|
||||||||||
|
Fumihiko Urano, Ph.D.,M.D.Academic Role: Assistant Professor
Faculty Appointment(s) In:
Other Affiliation(s):
Role of ER Stress in Diabetes and Aging
What is Endoplasmic Reticulum (ER)?Proteins are needed for the body to function properly. They are the basis of body structures and are used to synthesize enzymes and antibodies in cells. Proteins are synthesized in our cells. However, newly synthesized proteins are not functional yet. To be functional, they should mature inside of a cellular compartment called the Endoplasmic Reticulum (ER). It is like that a baby is growing in the uterus. In the lumen of the ER, proteins obtain their proper three-dimensional structure and mature to carry out their functions (i.e., become functional). This process is called protein folding. ER has an essential function in this process, especially for secreted protein and receptors such as insulin, amyloid beta and serotonin transporter. Defects of these proteins have been known to cause diabetes, Alzheimer's disease, and bipolar disorder respectively. What are "Endoplasmic Reticulum Stress (ER stress) Diseases"?Protein folding in the ER is crucial for us. However, in some instances, the sensitive environment in the ER can be perturbed by pathophysiological processes such as viral infections, environmental toxins, and mutant protein expression, as well as natural processes such as the large biosynthetic load placed on the ER. This causes the accumulation of immature and abnormal proteins in cells, leading to ER stress. Our body has an adaptive response that counteracts ER stress termed "Unfolded Protein Response (UPR)". Therefore, as long as the UPR can mitigate ER stress, our body functions properly. However, under some pathological circumstances, a lot of abnormal proteins accumulate, leading to a high level of ER stress. This high level of ER stress cannot be mitigated by an adaptive response (i.e., the UPR), leading to malfunction of our cells. These pathological circumstances include environmental stress, virus infection, genetic defects, and obesity. We group the human diseases that are associated with the accumulation of abnormal proteins in the ER into "ER Stress Diseases". ER stress and DiabetesDiabetes is a group of disorders defined by a state of high blood sugar caused by an absolute deficiency of insulin (type 1 diabetes) or a relative deficiency of insulin (type 2 diabetes). Secreted from pancreatic beta cells, insulin is essential to lowering blood sugar. While patients with type 2 diabetes need to take medications that stimulate insulin secretion from beta cells, patients with type 1 diabetes lack insulin-producing beta cells and need to inject themselves with synthetic insulin. We have found that a high level of ER stress has an important function in the pathogenesis of both tyep 1 and type 2 diabetes. We seek to develop new clinical approaches based on the prevention of diabetes by the development of drugs that block the ER stress-mediated cellular dysfunction.
Office: LRB - 522
|
|
||||||||
| INTRANET |
|
top print |
|
|||||||
| ||||||||||
The goal of our laboratory is to understand the molecular mechanisms of Endoplasmic Retiuculm stress (ER stress) diseases such as Alzheimer's disease, Parkinson's disease, Prion disease, ALS and diabetes mellitus. These most devastating human diseases are associated with pathological accumulations of abnormal proteins in cells. An overwhelming body of evidence suggests that a special type of cell stress called Endoplasmic Reticulum stress (ER stress) has an important function in the pathogenesis of such diseases. We are also studying the relationship between ER stress and Aging because accumulations of abnormal proteins may accelerate age-related cellular dysfunction.
373 Plantation Street Worcester, MA 01605