Immunosuppressive medications are associated with significant body toxicity. Novel treatments to minimize their use are highly needed to prevent rejection and treat autoimmunity. Using cutting-edge technologies, murine and humanized transplant models, we study the mechanisms involved in the regulation of the immune system. Our ultimate goal is to develop novel therapeutics that would help re-educate the immune system to tolerate the transplanted organ such as the mutein IL-2 (JCI 2024). We are actively investigating regulatory immune pathways and cells, such as regulatory T cells, PD1, CTLA4, and Notch pathways. See also some of our groundbreaking research in the following publications at Circulation, Nature Comm, JCI, JCI Insight, American Journal Transp, and Transplantation.
We’re tackling the organ transplant shortage head-on by pioneering two extraordinary paths: bioengineering kidneys from human stem cells (iScience 2024) and turning to gene-modified pigs as potential kidney donors (Harvard, AJT, Transp, Ann Surg, Xenotransp). These innovative approaches could drastically increase the availability of organs and transform the transplant landscape.
Prevention of organ rejection without the need of life-long immunosuppressive drugs is the Holy Grail of transplantation. We have established the first center for transplant tolerance in the world – the Legorreta Center for Clinical Transplant Tolerance. We offer to patients a novel strategy to promote transplant tolerance involving a combined kidney and bone marrow transplantation.
Currently, detecting issues with transplanted organs often requires costly and invasive tests, such as biopsies. At our center, we use a unique biobank of human transplant samples to study each patient’s genetics, clinical profile, and blood and urine biomarkers, aiming to tailor and personalize transplant care (JCI, JCI Insight). Among our innovations, we have developed a novel, affordable, and highly sensitive urine test that uses CRISPR/Cas13 technology to detect early signs of rejection (Nat Biomed Eng 2020). We’ve also adapted the CRISPR/Cas platform to identify genetic mutations, further advancing precision in transplant monitoring (EMBO 2024). Additionally, we’re exploring how wearable devices can help detect transplant-related complications earlier, enhancing proactive patient care.
For patients facing severe body injuries, traditional reconstruction options can be insufficient. Our team is at the forefront of vascular composite tissue transplantation (VCA), leveraging animal models, advanced multiomics platforms, and a unique biobank from human recipients of face and limb transplants (eg. Am J Transp 2016, Nat Scientific Report 2018, NEJM 2019, J Clin Invest. 2021, Cell Report 2022, AJT 2023). Our goal is to deepen our understanding of the underlying biology, identify novel biomarkers, and improve outcomes for those undergoing limb and facial transplantation.
In the face of COVID-19, solid organ transplant recipients emerged as a particularly vulnerable group, experiencing heightened risk of severe illness and mortality. Our lab led forward-looking studies on the safety and efficacy of mRNA SARS-CoV-2 vaccinations, alongside mechanistic research aimed at identifying immune biomarkers to predict COVID-19 response and severity (eg. AJT 2020, Kidney Int 2022). Furthermore, our team’s exploration into the preventative potential of monoclonal antibodies marks a significant stride towards safeguarding this at-risk population against COVID-19 (eg. AJT 2022).
© 2024 Leo Riella
