Center, Israel.

Screening for candidate genes associated Prostate, Bladder, colon and lung cancer and other neurological disorders. Converting traditional DNA diagnosis to the DHPLC apparatus.

Partners:

• Avi Orr-Urtreger, MD, Ph.D. Director of Genetic Institute, Tel-Aviv Sourasky Medical Center. ( See: Rennert et al. Am J Hum Genet 2002 Jul 23;71(4); Gavert et al. Hum Mutat 2002 Jun;19(6):664

Contact us:

Dani Bercovich PhD.
Scientific Director,
Human Molecular Genetics & Pharmacogenetics,
Migal - Galilee Bio-Technology Center
P.O Box 831
Kiryat-Shmona, 11016,
Israel.
Tel: 972-4-6953523
Fax: 972-4-6944980
Email: danib@migal.org.il