Targeting trained immunity in transplantation
Active Project Grant Awarded Last action
- Award ID
- P01AI168258
- Recipient
-
Icahn School Of Medicine At Mount Sinai UEI C8H9CNG1VBD9
- Awarding agency
-
National Institute of Allergy and Infectious Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $18,082,049
Award facts
- Assistance listing
- 93.855 Allergy and Infectious Diseases Research
- Completion date 70% complete
- Place of performance
- New York, NY 10029, USA
Award details come from USAspending.gov.
Description
- Abstract
- Overview transplantation has revolutionized the lives of patients suffering from organ failure. The design of modern immunosuppression has employed a time-honored focus on controlling t cell-mediated responses. However, current immunosuppressive therapies have suboptimal success rates and induce significant side effects, including increased susceptibility to infections, metabolic toxicity, and cancer risk. Given the growing body of evidence showing that innate immunity is also critical to alloresponse initiation and allograft survival, IT is not surprising that current immunosuppressive regimens do not achieve satisfactory long-term graft and patient survival. Recent work by this P01's investigators has shown that trained immunity plays a vital role in allograft survival. Trained immunity is a long-term increase in the functional responsiveness of innate immune cells, which is maintained by epigenetic modifications and can be considered DE facto innate immune memory. On a systems level, we demonstrated that trained immunity is regulated and maintained by epigenetic modifications in bone marrow hematopoietic progenitors, which consequently release trained innate immune cells with augmented inflammatory and antimicrobial function. Our preclinical and clinical preliminary data revealed a discrete causative connection between allograft transplantation, the induction of trained immunity, systemic inflammatory response, and activated or amplified t cell-mediated alloimmunity. Furthermore, we identified trained immunity as a compelling therapeutic target in mouse and non-human primate heart allograft models. Based on these results, our central hypothesis is that trained immunity is a critical mechanism that amplifies and sustains both innate and adaptive rejection responses and is therefore a compelling clinical therapeutic target for achieving long-term allograft survival without requiring chronic immunosuppression. In this P01, we will address our central hypothesis by drawing on the expertise of authorities in the fields of immunology and bioengineering. This multidisciplinary team of scientists and clinicians will work together to i) understand trained immunity's clinical relevance in kidney transplantation, II) elucidate the mechanisms by which trained immunity is induced and leads to organ rejection, and III) develop bioengineering solutions for diagnosing and therapeutically regulating trained immunity in transplantation. We anticipate that, together, these highly interactive projects will generate innovative new therapeutic strategies to more effectively prevent rejection and potentially achieve immune tolerance. If successful, these studies could impact the entire field of transplantation and provide insights that could also be highly relevant for bone marrow transplantation and autoimmune disease.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $323,678 | |
| Amendment | $2,685,855 | |
| Amendment | $3,010,650 | |
| Amendment | $3,018,892 | |
| Amendment | $3,018,892 | |
| Amendment | $3,012,041 | |
| Original award | $3,012,041 |
Subawards
| Subrecipient | Amount | Awarded |
|---|---|---|
| Stichting Radboud Universitair Medisch Centrum | $323,678 | |
| The General Hospital Corporation | $55,403 | |
| The Research Foundation For The State University Of New York | $104,520 | |
| Stichting Radboud Universitair Medisch Centrum | $957,502 | |
| Stichting Radboud Universitair Medisch Centrum | $155,098 | |
| The General Hospital Corporation | $3,679,516 |
Quick answers
Who received award P01AI168258?
P01AI168258 was awarded to Icahn School Of Medicine At Mount Sinai by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on June 1, 2023.
How much is award P01AI168258 worth?
$18,082,049 has been obligated on P01AI168258.
On GovTribe
See this award's full record
- Every transaction and subaward
- The recipient's other awards and teaming partners
- Similar grant awards
- Ask GovTribe AI about this award