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Generation of Novel Genomic Tools for Use in the Normalization of Endogeneous RNA Expression Between Different Samples

Genome searching tools are a growing field within the medical and biological research communities. There are now a large number of companies offering services relating to understanding genetic information, and typical laboratory functional genomic assays produce a range of data, including sequencing of transcription factors and regulatory regions. Researchers routinely search over 1,417 functional genomic datasets that are publically available, and users have a range of tools to search the data, including many online. Genetic information requires further processing to become biologically meaningful and a pressing challenge is to effectively search functional genomic data and new tools and processes are needed for searching genomic information.

A New Preventive And Therapeutic Strategy For Liver Cancer

While the overall cancer incidences and mortality are decreasing, primary liver cancer, in particular hepatocellular carcinoma (HCC), is increasing rapidly  and has become the second leading cause of cancer-related death worldwide attributing to the rise of metabolic disorders, including alcoholic and non-alcoholic fatty liver diseases, and viral hepatitis. The significance for development of an effective prevention strategy cannot be over-emphasized, given the extremely poor prognosis of liver cancer patients at the advanced stages and the rapidly expanding population with chronic liver diseases and at high risk for subsequent liver tumorigenesis. Unfortunately, this rapid increase of the malignant disease is unmet by more efficient therapeutics in the clinic.

A Method for Making a Human Alzheimer’s Disease Neuronal Model Using Purified ApoE-HDL

Alzheimer's disease (AD) is a common neurodegenerative disease and the most common cause of dementia. Alzheimer’s disease is defined post-mortem by the increased presence of amyloid plaques and neurofibrillary tangles (NFTs) in the brain. Amyloid plaques are extracellular deposits consisting primarily of amyloid-ß (Aß) peptides, and NFTs are intraneuronal aggregations of hyperphosphorylated tau, a microtubule-associated protein involved in microtubule stabilization. The discovery of new drugs for treating Alzheimer’s disease is currently limited by difficulties in obtaining live neurons from patients and the inability to accurately model Alzheimer’s disease. Animal models of Alzheimer’s disease have been developed, however, these animal models do not completely mimic true human disease, and none of these animal models are neuronal models of the disease. There is a need to develop a human neuronal model that more accurately mimics true human Alzheimer’s disease, and then use such a model for Alzheimer’s disease drug discovery and research.

A Photo-Activated Transcription System for Controlling Cas9 Utilizing Red/Far Red Light

The type II bacterial clustered, regularly interspaced, short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9), referred to as CRISPR-Cas9, serves as a breakthrough technology and platform that is used for genome editing and transcriptional modulation. Recent work has shown that this technology has be adapted to examine the temporal regulation of transcriptional repression or activation by Cas9-based systems utilizing either drugs or via optical regulation.  

Functional Manipulation of the Gut Microbiome Using a Personalized Approach

The use of traditional probiotic microorganisms to provide therapeutic function for the gut microbiome has a number of limitations. Probiotic bacteria do not colonize the gut because they can’t compete with the resident flora that have evolved for that environment. Current probiotics are a single strain which when used in multiple hosts have not had great success in broad populations and are therefore unpredictable. To alleviate the above problem, a new approach is necessary to colonize the human gastrointestinal tract with greater reliability and for therapeutic value to the patient. 

New Anti-Arthritis Compounds Utilizing Oligosaccharides as a Treatment Modality for Rheumatoid arthritis

Rheumatoid arthritis (RA) is a lifelong, systemic autoimmune disease that affects women three times more frequently than men, often in their most productive and childbearing years. Pregnancy in women with RA poses a therapeutic challenge. Some anti-rheumatic drugs can cross the placenta and harm the fetus and/or are transferred into breast milk and harm the breastfed baby. Teratogenic compounds like methotrexate and leflunamide are to be avoided and high dose steroids may be associated with a premature rupture of the membranes. The high risk of drug transfer into breast milk often leads to the recommendation for women to cease breastfeeding.  While the exact cause of RA remains to be elucidated, it is known that chronic macrophage inflammation plays a key role in the development and progression of rheumatoid arthritis. The ability to attenuate macrophage inflammation and suppress the secretion of pro-inflammatory cytokines, like interleukin (IL)-1beta and IL-6 would help in the treatment of RA.  

A Novel Air/Water Retention Device for Improved Visibility in Colonoscopies

Colon cancer is the third most common cancer diagnosed in men and women in the United States. It is also the third leading cause of cancer-related death in women and the second leading cause in men. Fortunately, over the last 20 years the death rate for this cancer has been decreasing. There are two primary reasons for this decrease, improvements in therapy and the increase in screening for and removal of colorectal polyps. A colonoscopy is recommended for adults over the age of fifty in the US. It is an examination of the colon performed by a gastroenterologist whereby an endoscope is inserted through the anus and into the colon. Most endoscopes have a camera and a light for visualization of the colon. In order to clearly see within the colon, which is in a naturally collapsed state, air or water is used to inflate the organ. Normally, a tight seal is formed around the scope to retain pressure inside the colon. But in some patients, a tight seal is not possible and is not able to retain the pressure making the procedure difficult to perform. Currently, the standard practice in these occasions is for a technician to use a towel to hold the anus shut.

A Gene Therapy Strategy To Restore Electrical And Cardiac Function In Arrhythmogenic Right Ventricular Cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a predominantly genetic-based heart disease characterized by right but also recently left ventricular dysfunction, fibrofatty replacement of the myocardium leading to fatal/severe ventricular arrhythmias leading to sudden cardiac death in young people and athletes. ARVC is responsible for 10% of sudden cardiac deaths in people ≥65 years of age and 24% in people ≤30 years of age. ARVC is thought to be a rare disease as it occurs in 1 in 1000-5000 people, although the prevalence may be higher as some patients are undiagnosed or misdiagnosed due to poor diagnostic markers. Growing evidence also reveals earlier onset since pediatric populations ranging from infants to children in their teens are also particularly vulnerable to ARVC, highlighting the critical need to identify and treat patients at an earlier stage of the disease.At present there are no effective treatments for ARVC nor has there been any randomized clinical trials conducted to examine treatment modalities, screening regimens, or medications specific for ARVC. As a result, treatment strategies for ARVC patients are directed at symptomatic relief of electrophysiological defects, based on clinical expertise, results of retrospective registry-based studies, and the results of studies on model systems. The current standard of care is the use of anti-arrhythmic drugs (sotalol, amniodarone and beta-blockers) that transition into more invasive actions, which include implantable cardioverter defibrillators and cardiac catheter ablation, if the patient becomes unresponsive or intolerant to anti-arrhythmic therapies. However, current therapeutic modalities have limited effectiveness in managing the disease, 40% of ARVC patients (a young heart disease) die within 10-11 years after initial diagnosis, highlighting the need for development of more effective therapies for patients with ARVC.