William  M. Baldwin,  MD, PhD

William M. Baldwin, MD, PhD

Staff

Lerner Research Institute, 9500 Euclid Avenue, Cleveland, Ohio 44195
Phone: (216) 445-2384

 

Overall areas of interest

  • Inflammation resulting from antibody and complement interactions with endothelial cells.
  • Immune functions of platelets
  • Modulation of immunity by complement, and platelets

Tools and expertise of the lab

  • Immunohistochemistry (Shim et al, Kidney International 2020)

Examples of collaborators

  • Rob Fairchild/Anna Valujskikh – immune responses to organ transplants.
  • Craig Morrell (University of Rocheter)- immune functions of platelets
  • Booki Min (Northwestern)- regulation of immune responses
  • Barsanjit Mazumder (CSU)- inflammatory macrophages

Lab discoveries

  • Demonstrated complement markers of rejection in human heart transplants (
  • Discovered impact of platelets in rejection of organ transplants (Morrell Circ Res 2008; Kuo JASN 2014).
  • Discovered antigen presentation function of platelets (Chapman JI 2012)
  • Demonstrated tissue compartmentalization of immune responses to organ transplants (Kaul Am J Transpl 20
  • Discovered early modulation of kidney transplant rejection by the check point inhibitor PD-1 (Shin Kid Int 2020)

How could these discoveries help patients?

  • Complement markers are now routinely used to diagnose rejection in human heart transplants (Morrell Circ Res 2008; Kuo JASN 2014).
  • Modulation of platelet function is a potential target of modifying transplant rejection
  • Adjustment of immune suppressive protocols to allow normal function of checkpoint inhibitors

Lay Summary

  • Determine the effects of intermittent interactions of antibodies and complement on endothelial cells.
  • Determine the mechanisms by which T cells promote antibody and complement interactions with endothelial cells resulting in activatation and release of cytokines.
  • Determine the mechanisms by which complement interactions with endothelial cells stimulate memory B cells resulting in local antibody production.
  • Modulation of T cell and B cell interactions with vascular endothelial cells by antibodies, complement, and platelets


Selected original articles:

Kuo H-H, Fan R, Dvorina N, Chiesa-Vottero A, Baldwin WM III.  Platelets in early antibody -mediated rejection of renal transplants. JASN 26(4):855-63, 2015. PMC4378099 (Highlighted by Allison, Susan J. Transplantation: The role of platelets in antibody-mediated rejection. Nature Reviews Nephrology 10(11):614, 2014).

Yagisawa T, Tanaka T, Miyairi S, Tanabe K, Dvorina N, Yokoyama WM, Valujskikh A, Baldwin WM III, Fairchild RL. In the absence of natural killer cell activation donor-specific antibody mediates chronic, but not acute, kidney allograft rejection. Kidney Int. 2019 Feb;95(2):350-362. doi: 10.1016/j.kint.2018.08.041. Epub 2018 Nov 29. PMID: 30503624; PMCID: PMC6342643.

Gorbacheva V, Fan R, Beavers A, Fairchild RL, Baldwin WM III, Valujskikh A. Anti-donor MHC Class II Alloantibody Induces Glomerular Injury in Mouse Renal Allografts Subjected to Prolonged Cold Ischemia. J Am Soc Nephrol. 2019 Dec;30(12):2413-2425. doi: 10.1681/ASN.2018111169. Epub 2019 Oct 9. PMID: 31597715; PMCID: PMC6900787.

Basu A, Dvorina N, Baldwin WM 3rd, Mazumder B. High-fat diet-induced GAIT element-mediated translational silencing of mRNAs encoding inflammatory proteins in macrophage protects against atherosclerosisFASEB J. 2020 May;34(5):6888-6906. doi: 10.1096/fj.201903119R. Epub 2020 Mar 30. PubMed PMID: 32232901; NIHMSID:NIHMS1580353.

Shim YJ, Khedraki R, Dhar J, Fan R, Dvorina N, Valujskikh A, Fairchild RL, Baldwin WM III. Early T cell infiltration is modulated by programed cell death-1 protein and its ligand (PD-1/PD-L1) interactions in murine kidney transplants. Kidney Int. 2020 (Available online 25 April). doi.org/10.1016/j.kint.2020.03.037.

Liu Q, Hassan A, Pezzati D, Soliman B, Lomaglio L, Grady P, Del Angel Diaz L, Simioni A, Maikhor S, Etterling J, D'Amico G, Iuppa G, Diago Uso T, Hashimoto K, Aucejo F, Fujiki M, Eghtesad B, Sasaki K, Kwon CHD, Cywinski J, Irefin S, Bennett A, Baldwin W, Miller C, Quintini C. Ex Situ Liver Machine Perfusion: The Impact of Fresh Frozen Plasma. Liver Transpl. 2020 Feb;26(2):215-226. doi: 10.1002/lt.25668. PMID: 31642164.

Reviews:

Baldwin WM 3rd, Valujskikh A, Fairchild RL. The neonatal Fc receptor: Key to homeostasic control of IgG and IgG-related biopharmaceuticals. Am J Transplant. 2019 Jul;19(7):1881-1887 PMID: 30903736; PMCID: PMC6591018.

Khedraki R, Dhar J, Baldwin WM 3rd. Platelets: Mechanistic and Diagnostic Significance in Transplantation. Curr Transpl Rep. 2020, 7(2), 124-130.

Miyairi S, Baldwin WM, 3rd, Valujskikh A, Fairchild RL. Natural Killer Cells: Critical Effectors During Antibody-Mediated Rejection of Solid Organ Allografts. Transplantation. 2020. PMID: 32384380.

Complete List of Published Work in MyBibliography:

https://www.ncbi.nlm.nih.gov/myncbi/william.baldwin.2/bibliography/public/


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