Metabolic, Liver, Bowel, and Cardiovascular Diseases Research at UMass Medical School.
Research topics on Metabolic, Liver, Bowl, and Cardiovascular Diseases at UMMS includes:
Type 1 and 2 diabetes, Metabolic inflammation, blood lipids, Ischemia, Obesity and more. Browse our innovation by scrolling though below.
Browse Our Metabolic, Liver, Bowl, and Cardiovascular Diseases Research Inventions:
Title: Genetically Modified Non-Human Animals and Methods Relating to Complement Dependent Cytotoxicity. UMMS16-63; Patent Pending.
The present invention provides a genetically modified immunodeficient mouse, wherein the genome of the mouse comprises a repaired C5 complement component structural gene such that the 5 genetically modified immunodeficient mouse expresses the C5 complement component structural gene and is characterized by an intact complement system. The present invention relates to immunodeficient non-obese diabetic (NOD), A/J, A/He, AKR, DBA/2, NZB/B1N, BlO.D2/oSn and other mouse strains genetically modified to restore complement-dependent cytotoxicity which is lacking in the unmodified immunodeficient mice.
Title: Use of miR-122 to Treat Liver Diseases. UMMS16-56; Patent Pending.
This invention builds on the new discovery that grainyhead-like 1 and 2 (GRHL-1 and -2) proteins inhibit tumor suppressor, microRNA-122 (miR-122). Increasing the bioavailability of miR-122 may potentially help to treat liver diseases such as steatosis, inflammation, fibrosis, and liver cancer such as hepatocellular carcinoma. Therapeutic inhibition GRHL-1&2 may restore the positive therapeutic effects of miR-122 in liver.
Title: TARGETING HEPATITIS B VIRUS (HBV) HOST FACTORS. UMMS15-60; Patent 9,771,590.
This invention discloses the first ever genetic screen to identify Hepatitis B virus host factors. The invention further encompasses the factors, such as Zinc finger, CCHC domain containing 14 (ZCCHC14), identified by those methods and methods of treating Hepatitis B virus infections by targeting those factors.
Title: New XCI Inhibitors as Potential Rett Syndrome Therapeutics. UMMS15-53; Patent Pending.
This invention provides methods of treating a subject having a dominant X-linked disease, the method comprising administering to the subject an X chromosome inactivation factor (XCIF) inhibitor in an amount effective for inducing expression a target X-linked gene. The invention provides small molecule and oligonucleotide XCIF inhibitors. In some embodiments, the X-linked gene is MECP2 and the X-linked disease is Rett Syndrome.
Title: Creation of RIPK3 Reporter and Conditional Deletion Mouse Model. UMMS15-05; Patent Pending.
This invention allows investigators to track endogenous RIPK3 expression in live cells and enables tissue-specific inactivation of RIPK3. Specifically, the last coding exon of the mouse RIPK3 gene is fused in-frame to the enhanced green fluorescent protein (GFP). LoxP sites flank the last coding exon of RIPK3. Crossing the RIPK3-GFP “floxed” mice to transgenic mice expressing Cre recombinase under the control of tissue-specific promoter enables conditional deletion and inactivation of RIPK3 in distinct tissues.
Title: Novel High Efficiency Library-identified CNS-tropic AAV Vectors. UMMS14-59; Patent Pending.
Newly designed recombinant AAV capsids with greater efficiency for CNS delivery than AAV9, the natural variant with the currently highest known CNS transduction efficiency. These new AAV capsids, B1-B4, show considerably lower off-target effects in the liver when compared to AAV9. Additionally, each of these AAV capsids show selectively higher efficiency for specific peripheral tissues (e.g. pancreas, sk. muscle, heart, adipocyte).
Title: A New Medical Use of Gadoxetate Disodium to Evaluate Cystic Duct Patency Using CT Scan. UMMS14-33; Patent Pending.
A method of diagnosing a condition in a patient experiencing cholecystitis that uses gadoxeate disodium as a contrast agent for making images such as CT scans of the biliary tree and related anatomical structures. The method uses x-ray radiation generated with excitation voltages in the range of 70 KV to 140 KV. The x-ray radiation is preferably filtered to suppress or practically remove x-rays having energy lower than 50.2 KeV.
Title: REBISS Score and REBISS Score Calculator. UMMS14-32; Patent Pending.
To prevent misdiagnosis, this technology discloses a clinical scoring system that effectively and efficiently utilizes a number of different data sources to determine a diagnosis of patient conditions. The score is compared to a spectrum of scores in order to identify between disorders, such as Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBSd) or gastroesophageal reflux disease (GERD) and functional dyspepsia for which there are currently no validated scoring systems.
Title: Expansion of Human Adipocyte White and "Brite/Beige" Progenitors through Angiogenic Expansion of their Vascular Niche. UMMS14-26; Patent Pending.
This invention relates to methods of making human adipose capillary progenitor cells (HACAPS), which are capable of giving rise to either white or "Brown-on-white" (Brite) adipose cells, and enriched populations thereof, for reconstructive and metabolic therapy, and for drug discovery. Further, methods of treating subjects by administering HACAPS are provided.
Title: Method and Application for Vascular Phantoms. UMMS14-11; Patent Pending.
This invention provides a novel method of imaging intracranial atherosclerotic disease (ICAD) by creating a 3D vascular phantom based on imaging data of vasculature of a subject. This technology is non-invasive thereby overcoming the significant risk of morbidity and mortality due to catheter angiography, the current gold standard for imaging ICAD. Further, unlike catheter angiography this technology can provide characteristics of the atherosclerotic plaque, vessel wall and information regarding the underlying etiology.
Title: Application of Hematocrit/Hemoglobin-derived Correction Algorithm to Whole Blood Platelet Reactivity Tests. UMMS14-02; Patent Pending.
The invention relates to novel methods and assays, which provide accurate and easily implemented measurement and analyses of whole blood platelet reactivity. These assays can be used to identify patients at high risk of thrombotic complications and recurrent ischemic events, especially those with lowered response to clopidogrel. These patients can then be targeted with enhanced anti-platelet therapy.
Title: Anti-fracCRP Hybridomas and Monoclonal Antibodies. UMMS13-71; Patent Pending.
This invention provides antibodies and antibody fragments that bind to human fractional C-Reactive Protein (fracCRP), kits and assays using these antibodies and antibody fragments to diagnose low to moderate risk for Acute Coronary Syndrome (ACS). This invention is based on two clinical studies (one prospective, one retrospective) that measured fracCRP, Troponin I (TnI), and the fracCRPxTnI metric on 210 patients (105 each with final diagnoses of ACS negative or ACS positive). Overall, the method demonstrated strong diagnostic rule-in value for these patients on arrival, with a specificity of 96.2%, positive predictive value of 91.7%, sensitivity of 41.9%, and negative predictive value of 62.3%.
Title: Chemical Exchange Saturation Transfer Angiography (angioCEST). UMMS13-56; Patent Pending.
The invention provides a novel approach for effective ex vivo and in vivo imaging of blood and establishes the feasibility of blood as an effective agent for Chemical Exchange Transfer Saturation (CEST). The method of the invention is based on the measurement of the labile protons that are associated with various amino acids, proteins, peptides and other molecules that are naturally present in blood. These components are not detectable with currently available clinical MRI sequences, but generate a clear signal by using CEST. MR imaging of blood in vivo remains a major challenge in part because blood flow affects the intensity of MR images in many nonlinear ways that depend both on details of the particular imaging technique and on blood vessel and flow geometry.
Title: Selective, siRNA-Mediated Knockdown of CB1 Receptors in Macrophages for the Treatment of Diabetes. UMMS13-52; Patent Pending.
Novel compositions and methods for the treatment of type 2 diabetes mellitus using glucagon-encapsulated siRNA directed against human cannabinoid receptor 1 (CB1). The glucan-encapsulated siRNA's specifically target phagocytic macrophages upon administration.
Title: COMPOSITIONSANDMETHODSFOR DECREASING LEUKOCYTE EXTRAVASATION AND VESSEL FLUID LEAKAGE. UMMS12-52; 9,434,951.
The technology provides novels compositions and methods for preventing formation of atherosclerotic plaques by administering inhibitory oligonucleotides, e.g. miRNA, that decrease Mitogen-activated protein kinase kinase kinase kinase 4 (Map4k4). This invention is based on the discovery that oligonucleotides that decrease the expression of Map4k4 mRNA in an endothelial cell reduce the induction of leukocyte adhesion molecules and reduce endothelial cell monolayer permeability. Further provided are methods of using oligonucleotides targeting Map4k4 therapeutic agents for atherosclerosis.
Title: MOLECULAR PROBE FOR MULTIMODALITY IMAGING AND TRACKING OF STEM CELLS. UMMS12-33; Patent 9,492,571.
To better understand the risks associated with stem cell therapies, this invention provides compounds to track transplanted stem cells in vivo overtime using noninvasive imaging techniques. Specifically, the invention provides novel multi-modality probes constructed by utilizing (a) the high selectivity of long hydrocarbon chains for binding to plasma membranes of cells, (b) a near-infrared (NIR) dye for optical imaging, and (c) a radionuclide for PET or SPECT imaging.
Title: FRACTIONAL C-REACTIVE PROTEIN (FRACCRP) ANTIBODIES AND ASSAYS. UMS10-49; Patent 9,841,430.
This invention discloses antibodies that bind to human fractional C-Reactive Protein (fracCRP), kits containing these antibodies and antibody fragments, and assays using these antibodies and antibody fragments to assess patients at low to moderate risk for Acute Coronary Syndrome (ACS). Overall, this method demonstrated strong diagnostic rule-in value for these patients, with a specificity of 96.2%, positive predictive value of 91.7%, sensitivity of 41.9%, and negative predictive value of 62.3%.
Title: AAV-BASED TREATMENT OF CHOLESTEROL-RELATED DISORDERS. UMMS10-37; Patent 9,272,053.
Novel therapeutic to treat cholesterol-related disorders by recombinant adeno-associated (rAAV)-based gene therapy. Introduction of miR122-inhibitor transgene in the liver significantly reduces cholesterol levels up to 50% for at least 14 weeks in mice.
Title: Immunotherapy for T Cell-Mediated Autoimmune Diseases Using ITK Inhibitors. UMMS10-05; Patent Pending.
The present disclosure is based, in part, on the discovery that interleukin-2-inducible T cell kinase (ITK) and CD28 signals regulate auto-reactive T cell trafficking and that organ-specific T cell mediated autoimmune diseases such as Type 1 diabetes and multiple sclerosis. Accordingly, the present specification provides methods of treating organ-specific T cell mediated autoimmune diseases by inhibiting ITK with a therapeutically effective amount of an ITK inhibitor, e.g., BMS509744, ibrutinib, 10n, 2-amino-5-(thioaryl)thiazole, 5 aminomethylbenzimidazole, 2-amino-5-[(thiomethyparyl]thiazole, and biaryl thiophene.
The present invention provides a screw and plate assembly for sternal fixation. This technology provides an improvement over steel wire fixation, the method currently used for sternal fixation. Specifically, this technology decreases unwanted loosening and failure of the fixation system, a problem common in osteoporotic or lower-density bones.
Title: Use of Cathepsin B Inhibitors for the Treatment of IL-1 Related Diseases. UMMS08-51; Patent Pending.
This innovation describes detailed mechanisms of how immune cells recognize microorganisms (non-self) from host (self). The cytoplasmic receptor complex NALP3 inflammasome has been found to react to a variety of crystals such as silica crystals or cholesterol crystals, all of which were found to require phagocytosis for activation. By inhibiting phagosomal acidification, the inventors were able to prevent activation of NALP3 in the presence of the crystal activators. Understanding these mechanisms may be valuable to research into IL-1 related diseases of sterile inflammation including atherlosclerosis, amyloidosis, Alzheimer silicosis, asbestosis and others.
Title: METHODS AND SYSTEMS FOR ANALYTE MEASUREMENT. UMMS08-50; Patent 9,057,689.
This invention builds on the existing non invasive spectroscopic sensor that can detect information from tissues of different thicknesses to aid diagnoses. This invention uses a mathematical approach to calculate capillary SO2, pO2, pH, pCO2, and temperature. The calibration equation for all parameters uses PCA Loading Correction factor to account for subject-to-subject variation that has been used to determine the calibration equation.
Title: WFS1: A Master Negative Regulator of Endoplasmic Reticulum Stress Signaling and an Effective Inducer of Insulin-Producing Cells. UMMS08-40; Patent Pending.
This new discovery provides a potential therapeutic target for type 1 and 2 diabetes. WFS1 has been identified as a master regulator of the endoplasmic reticulum (ER) stress response pathway and helps maintain ER homeostatsis and consequently protection of beta cell insulin production. High levels of ER stress have been associated with premature death of pancreatic cells. Lentivirus-mediated WFS1 introduction has been developed to convert exocrine cells into insulin-producing cells in patients with type 1 and 2 diabetes. This innovation application may also prove to be beneficial to other diseases that arise from ER including neurodegenerative diseases.
Title: SPECTROSCOPIC SENSORS. UMMS08-39; Patent 9,095,291.
This technology is a miniature sensor optimized to collect spectra from the tissue of living subjects. The device accommodates tissues of different thicknesses with just a single sensor. The devices are made of solid state materials that are easy and inexpensive to manufacture. The broad spectrum of readings can detect oxygen tension, pH, hematocrit and potentially more parameters.
Title: METHODS FOR EARLY DIAGNOSIS OF ACUTE CORONARY SYNDROME. UMMS08-26; Patent 9,116,155.
This innovation provides a method to assess acute tissue damage and stratify acute coronary syndrome. Analysis of circulating C-reactive protein (CRP) and fractional forms of CRP (fracCRP), permits early measurement of tissue damage than fracCRP values only in a specific diseases context previous inventions, thus, broadening the scope of application for this established laboratory value. of the use of fraCRP values. This process provides a method for a more comprehensive analysis of acute tissue damage that may be applicable to a variety of clinical scenarios.
Title: ENCAPSULATED NANOPARTICLES FOR NUCLEIC ACID DELIVERY. UMMS08-09; Patent 8,389,485.
This invention discloses a new method for delivery of nucleic acids, including agents for gene silencing (e.g. siRNAs). This new system is developed with exterior of yeast cell wall particle (YCWP) and interior comprising multilayer nanoparticle core with a payload complex. Using this technology, inventors have effectively shown siRNA can be delivered effectively in macrophages.