[1] An internationally recognized expert in anti-neutrophil cytoplasmic autoantibody (ANCA)-induced vasculitis and autoimmune kidney disease,[2] his career as a translational physician-scientist spans more than three decades.
[2] Falk has served in various capacities for the American Society of Nephrology, including post-graduate education, finance and nomination committees, as well as Training Program Director.
In 1994, Falk and Jennette convened an International Consensus Conference that yielded the Chapel Hill Nomenclature for Small Vessel Vasculitis,[11] which has now been adopted on a worldwide basis.
In 2002, they demonstrated in a mouse model that passively transferred anti-myeloperoxidase antibodies were capable of inducing pauci-immune necrotizing and crescentic glomerulonephritis.
The Falk lab recently identified HLA-DB1*15 as a genetic trait that is a risk factor PR3-ANCA disease in African-American patients with an odds ratio of 73.3 (p=2.3x10-9).
Falk’s seminal work published in the 1988 article[17] in the New England Journal of Medicine described the discovery that ANCA vasculitis is an autoimmune disease with increased expression of the autoantigen genes, myeloperoxidase (MPO) and proteinase 3 (PRTN3) To clarify this, in 2020 Falk and colleagues measured MPO and PRTN3 messenger RNA in monocytes, normal-density neutrophils, and in enriched leukocytes from peripheral blood mononuclear cells.
[18] Increased autoantigen gene expression was detected in normal-density neutrophils and enriched leukocytes from patients during active disease as compared to those from healthy individuals.
Increased autoantigen gene expression originating from the mature low-density and normal-density neutrophils suggests transcriptional dysregulation is a hallmark of ANCA vasculitis.
Knowledge of specific interactions between human leukocyte antigen (HLA), the autoantigen, and effector immune cells, provides the foundation for antigen-specific therapies.
This restricted MPO region was targeted by both T cells and antibodies but is not accessible to solvent or chemical modification, indicating that these epitopes are buried.
These observations reveal interactions between restricted MPO epitopes and the adaptive immune system within ANCA vasculitis that may inform new antigen-specific therapies in autoimmune disease while providing insight into immunopathogenesis.
Falk and colleagues continue to conduct innovative research that focuses on the basic science and clinical observations of immune mechanisms of glomerular and vascular injury as well as the discovery and development of disease biomarkers.
The GDCN has initiated or participated in numerous single-center and multicenter clinical trials, epidemiologic studies and a wide range of basic science and translational research projects.
The success of the GDCN helped lay the groundwork for UNC’s involvement as a participating clinical center (PCC) in the CureGN Network.
[citation needed] Falk organized and continues to conduct a weekly multidisciplinary vasculitis and glomerular disease outpatient clinic that is one of the largest in the United States.
The UNCKC provides a multidisciplinary and multi-school approach to research pertaining to kidney disease spanning the gamut from basic molecular biology and genetics to broad epidemiological studies and clinical treatment trials.
[citation needed] In 2008, the UNCKC received a generous donation from Shirley Gilman to create the Allan Brewster Memorial Fund.
He has been recognized as one of the “Best Doctors in America” every year since 1992 and is the recipient of a number of invited lectureships, including the prestigious Norma Berryhill Distinguished Lecture in 2011.