01/10/2023

محمد أحمد محمد الثبيتي

محمد أحمد محمد الثبيتي
دكتوراه
Biochemistry
University of Leicester

مجال
التميز

تميز دراسي وبحثي

البحوث المنشورة

 

البحث (1):

 

عنوان البحث:

The Role of the HIF-1α Transcription Factor
in Increased Cell Division at Physiological Oxygen Tensions

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تاريخ النشر:

16 May 2014

موجز عن البحث:

HIF-1 is a transcription factor that
mediates the cellular responses to low oxygen environments, mainly as a
result of having an oxygen-labile subunit, HIF-1a. HIF-1a has been carefully
studied in the context of severe hypoxic stresses (,1% O2), but itis also
known to be present at oxygen tensions commonly found in normal tissues in
vivo (,1–13% O2), albeit at much lower levels. Its role under these
physiological conditions is not fully understood. Here, we show that a transcriptionally
active HIF-1a was up-regulated at 5% O2, both in normal and cancer cells, but
only some of its target genes were elevated as a result. HIF-1a induction was
in part dependent on the activation of the ERK1/2 MAPK signalling pathway,
which we have previously shown is active at 5% O2. We also found that HIF-1a
does not contribute to the protection against DNA damage that can be observed
in low oxygen environments, and that there are certain DNA damaging agents,
such as doxorubicin and actinomycin D, that prevent HIF-1a induction
independently of p53. Moreover, absence of HIF-1a significantly reduced the
growth advantage of cells cultured at 5% O2. In view of these data, we
conclude that HIF-1a can be induced and activated at physiological oxygen tensions
in a MAPK-dependent manner and that, although this does not lead to
pro-survival responses to stress, it determines the increased cell
proliferation rates that are common under these conditions.

البحث (2):

 

عنوان البحث:

Characterization of
novel markers of senescence and their prognostic potential in cancer.

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تاريخ النشر:

20 November
2014

موجز عن البحث:

Cellular senescence
is a terminal differentiation state that has been proposed to have a role in
both tumour suppression and ageing. This view is supported by the fact that
accumulation of senescent cells can be observed in response to oncogenic
stress as well as a result of normal organismal ageing. Thus, identifying
senescent cells in in vivo and in vitro has an important diagnostic and
therapeutic potential. The molecular pathways involved in triggering and/or
maintaining the senescent phenotype are not fully understood. As a
consequence, the markers currently utilized to detect senescent cells are
limited and lack specificity. In order to address this issue, we screened for
plasma membrane-associated proteins that are preferentially expressed in
senescent cells. We identified 107 proteins that could be potential markers
of senescence and validated 10 of them (DEP1, NTAL, EBP50, STX4, VAMP3, ARMX3,
B2MG, LANCL1, VPS26A and PLD3). We demonstrated that acombination of these
proteins can be used to specifically recognize senescent cells in culture and
in tissue samples and we developed a straightforward fluorescence-activated
cell sortingbased detection approach using two of them (DEP1 and B2MG). Of
note, we found that expression of several of these markers correlated with
increased survival in different tumours, especially in breast cancer. Thus,
our results could facilitate the study of senescence, define potential new
effectors and modulators of this cellular mechanism and provide potential
diagnostic and prognostic tools to be used clinically.

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