Dr Tarek Abd El-Aziz is a postdoctoral Fellow at the University of Texas Health Science Center in San Antonio, USA. He recently received the 2021 Excellence in Renal Research Award from the American Physiological Society in the field of renal research. SASTA invited Dr Abd El-Aziz to write about his background and research journey. He kindly accepted and wrote to SASTA the following article.
I am Tarek M. Abd El-Aziz, a Lecturer of Cellular and Molecular Neurophysiology and Toxicology at Minia University, Egypt. I received my MSc and BSc degrees in Biology (Zoology) from the Faculty of Science, Minia University, Egypt. I obtained my PhD in 2016 from the University of Grenoble Alpes, France. I joined my current laboratory at the University of Texas Health Science Center San Antonio, USA as a postdoctoral fellow in July 2019, following the completion of a 6-month fellowship at Kyoto University, Japan.
Tarek Abd El-Aziz, PhD
The focus of my research is to understand the molecular mechanisms that govern the regulation of ion channels and cell surface receptors in physiological and pathological states. Our understanding of their function is critical for the development of therapeutic approaches aimed at treating and preventing “channelopathies”, human diseases related to the dysfunction of ion channels. Experimental approaches that I commonly use to study ion channels include electrophysiology, structural biology, cell biology, biochemistry, and animal models. My research is multidisciplinary, and I am interested in understanding biology from the level of molecules to the whole animal.
During my PhD thesis, my research focused on exploiting bioactive components in animal venom for drug discovery. Animal venoms are a complex mixture of toxic and biologically active proteins and peptides which may have therapeutic applications. Peptide toxins isolated from animal venoms mainly target ion channels, membrane receptors, and components of the hemostatic system with high selectivity and affinity. Working in this area has led to the identification of two new neurotoxins with novel modes of action on ion channels that are currently being investigated as lead compounds for the development of novel sperm motility activators. Another aim of my PhD studies was to develop a new method for the neutralization of deadly animal toxins. Instead of using antibodies and horse serum production, we turned towards aptamers. Aptamers are in-vitro selected single-stranded oligonucleotides (ssDNA) or RNA that can bind to certain targets (proteins, peptides, small molecules, metal ions and living cells) with high affinity and specificity. I have demonstrated that DNA-based aptamers represent powerful neutralizing tools for lethal animal toxins of venomous origin.
My ion channel research was continued throughout my first postdoctoral studies at Kyoto University, Japan. There, I started a new project titled “Pharmacological regulation of inflammation via transient receptor potential melastatin 2 (TRPM2) channels by animal toxins”. The project’s purpose was to isolate new TRPM2-specific inhibitors from natural sources. To achieve this, animal neurotoxins were isolated and characterized using chromatography techniques and mass spectrometry combined with functional assays, in which calcium influx activity of the TRPM2 channel was measured by electrophysiology and intracellular calcium imaging.
Now under the supervision of Dr. James D. Stockand, I have the opportunity to carry on my training and to improve my expertise in ion channels. Dr. Stockand’s laboratory provides a unique opportunity to study the regulation of the epithelial sodium channel (ENaC). Here, I am learning new thinking and experimentation methods including fluorescence imaging combining total internal reflection fluorescence (TIRF) microscopy with fluorescence recovery after photo-bleaching (FRAP), whole-animal imaging, radio telemetry analysis of blood pressure and mouse metabolic studies, which I will incorporate into my future independent research program. I am working on a multidisciplinary project that we expect will reveal the molecular mechanisms and consequences of Casein Kinase II (CKII) regulation of ENaC. Because ENaC fine-tunes renal sodium excretion, its activity plays an important role in setting blood pressure. My results, to date, demonstrate that phosphorylation by CKII is necessary for normal ENaC activity and renal Na+ excretion. The CKII phosphorylation site within ENaC shares similarities to CKII phosphorylation sites in the unrelated voltage-gated sodium channels (Nav) and KCNQ channels (KCNQ is a potassium channel).
Phosphorylation of Nav and KCNQ channels by CKII acts as a molecular “switch” favoring the binding of ankyrin-3 (Ank-3). The binding of Ank-3 facilitates the proper membrane localization of these channels, increasing their activity. I am testing the idea that because of convergent evolution, phosphorylation of ENaC by CKII is also sufficient for Ank-3 binding to this channel, which is required for normal channel locale and function, and the proper regulation of renal sodium excretion and consequently, regulation of blood pressure.
In May 2021, I was awarded the Best Postdoctoral Researcher Award from the Department of Cellular and Integrative Physiology at the University of Texas Health Science Center San Antonio, USA. The award is bestowed on current postdoctoral fellows who have made outstanding scientific contributions to their field and have also contributed to the department through engagement and collaborations within the 5 postdoctoral training years.
In April 2021, I was awarded the 2021 Excellence in Renal Research Award from the American Physiological Society in the field of renal research, as one of the top 5 postdoctoral researchers. Awardees were selected from among 300+ researchers participating in the 2021 Experimental Biology meeting, one of the largest scientific events in the United States of America.
I envision that my future independent research program will continue to focus on ion channels and will incorporate many of the tools and thinking that I have learned from my graduate and fellowship work. The unifying theme of my independent research will be the discovery of novel regulatory pathways and inhibitors/activators of ion channels.
You may check Dr Abd El-Aziz’s publications here.
(Cover Image: Freepik)
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