Nicholas Jacobson: Voxel Printed Microstructures with Cells for Patient Specific Coronary Stents
Nicholas Jacobson is a research faculty member affiliated with the Inworks Innovation Initiative within the School of Engineering, Computation, and Design at the University of Colorado Denver and Anschutz Medical Campus. Nick and his team, which includes Dr. Mitchel Vedepo, a post-doctoral fellow in the Department of Bioengineering, and Dr. Gareth Morgan, the Director of Interventional Cardiology at Children's Hospital, received a Grubstake Award to design and test a 3D printed patient-specific heart valve with cellular ingrowth. The unique 3D printing technology that will be utilized was invented at Inworks and is currently being tested in numerous clinical studies for surgical planning. Building on this technology with biocompatible materials to focus on congenital heart disease will allow for over 800,000 patients to receive a heart valve replacement. This funding will accelerate development toward a working prototype for large animal testing.
Traci Lyons, Ph.D.: A Novel Therapeutic for Breast Cancer
Dr. Traci Lyons is an Associate Professor in the Department of Medicine at the University of Colorado Anschutz Medical Campus. Dr. Lyons received a Gates Grubstake Award to perform animal testing of monoclonal antibody based therapeutic in-mouse models of breast cancer stem cells and postpartum breast cancers (PPBCs), which are defined as breast cancers diagnosed within 10 years of recent childbirth. PPBCs appear to be enriched for therapy-resistant cancer stem cells, which may account for the high rates of metastasis observed in these patients. The therapeutic antibody has already proven efficacious in multiple mouse models of breast cancer, and exploration of its role in killing breast cancer stem cells will be evaluated. Thus far, the antibody appears to have minimal toxicities in mice. Worldwide estimates of PPBC range from ~150,000 to 350,000 cases annually, based on global breast cancer and/or childbirth rates, respectively. Since PPBC 5-year survival rates of PPBCs are low, PPBC puts thousands of children at risk to grow up without their mothers. If successful, this therapeutic may result in life-extending or life-saving improvements by eliminating the effects, in part, of therapeutic resistance driven by cancer stem cell populations.
Michael Verneris, M.D.: Therapeutic Development of Innate Lymphoid Cells
Dr. Michael Verneris, the Barton Endowed Chair of Pediatric Bone Marrow Transplant, received a Gates Grubstake Award to perform studies using stem cell-derived innate lymphoid cells. These tissue resident lymphocytes play a critical role in ameliorating intestinal inflammation and thus have promise in the treatment of intestinal inflammatory disorders, such as Crohn’s disease (occurring in ~1% of the population). Crohn’s disease is a devastating and life-threatening disorder that causes considerable physical, financial and societal burden. Dr. Verneris’s laboratory has pioneered techniques to differentiate hematopoietic stem cells into Innate lymphoid cells, paving the way for clinical trials of cellular therapy for patients with Crohn’s disease. Grubstake funding will be used to establish the activity of these cells in animal models, to scale these techniques to levels necessary to treat humans and to transfer this technology to the Gates Biomanufacturing Facility.
Chaitanya Puranik, B.D.S., M.S., M.Dent.Sci., Ph. D.: Dental Filling for Regeneration of Dental Pulp
Dr. Puranik is an Assistant Professor and Director of Predoctoral Dental Education in the Department of Pediatric Dentistry at the School of Dental Medicine and Children’s Hospital Colorado, University of Colorado Anschutz Medical Campus. Dr. Puranik and his co-PIs, Drs. Devatha Nair and Michael Schurr, received a Gates Grubstake Award to develop a dental coating for dental pulp regeneration. Dental pulp is the living part of a tooth with blood vessels, nerves, and connective tissue. Unlike the outer covering of the teeth, pulp houses numerous stem cells which are capable of regenerative response after an insult, such as deep dental caries. Damage to dental pulp can cause patients to need root canals or even suffer the loss of their teeth. The annual estimated health care expense for management of dental caries in children alone is $5.2 billion. This funding will help complete studies for pre-IND filing with the FDA.
Refractory cancers are an increasing cause of early death in adults and children. Recent breakthroughs in cell based immunotherapeutic treatments (primarily CAR T cell therapy) are changing that rapidly, with hundreds of trials ongoing in the US and around the world. Although some patients may be cured with current monovalent CAR T cell therapy (targets only CD19), relapses shorten remissions in a majority of patients. Dr. Terry Fry and his team are developing a next generation bicistronic CAR T cell therapy (targets both CD19 and CD22) designed to prolong remissions in patients, improving patient well-being and decreasing healthcare costs. The Grubstake Award will allow them to develop the manufacturing process at the Gates Biomanufacturing Facility.
One of the challenges following bone marrow transplants for cancer therapy are often lethal complications including bacterial pneumonia and graft versus host disease. Although reconstitution of blood forming cells is rapid following transplantation, T cell reconstitution is very slow and incomplete due to the lack of a functional thymus in the patient. To resolve this, Dr. Russ and his team are generating functional, patient specific thymi for co-transplantation into bone marrow transplant recipients. Dr. Russ’s approach can also be used to treat patients with a congenital absence of a thymus. The Grubstake Award will allow them to transfer the technology to the Gates Biomanufacturing Facility for manufacturing scale up and to prepare for pre-IND filing with the FDA.
Glaucoma is the leading cause of irreversible blindness, with an estimated 80 million people worldwide affected by 2020. Retinal ganglion cell death (RGC), a hallmark of the disease, leads to degeneration of the optic nerve, resulting in visual field loss. RGC death correlates with increased intraocular pressure (IOP) due to defects in the drainage of fluid from the anterior chamber of the eye. In acute angle closure glaucoma, there is a sudden rapid rise in IOP with damage that requires immediate medical attention, typically surgery. Despite immediate care, RGC continue to die and cause a permanent reduction in vision within three months. Dr. Nagaraj and his team are developing a peptide-based therapy designed to prevent the rapid loss of RGC from acute angle closure glaucoma. The Grubstake Award will allow them to assess treatment schedules to assess whether additional formulation work is required.
Artificial reproductive technology (a $1.5 billion market) may be used when women do not produce sufficient Follicle-Stimulating Hormone (FSH) for optimal ovarian follicle growth and estrogen production to support pregnancy. Currently, the response rate to standard FSH is very poor. Dr. Kumar and his team have discovered that reason appears to be the glycosylation pattern (location sugars are added to the protein) of the FSH. Dr. Kumar has shown that FSH21, expressed in women with normal reproductive cycles, is also more biologically active in animal models. He plans to use funds from the Gates Grubstake Award to begin the process of developing the tools needed for manufacturing FSH21 for clinical testing.
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