Dr. Melkani's Lab Home Page

Dr. Melkani's research laboratory is located on the beautiful campus of San Diego State University within the Biology Department.

Girish Melkani muscle PLos

Introduction to Dr. Melkani's Research:

We are using multidisciplinary integrative approaches to investigate the mechanism of amyloid‐induced protein‐unfolding, aggregation and metabolic defects that lead to cardiomyopathies, diabetes mellitus, muscle atrophy and inclusion body myopathy in a Drosophila melanogaster (fruit fly) model. Amyloid precursor proteins are prone to misfolding and are involved in cardiac amyloidosis. Amyloidosis constitutes a large group of proteinopathies characterized by the accumulation of misfolded proteins into aggregates in various tissues. Several amyloid‐linked neurodegenerative and metabolic diseases, including Huntington's disease, Alzheimer's disease, tauopathy, Parkinson's disease, amyotrophic lateral sclerosis, and diabetes mellitus exhibit pathological protein aggregates and are often associated with striated muscle defects. Amyloidosis' relationship with striated muscle defects and metabolic disorders has been largely overlooked and the mechanisms of amyloid‐related striated muscle and metabolic disorders are poorly understood.

Diabetes and other metabolic disorders significantly enhance susceptibility to a range of chronic diseases including cardiovascular diseases. Common cellular mechanisms' underlying these chronic diseases includes disrupted cellular energetics and protein misfolding. Both genetic factors and lifestyle changes trigger the onset and progression of these chronic diseases. My long term research interest lies in understanding how genes and lifestyle interact in determining predisposition to chronic diseases. We recently developed Drosophila models to delay age-associated cardiac dysfunction with time-restricted feeding without affecting caloric intake. We discovered novel pathways that preserve age-associated deterioration of cardiac defects under time-restricted feeding conditions. Now we are using this non-pharmacological novel strategy to prevent cardiac defects and metabolic disorders associated with diabetes mellitus, obesity and other metabolic diseases.

We are investigating the mechanisms of laminopathiy-induced cardiac and skeletal muscle dysfunction. Laminopathies are a group of genetic disorders caused by mutations in the LMNA gene encoding A-type lamins, intermediate filaments that line the inside of the nuclear envelope. Patients with laminopathies exhibit a spectrum of phenotypes including cardiac and skeletal muscle dysfunction, dysplasia, diabetes and progeria. Among these, dilated cardiomyopathy is a major cause of death, yet the underlying mechanisms of pathology remain unknown. Our fruit fly model is a unique in vivo system, which is genetically tractable and suitable to define the cardiac and skeletal muscle pathological events associated with laminopathies.


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