Allan Kirk

Positions:

David C. Sabiston, Jr. Distinguished Professor of Surgery

Surgery, Abdominal Transplant Surgery
School of Medicine

Professor of Surgery

Surgery, Abdominal Transplant Surgery
School of Medicine

Chair of Surgery

Surgery
School of Medicine

Professor in Pediatrics

Pediatrics
School of Medicine

Professor in the Department of Immunology

Immunology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

B.S. 1983

Old Dominion University

M.D. 1987

Duke University School of Medicine

Ph.D. 1992

Duke University

Intern & Junior Resident, Surgery

Duke University

Research Fellow, Surgery

Duke University

Senior Resident, Surgery

Duke University

Chief Resident, Surgery

Duke University

Fellow, Multi Organ Transplantation

University of Wisconsin at Madison

Grants:

Neonatal Porcine Islet Xenografts for the Treatment of Type 1 Diabetes

Administered By
Surgery
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Immune Tolerance Network - Flow Cytometry

Administered By
Surgery
Role
Principal Investigator
Start Date
End Date

American Journal of Transplantation

Administered By
Surgery, Abdominal Transplant Surgery
Role
Principal Investigator
Start Date
End Date

Phase 2 Study of Belatacept, Alemtuzumab, and Sirolimus in Renal Transplantation

Administered By
Surgery
Awarded By
Food and Drug Administration
Role
Principal Investigator
Start Date
End Date

T cell Receptor Diversity as a Determinant of Co-stimulation Blockade Resistance

Administered By
Surgery
Role
Principal Investigator
Start Date
End Date

Publications:

Rejection of xenogeneic porcine islets in humanized mice is characterized by graft-infiltrating Th17 cells and activated B cells.

Xenogeneic porcine islet transplantation is a promising potential therapy for type 1 diabetes (T1D). Understanding human immune responses against porcine islets is crucial for the design of optimal immunomodulatory regimens for effective control of xenogeneic rejection of porcine islets in humans. Humanized mice are a valuable tool for studying human immune responses and therefore present an attractive alternative to human subject research. Here, by using a pig-to-humanized mouse model of xenogeneic islet transplantation, we described the human immune response to transplanted porcine islets, a process characterized by dense islet xenograft infiltration of human CD45+ cells comprised of activated human B cells, CD4+ CD44+ IL-17+ Th17 cells and CD68+ macrophages. We also tested an experimental immunomodulatory regimen in promoting long-term islet xenograft survival, a triple therapy consisting of donor splenocytes treated with ethylcarbodiimide (ECDI-SP), and peri-transplant rituximab and rapamycin. We observed that the triple therapy effectively inhibited graft infiltration of T and B cells as well as macrophages, promoted transitional B cells both in the periphery and in the islet xenografts, and provided a superior islet xenograft protection. Our study therefore indicates an advantage of donor ECDI-SP treatment in controlling human immune cells in promoting long-term islet xenograft survival.
Authors
Lee, FT; Dangi, A; Shah, S; Burnette, M; Yang, Y-G; Kirk, AD; Hering, BJ; Miller, SD; Luo, X
MLA Citation
Lee, Frances T., et al. “Rejection of xenogeneic porcine islets in humanized mice is characterized by graft-infiltrating Th17 cells and activated B cells..” Am J Transplant, Dec. 2019. Pubmed, doi:10.1111/ajt.15763.
URI
https://scholars.duke.edu/individual/pub1425302
PMID
31883299
Source
pubmed
Published In
Am J Transplant
Published Date
DOI
10.1111/ajt.15763

Immunosuppression withdrawal in liver transplant recipients on sirolimus.

As conversion from calcineurin inhibitor (CNI) to sirolimus (SRL), an mTOR-inhibitor (mTOR-I), has been shown to enhance immunoregulatory profiles in liver transplant recipients (LTR), mTOR-I therapy might allow for increased success with immunosuppression withdrawal. Our aim was to determine if operational tolerance could be observed in LTR withdrawn from SRL and if blood/graft tolerance biomarkers were predictive of successful withdrawal. We performed a prospective trial of SRL monotherapy withdrawal in non-immune, non-viremic LTR > 3 years post-LT. Sirolimus was weaned over ~6 months and biopsies performed 12 months post-weaning or at concern for acute rejection (AR). Twenty-one LTR were consented; 6 were excluded due to subclinical AR on baseline biopsy or other reasons; 15 underwent weaning (age 61.3±8.8 yrs; LT to SRL weaning 6.7±3 yrs). Eight (53%) achieved operational tolerance (TOL). Of the 7 non-TOL, 6 had mild AR on biopsy near the end of weaning or at study end; 1 was removed due to liver cancer recurrence. At baseline preweaning, there were statistically higher blood tolerogenic dendritic cells, regulatory B cells, and cell phenotypes correlating with chronic antigen presentation in the TOL vs. non-TOL groups. At baseline preweaning, a previously identified biopsy gene signature accurately predicted TOL vs. non-TOL in 12/14 LTR. At study end, biopsy staining revealed statistically significant increases in antigen presenting cell:leukocyte pairings, Foxp3+CD4+ T cells, T-bet+CD8+ T cells, and lobular dendritic cells in the non-TOL group. CONCLUSION: This study is the first to evaluate IS withdrawal directly from mTOR-I therapy in LTR and achieved >50% operational tolerance. Pre-weaning blood/graft gene expression and PBMC profiling may be useful as predictors of successful mTOR-I therapy withdrawal. NCT02062944.
Authors
Levitsky, J; Burrell, BE; Kanaparthi, S; Turka, LA; Kurian, S; Sanchez-Fueyo, A; Lozano, JJ; Demetris, A; Lesniak, A; Kirk, AD; Stempora, L; Yang, G-Y; Mathew, JM
MLA Citation
Levitsky, Josh, et al. “Immunosuppression withdrawal in liver transplant recipients on sirolimus..” Hepatology, Nov. 2019. Pubmed, doi:10.1002/hep.31036.
URI
https://scholars.duke.edu/individual/pub1421709
PMID
31721246
Source
pubmed
Published In
Hepatology
Published Date
DOI
10.1002/hep.31036

Assessing Quality of Real-World Data Supplied by an Automated Surgical Data Pipeline

Authors
Corey, K; Helmkamp, J; Kirk, AD; Balu, S; Thompson, D; Mureebe, L; Watson, J; Marsolo, K; Curtis, L; Sendak, M
MLA Citation
Corey, Kristin, et al. “Assessing Quality of Real-World Data Supplied by an Automated Surgical Data Pipeline.” Journal of the American College of Surgeons, vol. 229, no. 4, ELSEVIER SCIENCE INC, 2019, pp. S89–S89.
URI
https://scholars.duke.edu/individual/pub1418693
Source
wos
Published In
Journal of the American College of Surgeons
Volume
229
Published Date
Start Page
S89
End Page
S89

Kwun J, Burghuber C, Manook M, et al. Successful desensitization with proteasome inhibition and costimulation blockade in sensitized nonhuman primates. Blood Adv. 2017;1(24):2115-2119.

URI
https://scholars.duke.edu/individual/pub1306055
PMID
29365315
Source
pubmed
Published In
Blood Adv
Volume
2
Published Date
Start Page
89
DOI
10.1182/bloodadvances.2017015446

Preoperative Optimization: A Continued Call to Action.

Authors
Aronson, S; Martin, G; Gulur, P; Lipkin, ME; Lagoo-Deenadayalan, SA; Mantyh, CR; Attarian, DE; Mathew, JP; Kirk, AD
MLA Citation
Aronson, Solomon, et al. “Preoperative Optimization: A Continued Call to Action..” Anesth Analg, Oct. 2019. Pubmed, doi:10.1213/ANE.0000000000004492.
URI
https://scholars.duke.edu/individual/pub1416593
PMID
31633503
Source
pubmed
Published In
Anesth Analg
Published Date
DOI
10.1213/ANE.0000000000004492