Center for Transplantation Sciences
Riella Laboratory
Riella Laboratory
55 Fruit Street
Boston,
MA
02114
Research Summary
Our bodies are constantly under attack by bacteria, viruses, fungi and parasites. In addition, sometimes our own cells proliferate out of control—as seen with cancer—or attack our own body—as seen with autoimmune diseases.
The immune system is our body’s army and protects us against all of the above enemies at all times. The immune system must be tightly regulated, since fighting an infection with too much ammunition may cause significant collateral damage. In 1995, one of the most critical immunological advances in the past 50 years occurred: the discovery of regulatory immune cells that inhibit the immune response, preventing it from getting out of control. We now know that there are many regulatory immune cells in our bodies that keeps the immune system under a tight control.
The Riella Laboratory is focused on understanding these mechanisms of immune regulation in order to develop smarter and more efficient ways to control the immune system and prevent organ rejection after transplantation.
Significance to Patient Care
The research conducted by Leonardo V. Riella, MD, PhD, and his laboratory team has the goal of prolonging the life of transplanted organs by better detecting transplant rejection and applying novel treatments to re-educate the immune cells to tolerate the transplanted organ.
Research Projects
Development of novel drugs to promote immune regulation
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.
Investigation of antibody-mediated rejection
Antibody-mediated rejection is the leading cause of kidney loss after transplantation. We are studying how antibodies cause injury post-transplant and how to use the regulatory mechanisms of the immune system to shut off antibody production.
Development of a urine test to earlier detect transplant rejection
Currently, expensive and invasive tests such as biopsies are needed to detect problems with the transplanted organ. We have developed a novel, inexpensive and sensitive urine test to detect early signs of rejection after transplantation, adapting a CRISPR/Cas13 platform technology. We are now validating the technology in our transplanted patients to help guide their management.
Recurrence of glomerular disease post-transplant (in particular FSGS)
Recurrence of kidney disease is the third leading cause of kidney transplant loss. To tackle this problem, we have established the largest collaborative international effort to study glomerular disease recurrence, the TANGO study. The goal of TANGO is to better understand the underlying causes of recurrence (genetic, environmental, immune dysregulation) and promote the development of novel therapies.
Impact of nutrition on the immune system
The diet has an enormous influence on the microbiota and on the immune system. Our group investigates the complementary role of certain dietary changes in regulating auto-immune diseases (GENIE study) and the rejection process post-transplantation (JASN).
Research Positions
To apply for a research position in the Riella Laboratory, please email the following items to Dr. Riella:
- A curriculum vitae
- A statement of interest and career goals
- Names and contact information of at least three references
Our Team
Principal Investigator
Leonardo V. Riella, MD, PhD
Team Members
- Thiago Borges, PhD, instructor
- Pedro Ventura Abreu Aguiar, MD, post-doc
- Nora Alzahrani, MD, post-doc
- Orhan Efe, MD, post-doc
- Yoshikazu Ganchiku, MD, post-doc
- Rodrigo Gassen, PhD, post-doc
- Frank Hullekes, graduate student
- Ayman Al Jurdi, MD, post-doc
- Isadora Lape, research assistant
- Daniel Marconi Mendes, PhD candidate
- Guilherme Ribas, PhD, post-doc
- Audrey Uffing, MD, PhD student
- Karim Yatim, MD, post-doc
Publications
View all publications
- Borges TJ, Murakami N, Lape IT, Gassen RB, Liu K, Cai S, Daccache J, Safa K, Shimizu T, Ohori S, Paterson AM, Cravedi P, Azzi J, Sage PT, Sharpe AH, Li XC, Riella LV. Overexpression of PD-1 on T Cells Promotes Tolerance in Cardiac Transplantation via ICOS-Dependent Mechanisms. JCI Insight. 2021. 6(24):e142909. doi: 10.1172/jci.insight.142909. PMID: 34752418
- Uffing A, Hullekes F, Riella LV, Hogan JJ. Recurrent Glomerular Disease after Kidney Transplantation: Diagnostic and Management Dilemmas. Clin J Am Soc Nephrol. 2021. (11):1730-1742. doi: 10.2215/CJN.00280121. 2021. PMID: 34686531
- Uffing A, Pérez-Saéz MJ, Jouve T, Bugnazet M, Malvezzi P, Muhsin SA, Lafargue MC, Reindl-Schwaighofer R, Morlock A, Oberbauer R, Buxeda A, Burballa C, Pascual J, von Moos S, Seeger H, La Manna G, Comai G, Bini C, Russo LS, Farouk S, Nissaisorakarn P, Patel H, Agrawal N, Mastroianni-Kirsztajn G, Mansur J, Tedesco-Silva H, Ventura CG, Agena F, David-Neto E, Akalin E, Alani O, Mazzali M, Manfro RC, Bauer AC, Wang AX, Cheng XS, Schold JD, Berger SP, Cravedi P, Riella LV. Recurrence of IgA Nephropathy after Kidney Transplantation in Adults. Clin J Am Soc Nephrol. 2021. (8):1247-1255. doi: 10.2215/CJN.00910121.PMID: 34362788
- Gassen RB, Borges TJ, Pérez-Sáez MJ, Zhang H, Al Jurdi A, Llinàs-Mallol L, Aoyama B, Lima M, Pascual J, Sage PT, Murakami N, Riella LV. T Cell Depletion Increases Humoral Response by Favoring T Follicular Helper Cells Expansion. Am J Transplant. 2022. 22(7):1766-1778. doi: 10.1111/ajt.17038. PMID: 35320600
- Kaminski MM, Alcantar MA, Lape IT, Greensmith R, Huske AC, Valeri JA, Marty FM, Klambt V, Azzi J, Akalin E, Riella, LV, Collins JJ. A CRISPR-Based Assay for the Detection of Opportunistic Infections Post-Transplantation and for the Monitoring of Transplant Rejection. Nature Biomedical Engineering. 2020
- Uffing A, Pérez-Sáez MJ, Mazzali, M, Manfro RC, Bauer AC LaManna G, Comai G, Fischman C, Farouk S, Lichtenfels B, Mansur JB, Tedesco-Silva H, Kirztajn, GM, Manonelles A, Bestard O. Riella MC, Hokazono R, Arias-Cabrales C, David Neto E, Ventura CG, Akalin E, Mohammed O, Khankin EV, Malvezzi P, Conlon PJ, Cravedi P, Riella LV. Recurrence of FSGS after Kidney Transplantation in Adults. Clin J Am Soc Nephrol. 2020. 15(2):247-256
- Magee CN, Murakami N, Borges TJ, Shimizu T, Safa K, Ohori S, Cai S, Uffing A, Azzi J, Elyaman W, Charbonnier LM, Liu K, Toprak D, Visner G, Chatila TA, Siebel CW, Najafian N, Riella LV. Notch-1 Inhibition Promotes Immune Regulation in Transplantation via Treg-Dependent Mechanisms. Circulation. 2019. 140(10):846-863
- Tasigiorgos S, Kollar B, Turk M, Perry B, Alhefzi M, Kiwanuka H, Nizzi MC, Marty FM, Chandraker A, Tullius SG, Riella LV, Pomahac B. Five-Year Follow-Up after Face Transplantation. New England Journal of Medicine. 2019. 380(26):2579-2581
- Borges TJ, Murakami N, Machado FD, Lopes RL, Calderwood S, Riella LV, Bonorino C. March1-Dependent Modulation of Donor MHC II on CD103+ Dendritic Cells Mitigates Alloimmunity. Nature Commun. 2018. 9(1):3482
- Uffing A, Pérez-Sáez MJ, LaManna G, Comai G, Fischman C, Farouk S, Manfro RC, Bauer AC, Lichtenfels B, Mansur JB, Tedesco-Silva H, Kirztajn, GM, Manonelles A, Bestard O. Riella MC, Hokazono R, Arias-Cabrales C, David Neto E, Ventura CG, Akalin E, Mohammed O, Khankin EV, Safa K, Malvezzi P, Conlon PJ, Cravedi P, Riella LV. A Large International Study on Post-Transplant Glomerular Diseases: the TANGO Project. BMC Nephrology. 2018. 19:229
- Borges TJ , O’Malley JT, Wo L, Murakami N, Smith B, Azzi J, Tripathi S, Lane JD, Bueno EM, Clark RA, Tullius SG, Chandraker A, Lian CG, Murphy GF, Strom TB, Pomahac B, Najafian N, Riella LV. Co-Dominant Role of IFN-γ- and IL-17-Producing T Cells During Rejection in Full Facial Transplant Recipients. American Journal of Transplantation. 2016. 16(7):2158-71
- Safa K, Ohori S, Borges HJ, Uehara M, Batal I, Shimizu T, Magee CN, Belizaire R, Abdi R, Wu C, Chandraker A, Riella LV. Salt Accelerates Allograft Rejection through SGK1-dependent Treg Inhibition. Journal of American Society of Nephrology. 2015. 26(10):2341-7
Center for Transplantation Sciences
The Center for Transplantation Sciences (CTS) at Massachusetts General Hospital conducts critical research to increase the success rates of transplantation and meet the growing demand for organ and bone marrow transplantation.