Age-related macular degeneration (AMD) is a leading cause of vision loss in the US. Like many other autoimmune diseases, AMD has been a challenge to treat despite years of rigorous research. Dr. Dimitrios Morikis, Professor of Bioengineering at the University of California, Riverside, uses computational and experimental approaches for knowledge-based drug and biomarker discovery. He and his team target the complement system, a part of the immune system that is involved in nearly every autoimmune disease. Currently, there are only two FDA-approved drugs against the complement system, both being protein-based therapeutics and part of the list of the five most expensive drugs in the clinic. Therefore, there is a need for less expensive peptidic or small molecule drugs to target diseases that involve the complement system. Dr. Morikis’ research can help meet that need through his well-established efforts against AMD which will lead to other suitable drugs for complement system-mediated diseases, including rare diseases.

For over twentyfive years, Dr. Morikis first has been elaborating on the field he created, immunophysics, or the study of the physical basis of immune system function and regulation and immunoengineering, or the use of immunophysics knowledge to design regulators and inhibitors of the immune system with tailored properties and functions. This approach has allowed him to actively translate computational approaches to clinical applications. His commitment to mentoring students, in addition to his many active collaborations in four continents, has propelled him to become a leader within his field. Dr. Morikis and his team develop and test mechanistic hypotheses to quantitatively understand structure-function relations at the molecular level, and protein-protein interactions at the systems biology level. Thus, their unique approach is an empirical way to achieve results that matter in clinics.

Current research includes:

• Developing Drugs: Dr. Morikis specializes in the development of drugs and early-stage diagnostics. He has contributed significantly to targeting age-related macular degeneration (AMD) and expects that, in the future, drugs developed for AMD will also aid in treating other autoimmune and inflammatory diseases.

• Biomarkers: Biomarkers are an important diagnostic tool for detecting diseases earlier than ever before. Dr. Morikis and his team are developing biomarkers for complement system-mediated autoimmune and autoinflammatory diseases, which will be important for clinical applications.

• Systems Biology Approaches: Dr. Morikis develops systems of biochemical reactions that describe the activation, propagation, regulation, and termination of the complement system, and uses mathematical modeling approaches to trace the dynamics of pathways and networks of protein-protein interactions. These models not only provide basic science knowledge on the mechanisms of immune system function against pathogens, but they can be tailored to describe complement-mediated autoimmune and inflammatory diseases when complement system regulation fails.

• Bioinformatics Tools: Dr. Morikis develops both structural bioinformatics tools for the study of protein-protein interactions and translational bioinformatics methods for the analysis of the effects of drugs in computational disease models. His group has published a computational tool, called AESOP (acronym for Analysis of Electrostatic Structures Of Proteins) that has predictive power on the effects of mutations on interacting protein interfaces, based on computational mutagenesis and electrostatic calculations. His group is also developing translational computational models for complement-mediated diseases, such as AMD, atypical hemolytic uremic syndrome (aHUS), paroxysmal nocturnal hemoglobinuria (PNH), among others, and the effects of drugs in restoring disease-free conditions, based on systems of differential equations. Another computational model developed by Dr. Morikis group is an in silico diagnostic for HIV cell entry. Although structural bioinformatics methods are useful for understanding basic science at molecular level, translational bioinformatics methods are expected to revolutionize personalized medicine, in identifying drug targets, selecting drug treatment, and selecting biomarkers for in silico prediction of disease progression.

• Molecular Mechanisms: Dr. Morikis will continue to study immunophysics with an aim to understand the molecular mechanisms of immune system function and regulation, and interactions of immune system with pathogens. By contributing to basic research, applied research is able to meet new demands and provide solutions for some of the most challenging questions. Likewise, he and his team are continuing efforts in immunoengineering, aiming at the design or redesign of immune system regulators or inhibitors with tailored physicochemical properties and desired biological functions.