Molecular Endocrinology and Diabetes

המעבדה לאנדוקרינולוגיה מולקולרית וסוכרת
Head of the lab:
Prof. Moshe Phillip, MD
Phone: 054-4795995
Lab Manager:
Dr. Galia Gat-Yablonski, PhD
Phone: 03-9376133
Research team:
    עובדות מחקר: ביאנה שטייף (M.Sc.), מיטל בר- מייזלס (M.Sc)    
Students:
    סטודנטים לתואר שני: חן מנחם    
Research Areas:

Research topics in the lab

Our lab is studying the processes involved in linear growth in children, in close collaboration with the Institute for Endocrinology and Diabetes sat the SCMCI. The study aims to decipher novel regulatory mechanisms for enabling the development of better monitoring and treatment modalities which are much needed in this field. Every year 1500 children with short stature visit our institute, most of them with a normal hormonal profile, therefore we decided to focus our attention on studying the target organ, the epiphyseal growth plate (EGP). Our model is based on the well-known connection between nutrition and linear growth.

1.      We were the first to show that leptin, the satiety hormone secreted from adipocytes directly activates the growth plate. We have shown that leptin administration to food restricted animals compensated for the reduced amount of food, leading to almost normal growth. We have further showed that leptin binds directly to specific receptors in the EGP and activates its known signal transduction pathways including stat3/Jnk/ERK and that it activates the regulatory pathway of Ihh/PthrP. Recently we found that high levels of leptin, especially during puberty activates aromatase enzyme, which acts to produce estrogen from testosterone. This activation leads to growth cessation and premature closure of the EGP, culminating in short stature. These findings were supported by a clinical observation made in our clinic, showing that obese children may sometimes end up with short stature compared to their peers.

2.      Short children may sometimes be treated with growth hormone even in the presence of adequate amount of the hormone, if they are very short. In order to follow their response to treatment, a sensitive biomarker is required, apart from height measuring, as this gives indication only after 6 months or more. We are studying different biomarkers in several setups both clinical and pre-clinical.

3.      Animal studies are performed to study the effect of nutrition on growth. We are using a model of food restriction induced growth attenuation followed by re-feeding in order to cause catch up growth, which is robust than average growth. We were studying the changes in gene expression, identifying the role of the transcription factor HIF1alpha, several micro RNAs and HDACs. A transgenic model we developed in which Sirt1 (an HDAC) was specifically knocked down in the EGP showed that the affected animals had significantly less efficient growth and less efficient response to nutritional manipulation.

4.      Microbiome analysis at different nutritional states revealed that food restriction lead to significant changes in gut microbiota, similar to the differences reported between fat and lean humans. Using several different diets we noted that specific ingredients in the diet, even when calories and macromolecules are similar, significantly affect gut microbiota and growth. These finding enable us to suggest future improvements to the growth stimulating formula that was developed by the clinic.

 

Future studies

1.      Further analysis of the Sirt1 KO mice

2.      Effect of nutrition on linear growth in the absence of GH

3.      Effect of different diets ( containing different proteins) on linear growth

4.      Involvement of microbiome in mediation of the effect of nutrition on growth

5.      Identification of specific and sensitive growth biomarkers

6.      Early identification of diabetes type 1 associated autoantibodies in children of the general population.

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Publications:
Contact details
Galia Gat-Yavlonski Mobile: 050-7658446
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