Funding: Research supported by the Khalifa University of Science and Technology
Organophosphorus esters (organophosphates and organophosphonates) which are used as pesticides and parasiticides are amongst the most frequent causes of accidental and suicidal intoxications.
Their acute toxicity is due to the inhibition of the enzyme acetylcholinesterase (AChE), which inactivates the neurotransmitter acetylcholine (ACh) at cholinergic synapses. Esterase inhibition results from phosphylation (i.e. either phosphorylation or phosphonylation) of the serine hydroxyl group in the active center of the enzyme and translates into an “endogenous acetylcholine poisoning”.
The therapy of poisoning with organophosphorus compounds, which is summarized by the acronym A FLOP = Atropine, FLuids, Oxygen, Pralidoxime (aldoxime cholinesterase reactivator), is generally disappointing. Pyridinium oximes reactivate phosphylated AChE by interacting with the anionic site of the enzyme. An optimal orientation of the reactivator at the catalytic site of the enzyme is facilitated by the pyridinium moiety, which thus increases efficacy. It is generally accepted that nerve gas exposure can be treated with oximes; however, the therapeutic value of oximes in human organophosphate pesticide poisoning is controversial. One possible reason for the disappointing efficacy may be the very limited ability of oximes (< 5%) to penetrate the blood-brain-barrier.
The key goal of the proposed research is to improve the way we evaluate whole kidney scaffold integrity at the microvascular level. We will directly address this proposed goal by testing the following specific aims:
1) Design and characterize an approach to assess and enhance decellularized kidney scaffold integrity at the cellular level. Using two-photon microscopy, we hypothesize that our experiments will access traces of cellular debris left after the decellularization process and define ways to remove such debris. Moreover, we will inspect microvascular patency and scaffold integrity in various in vitro and in vivo conditions.
2) Model pertinent characteristics that can be used to optimize recellularization. We hypothesize that our theoretical/computational models will be able to identify fluid forces that can support successful and widespread cellular delivery and integration into scaffolds that do not contain cells. We will determine various biomechanical parameters of scaffolds and create 3D reconstructions of microvascular geometry to help us characterize scaffold integrity throughout the decellularization, recellularization and transplantation processes.
3) Develop a novel cellular re-seeding technique that can rapidly and effectively repopulate kidney scaffolds. Our studies will specifically examine how normal and genetically modified renal cells can be effectively delivered throughout scaffolds using our patented hydrodynamic delivery technique. We will also determine if this proposed delivery methods can support better support cellular integration into whole scaffolds that are subjected to various in vivo conditions.
PI: Dr. Ovidiu Constantin Baltatu
Funding: Research supported by the Khalifa University of Science and Technology under Award No. FSU- 2020-33.
Early detection of cardiovascular diseases and risk factors through biomarker research and prevention through nonpharmacological strategies represent a subject of strategic health and medical importance. This project proposal focuses on 2 major aspects of cardiovascular risk, which have been a topic of our research group, with the objectives to investigate:
PI: Dr. Ovidiu Constantin Baltatu
Funding: Research was supported by the Khalifa University of Science and Technology under Award No. FSU- 2020-33.
Lifestyle factors, such as diet, physical activity and sleep, are associated with the development of cardiovascular diseases. The objective of The Khalifa Healthy Heart Study is to characterize the cardiovascular risk distribution and understand how this is associated with lifestyle factors in academic environment. This is an exploratory cross-sectional observational community study of adults.
The specific objectives of the Khalifa Healthy Heart Study are as follows:
PI: Dr. Ovidiu Constantin Baltatu
Funding: Research supported by the Khalifa University of Science and Technology under Award No. CPRA 2020-034.
Healthcare professionals are risking their lives, threatened not only by exposure to the virus but also by pervasive and deleterious effects on their mental health. We are now facing a surge of physical and emotional harm that amounts to a parallel pandemic. Burnout has been associated with higher rates of anxiety disorders, increased cardiovascular risk and immune dysfunction — trends that will be aggravated by the pandemic. Such injuries may be most acute and long lasting in the young physicians, nurses, and other health professionals serving on the front lines during their formative years of training.
The main objective of this project is to investigate the evolution of psychosocial, cardiovascular and immune markers in healthcare with different levels of exposure to the COVID-19 pandemic.
Melatonin is an important endogenous neurohormone produced by the pineal gland that, it possess both circuannual and circadian rhythms. Circadian disruptions have been reported to be associated with increased susceptibility to several metabolic disease with inflammatory component such as type 2 diabetes, neurodegenerative diseases, and cancer and their complications. One of the consequences of advancing age is the decline in circulating levels of melatonin and circadian disruption. A number of studies suggested that in patients with low melatonin levels, melatonin replacement can be beneficial to treat patients with mild cognitive impairment. It has been reported that melatonin has a neuroprotective effect via reducing the levels of amyloid β (Aβ), the neurotoxic compound which plays a central role in the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease (AD). The exact mechanism through which melatonin affect Aβ levels is not confirmed. Recently, using in vivo and in vitro models, ROCK 1 have been found to be elevated in AD, ROCK 1 depletion reduced Aβ levels in the brain. No studies have investigated the effect of melatonin on ROCK.
PI: Dr. Ali Khraibi
Funding: Research supported by the Khalifa University of Science and Technology
Due to its importance in cardiac contraction, we propose to evaluate the expression and role of striatin, a cardiac protein, in the development of maladaptive remodeling using an established animal model of essential hypertension, the Okamoto Spontaneously Hypertensive Rat (SHR).
The SHR is a well-established animal model for human essential hypertension. Striatin (STRN) is a cardiac protein that possesses binding domains to calmodulin (CaM) and caveolin (Cav), both of which are regulators of myocardial function. The calcium sensitive interaction between cardiac STRN, CaM, and Cav-3 has been previously reported; however, the dynamics of this interaction and its impact on cardiac remodeling was not yet addressed. During hypertension, cardiac maladaptive remodeling can occur. Therefore, in our proposed studies, we will first investigate (1) the changes in the expression of striatin in SHR hearts at different time points of the onset/progression of hypertension, as well as (2) the interaction of striatin, CaM, and Cav-3 in the SHR heart. Subsequently, (3) the effect of striatin on cardiac hypertrophy and on intracellular calcium will be further evaluated.
Data from these proposals will provide new insights on the changes in the contractile apparatus in cardiomyocytes in response to hypertension, which is accompanied by cardiac dilation. It will serve as a translational platform for therapeutic strategies in an effort to attenuate the burden of maladaptive remodeling of the heart in humans, particularly within the United Arab Emirates population.
PI: Dr. Sabina Semiz
Funding: Research supported by the Khalifa University of Science and Technology, Award # FSU-2020-29/2020
Precision medicine has the capacity to optimize the disease treatment and to identify novel therapeutic targets leading to development of novel medicines. This project is focused on use of precision medicine in Type 2 diabetes (T2D), including precise T2D diagnosis and precise T2D treatment in the UAE population. In line with these objectives, this study will analyze for the first time the genomic, metabolic, life style and other factors associated with the T2D risk, its traits and response to therapy in the Emirates. Given the high incidence of T2D, consanguineous marriages, lifestyle influence, and total healthcare costs allocated to diabetes management in the Middle East population that are being among of the highest in the world, it is pertinent to understand better genetic and other factors associated with T2D risk, traits, and response to treatment. Furthermore, an optimal treatment also appears to be crucial in diabetic patients diagnosed with COVID-19, who are exposed to the higher risk of morbidity and mortality as compared to nondiabetic patients. It is expected that results of this project will enhance the translation of precision medicine in clinical practice, where an optimal treatment is targeted to an individual’s genome
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