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 ultimately find ways to ameliorate the organ damage it causes and eventually find new therapeutic strategies to improve organ function and quality of life for patients and increase overall survival.
The amyloidoses are a group of protein misfolding diseases characterized by the accumulation of insoluble amyloid fibrils that leads to cell death and tissue degeneration. There are more than 20 different amyloid diseases described in humans.
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 devastating effects behind amyloidogenesis.
Dr. Ramirez-Alvarado works very closely with clinical investigators in the Division of Hematology, the Division of Nephrology and Hypertension, and the Division of Cardiovascular Diseases.
Toxicity in immunoglobin light chain (AL) 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.
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.
Dr. Ramirez-Alvarado's current projects aim at understanding the structural basis for toxicity in light chain amyloidosis. It is now accepted that soluble species populated in the initial steps of amyloid formation are quite toxic and can cause severe organ damage. 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 AL amyloidosis. Additional work involves using urinary exosomes as noninvasive tools to understand organ damage and progression in AL amyloidosis.
- Determinants and stabilizers in AL amyloidosis. Dr. Ramirez-Alvarado's lab is studying determinants of sequence or structure in AL amyloidosis, as well as screening small molecules that can act as stabilizers of light chains and potentially act as inhibitors of amyloid formation and toxicity.
- AL amyloidosis proteomics. Research is also focused on studying the proteome of amyloid deposits and studying correlations between the proteome and organ involvement, organ response and survival in AL amyloidosis.
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.
- Program committee representative, Committee for the Professional Opportunities for Women, Biophysical Society, 2014-present
- Member, Biophysics of Neural Systems Study Section, National Institutes of Health (NIH), 2012-present
- The NIH Director's ARRA Pathfinder Award to Promote Diversity in the Scientific Workforce, biomedical research community, NIH, 2011-present
- Organizer, 2nd USA-Mexico Workshop in Biological Chemistry: Protein Folding, Misfolding and Design, Mexico City, 2011
- Editor-in-chief, "Protein Misfolding Diseases: Basis of Protein Misfolding, Pathophysiology, Current, and Emerging Therapies," John Wiley & Sons Inc., 2010