The Hageman Laboratory
Dr. Hageman's primary research interest over the past 20 years has been directed toward assessment of pathways involved in the etiology of age-related macular degeneration (AMD), the leading cause of irreversible worldwide blindness. He and his colleagues have generated a definitive body of evidence that implicates a role for immune-mediated processes, specifically that of the complement system, in AMD pathogenesis and progression. Early pathobiologic investigations of eyes from human donors led to the identification of numerous complement proteins, complement activators, and complement regulatory proteins in drusen, the hallmark pathological biomarkers of the disease. More recent genetic studies led to the discovery that common variants in several complement genes - including Complement Factor H (CFH), Complement Factor H Related 1 and 3 (CFHR1 and CFHR3), Complement Factor B (CFB), Complement Factor I (CFI) and Complement Components 2 and 3 (C2 and C3) -- confer significant risk for, or protection from, the development of AMD late in life. A former director of the Human Genome Project called this breakthrough, "The first major translational research discovery to come from the Human Genome Project."
Dr. Hageman came to the Moran Eye Center in the Fall of 2009, bringing with him the largest known research laboratory transfer in the university's history - 8,000 human eyes donated for research over his career. His laboratory is focused on extending and refining his previous observations, identifying new genetic markers for AMD and examining diseases that co-segregate with AMD. Among other approaches, they are mining the state's extensive genealogical records in hopes of identifying new treatments and cures for AMD and related conditions.
Education: B.A., Biological Sciences, University of Southern California
Ph.D., Biology, University of Southern California
John A. Moran Presidential Professor, Department of Ophthalmology and Visual Sciences, University of Utah School of Medicine
Director, Moran Center for Translational Medicine
Associate Faculty, Center for the Study of Macular Degeneration, University of California Santa Barbara
Honorary Professorship, Queen's University, Belfast, UK
Honorary Professorship, Shandong Eye Institute, Qingdao, China
Patient Care Significance
Age-related macular degeneration (AMD) is the most common cause of irreversible blindness in western populations. It blurs a person's central vision that is required to see fine detail, thus causing an enormous impact on one's productivity, independence, and quality of life.
Dr. Hageman's team continues its research with the expectation that previous breakthroughs will soon lead to diagnoses and treatments for AMD. Importantly, their discoveries point to the human eye as a window to understanding and predicting other diseases, including heart and liver disease and others.
A sample of major publications from the Hageman Laboratory
Abrera-Abeleda MA, Nishimura C, Smith JLH, Sethi S, McRae JL, Murphy BF, Silvestri G, Skerka C, Jozsi M, Zipfel PF, Hageman GS, Smith RJH. (2005). Variations in the Complement Regulatory Genes Factor H (CFH) and Factor H Related 5 (CFHR5) are Associated with Membranoproliferative Glomerulonephritis Type II (Dense Deposit Disease). J Med Genet, 43, 582-589.
Allikmets R, Dean M, Hageman GS, Baird PN, Klaver CC, Bergen AA, Weber BH; International AMD Genetics Consortium. (2009). The SERPING1 gene and age-related macular degeneration. Lancet, 374(9693), 875-6.
Allikmets R, Bergen AA, Dean M, Guymer RH, Hageman GS, Klaver CC, Stefansson K, Weber BH; International Age-related Macular Degeneration Genetics Consortium. (2009). Geographic atrophy in age-related macular degeneration and TLR3. N Engl J Med., 360(21), 2252-4.
Anderson DH, Mullins RF, Hageman GS, Johnson LV. (2002). A role for local inflammation in the formation of drusen in the aging eye. Am J Ophthalmol, 134, 411-431.
Anderson DH, Radeke MJ, Gallo NB, Chapin EA, Johnson PT, Curletti CR, Hancox LS, Hu J, Ebright JN, Malek G, Hauser MA, Rickman CB, Bok D, Hageman GS, Johnson LV. (2010). The pivotal role of the complement system in aging and age-related macular degeneration: hypothesis re-visited. Prog Retin Eye Res., 29(2), 95-112.
Baird PN, Hageman GS, Guymer RH. (2009). New era for personalized medicine: the diagnosis and management of age-related macular degeneration. Clin Experiment Ophthalmol., 37(8), 814-21.
Barlow PN, Hageman GS, Lea SM. (2008). Complement factor H: using atomic resolution structure to illuminate disease mechanisms. Adv Exp Med Biol., 632, 117-42.
Chong NH, Keonin J, Luthert PJ, Frennesson CI, Weingeist DM, Wolf RL, Mullins RF, Hageman GS. (2005). Decreased thickness and integrity of the macular elastic layer of Bruch's membrane correspond to the distribution of lesions associated with age-related macular degeneration. Am J Pathol, 166(1), 241-51.
Gehrs KM, Anderson DH, Johnson LV, Hageman GS. (2006). Age-Related Macular Degeneration - Emerging Pathogenetic and Therapeutic Concepts. Ann Med, 38, 450-471.
Gehrs KM, Jackson JR, Brown EN, Allikmets R, Hageman GS. (2010). Complement, age-related macular degeneration and a vision of the future. Arch Ophthalmol., 128(3), 349-58.
Gold B, Merriam JE, Zernant J, Hancox LS, Taiber AJ, Gehrs K, Cramer K, Neel J, Bergeron J, Barile GR, Smith RT, Hageman GS, Dean M, Allikmets R. (2006). Variation in factor B (BF) and complement component 2 (C2) genes is associated with age-related macular degeneration. Nat Genet, 38(4), 458-62.
Hageman GS, Luthert PJ, Victor Chong NH, Johnson LV, Anderson DH, Mullins RF. (2001). An integrated hypothesis that considers drusen as biomarkers of immune-mediated processes at the RPE-Bruch's membrane interface in aging and age-related macular degeneration. Prog Retin Eye Res, 20(6), 705-32.
Hageman GS, Anderson DH, Johnson LV, Hancox LS, Taiber AJ, Hardisty LI, Hageman JL, Stockman HA, Borchardt JD, Gehrs KM, Smith RJ, Silvestri G, Russell SR, Klaver CC, Barbazetto I, Chang S, Yannuzzi LA, Barile GR, Merriam JC, Smith RT, Olsh AK, Bergeron J, Zernant J, Merriam JE, Gold B, Dean M, Allikmets R. (2005). A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration. PNAS, 102(20), 7227-32.
Hageman GS, Hancox LS, Taiber AJ, Gehrs KM, Anderson DH, Johnson LV, Radeke MJ, Kavanagh D, Richards A, Atkinson J, Meri S, Bergeron J, Zernant J, Merriam J, Gold B, Allikmets R, Dean M. (2006). Extended haplotypes in the complement factor H (CFH) and CFH-related (CFHR) family of genes protect against age-related macular degeneration: characterization, ethnic distribution and evolutionary implications. Ann Med, 38(8), 592-604.
Kelly U, Rickman CB, Postel EA, Hauser MA, Hageman GS, Arshavsky VY, Skiba NP. (2009). Rapid and sensitive method for detection of Y402, H402, I62, and V62 variants of complement factor H in human plasma samples using mass spectrometry. Invest Ophthalmol Vis Sci., 50(4), 1540-5.