One major focus of research in the Bridgewater Lab is the novel nuclear variant of BMP2, which we discovered in 2010 and named nBMP2. BMP2 has previously been recognized as a secreted growth factor that participates in bone and cartilage formation, limb formation, patterning, heart development, and apoptosis. We have discovered another form of BMP2 that is translated from the same mRNA transcript but from an alternative downstream start codon, which eliminates the signal peptide and thus prevents trafficking through the endoplasmic reticulum (ER) and Golgi. Instead, translation occurs in the cytoplasm and a nuclear localization signal directs translocation to the nucleus. We have generated a “knock-in” mouse line in which nuclear translocation of nBMP2 is blocked while secreted BMP2 is produced normally. We have discovered that nBMP2 affects skeletal muscle contractions, learning and memory, and immune response. Ongoing work is focused on identifying specific mechanisms by which loss of nBMP2 interferes with immune function.
Our second area of emphasis is the gut microbiota and its effects on obesity, type 2 diabetes, anxiety, and depression. We have recently published evidence suggesting that stress can alter the composition of the gut microbiota in females much the same way a high fat diet does. We are testing the hypothesis that phages (viruses that target bacteria) can be used therapeutically to inhibit the growth of obesity-causing bacteria in the gut.
