According to the US Food and Drug Authority, the term Personalized Medicine (PM) is the process of customizing medical treatment to the individual characteristics, needs and preferences of a patient during all stages of care, including prevention, diagnosis, treatment, and follow-up. An alternate term, Precision Medicine is often used interchangeably. The US National Institute of Health (NIH) defines precision medicine as “an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment and lifestyle of each person.” This paradigm shift in medicine is now possible through the availability of large datasets compiled by healthcare systems, technological advancements in high-throughput DNA sequencing, and the development of proper analytical tools to identify relationships in vast datasets. To be more exact, P4 Medicine (a term coined by Leroy Hood and his colleagues) is “Predictive, Preventive, Personalized and Participatory.” It is a systems biology approach that uses genome, phenome, and microbiome data to quantify the wellness of an individual and provide indicators of the impending disease state.
The prevalence of chronic disease, in particular diabetes and complications, arising in the UAE are alarmingly high. According to the 2017 report from the International Diabetes Federation (IDF), 11% of the population in the Middle East and North Africa (MENA) region had type 2 diabetes. Disturbingly, the prevalence is higher in the UAE population, with 19.3% of those between the ages of 20 and 79 with type 2 diabetes1. A number of major co-morbidities are linked to diabetes and of these, cardiovascular disease is the highest cause of mortality in the UAE at 34.9% of all deaths recorded in the UAE in 2015 (source: Health Authority of Abu Dhabi, 2016). In this project, we propose a study to evaluate the proactive approach of P4 Medicine. Specifically, the project will take the holistic approach of analyzing the whole genome sequences, phenome and clinical data, the microbiome, as well as activity measurements of at least 100 Emiratis who are at risk of cardiac heart disease (CHD), toward positively impacting on the health status of these individuals.
Encouraged by the very positive feedback from our ADEK 2018 submission and our recent publication in Nature34, we present here our updated proposal on the epitranscriptome of skin stem cells.
Harnessing adult stem cells for regenerative medicine (RM) is a global initiative that holds great promise in saving daily lives. This field is evermore needed in the Gulf Region, particularly the United Arab Emirates (UAE), due to high road-related injuries. According to the World Health Organization, road accidents in the UAE are the number one cause of death in children and the second in adults. Among the many health adverse-effects of road collisions, skin injuries are by far the most prevalent. Skin is a very regenerative organ as it is composed of many stem cell (SC) populations residing at different niches with diverse capacity of regeneration. However, when extensively damaged the inherent process of regeneration is hampered. One method to externally support skin regeneration after severe damage is by epidermal SC transplants.
Utilizing epidermal SCs for regeneration requires full understanding of their biology during self-renewal and differentiation. Self-renewal is a process whereby SCs maintain their pool by dividing and inhibiting differentiation. Differentiation is, however, when SCs divide to give rise to a specialized cell. By comprehending these states, we would be able to overcome the current limitations of growing epidermal SCs in culture. Previous attempts to successfully propagate epidermal SCs required unknown factors derived from bovine serum and mouse feeder cells. Recently, efforts to use chemically defined serum-free conditions to culture epidermal SCs have been successful, albeit not without problems. Indeed, when tested chemically, cultured epidermal SCs fail to form skin. Here, we propose to overcome the limitation of epidermal SCs grown in chemically defined conditions by using our recent discovered RNA pathway controlling epidermal SC differentiation. Enhancing skin SC research would position Abu Dhabi in the forefront of skin healthcare; hence, achieving its strategic goal in becoming a knowledge-based economy.
An understanding of genome organization of an individual is key toward both understanding the nature or type of cancer that a patient may be predisposed to, as well as the course of treatment of the malignancy itself. Not only does genomic information provide more accurate diagnosis, it provides actionable opportunities to prevent the disease. In cases where treatment of cancers is required, genome information will provide an opportunity to define the appropriate medication at the optimal dose (i.e., the discipline known as pharmacogenomics). In some cancers, solid organ transplantation may be required. Leukemia is treated by replenishment of compatible haematopoietic stem cells (HSC) following total immune ablation by chemo- and/or radiotherapy. In these cases, the genetics of the donor and the recipient at a region of human chromosome 6 known as the Major Histocompatibility Complex (MHC) has to be identical. Irrespective of whether for diagnosis, prevention, or treatment, data collaged from the genome of an individual is increasingly playing an important role.
There is a dearth of genome information from subjects of Arabian ancestry, and this study was conceived to improve on this unacceptable position, particularly among the local ethnic groups of the United Arab Emirates.
In the development of novel pharmaceutics and cell-mediated therapeutics, the immune system has to be well considered as part of the response mechanism or as a potential collateral for drug toxicity. To reduce the attrition of such developments, the interaction of immune cells with drugs and/or with other cell types should be mechanistically investigated.
As the lymph node (LN) is the integrating center for immune cells, whereby the body invokes immune responses against foreign substances, it is an ideal site for the study of drug interaction with biological components. We have developed a novel microfluidic platform replicating the LN microenvironment, called LN-on-Chip, to facilitate biological investigations of immune cellular kinetics, cell-cell interactions, cell-drug interactions, and sampling. We recreated the biological scaffold and reintroduced the cellular residents in an in vivo-like distribution into the device. We showed that the developed LN-on-Chip incorporates key features of the native human LN, namely the compartmentalization of immune cells within distinct structural domains and the replication of lymphatic fluid flow pattern supports 3D cell culture in biomimetic matrices, and sustains high rates of cell viability over the typical timeframe of immunotoxicity experiments. Further, we demonstrated enhanced proliferation of immune cell coculture in a low-flow perfusion LN system and observed immune cellular interactions. The ultimate goal of this platform is to enable investigations into the effects of pharmaceutics to downstream immunology in more physiologically relevant microenvironments, thus, contributing to increased safety, lowered cost, and shorter cycles for drug development.
The objective of this research is to present a novel ultra-low power wearable system for Congestive Heart Failure (CHF) monitoring using the continuous measurement of a patient’s weight to detect changes in body mass and fluid composition. This highly modular system will be used to implement, analyze, and compare various pattern detection algorithms for the early detection of congestive heart failures.
The main purpose of the development of Caps-Sim is to create a comprehensive simulation environment for magnetically-driven active endoscopic capsules. Caps-Sim can be easily used to test new vision and navigation concepts applied to active endoscopic capsule applications. Caps-Sim is a simulator but also represents in a graphical environment the real motion and trajectory of an active magnetic endoscopic capsule system.
Robot simulators are fast, efficient, and cheap ways to test the efficiency, safety, and robustness of new concepts and algorithms. They can provide robust physics engine simulation, customized graphical interfaces, and high quality graphics rendering. In this proposal, the development of a virtual reality interface (Caps-Sim) for magnetically-driven active endoscopic capsules is described. The simulator intends to provide researchers with an environment to test their design concepts, as well as vision and navigation algorithms applied to endoscopic capsule procedures.
Caps-Sim will be made up of four main components: i) haptic station; ii) vision station; iii) control station; and iv) human machine interface (HMI). The haptic station provides the operator with the force information from virtual or remote environments, and is also used to read the operator’s hand motion. In order to provide image and force feedback, the vision station is used to capture images and generate 3D mapping and computer “virtual interaction” forces. The capsule movements are controlled using the control station. The HMI runs a simulation engine where the capsule device and its main components are modeled and visualized. The magnetic actuation of the capsule is performed in the HMI simulation engine. The HMI also has a display unit where the colon images are visualized and rendered to the user using a 3D virtual reality glass. The proposed version of Caps-Sim provides a simulator to develop and test endoscopic capsules main functions: i) capsule tele-operation; ii) haptic feedback for capsule navigation; iii) 3D virtual reality navigation; and iv) region of interest (ROI) tracking. The proposed Caps-Sim is modular and can be applied to any capsule type or any other robotic endoscopes regardless of its underlying technology.
Cardiovascular disease (CVD) is the major cause of death in the UAE, causing one in every five deaths. Effective Cardiac Rehabilitation (CR) can significantly improve mortality and morbidity rates, leading to longer independent living and a reduced use of healthcare resources. The proposed project, named Care4MyHeart, sets an overall goal to introduce a personalized home-based CR program, enabling lifestyle behavioral change towards increased quality of life, surpassing the currently unsustainable provision of healthcare for CVD. This multidisciplinary project aims to empower ordinary CVD patients to become “expert patients” and be their own primary caregiver with the know-how to self-manage their CVD.
The proposed Care4MyHeart platform will help reduce patients’ CVD risk by gradually establishing a behavior change in their everyday living routine. It will utilize advanced machine learning and modeling techniques to provide gender- and age-specific CVD exercise programs and an autonomous helper-agent, providing informed feedback to the patient and the healthcare provider, establishing a collaborative patient-professional partnership. Overall outcome will be a ‘co-production of health’ business model from a multi-stakeholder eco-system, towards the integration of Care4MyHeart into healthcare systems across Arab countries and internationally. Care4MyHeart will be realized via motion capture, exercise evaluation, physiological and lifestyle monitoring, exercise gaming, home-based human-computer interfacing, multi-parametric data modeling, and advanced decision support systems. The overall concept and system are easily transferable to address other diseases/conditions (e.g., diabetes, osteoporosis, obesity), providing market opportunities for the commercialization of Care4MyHeart beyond CVD, thus aligning with the major targets of the Abu Dhabi 2030 healthcare plan. Care4MyHeart will be realized in collaboration with the Cleveland Clinic AD and it is expected to establish Khalifa University as an internationally recognized center of excellence in personalized healthcare, generate intellectual property, and expose graduate and undergraduate students to the state-of-the-art in signal processing-, biomedical engineering- and healthcare-related research.
Genome editing holds great potential for significantly improving the way we treat and understand diseases. Modern genome editing tools like CRISPR-based systems require the design of guide RNA sequence (gRNA) that binds to an area of interest within the DNA. Guide sequences vary considerably in efficacy. In this project, we will develop computational tools that predict the efficacy of a given guide sequence.
Computational tools for predicting guide efficacy are used when designing genome editing experiments. The accuracy of available tools for predicting the activity of guide sequences is low and this delays the progress of genome editing experiments.
In this proposal, our goal is to shorten the time needed to carry successful genome editing experiments by developing better tools for predicting guide-sequence activity. Results obtained using the new prediction algorithms will also be used to gain insights into the factors influencing the efficiency of different guide sequences. Modern tools based on resent innovations in artificial intelligence and computer vision research will be utilized to develop the proposed tools.
Harnessing adult stem cells (SC) for regenerative medicine is a global initiative that holds great promise in the UAE’s healthcare system. Indeed, regenerative medicine is crucially needed in the UAE to care for the high number of injuries caused by road accidents such as skin burns. To safely induce regeneration, we must be able to maintain SCs in culture by supporting self-renewal and inhibiting differentiation. Self-renewal is a process whereby SCs maintain their pool by dividing and inhibiting differentiation. Differentiation, however, is when SCs lose stemness and become specialized cells. Human epidermal SCs have been successfully maintained in culture with the aid of mouse feeder cells, hence limiting their medical use. Alternatively, feeder free cultures have been developed, but fail to reconstitute skin in vitro. Here, we propose to support the self-renewal of human epidermal SCs in culture by recapitulating a recent discovered epitranscriptome dependent small vault-RNA pathway inhibiting differentiation.
Cardiovascular disease (CVD) is the major cause of death in the UAE and Korea, causing one in every five deaths. Some lifestyle factors (such as an unhealthy diet, lack of exercise, and smoking), known to contribute to a higher risk of CVD, are also common in people with mental health issues (such as depression). Integrated Cardiac and Mental Rehabilitation can significantly improve mortality and morbidity rates, leading to longer independent living and a reduced use of healthcare resources. The proposed collaborative project, named Mind My Heart, sets as an overall goal to introduce a personalized home-based rehabilitation program, enabling lifestyle behavioral change towards increased quality of life with personalized management for CVD and mental health issues. The overall concept of the Mind My Heart platform is easily transferable to address other diseases providing market opportunities for the commercialization.
Diabetes is a chronic disease that has become a serious public health concern as it affects around 382 million people worldwide. Diabetic patients require multiple-dose insulin injection or pump therapy to regulate glucose concentration in the body. Our aim is to develop a self-powered, wearable sensor capable of continuously measuring glucose concentration of the interstitial fluid in subcutaneous tissue. We will also provide cytotoxicity data using in vitro and in vivo studies to assess the feasible operation of our sensor. Pilot in vivo experiments involving rats will test sensor’s selectivity, sensitivity, reversibility, and biocompatibility. We anticipate that the wearable readout device coupled with label-free optical biosensors will aid in realizing prolonged glucose monitoring systems that will advance diabetes management at clinical and point-of-care settings. These devices may provide real-time, long-term glucose measurements that can be integrated with insulin pumps to form an automated feedback loop in glycemic management.
Cardiovascular disease (CVD), including congestive heart failure, hypertension, atherosclerosis, stroke, aneurysms, and vascular auto-immune disease, is currently the leading cause of mortality and morbidity in the UAE (HAAD statistics 2017). The mission of the proposed Healthcare Engineering Innovation Center (HEIC) is to develop novel methodologies, devices, and tools for the diagnosis, intervention/treatment, and rehabilitation of the wide spectrum of health challenges associated with CVD. Towards this, the HEIC integrates a multidisciplinary team of researchers with the leading healthcare providers/regulators in the UAE [SEHA, HAAD, Heart and Vascular and Stroke Institutes at the Cleveland Clinic Abu Dhabi (CCAD)] to define and build population-specific, clinically implementable innovative approaches and engineering solutions.
The Center also provides a robust framework for tackling other relevant health challenges in the UAE including T2D, obesity and cancer in collaboration with KU’s Center for Biotechnology.
The Khalifa University Center for Biotechnology (BTC) was established on 2 June 2015 to develop the University’s capabilities in training and research to respond to three of the six priority areas under the four pillars of the UAE 2021 vision. Without local effort in genome research, the targets set and the vision to develop a knowledge economy in bioscience and competencies in laboratory diagnostic practice is highly problematic. Since its foundation, the BTC has developed competencies in genomics and bioinformatics in collaboration with a plethora of external stakeholders.
In 2018, as the Center takes possession of a customized laboratory to provide a base to accelerate the process of discovery, its mandate is to improve the body of information on genetic predisposition to diseases that are common to the UAE population. In these new premises, the Center intends to add capabilities in functional biology, the third cog in the repertoire that is molecular biology. This strategic addition coincides with the consummation of a memorandum of understanding (MOU) with Al Ain Fertility Center. It will provide the capability to study the functional relevance of novel genetic associations that are identified. This addition will further expand BTC’s current network of local, regional and international collaborators.
Cardiovascular diseases (CVDs) are a leading cause of death globally (Mc Namara et al., 2019). Recent national studies in the UAE revealed that hypertension, obesity, diabetes, and hyperlipidemia are already highly prevalent (Alzaabi et al., 2019; Al Mahmeed et al., 2019; Al-Shamsi et al., 2019).
The rising prevalence of cardio‐metabolic conditions in Arabian countries may be associated with the major social changes in these countries over the past 50 years, which have evolved from a traditional semi‐rural lifestyle to a sedentarized, urban society (Meo et al., 2017; Ng et al., 2011). Comparably, such lifestyle transitions with related increase in cardiovascular risk occurred in South American countries, including Brazil (Sentalin et al., 2019). The Prospective Urban Rural Epidemiology (PURE) study measured the effect of modifiable risk factors on cardiovascular disease and mortality across 21 countries (spanning five continents) grouped by different economic levels, including United Arab Emirates (high-income) and Brazil (middle-income) (Yusuf et al., 2019). The overall findings of PURE study indicate that over 70% of cardiovascular disease cases can be attributed to a cluster of modifiable risk factors including hypertension, metabolic (ie, abdominal obesity, elevated non-HDL cholesterol) and behavioral risk factors (i.e., physical inactivity, tobacco use).
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 two major aspects of cardiovascular risk that have been a topic of our research group with the objectives to investigate:
Our studies on cardiovascular risk prediction biomarkers and their association with modifiable cardiovascular risk factors will hopefully facilitate the development of early diagnosis and prevention strategies for cardiovascular diseases.
This project aims to use adaptive choice based conjoint (ACBC) analysis to elicit patients’ preferences for osteoarthritis (OA) medications. The project will assist in saving clinicians’ time by introducing the ACBC as a method for eliciting patients’ preferences prior to consultation. It also examines the application of ACBC as a method to facilitate the informed shared decision making between OA patients and their clinicians.
This is a study that complements previous studies conducted in the United Kingdom (UK). In the United Arab Emirates (UAE) setting, this study will use both Arabic and English versions of the ACBC questionnaire. ACBC is a computerized web-based interactive questionnaire that is instantly customised to elicit individual patients’ preferences. The main advantages of ACBC questionnaire are that it is user friendly, engaging, and spontaneously tailored for each individual patient preferences. This method of eliciting patients’ preferences could be a very useful tool for practitioners to involve their patients in the informed shared decision-making process of OA medication.
The patients in this study will be able to complete the ACBC questionnaire about OA medication preferences using any smart device (PC, tablet, smart phone, etc.). The data will then be analyzed for each individual patient and the clinician will be provided with a report detailing patients preferences. This report can also be kept in the patients file for future reviews. The patients and clinicians will provide feedback regarding the usefulness of the ACBC tool in the consultation and the convenience of this tool. This will help the research better understand the value and application of the ACBC tool.
Studying the development, anatomy, biomechanics, and function of the knee is important for preventative methods/procedures, improved diagnosis, and successful surgical treatment. Many individuals with knee injuries seek medical treatment, often involving surgical intervention. The most common knee surgery is meniscus surgery followed by anterior cruciate ligament reconstruction.
However, these surgeries potentially alter the biomechanical stability/integrity of the joint. Additionally, the role of partial meniscal resection in several postoperative biomechanical scenarios has yet to be fully understood. Therefore, the role of this project would be to describe the gross developmental anatomy of neonatal and adult knees and to investigate key elements pertaining to pressure changes on the tibial plateau with partial meniscectomies. These objectives will be achieved by using a combination of fresh and embalmed tissue dissection and biomechanical testing devices to describe, evaluate, and quantitatively examine the various material properties of the knee and meniscus under predefined mechanical parameters. This study will be multidisciplinary and form collaborations that incorporate anatomy, biomechanics, and orthopedics.
Precision medicine has the potential to revolutionize healthcare. Increasing evidence is demonstrating that a patient’s unique genetic profile can be used to detect the disease’s onset, prevent its progression, and optimize its treatment. This led to the increased global efforts to implement personalized medicine and pharmacogenomics in clinical practice, particularly in a case of chronic pandemic diseases, such as Type 2 diabetes mellitus (T2DM). Diabetes represents one of the major public health issues affecting hundreds of millions of people worldwide, with an increasing prevalence of 16% in the United Arab Emirates (UAE). If left untreated, diabetes can lead to severe complications including blindness, kidney and heart disease, stroke, and reduced life expectancy. Up to one-third of all deaths in adult UAE nationals with T2DM could be attributed to non-optimal glucose level control.
Although there is an increasing evidence of genetic factors being involved in T2DM development in different ethnic groups around the world, there are limited studies performed in the Arab population. Therapeutic response to metformin, a first‐line drug for T2DM, is highly variable, which can also be partially attributed to genetic factors. However, metformin pharmacogenomic studies have inconsistent results in different ethnicities and no studies were performed yet in the Emirati population.
Therefore, this project is focused on two major objectives related to use of precision medicine in T2DM, including precise disease diagnosis by identifying potential new biomarkers, and precise treatment by analyzing pharmacogenetic variants associated with glycemic response to oral antidiabetic medications, such as metformin. This project has a high potential to enhance the quality of life of affected individuals, as well as to develop additional strategies for T2DM prevention, optimization of its treatment, all potentially leading to reduced healthcare costs in the UAE. This may also result in the identification of novel target genes, leading to development of novel medicines to treat diabetes.
With the expectation of increased duration of extraterrestrial travel to the planet Mars, the need for medical and surgical care will likely increase. If an injury occurs, surgical techniques for rapid hemostasis and tissue closure should be developed. A mission to Mars will preclude the return of a crew member to earth for treatment. A contingency evacuation plan is not possible. There is no possibility for real-time consultation with an Earth-based expert. When performing surgery in microgravity, all fluids, blood, and surgical materials should be contained so as not to contaminate the space craft. Moreover, a sterile environment should be maintained.
The principal investigator has developed and tested a surgical isolation chamber in conditions of weightlessness. Long duration space travel to Mars will require modifications to the Surgical Isolation Containment System to meet the requirements for weight and size. In partnership with the UAE Space Agency, NASA-USA, Khalifa University Aerospace Research and Innovation Center, and the Khalifa Department of Mechanical Engineering, additional refinements and internal design modifications of the Surgical Isolation Containment System will be developed and tested.
The goal of this project is to deliver a functional Surgical Isolation Chamber with surgical instrumentation that meet weight and size requirements for long duration space flight and for the surgical requirements for the repair of a laceration or penetrating injury to the extremities in conditions of weightlessness.
Currently, it is estimated that 10% of the healthcare workforce in the UAE is composed of UAE nationals. Despite the large-scale importation of physicians, access to skilled health professions is inconsistent. Khalifa University College of Medicine and Health Sciences is the first medical school developed in the city of Abu Dhabi and the first 4 tier post baccalaureate MD program in the UAE. It intends to address the economic, social, and developmental priorities of the country (UAE Vision 2021: United in Ambition and Determination). The aims of the MD program are to increase the number of highly qualified physicians. This first MD cohort is comprised of approximately 50% UAE nationals
Professionalism forms a key part of core Entrustable Professional Activities (EPAs), which students require on entering medical education and in residency programs.
The Association of American Medical Colleges (AAMC) lists the EPAs that all graduate medical students are expected to achieve on completion of medical school. There are 13 EPAs and EPA 9, “collaborate as a member of an interprofessional team” is assessed in group work activities. Competency-based education involves aligning the EPAs required for practice with the activities in the classroom. Medical students perceive the didactic lecture to be the least effective learning tool within lecture time.
Active learning exercises such as teamwork, self-reflection, and problem-based activities engage learners and improves their motivation. Today’s medical students are millennial learners raised on rapidly evolving technologies. A “flipped classroom” approach can be used to focus teaching activity on what the student actively does. Theoretical benefits of a flipped classroom center on social constructivism and active learning embedding Bloom’s higher level of analysis, synthesis and evaluation.
This educational research project aims to assess the effectiveness of the flipped classroom approach and collaborative- and team-based learning activities with the first cohort of medical students on the MD program. Courses MDBS 600 Molecules, Genes and Cells and MDBS 605 Microbiology and Infectious Diseases, both contain a myriad of pedagogical methods of instruction: didactic lectures, flipped classrooms, classroom-based discussions, and application exercises. The project also aims to assess the effectiveness of these activities through measurements of student performance in course assessments, National Board Medical Examinations (NBME) course examinations, and student feedback questionnaires and qualitatively through student interviews.
There is a large body of medical education literature describing barriers and facilitators to medical student success. These studies, however, primarily focus on Western pedagogy in established medical education systems. There is limited research on medical student professional identity formation within a new medical school (KU) and a new hospital system (SSMC). Further, implementing a US-based curriculum within an international, multicultural context is likely to have its own unique challenges that have not yet been explored.
As such, we propose a series of medical education studies primarily looking at the influence of a multicultural faculty on the learning environment and student professional identity formation, with a longitudinal focus on gender issues in international academic medicine. Research techniques will include surveys, focus groups and semi-structured interviews of both students and faculty.
We will also explore the impact of Standardized Patient training on student education in this context.
The United Arab Emirates (UAE) has one of the highest diabetic prevalence rates in the world. By 2020, 30% of the UAE’s adult population will be diabetic. Furthermore, up to 40% of people with diabetes develop diabetic nephropathy, which generally progresses to end-stage renal failure. Existing clinical strategies are incapable of stopping this progression. Thus, once renal injuries progress to complete kidney failure, the only form of definitive treatment is transplantation. However, the demand for kidneys greatly outmatches the supply. This substantial public health problem has prompted the need for safe, effective, and novel interventions to treat/prevent such downstream diabetic pathologies. Recent evidence suggests that proximal tubule cellular damage is a significant contributor to the pathogenesis of diabetic nephropathy. Emerging evidence supports a potential therapeutic role of relaxin in fibrotic diseases, including chronic kidney disease that can result from diabetic nephropathy. Another promising finding illustrates that the administration of recombinant relaxin can help prevent renal fibrosis.
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 or nerve gas exposure is controversial. One possible reason for the disappointing efficacy may be the very limited ability of oximes (< 5%) to penetrate the blood-brain-barrier (Curr Med Chem. 2008;15:743-753).
Nanoized therapeutic agents display superior kinetic properties translating in enhanced efficacy (higher survival). Oxime nanoization was difficult to achieve due to the very high hydrophilicity of pyridinium alsoximes; recently small volume nanoxime synthesis was achieved possibly opening the way towards enhanced protection. We have recently shown that oxime administration prior to toxic agent exposure is superior to the US Army standard, which is prophylactic pyridostigmin (carbamate) administration.
These proposed investigations represent an organic continuation of past national and international collaborations. The work has the potential to shift the treatment paradigm of pesticide/nerve gas exposure towards the use of nanoized therapeutic agents.
Melatonin (N-acetyl-5-methoxytryptamine) is an important endogenous neurohormone produced by the pineal gland that possess both circuannual and circadian rhythms. Melatonin promotes sleep by acting as SCN to attenuate the wake‐promoting signal of the circadian clock and improves disruptions in circadian rhythm. Circadian disruptions have been reported to be associated with increased susceptibility to several metabolic diseases with inflammatory component such as type 2 diabetes, neurodegenerative diseases, and cancer and their complications. Some of these studies reported a 50–100% higher incidence of cancer among shift workers.
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, diabetic nephropathy, and sleep disorders. Several mechanisms have been suggested for the role of melatonin; endothelial to mesenchymal transition that leads to diabetic nephropathy have been reported to be inhibited by melatonin in the glomeruli of diabetic rats, this beneficial effect of exogenous melatonin was shown to be mediated via elevating miR-497 and suppressing Rho-associated protein kinase (ROCK) 1 and ROCK 2 activity. It has been concluded that melatonin has a neuroprotective effect via reducing the levels of amyloid β (Aβ), the neurotoxic compound that 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.
The aim of this project is to investigate whether the previously reported effect of melatonin on the Aβ levels is mediated through the ROCK. Primary cortical neurons and HEK293 cells will be used to study the effect of melatonin treatment on the Aβ levels, this will be investigated two states: baseline and post-treatment with melatonin on control cells those where ROCK1 activity has been significantly reduced or eliminated. We will use Western Blot analysis to determine protein expression levels for these cellular studies.
Organophosphates (OPs) are useful agents as pesticides, but they also represent a serious threat when abused for terrorist attacks and chemical warfare. OP toxicity is due to the inhibition of acetylcholine esterase (AChE), the enzyme terminating the synaptic action of acetylcholine, resulting in a cholinergic crisis, which can be fatal due to respiratory failure and/or generalized seizures. Since standard therapy with atropine and established oxime-type enzyme reactivators (pralidoxime, obidoxime) is unsatisfactory, new bispyridinium (K-) oximes have been synthesized at the University of Hradec Kralove, Czech Republic, and are still continuously being developed. Over the last few years, we have been able to demonstrate that some of the K-oximes (K-27, K-48) have superior efficacy compared to pralidoxime and obidoxime. Even better, therapeutic results are obtained when oximes are administered before OP exposure. We have previously been able to show that the prophylactic efficacy of K-48 to protect from the toxic effects of the OP paraoxon exceeds that of the FDA-approved pretreatment compound pyridostigmine.
The maintenance of a normal pregnancy requires significant and sustained plasma volume expansion. In normotensive pregnant rats, the process is achieved by significant attenuation of pressure natriuresis and diuresis. Relaxin is a peptide hormone that has been traditionally associated with pregnancy in mammals. Increasing evidence suggests that relaxin plays a role in the systemic hemodynamic changes of pregnancy, including the generalized vasodilation. Relaxin reduces fibrosis in the kidney, heart, and lung and significantly decreases the total collagen content in non-pregnant female Sprague-Dawley (SD) rats. Also, nitric oxide (NO), which is a vasodilator, is increased during normal pregnancy. Based on these established effects of relaxin and NO, it is reasonable to suggest that relaxin, NO, as well as other factors that are increased or activated during pregnancy may play an important role in the increase in renal interstitial compliance (∆ in renal interstitial volume/∆ in renal interstitial hydrostatic pressure) and renal sodium handling during pregnancy.
Therefore, we propose to investigate the role of relaxin on affecting various transporters in Human Renal Proximal Tubule Epithelial Cells (RPTEC). The possible interaction between relaxin and NO on these transporters will be determined in RPTEC.
The objective of this project is to determine the specific effects of relaxin and NO on the activity of proximal tubule transporters Na+-K+-ATPase and sodium hydrogen exchanger-3 (NHE-3) in RPTEC.
Gestational diabetes mellitus (GDM) is a major health problem as it carries devastating effects for women during their reproductive age as well as their babies. The exact mechanisms underlying this condition remain unknown. Currently, there are no diagnostic markers for GDM in early pregnancy; although early diagnosis was found to correlate with better outcomes from the disease. With the increasing prevalence of GDM all over the word, including the UAE, certain questions arise such as:
The aim of this project is to demonstrate the application of nanotechnology in ophthalmology through the use of holographic nanostructures on low-cost commercial contact lenses. The nanostructures will allow for a visual method of monitoring the physical changes induced by the diseases on the ocular surface. Diseases, such as Glaucoma and Keratoconus, have measurable symptoms but at a small scale. The disease’s presence may not be visually apparent to an onlooker or the patient themselves until the latter stages, at which point irreversible damage to the retinal nerve may have occurred causing permanent or partial vision loss.
The proposed nanotextured contact lenses are expected to change color as the disease progresses, allowing continuous monitoring of the condition and various other parameters on the complex ocular surface. Such lenses would appeal to patients with a family history of Glaucoma, Keratoconus, or other ophthalmic conditions that lead to eye curvature changes. These contact lenses will act as a preventative means, alerting the wearer who would self-monitor their condition, regulate their drug usage, and seek medical advice when the apparent color changes occur.
In 2015, there were over 1 million people living with diabetes in the UAE, placing the country 13th worldwide for age-adjusted comparative prevalence. It is important to note that diabetes is a regional affliction in Saudi Arabia, Bahrain, Kuwait, and Qatar, all featuring in the top 15 countries in terms of prevalence worldwide. The first key area of our research is to extract metabolic, genomic, and socioeconomic markers associated with the early onset of type 2 diabetes (T2D) in UAE populations since no current studies have focused on the integrative system analysis to predict T2D in UAE populations. The anticipated outputs of this project are identification of the factors contributing to the high prevalence of T2D in the UAE. Secondly, we would like to develop an optimization strategy around prevention of these conditions. Thirdly, this model will contribute to understanding the etiology of T2D through probing the interactions between key genetic and environmental domains.
OsteoMentor will innovate, push technological barriers, develop and pilot-validate intelligent and personalized digital solutions for sustaining and extending healthy and independent living with osteoporosis, a progressive and chronic metabolic bone disease that causes more than 8M fractures annually (1 per 3 sec). It will offer an integrated platform for smart informed healthy living in(out)doors, assisting patients with osteoporosis (or at risk) in physical exercise, nutrition, medication control, bone fracture/fall prevention, emotional wellness, and socialization, fostering healthcare self-management set within a collaborative care context with health professionals. OsteoMentor will leverage knowledge from psychological and medical disciplines into a digital open platform comprised of advanced ICT means, including everyday smart devices, privacy-aware Internet-of-Things setting, a personalized communicative and supportive virtual coach, AI, and big data analysis. From the latter, users’ behavioral and emotional profiles will be inferred, using fuzzy deep learning and affective computing, enabling the development of user-centric, data-driven coaching recommendations.
According to the World Health Organization (WHO), cancer is the second leading cause of death in 2018. Health authorities and research institutions dedicate vast resources to improve early detection and prevention techniques. Importance of preventative medicine and seeking to reduce cancers is highly emphasized in the UAE Vision 2021 National Agenda. This research aims at studying structure/function basis for disruptions in Base Excision DNA repair due to posttranslational modifications (PTMs) affecting DNA polymerase β (Pol β), an enzyme that is part of a DNA repair mechanism that protects against cancers. This project will bring together complementary skills to deliver a whole-system approach to investigate the impact of PTMs with a view to identifying key phosphorylation-induced structural changes affecting enzyme function. The study has the potential to provide novel pre-cancer indicators.
Data intensive Whole Genome Sequencing projects are central to the currently ongoing transformation in 21st century medicine. The challenge to utilize the collective genomic population data for personalized medicine in the country is threefold—lack of data, capabilities to Big Genomic Data, and finally making sense of it. The Genomics community has established a versatile analysis ecosystem, which, however, is based on flat-file data storage, thus bypassing decades of modern database development such as schema-free, scalable NoSQL. The envisioned Genomic Data Science framework constitutes will deploy and extend OpenCB, a Big Data system for genomic analysis, successfully deployed in very large scale applications. It bears potential for additional functionality such as extended hierarchical queries, integration with genotype array data, and the derivation of artificial intelligence applications. We aim to exemplify our novel methodology on the 1,000 Arab Genome project, addressing the lack of human sequences in the UAE.
Genomic data are crucial to the vision of predictive and personalized healthcare. Despite the massive amounts of genomic data already collected, their noise and high dimensionality (containing millions of variables) pose serious challenges to prediction beyond classical Mendelian diseases. Toward the automated data-driven prediction of common complex diseases (e.g., obesity and diabetes), there remains a severe lack of tools for adequately utilizing our genetic data. Similarly, researchers lack principled methods for fusing genomics with other modalities of biomedical data (e.g., medical imaging and blood chemistry), and for discovering interactions between multiple gene sites. Our research will incorporate manifold learning via diffusion maps into deep learning architectures, resulting in a suite of tools that can overcome these challenges with existing genomic data. Consequently, our approach will enable the efficient discovery of high-order gene interactions and better predictions for common disease.
Date (phoenix dactylifera) fruits contain high amounts of fructose and glucose sugars. These naturally blended sugar forms are simple and easily assimilated sugar forms for human metabolism. The main goal of the proposed project is to produce soluble sugar powder from date fruits using an innovative technology. The derived date sugar will be a suitable and superior alternative to commercial refined sugar. The technological scheme will involve date pulp freezing followed by supercritical fluid micronization, producing micro-size date pulp particles. These particles will be easily and effectively shredded off to extract its sugar components by ultrasonication in selective solvents. Subsequent to centrifugation, the final concentrate will be spray dried for the production of powdered sugar. The production process would also aim for maximum sugar recovery from the date fruits. The obtained natural date sugar powder would be sweeter and nutritive than the commercial refined sugar.
Fetal brain damage is a common contributing cause of preventable death and adverse neurological outcome (e.g., cerebral palsy) all over the world. At present, there is no device (invasive or non-invasive) in the market to measure fetal brain electrical activity. In this project, we, therefore, will first examine the patterns of fetal brain waves in pregnant animal model (mice) and then investigate a new method for non-invasive measurement of human fetal brain development (32-week gestation till birth) by abdominal surface electrical signal with inexpensive gel electrodes, comparing with fetal fMRI images of fetal brain and direct lead scalp electroencephagram during labor. The industry partner’s cash contributions for three years can ultimately be incorporated into their existing monitoring device with clear potential for commercialization. The outcomes of this project would make fundamental, as well as translational research outputs for fetal neurological screening and its potential to reduce fetal deaths.
Cancer is a leading cause of death worldwide and the death toll by cancer is feared to increase by 2030. In order to combat the deadly disease, early diagnosis is essential. The PI and associates propose a novel, hybrid microfluidic Lab-on-a-Chip platform that utilizes Surface Acoustic Wave (SAW) and Dielectrophoresis (DEP) for early detection/isolation and characterization of Circulating Tumor Cells (CTCs) from blood. The device will perform the separation irrespective of the size of the cancer cells, hence it not only isolates cancer cells from blood but can also differentiate a variety of cancer cells even if their sizes overlap. Mathematical/numerical models of the microdevice/cells will also be developed using a sophisticated particle-based technique called Dissipative Particle Dynamics (DPD). The DPD technique will also be utilized to characterize cancer/blood cells. Finally, the hybrid microfluidic device will be fabricated in the cleanroom to validate the model and perform experimentations.
