John Yi

Overview:

I am an immunologist, with a focus to characterize the immune system in response to infectious and non-infectious diseases including cancer, HIV, autoimmune disease, and transplantation. My goals are to identify novel biomarkers/immune signatures that clinicians can utilize to diagnosis, predict disease outcomes, and determine patients' response to treatment. 

Positions:

Adjunct Assistant Professor in the Department of Surgery

Surgery, Surgical Sciences
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 2010

University of Alabama Birmingham

Grants:

Immune modulation of CaMKK2 in the ovarian tumor microenvironment

Administered By
Obstetrics and Gynecology, Gynecologic Oncology
Awarded By
American Association of Obstetricians and Gynecologists Foundation
Role
Collaborator
Start Date
End Date

Magnetically directed single cell transcriptome analysis in HIV latency

Administered By
Medicine, Pulmonary, Allergy, and Critical Care Medicine
Awarded By
National Institutes of Health
Role
Collaborator
Start Date
End Date

Feasibility of using Bortezomib-based immunosuppressive approach to deplete anti-AAV antibodies in mice

Administered By
Pediatrics, Medical Genetics
Awarded By
Asklepios BioPharmaceutical, Inc.
Role
Co Investigator
Start Date
End Date

VTEU Task D Option 2 Protocol FY.2015.A4D14.0033

Administered By
Duke Human Vaccine Institute
Awarded By
National Institutes of Health
Role
Investigator
Start Date
End Date

VTEU Task D Option 3 Protocol FY.2015.A4D14.0033

Administered By
Duke Human Vaccine Institute
Awarded By
National Institutes of Health
Role
Investigator
Start Date
End Date

Publications:

Immune cell profiles in synovial fluid after anterior cruciate ligament and meniscus injuries.

BACKGROUND: Anterior cruciate ligament (ACL) and meniscus tears are common knee injuries. Despite the high rate of post-traumatic osteoarthritis (PTOA) following these injuries, the contributing factors remain unclear. In this study, we characterized the immune cell profiles of normal and injured joints at the time of ACL and meniscal surgeries. METHODS: Twenty-nine patients (14 meniscus-injured and 15 ACL-injured) undergoing ACL and/or meniscus surgery but with a normal contralateral knee were recruited. During surgery, synovial fluid was aspirated from both normal and injured knees. Synovial fluid cells were pelleted, washed, and stained with an antibody cocktail consisting of fluorescent antibodies for cell surface proteins. Analysis of immune cells in the synovial fluid was performed by polychromatic flow cytometry. A broad spectrum immune cell panel was used in the first 10 subjects. Based on these results, a T cell-specific panel was used in the subsequent 19 subjects. RESULTS: Using the broad spectrum immune cell panel, we detected significantly more total viable cells and CD3 T cells in the injured compared to the paired normal knees. In addition, there were significantly more injured knees with T cells above a 500-cell threshold. Within the injured knees, CD4 and CD8 T cells were able to be differentiated into subsets. The frequency of total CD4 T cells was significantly different among injury types, but no statistical differences were detected among CD4 and CD8 T cell subsets by injury type. CONCLUSIONS: Our findings provide foundational data showing that ACL and meniscus injuries induce an immune cell-rich microenvironment that consists primarily of T cells with multiple T helper phenotypes. Future studies investigating the relationship between immune cells and joint degeneration may provide an enhanced understanding of the pathophysiology of PTOA following joint injury.
Authors
Kim-Wang, SY; Holt, AG; McGowan, AM; Danyluk, ST; Goode, AP; Lau, BC; Toth, AP; Wittstein, JR; DeFrate, LE; Yi, JS; McNulty, AL
MLA Citation
Kim-Wang, Sophia Y., et al. “Immune cell profiles in synovial fluid after anterior cruciate ligament and meniscus injuries.Arthritis Res Ther, vol. 23, no. 1, Nov. 2021, p. 280. Pubmed, doi:10.1186/s13075-021-02661-1.
URI
https://scholars.duke.edu/individual/pub1500705
PMID
34736523
Source
pubmed
Published In
Arthritis Research & Therapy
Volume
23
Published Date
Start Page
280
DOI
10.1186/s13075-021-02661-1

Immune Tolerance-Adjusted Personalized Immunogenicity Prediction for Pompe Disease.

Infantile-onset Pompe disease (IOPD) is a glycogen storage disease caused by a deficiency of acid alpha-glucosidase (GAA). Treatment with recombinant human GAA (rhGAA, alglucosidase alfa) enzyme replacement therapy (ERT) significantly improves clinical outcomes; however, many IOPD children treated with rhGAA develop anti-drug antibodies (ADA) that render the therapy ineffective. Antibodies to rhGAA are driven by T cell responses to sequences in rhGAA that differ from the individuals' native GAA (nGAA). The goal of this study was to develop a tool for personalized immunogenicity risk assessment (PIMA) that quantifies T cell epitopes that differ between nGAA and rhGAA using information about an individual's native GAA gene and their HLA DR haplotype, and to use this information to predict the risk of developing ADA. Four versions of PIMA have been developed. They use EpiMatrix, a computational tool for T cell epitope identification, combined with an HLA-restricted epitope-specific scoring feature (iTEM), to assess ADA risk. One version of PIMA also integrates JanusMatrix, a Treg epitope prediction tool to identify putative immunomodulatory (regulatory) T cell epitopes in self-proteins. Using the JanusMatrix-adjusted version of PIMA in a logistic regression model with data from 48 cross-reactive immunological material (CRIM)-positive IOPD subjects, those with scores greater than 10 were 4-fold more likely to develop ADA (p<0.03) than those that had scores less than 10. We also confirmed the hypothesis that some GAA epitopes are immunomodulatory. Twenty-one epitopes were tested, of which four were determined to have an immunomodulatory effect on T effector response in vitro. The implementation of PIMA V3J on a secure-access website would allow clinicians to input the individual HLA DR haplotype of their IOPD patient and the GAA pathogenic variants associated with each GAA allele to calculate the patient's relative risk of developing ADA, enhancing clinical decision-making prior to initiating treatment with ERT. A better understanding of immunogenicity risk will allow the implementation of targeted immunomodulatory approaches in ERT-naïve settings, especially in CRIM-positive patients, which may in turn improve the overall clinical outcomes by minimizing the development of ADA. The PIMA approach may also be useful for other types of enzyme or factor replacement therapies.
Authors
De Groot, AS; Desai, AK; Lelias, S; Miah, SMS; Terry, FE; Khan, S; Li, C; Yi, JS; Ardito, M; Martin, WD; Kishnani, PS
MLA Citation
De Groot, Anne S., et al. “Immune Tolerance-Adjusted Personalized Immunogenicity Prediction for Pompe Disease.Front Immunol, vol. 12, 2021, p. 636731. Pubmed, doi:10.3389/fimmu.2021.636731.
URI
https://scholars.duke.edu/individual/pub1487554
PMID
34220802
Source
pubmed
Published In
Frontiers in Immunology
Volume
12
Published Date
Start Page
636731
DOI
10.3389/fimmu.2021.636731

Opportunities, barriers, and recommendations in down syndrome research.

BACKGROUND: Recent advances in medical care have increased life expectancy and improved the quality of life for people with Down syndrome (DS). These advances are the result of both pre-clinical and clinical research but much about DS is still poorly understood. In 2020, the NIH announced their plan to update their DS research plan and requested input from the scientific and advocacy community. OBJECTIVE: The National Down Syndrome Society (NDSS) and the LuMind IDSC Foundation worked together with scientific and medical experts to develop recommendations for the NIH research plan. METHODS: NDSS and LuMind IDSC assembled over 50 experts across multiple disciplines and organized them in eleven working groups focused on specific issues for people with DS. RESULTS: This review article summarizes the research gaps and recommendations that have the potential to improve the health and quality of life for people with DS within the next decade. CONCLUSIONS: This review highlights many of the scientific gaps that exist in DS research. Based on these gaps, a multidisciplinary group of DS experts has made recommendations to advance DS research. This paper may also aid policymakers and the DS community to build a comprehensive national DS research strategy.
Authors
Hendrix, JA; Amon, A; Abbeduto, L; Agiovlasitis, S; Alsaied, T; Anderson, HA; Bain, LJ; Baumer, N; Bhattacharyya, A; Bogunovic, D; Botteron, KN; Capone, G; Chandan, P; Chase, I; Chicoine, B; Cieuta-Walti, C; DeRuisseau, LR; Durand, S; Esbensen, A; Fortea, J; Giménez, S; Granholm, A-C; Hahn, LJ; Head, E; Hillerstrom, H; Jacola, LM; Janicki, MP; Jasien, JM; Kamer, AR; Kent, RD; Khor, B; Lawrence, JB; Lemonnier, C; Lewanda, AF; Mobley, W; Moore, PE; Nelson, LP; Oreskovic, NM; Osorio, RS; Patterson, D; Rasmussen, SA; Reeves, RH; Roizen, N; Santoro, S; Sherman, SL; Talib, N; Tapia, IE; Walsh, KM; Warren, SF; White, AN; Wong, GW; Yi, JS
MLA Citation
Hendrix, James A., et al. “Opportunities, barriers, and recommendations in down syndrome research.Transl Sci Rare Dis, vol. 5, no. 3–4, 2021, pp. 99–129. Pubmed, doi:10.3233/trd-200090.
URI
https://scholars.duke.edu/individual/pub1488667
PMID
34268067
Source
pubmed
Published In
Transl Sci Rare Dis
Volume
5
Published Date
Start Page
99
End Page
129
DOI
10.3233/trd-200090

Cellular changes in eculizumab early responders with generalized myasthenia gravis.

Eculizumab (ECU), a C5 complement inhibitor, is approved to treat acetylcholine receptor autoantibody positive generalized myasthenia gravis (AChR MG). The clinical effect of ECU relies on inhibition of the terminal complement complex; however, the effect of ECU on lymphocytes is largely unknown. We evaluated innate and adaptive immunity among AChR MG patients (N = 3) before ECU and ≥3 months later while on stable therapy, and found reduced activation markers in memory CD4+ T cell subsets, increased regulatory T cell populations, and reduced frequencies of CXCR5+HLA-DR+CCR7+ Tfh subsets and CD11b+ migratory memory B cells. We observed increases within CD8+ T cell subsets that were terminally differentiated and senescent. Our data suggest complement inhibition with ECU modulates the adaptive immunity in patients with MG, consistent with preclinical data showing changes in complement-mediated signaling by T- and antigen-presenting cells. These findings extend our understanding of ECU's mechanism of action when treating patients with MG.
Authors
Li, Y; Yi, JS; Howard, JF; Chopra, M; Russo, MA; Guptill, JT
MLA Citation
Li, Yingkai, et al. “Cellular changes in eculizumab early responders with generalized myasthenia gravis.Clin Immunol, vol. 231, Oct. 2021, p. 108830. Pubmed, doi:10.1016/j.clim.2021.108830.
URI
https://scholars.duke.edu/individual/pub1495084
PMID
34450290
Source
pubmed
Published In
Clin Immunol
Volume
231
Published Date
Start Page
108830
DOI
10.1016/j.clim.2021.108830

C3 complement inhibition prevents antibody-mediated rejection and prolongs renal allograft survival in sensitized non-human primates.

Sensitized kidney transplant recipients experience high rates of antibody-mediated rejection due to the presence of donor-specific antibodies and immunologic memory. Here we show that transient peri-transplant treatment with the central complement component C3 inhibitor Cp40 significantly prolongs median allograft survival in a sensitized nonhuman primate model. Despite donor-specific antibody levels remaining high, fifty percent of Cp40-treated primates maintain normal kidney function beyond the last day of treatment. Interestingly, presence of antibodies of the IgM class associates with reduced median graft survival (8 vs. 40 days; p = 0.02). Cp40 does not alter lymphocyte depletion by rhesus-specific anti-thymocyte globulin, but inhibits lymphocyte activation and proliferation, resulting in reduced antibody-mediated injury and complement deposition. In summary, Cp40 prevents acute antibody-mediated rejection and prolongs graft survival in primates, and inhibits T and B cell activation and proliferation, suggesting an immunomodulatory effect beyond its direct impact on antibody-mediated injury.
Authors
Schmitz, R; Fitch, ZW; Schroder, PM; Choi, AY; Manook, M; Yoon, J; Song, M; Yi, JS; Khandelwal, S; Arepally, GM; Farris, AB; Reis, ES; Lambris, JD; Kwun, J; Knechtle, SJ
MLA Citation
Schmitz, Robin, et al. “C3 complement inhibition prevents antibody-mediated rejection and prolongs renal allograft survival in sensitized non-human primates.Nat Commun, vol. 12, no. 1, Sept. 2021, p. 5456. Pubmed, doi:10.1038/s41467-021-25745-7.
URI
https://scholars.duke.edu/individual/pub1497202
PMID
34526511
Source
pubmed
Published In
Nature Communications
Volume
12
Published Date
Start Page
5456
DOI
10.1038/s41467-021-25745-7

Research Areas:

Autoimmune Diseases
Biomarkers, Pharmacological
Cancer
Flow Cytometry
Immunologic Deficiency Syndromes
Immunology
Lungs--Transplantation
Neuromuscular Diseases