My lab has had a long-standing interest in understanding the basis of immunological tolerance and humoral immunity following allogeneic transplantation. We have been collaborating extensively with Dr. Marisa Alegre in studying how infections prevent the induction of transplantation tolerance or destabilize established tolerance, and understanding the fundamental mechanisms of robust transplantation tolerance. We recently have developed new approaches to track a defined population of endogenous allospecific T (CD4+effectors (Th1 and Tfh), CD4+Tregs and CD8 effector) and B cells (Class I and Class II reactive), and are now asking how each of these subsets of cells behave under conditions of rejection, memory/sensitization and tolerance, with the goal of identifying new biomarkers of tolerance and rejection.
We also actively investigating the behavior of memory alloreactive B cells in the setting of transplantation, and in identifying how these cells differ from naïve B cells, with the goal of identifying immunosuppressive and tolerance inducing strategies to control this clinically important subset of cells. We are conducting these studies in experimental rodent models, and also testing our findings in humans. These studies are performed in collaboration with Dr. Roger Sciammas at UCDavis, and the clinical transplant faculty at the University of Chicago and Ohio State University.
In addition, we have stretched our research into the prevention of infections through vaccination, with the long-term goal of using this strategy as an indirect but cost-effective means of stabilizing tolerance. Towards this goal, my lab has been collaborating with Dr. Chris Montgomery, a physician scientist in the Department of Pediatrics, to identify sub-unit vaccine candidates and to investigate the immunobiology of protection from Staphylococcus aureus skin infections. My lab also has a strong program of collaborative research with Dr. Joel Collier, a bioengineer at Duke University, to develop of nanoparticulate adjuvant-free vaccines that can elicit protective immune responses with minimal inflammation. Such a vaccine that elicits minimal inflammation may be ideal for tolerant patients, as we now appreciate that inflammation can destabilize established tolerance.
University of Arizona
Tucson, AZ
Research Associate
Tufts University
Boston, MA
Post-Doctoral Fellow
Australian National University
Australia
PhD
University of Malaya
Malaysia
BS (Hons)
Multi-modal profiling of transplant rejection: Discerning the forest from the trees.
Multi-modal profiling of transplant rejection: Discerning the forest from the trees. Am J Transplant. 2024 Nov 14.
PMID: 39550009
CAR Treg synergy with anti-CD154 mediates infectious tolerance to dictate heart transplant outcomes.
CAR Treg synergy with anti-CD154 mediates infectious tolerance to dictate heart transplant outcomes. bioRxiv. 2024 Oct 28.
PMID: 39386649
Isolation and transcriptional profiling of antigen-presenting cells from mouse lung and MLNs following intranasal immunization.
Isolation and transcriptional profiling of antigen-presenting cells from mouse lung and MLNs following intranasal immunization. STAR Protoc. 2024 Oct 19; 5(4):103400.
PMID: 39427311
Update on the immunological mechanisms of primary graft dysfunction and chronic lung allograft dysfunction.
Update on the immunological mechanisms of primary graft dysfunction and chronic lung allograft dysfunction. Curr Opin Organ Transplant. 2024 Dec 01; 29(6):412-419.
PMID: 39422603
Pregnancy dedifferentiates memory CD8+ T cells into hypofunctional cells with exhaustion-enriched programs.
Pregnancy dedifferentiates memory CD8+ T cells into hypofunctional cells with exhaustion-enriched programs. JCI Insight. 2024 May 21; 9(13).
PMID: 38771643
Integrative multi-omics profiling in human decedents receiving pig heart xenografts.
Integrative multi-omics profiling in human decedents receiving pig heart xenografts. Nat Med. 2024 May; 30(5):1448-1460.
PMID: 38760586
Low-affinity CD8+ T cells provide interclonal help to high-affinity CD8+ T cells to augment alloimmunity.
Low-affinity CD8+ T cells provide interclonal help to high-affinity CD8+ T cells to augment alloimmunity. Am J Transplant. 2024 Jun; 24(6):933-943.
PMID: 38228228
Advancing mouse models for transplantation research.
Advancing mouse models for transplantation research. Am J Transplant. 2024 Aug; 24(8):1362-1368.
PMID: 38219866
MHC Tetramers Specifically Identify High- and Low-avidity Donor-specific B Cells in Transplantation Tolerance and Rejection.
MHC Tetramers Specifically Identify High- and Low-avidity Donor-specific B Cells in Transplantation Tolerance and Rejection. Transplantation. 2023 Dec 01; 107(12):2526-2532.
PMID: 37493609
Heterogeneity in allospecific T cell function in transplant-tolerant hosts determines susceptibility to rejection following infection.
Heterogeneity in allospecific T cell function in transplant-tolerant hosts determines susceptibility to rejection following infection. J Clin Invest. 2023 11 01; 133(21).
PMID: 37676735