Investigators: Jane-Jane Chen, Ph.D. Institute of Medical Engineering & Science, MIT
Dr. Chen is a Principal Research Scientist at the Institute for Medical Engineering and Science, MIT. Her laboratory is among the leading groups in the translational regulation involving eIF2a kinases [1]. Phosphorylation of eIF2a is an ancient and conserved mechanism for stress adaptation from yeast to human. The heme-regulated eIF2a kinase (HRI) is essential for the adaptation of iron-deficiency anemia. Besides heme deficiency, HRI is also activated by oxidative stress and denatured proteins both of which occur in thalassemia. Furthermore, HRI is necessary for reducing the phenotypic severities of β-thalassemia in mice. In addition to understanding the molecular basis of erythroid cell (RBCs) adaptation to oxidative stress, Dr. Chen's Lab is also investigating genome-wide in vivo translational regulation during normal and stress erythropoiesis.
Anemia, caused by iron deficiency and thalassemia, is the single most prevalent disorder worldwide. Just iron deficiency anemia has a staggering rate of more than 30% and accounts for approximately 2 billion cases [2]. Likewise, thalassemia - the most common monogenic disease that limits the capability of affected hemoglobin to transport oxygen, accounts for ~5% of world's population carrying this trait. Increased oxidative stress and ineffective erythropoiesis in thalassemia may result in the major clinical manifestation of these chronic diseases, including slowed growth in children, bone deformities, and enlarged spleen, liver, or heart. In most cases of anemia, low immunity of individuals may lead morbidity from infections at all ages. While iron deficiency anemia can be treated with proper diet and iron supplements, mild to severe thalassemia is typically managed through blood transfusions and iron chelation therapy. In some cases, surgical interventions (e.g., splenectomy) may be needed to ensure optimal control of associated morbidity.
LBRC houses state-of-the-art interferometric instruments, quantitative phase microscopy, for measuring nanometer scale cell membrane fluctuations and hence quantitative assessment of red cell biomechanical properties at single cell level. The LBRC also houses tomographic phase microscopy units for corresponding 3D morphological measurements as well as cell dry mass, Hb concentration, and total Hb volume. For population level studies, LBRC is able to offer an automated microfabricated 'deformability cytometer' (developed by Dr. Ming Dao's Lab) capable of high throughput (103 - 104 individual red cells) in a population. Altogether, these technologies will provide a unique opportunity for Dr. Chen's Lab to study biophysical aspects of red cells from murine models of iron deficiency anemia while simultaneously investigating the molecular and genomic aspects of various heme-regulated protein kinases in these anemic diseases.