Research grants
grants
Type 1 Diabetes CAR Treg therapeutic approach - $220,956
Shahnawaz Imam’s Role in the Project: PI, with 15% effort
Leona M. and Harry B. Helmsley Charitable Trust - 129353-01 (Shahnawaz Imam and Juan C Jaume): 12/1/2021 to 5/31/2023
Helmsley Foundation
Normalizing arginine metabolism with sepiaptein for immunostimulatory-shift of HER2+ breast cancer- $353,419
Shahnawaz Imam's Role in the Project: Consultant
R01 - 248304 (Saori Furuta) 03/04/2020 -- 02/28/2025
NCI - National Cancer Institute
Sample Collection for Clinical Performance Evaluation of Elecsys Anti-TPO II. - $200,000
Protocol/Study No: CIM RD005629 – ICON 0165/0677 (Award Notification): Co-PI
Sponsor(s): Roche Diagnostics Operations, Inc.
Publication: Google Scholar PubMed
patents
US Patent App. 16/530,452: “Spontaneous Autoimmune Diabetes in Humanized Mice Carrying Human Type 1 Diabetes Susceptibility and Uses Therefor”University of Toledo, Office of Technology Transfer. 2020.
Background: Although the NOD mouse is current standard for studies on type I diabetes (T1D), no curative therapies resulting from this model have passed clinical trials. Knock in/out models cannot be used to mimic the total pathophysiology of diabetes. In order to develop a cure for T1D, there is a need for an animal model of human T1D that resembles the human disease and as such exhibits the complications of diabetes.
Invention Description: Researchers at the University of Toledo have developed a triple transgenic mouse model of type 1 diabetes (T1D) in which human GAD65 is expressed in pancreatic beta cells and human MHC II (DQ8) is expressed in antigen presenting cells with human T1D susceptibility that closely resembles the human disease and its complications. These mice express all three human transgenes simultaneously at β-cells of pancreas and human beta cell autoantigens are presented to effector T cells simulating human diabetes. Applications: (i) Animal model for autoimmune diabetes disease mechanisms. (ii) Animal model for the development of antigen-specific immune interventions. (iii) Animal model for the hyperglycemic complications of diabetes such as nephropathy, neuropathy and retinopathy.
Spontaneous Type I Diabetes Mouse Model
Imam, S., Alfonso-jaume, M., Jaume, J.C. (2020). Spontaneous Autoimmune Diabetes in Humanized Mice Carrying Human Type 1 Diabetes Susceptibility and Uses Therefor. United States Application No. 16530452, Publication Number. US20200037586.
United States Patent # 20220008522: Beta-Cell Antigen-Specific Chimeric Antigen Receptor Tregs (CAR-Tregs) for Type 1 Diabetes Prevention and Treatment: University of Toledo, Office of Technology Transfer 2022.
Background: The therapeutic application of regulatory T cells (Tregs) for the treatment of autoimmune diseases is limited by the scarcity of antigen-specific Tregs. If antigen-specific Tregs could be produced on demand against a desired autoimmune target, antigen-specific immune suppression of autoimmune diseases would be achievable. One approach to endow effector T cells with a desired antigen specificity uses chimeric T cell antigen receptors with antibody-type specificity. Cellular therapies with antibody-type specific chimeric antigen receptor (CAR)-redirected cytotoxic T cells has shown efficacy in the treatment of malignancies. Accordingly, employing such chimeric immune receptors to redirect Tregs to sites of autoimmune attack would be a useful therapeutic approach to alleviate a broad scope of diseases in which an uncontrolled autoimmune response plays a major role.
Invention Description: We have developed pancreatic beta cell–specific CAR Tregs with preventive and therapeutic capacity against T1D in our transgenic mouse model of type 1 diabetes (T1D). Our disclosure describes CAR technology to generate potent, functional, and stable, GAD65 antigen-specific CAR Tregs that can prevent and treat T1D. Also described herein is the antigen-specific CAR Treg development for prevention and treatment of other autoimmune diseases. Applications: (i) A composition comprising pancreatic beta cell–specific chimeric antigen receptor (CAR) regulatory T cells (Tregs) useful for prevention and treatment of type 1 diabetes (T1D). (ii) A method for preventing and treating diabetes, comprising administering to a diabetic or prediabetic subject an amount effective to treat diabetes. Advantages: (i) Target-specific immune suppression with preservation of host immune function (immune tolerance) for prevention and treatment of T1D.
Jaume JC, Imam S (2022) Immunosuppressive Antigen-Specific Chimeric Antigen Receptor Treg Cells for Prevention and/or Treatment of Autoimmune and Alloimmune Disorders”. United States, The University of Toledo (Toledo, OH, US) 20220008522 https://www.freepatentsonline.com/y2022/0008522.html
- US Patent Application # 62/956,769: Stratifying Risk of Malignancy in the Indeterminate Thyroid Nodules and Development of an Immuno-Genomic Marker for Early Detection of Thyroid Cancer: University of Toledo, Office of Technology Transfer. 2021.
Background: Thyroid cancer is the most common endocrine cancer globally, with an increasing incidence from 2.4 to 9.4% annually over the last three decades. Several molecular and gene mutation diagnostic tests have been developed to diagnose the indeterminate thyroid nodules in fine needle aspiration (FNA) specimens. The positive predictive value of these tests ranges from 40% to 50%. There is a need for more accurate diagnostic tools to predict likelihood of thyroid cancer or diagnosing thyroid cancer.
Invention Description: The FNA samples were subjected to cellular profiling and cytokine/chemokine analysis to integrate genomic and transcriptomics to produce a comprehensive biomarker. The novelty of this patent technology is the longitudinal analysis and the integration of a multitude of cellular and humoral ques relevant to the disease, at the time of diagnosis and during progression of thyroid cancer. This data also includes the most recent advances in micro-RNA (miRNA) analysis and expression profiling (RNA-Seq) of immune cells present in the microenvironment of thyroid cancer to pinpoint the mechanism(s) involved in the onset and/or progression of the disease.
Imam, S., Jaume, J.C. (2021). Stratifying risk of malignancy in indeterminate thyroid nodules and immuno-genomic markers for early detection of thyroid cancer. International Application No. PCT/US2021/012057, Publication Number WO/2021/138661.
United States Provisional Patent Application No. 63389391: Synergistic Inhibition of eIF5A and Notch Signaling. University of Toledo, Office of Technology Transfer. 2022.