Marina Ramirez-Alvarado, Ph.D., studies misfolding and amyloid formation in light chain amyloidosis. The overall goal of her research laboratory is to understand the molecular basis of this disease to find ways to ameliorate the organ damage it causes and find new therapeutic strategies to improve organ function and quality of life for patients, ultimately increasing overall survival.
The amyloidoses are a group of protein misfolding diseases characterized by the accumulation of insoluble amyloid fibrils that lead to cell death and tissue degeneration. There are 36 different human amyloid diseases. Understanding the molecular determinants that drive protein misfolding and aggregation will help Dr. Ramirez-Alvarado and her colleagues understand these diseases and guide them to design therapeutic strategies to overcome the effects of amyloidogenesis.
Dr. Ramirez-Alvarado works very closely with clinical investigators in the Division of Hematology, the Division of Nephrology and Hypertension, and the Department of Cardiovascular Medicine at Mayo Clinic.
- Toxicity in immunoglobulin light chain (AL) cardiac amyloidosis. Dr. Ramirez-Alvarado's laboratory applies biochemical, biophysical and cell biology principles to study the process of amyloid formation and the generation of toxic species. AL amyloidosis is an excellent model system to study amyloid diseases. As immunoglobulin chains, this family exhibits wide sequence diversity and allows the lab to understand different physicochemical patterns that the proteins may present that influence their aggregation and toxic behavior.
- Light chain proteins. The light chain protein family presents a unique opportunity for comparative studies that might uncover patterns and point to the general mechanisms of amyloid formation, which will be very useful for other amyloid diseases.
- Toxicity in AL amyloidosis. Dr. Ramirez-Alvarado's current projects aim at understanding the structural basis for toxicity in light chain amyloidosis by both soluble and fibrillar species. Dr. Ramirez-Alvarado is utilizing her well-characterized protein systems with incredible biophysical knowledge to determine which species are causing the devastating damage observed in AL amyloidosis.
- Organ damage in renal AL amyloidosis. Additional work involves using urinary exosomes as noninvasive tools to understand organ damage and progression in AL amyloidosis.
- Cofactors and accessory molecules. Dr. Ramirez-Alvarado's laboratory is in the early stages of studying the role of cofactors and accessory molecules in amyloid formation and toxicity as well as the role of post-translational modifications in amyloid formation and toxicity.
Significance to patient care
Through the interdisciplinary work done in Dr. Ramirez-Alvarado's laboratory, it will be possible to understand the mechanisms of amyloid formation and toxicity in AL amyloidosis, leading to the prediction of the behavior of other AL proteins with the ultimate goal of the development of new therapeutic strategies and better management to prevent the progression of the disease.
- Senior faculty representative, Council of Faculties and Academic Societies, Association of American Medical Colleges, 2016-present
- Co-organizer, The Protein Aggregation Conference, Federation of American Societies for Experimental Biology, 2021
- Chair, Committee for Inclusion and Diversity, Biophysical Society, 2016-2022
- Member, Public Affairs Advisory Committee, American Society for Biochemistry and Molecular Biology, 2016-2021
- Council member, Biophysical Society, 2017-2020