HITI/Helmsley Trust Pilot Grants in Type 1 Diabetes

Suggested Research Areas

The following five research areas were identified through the Harvard Catalyst/InnoCentive Ideation challenge.

1. Discovering inciting autoantigens in T1D and evaluating the local inflammatory response
   The targets of the immune response, which may change during the development of disease, are critical to understanding mechanisms underlying T1D and developing effective therapeutics.
   • Define the chemical nature of these antigens, preferentially focusing on the underappreciated role of lipids
   • Analyze in depth the T cell repertoire during the development of T1D in islet-infiltrating and peripheral T cells
2. Creating novel approaches to therapeutics delivery for T1D
   Strategies that would increase the efficacy of existing therapeutics for treating T1D are of great interest. Novel therapies that might benefit from improved delivery systems will also be considered.
   • Use of targeted liposomes containing multiple regulatory factors to address the key issues of replenishment of beta-cell mass, restoring immune tolerance, and/or reducing inflammation/immunoreactivity to residual beta-cell mass
3. Developing novel monitoring devices
   Improved glucose monitoring devices are an important goal for T1D patients. The device design should be informed by down-stream goals such as those listed in the examples below. Proof of concept proposals would be particularly relevant in the context of producing a viable outcome in the initial year of funding.
   • Non-invasive devices that provide continuous measurement of blood glucose levels
   • Development of continuous measurement capability and linkage to and control of an insulin injection system
   • Utilization of the beta cell itself as a glucose sensor
4. Identifying environmental and microbial contributions to T1D
   Compelling evidence is sought relating to the contribution of environmental factors, and, in particular, microbial associations, that may impact the development and progression of T1D.
   • Use of next-generation sequencing technology to search for microbial genetic sequences in patient tissue
   • Family-based genetic association studies to identify gene-environment interactions
5. Detecting biomarkers that are predictive of diagnosis, prognosis, and response to therapy
   The ability to treat patients would be facilitated by identifying and, critically, elucidating the functional relationship to T1D of:
   • Novel nucleic acid or peptide sequences or lipid or carbohydrate structures
   • Known markers, through better understanding of their structure/function