University of California, Riverside

Department of Bioengineering



Professor Morikis Receives NIH Funding for the Discovery of Diagnostic Biomarkers of Macular Degeneration


Professor Morikis Receives NIH Funding for the Discovery of Diagnostic Biomarkers of Macular Degeneration

September 26, 2017

Morikis

Bioengineering Professor Dimitrios Morikis is the Principal Investigator in a four-year $1.5M grant from the National Institutes of Health (NIH) to perform research on the Discovery of Biomarkers for Age-Related Macular Degeneration. This is an R01 grant from the National Eye Institute (NEI) of the NIH.

Age-related macular degeneration (AMD) typically affects people over the age of 50, and it is the most common cause of blindness in the Western world. Early-stage AMD is in most cases asymptomatic, whereas late-stage AMD exhibits an initial loss of central vision that expands radially as the individual ages, eventually resulting in complete blindness. There is a need for biomarkers to diagnose early-stage AMD for early therapeutic treatment and to track disease progression with age. The complement system, which is part of our innate immune system, provides such natural biomarkers through its activation and degradation products. In people who possess a genetic risk factor for a major regulating protein of the complement system, degradation products accumulate in the retina as a result of compromised immune regulation. This risk variant predisposes approximately 30% of those from European descent to AMD, though not all individuals with the risk variant develop AMD. Furthermore, the age of disease onset varies significantly among those who develop AMD.

Age-related macular degeneration (AMD) typically affects people over the age of 50, and it is the most common cause of blindness in the Western world. Early-stage AMD is in most cases asymptomatic, whereas late-stage AMD exhibits an initial loss of central vision that expands radially as the individual ages, eventually resulting in complete blindness. There is a need for biomarkers to diagnose early-stage AMD for early therapeutic treatment and to track disease progression with age. The complement system, which is part of our innate immune system, provides such natural biomarkers through its activation and degradation products. In people who possess a genetic risk factor for a major regulating protein of the complement system, degradation products accumulate in the retina as a result of compromised immune regulation. This risk variant predisposes approximately 30% of those from European descent to AMD, though not all individuals with the risk variant develop AMD. Furthermore, the age of disease onset varies significantly among those who develop AMD.

The project entails computational modeling, molecular simulations, virtual screening of drug-like molecules, peptide design, fluorescence spectroscopy and imaging, cell studies, and primate and human tissue studies. Professor Dimitrios Morikis is an expert in mechanistic studies of complement system function and regulation, and structure-based design of complement system inhibitors and fluorescent biomarkers, using computational and structural methods, and experimental binding and functional assays. An interdisciplinary team of experts has been assembled to perform various aspects of the design testing and validation work. Professor Kaustabh Ghosh (UCR) and his group will perform human retinal cell and tissue studies. Professors Trevor McGill and Martha Neuringer (Oregon Health and Science University) will perform primate retinal tissue studies. Professor Valentine Vullev (UCR) will oversee fluorescence spectroscopy and imaging studies. The project includes collaborators who will provide specific expertise, Professors Lincoln Johnson (UC Santa Barbara, retinal cell assays), Hyle Park (UCR, optical coherence tomography imaging), and SriniVas Sadda (UCLA, ophthalmology).

Professor Morikis will conduct this research at UCR with his bioengineering graduate students, Rohith Mohan, Reed Harrison, and Nehemiah Zewde.

For further information on Professor Morikis’ research, please visit his lab (BioMoDeL) website http://biomodel.engr.ucr.edu/

Relevant publication: Gorham RD Jr, Nuñez V, Lin J-H, Rooijakkers SHM, Vullev VI, Morikis D (2015) Discovery of small molecules for fluorescent detection of complement system activation product C3d, Journal of Medicinal Chemistry 58:9535-9545.

biomarkers
Image from Professor Morikis' biomarker research, showing the complement system protein C3d with 50 molecules, derived from virtual screening, docked on a surface cavity of the protein. Virtual screening was performed using 7 million molecules, from the UCSF ZINC database, with 1.1 billion conformations. For further details, see Gorham et al, 2015, Journal of Medicinal Chemistry.

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