Harvey Lodish

Question

How do aspects of the basic cell and molecular biology of genes and proteins, including those regulating red blood cell formation and adipocyte biology, impact human physiology and disease? 

Approach

In the early 1980s his research group was the first to clone a mammalian glucose transport protein, GLUT1, and then the insulin- responsive GLUT4 glucose transporter. They also cloned and characterized the first transporter proteins for anions and free fatty acids.  In 1988, the Lodish laboratory  pioneered a new cloning technology to isolate the gene encoding the receptor for erythropoietin (Epo), the hormone that controls the production of red blood cells. This led to a lengthy set of projects on the activation of, and signal transduction by, the erythropoietin receptor in erythroid progenitor cells and the regulation of transcription, apoptosis, and cell division. Later the lab characterized many novel genes that are important for terminal stages of erythropoiesis, including chromatin condensation and enucleation. Other projects focused on the regulation of self- renewal, proliferation, and differentiation of early (BFU-E) erythroid progenitor cells by extracellular signals including glucocorticoids and oxygen, with the goal of developing novel therapies for erythropoietin-resistant anemias.

The lab discovered several microRNAs and Long Non-coding RNAs that are specifically expressed in developing red blood cells and that regulate important aspects of development including cell death. One microRNA, miR-125b, causes leukemias when overexpressed in human or mouse stem cells. Another recent discovery revealed why patients with an underactive thyroid tend to have anemia: A lack of the thyroid hormone thyroxin inhibits maturation of red blood cell progenitors. 

Additionally, the Lodish lab researched hormones controlling fatty acid and glucose metabolism, broadening understanding of obesity and type 2 diabetes. In 1995, the lab cloned adiponectin, a hormone made exclusively by fat cells. A long series of studies showed that adiponectin causes muscle to burn fatty acids faster—so they are not stored as fat—and increases the metabolism of the sugar glucose. More recently the laboratory focused on identifying and characterizing microRNAs and Long Non-coding RNAs that are specifically expressed in adipose cells. One miRNA unique to brown fat, which burns rather than stores fatty acids as triglycerides, triggers other progenitor cells to become brown fat.

Lodish continues to teach undergraduate and graduate courses in biotechnology, and advises many companies in the development of cell and gene therapies to treat rare diseases and major unmet medical needs. 

Bio

Lodish earned his PhD at Rockefeller University in 1966 with Dr. Norton Zinder. After postdoctoral research with Drs. Francis Crick and Sydney Brenner, Lodish joined the MIT faculty in 1968. He has been a professor of biology since 1976 and a professor of biological engineering since 1999. He was elected a fellow of the American Association for the Advancement of Science in 1986, a member of the National Academy of Sciences in 1987, and a fellow of the American Academy of Arts and Sciences in 1999.  He is a member of the Board of Trustees of Boston Children’s Hospital, and was Chair of the Scientific Advisory Board of the Massachusetts Life Sciences Center, charged with oversight of the state’s 10- year, $1 billion investment in the life sciences. He is also the lead author of the textbook Molecular Cell Biology. Two of his postdoctoral fellows were recipients of Nobel Prizes and eight students and fellows are Members of the National Academies of Sciences or Medicine.