C3 glomerulopathy (C3G) is a complement-mediated renal disease with currently no disease-specific treatments. Patients with C3G are treated symptomatically to minimize renal inflammation and prevent progression to end-stage renal disease (ESRD). Diagnosis of C3G is based on immunofluorescence staining of complement protein C3 deposited in the renal glomerulus of two orders of magnitude or more than any other immunoreactant. This finding reflects dysregulation of the alternative pathway (AP) of complement, which can occur in the fluid phase (in the circulation) and also in the kidney microenvironment. Thus, there is a critical need to identify the underlying mechanism(s) of AP dysregulation in C3G to develop disease-specific treatments. Recently, AP activators, Factor H-related 1 (FHR1) and Factor H-related 5 (FHR5), have been shown to compete with the AP regulator, Factor H, in other complement-mediated diseases. Hence, the objective of my project is to determine how AP activators, FHR1 and FHR5, and the AP regulator, FH, impact complement control in the kidney microenvironment. 

Publications:
Heiderscheit, AK, Hauer JJ, Smith RJH. “The Nature of the Disease That Arise from Improper Regulation of the Alternative Pathway of Complement.” Manual of Molecular and Clinical Laboratory Immunology, 9th ed., ASM Press, Washington, District of Columbia, manuscript.

Heiderscheit AK, Hauer JJ, Smith RJH. C3 glomerulopathy: Understanding an ultra-rare complement-mediated renal disease. Am J Med Genet C Semin Med Genet. 2022 Jun 23. doi: 10.1002/ajmg.c.31986. PMID: 35734939.

Honors and Awards

Trainee Abstract Award - American Association of Immunologist Conference (2024)
Immunology T32 Pre-Doctoral Training Grant (2022-2024)