In this roundup, scientists and researchers at Massachusetts General Hospital answer your most frequently asked questions on COVID-19, vaccines, clinical trials and testing.
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The V-ATPase is an acid pumping protein that controls pH at sub-cellular, cellular, local and systemic levels. It is implicated in rare (e.g. renal distal tubular acidosis, osteopetrosis), as well as more common diseases, such as various types of cancer, osteoporosis, Alzheimer's and Parkinson's neurodegenerative diseases. This enzyme is, therefore, an emerging drug target for treatment of all these diseases. However, the mechanisms that are involved in V-ATPase regulation in both physiological and pathophysiological conditions are poorly understood. To address this question, we performed the first systematic proteome-wide analysis of V-ATPase protein-protein interactions (1). Some previously known as well as several novel V-ATPase interacting proteins were revealed; five of these proteins, called DMXL1, DMXL2, WDR7, NCOA7 and OXR1 were found to regulate V-ATPase activity in mammalian cells. We use a combination of biochemical, molecular biology, structural and bioinformatics methods to study the molecular mechanisms of this regulation, as well as mouse knockout models to study the potential role of these and other V-ATPase interacting proteins in kidney function and acid-base homeostasis. This work is currently supported by Dr. Dennis Brown, director of the Program in Membrane Biology (PMB), affiliated with the MGH interdisciplinary Center for Systems Biology (CSB).
- Merkulova M, Păunescu TG, Azroyan A, Marshansky V, Breton S, Brown D. Mapping the H(+) (V)-ATPase interactome: identification of proteins involved in trafficking, folding, assembly and phosphorylation.Sci. Rep. 2015; 5: 14827.
- Jun | 23 | 2020
Given the worldwide demand for vaccines to stop the spread of COVID-19, experts believe it will be important to move as many promising candidates forward as possible.
- Press Release
- Jun | 9 | 2020
A drug already in use for several cancers was found effective in a study of leptomeningeal dissemination of cancer.
- Press Release
- Jun | 2 | 2020
A team led by investigators at Mass General and the Broad Institute of MIT and Harvard recently found that applying “polygenic risk scores” can identify at-risk patients who are not presently identified through standard clinical evaluations.
- Press Release
- May | 15 | 2020
A team led by researchers from Mass General has uncovered key molecular step stones in alcohol-related liver disease that may provide targets for drug therapy development.
- May | 12 | 2020
Neutralizando los anticuerpos específicos del SARS-CoV-2 y las células T específicas del virus detectadas en personas que se recuperan del COVID-19
El más reciente estudio sobre la inmunidad protectora en pacientes que se recuperan del COVID-19, publicado en Immunity, es el más completo hasta ahora. Sus prometedores resultados son discutidos por Tiara Calhoun, MD, y Vladimir Vinarsky, MD, con la asesoría de Rod Rahimi, MD, PhD.
About the Nephrology Division
The Division of Nephrology at Massachusetts General Hospital is a leading provider of services for patients with kidney disease, including diagnosis and management of kidney diseases and medical management of renal transplantation.