Today, 1.6 million adults and children living with type 1 diabetes rely on insulin for day-to-day survival. For years, researchers have experimented with more permanent fixes, including transplanting pancreatic islets, which contain insulin- and glucagon-producing cells, into patients. One factor impeding progress on new cell therapies is a shortage of biological material. There simply aren’t enough viable cells from organ donors to meet the demand. Now an ongoing, multidisciplinary effort to address this obstacle has received significant funding from the NIH.
The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) has awarded an $8.6 million RC2 grant to a team of scientists at the Institute for Stem Cell and Regenerative Medicine (ISCRM).
The project, led by ISCRM faculty member Vincenzo Cirulli, MD, PhD, an Associate Professor in the departments of Medicine and Pharmacology, resulted from a close collaboration with Dr. Hannele Ruohola-Baker, Professor of Biochemistry; Dr. Laura Crisa, Associate Professor in the Departments of Medicine and Pharmacology; Dr. Shiri Levy, Acting Instructor of Biochemistry; Dr. Julie Mathieu, Associate Professor of Comparative Medicine; and Dr. Karol Bomsztyk, Professor of Medicine/Allergy and Infectious Diseases. This collaboration brings together complementary expertise, reflecting the shared commitment of ISCRM scientists to advancing regenerative medicine research
The transformative award will launch an ambitious interdisciplinary program to overcome one of the biggest challenges in stem cell–based therapies for diabetes: achieving the reliable and reproducible generation of fully functional pancreatic islets from multiple stem cell lines.
The ability to differentiate pluripotent stem cells into insulin-producing cells represents an extraordinary opportunity to address the critical shortage of donor tissue for diabetes cell replacement therapies. However, current protocols for deriving functional islet tissue remain relatively inefficient when applied to different stem cell lines, often yielding heterogeneous mixtures of mature and immature cells.
The RC2 project aims to overcome this barrier by deploying AI-designed mini-proteins, known as EpiBinders. The EpiBinders are developed through a collaboration between the Ruohola-Baker and Baker labs. EBdCas9, the first-in-class member of this platform, continues to advance under the RC2 grant. The new class of Epibinder proteins, along with EBdCas9, will be tested for their ability to epigenetically control islet-specific gene networks, a strategy that, in preliminary work by the ISCRM team, has already shown to dramatically improve the yield, maturation, and reproducibility of islet cell derivation from stem cells.
The investigation will also draw on the expertise and participation of other ISCRM faculty. These will include Mary Regier, Director of the ISCRM Genomic Core, and Sina Gharib, Director of the Computational Medicine Core at the Center for Lung Biology.
In addition to advancing this frontier in Regenerative Medicine, as part of the NIH RC2 program requirements, the team will establish a dedicated “RC2 Portal” within the ISCRM website to foster collaboration and broad community access. The portal will include a public-facing page with project goals and research highlights, secure internal access for investigators to share findings, and external access for the scientific community to request resources and download datasets.
By combining innovative, groundbreaking science with an open-access digital platform, this RC2 program will not only tackle a critical challenge in diabetes research but also ensure that the knowledge, tools, and resources it generates are broadly accessible and shared. This reflects the RC2 program’s core mission: to support large-scale, high-impact, interdisciplinary science with the power to accelerate progress toward transformative therapies.
This RC2 project builds on early investment made by ISCRM in 2022 through State funding in the form of a two-year $200,000 (ITA) Team Award. That seed funding provided the Cirulli, Crisa, Levy, and Ruohola-Baker labs with the foundation to successfully compete for extramural funding, first in the form of a two-year $500,000 Breakthrough T1D grant in 2023, and then in a one-year $875,000 pilot RC2 grant from the NIDDK, paving the way for the current large-scale five-year NIH RC2 program. With such an extraordinary return on investment, Cirulli, Crisa, Levy, and Ruohola-Baker labs’ collaboration highlighted the transformative impact of the ISCRM Team Award on the research program—one that not only catalyzes innovation through collaboration but also empowers other faculty to achieve similar success in securing high-impact, extramural funding.