Lodish Lab

For more than a century, the link between thyroid hormone and red blood cell production has remained elusive. Now, Whitehead scientists have teased about the mechanism that connects them, which could help scientists identify new therapies for specific types of anemia.

Rhogerry “Gerry” Deshycka, a graduating senior working in the lab of Whitehead Institute Founding Member Harvey Lodish, has received one of MIT’s two Randolph G. Wei Undergraduate Research Opportunities Program (UROP) awards for 2017 and MIT’s 2017 John L. Asinari Award. 

Using red blood cells modified to carry disease-specific antigens, a team of scientists from Whitehead Institute and Boston Children’s Hospital have prevented and alleviated two autoimmune diseases—multiple sclerosis (MS) and type 1 diabetes—in early stage mouse models.  This research is an exciting step toward therapeutics for autoimmune diseases, which affect an estimated 23 million Americans.

Countering the prevailing theory that cellular hydrogen peroxide signaling is broad and non-specific, Whitehead Institute scientists have discovered that this reactive oxygen species (ROS) in fact triggers a distinct signal transduction cascade under control of the mitochondrial respiratory chain—the Syk pathway—that regulates transcription, translation, metabolism, and the cell cycle in diverse cell types. Hydrogen peroxide and other ROS mediate cellular responses in aging and myriad common chronic diseases, including diabetes, heart disease, stroke, cancer, and neurodegeneration. Understanding how these signals function may point to new therapy targets for these conditions.

Using a mouse model, the lab of Whitehead Institute Founding Member Harvey Lodish, has now determined that combining the cholesterol-lowering drug fenofibrate with glucocorticoids could allow for dramatically lower steroid doses in the treatment of  Diamond Blackfan anemia and other erythropoietin-resistant anemias.

Researchers at Whitehead Institute have identified a key target protein of glucocorticoids, the drugs that are used to increase red blood cell production in patients with certain types of anemia, including those resulting from trauma, sepsis, malaria, kidney dialysis, and chemotherapy.

Whitehead Institute researchers report that 10 long noncoding RNAs (lncRNAs) play a vital role in the regulation of white fat cells. When each of these lncRNAs is individually knocked down, fat precursor cells fail to mature into white fat cells and have significantly reduced lipid droplets compared with white fat cells with unmodified lncRNA function.

By examining the results of genome-wide association studies (GWAS) in conjunction with experiments on mouse and human red blood cells (RBCs), researchers in the lab of Whitehead Institute Founding Member Harvey Lodish have identified the protein cyclin D3 as regulating the number of cell divisions RBC progenitors undergo, which ultimately affects the resulting size and quantity of RBCs.

Whitehead Institute scientists have identified the first microRNAs (miRs) that regulate the development of brown fat. Brown fat, which is found in small deposits in the neck, along the shoulders, and down the spine in adult humans, generates heat by burning the lipids. These miRs provide an opportunity to understand better how brown fat develops and may lead to methods for stimulating brown fat production to counter obesity.