Navigation Links
Scientists identify potential drug target for treatment-resistant anemias
Date:6/9/2013

CAMBRIDGE, Mass. (June 9, 2013) Researchers at Whitehead Institute have identified a protein that is the target 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. The discovery could spur development of drugs capable of increasing this protein's production without causing the severe side effects associated with glucocorticoids.

"This research is medically important, and we are using it to find a better way to increase the production of red blood cells for these patients," says Harvey Lodish, who is a Whitehead Institute Founding Member and a professor of biology at MIT. "It is also a new insight into how self-renewal in stem cells can be controlled, and a new way to think about how we can use an RNA binding protein to maintain stem and progenitor cells."

Anemia occurs due to a breakdown in erythropoiesis, the multi-step process that creates red blood cells. Some common anemias can be treated with a recombinant form of the hormone erythropoietin (EPO), which normally stimulates red blood-cell production at a fairly late stage of erythropoiesis.

However, certain anemias fail to respond to EPO, creating a large unmet medical need. In the case of Diamond Blackfan anemia (DBA), patients lack a sufficient number of EPO-responsive cells. Instead, glucocorticoids such as prednisone or prednisolone are used to treat DBA and other anemias resistant to EPO by increasing the numbers of the later progenitor cells that respond to EPO. These drugs cause a host of negative side effects, including decreased bone density, immunosuppression, stunted growth, and cataracts, all of which are particularly burdensome for young patients.

Earlier work in the Lodish lab determined that glucocorticoids increase red blood cell production by acting on early progenitors of red blood cells, called burst forming unit-erythroids (BFU-Es). During erythropoiesis, BFU-Es produce later progenitors called colony forming unit-erythroids (CFU-Es), which are then stimulated by EPO to generate the pro-erythroblasts that eventually become red blood cells. By dividing numerous times before maturing, BFU-Es have a limited ability to self-renew. After exposure to glucocorticoids, BFU-Es divide more times than usual, which ultimately increases the total number of red blood cells they produce.

To determine how glucocorticoids prolong BFU-Es' self-renewing phase, Lingbo Zhang, a graduate student in the Lodish lab, studied the drugs' effects in mouse BFU-Es. His work is described online this week on the website of the journal Nature.

Zhang determined that glucocorticoids increase the expression of the protein Zfp36l2, which binds to messenger RNAs (mRNAs) that otherwise would push BFU-Es to differentiate. Under the sway of Zfp36l2, BFU-Es undergo additional rounds of self-renewing cell divisions, forming eventually more EPO- responsive CFU-Es and that can increase red blood cell production by up to 20-fold in vitro.

"It's amazing that the body can trigger this process using one essential gene," says Zhang. "But this is still the very beginning. What glucocorticoids are doing in these cells has been like a black box and now we have one piece of what's happening in that box. And that will help us toward our goal to find a hormone or drug that could be used as a replacement for glucocorticoids."


'/>"/>

Contact: Nicole Rura
rura@wi.mit.edu
617-258-6851
Whitehead Institute for Biomedical Research
Source:Eurekalert

Related biology news :

1. Stanford scientists develop gene therapy approach to grow blood vessels in ischemic limbs
2. Queens scientists seek vaccine for Pseudomonas infection
3. Scientists produce eye structures from human blood-derived stem cells
4. American Society of Plant Biologists honors early career women scientists
5. Brandeis scientists win prestigious prize for circadian rhythms research
6. Scientists discover new method of proton transfer
7. Salk scientists open new window into how cancers override cellular growth controls
8. WileyChina.com - Now Featuring Bespoke Pages for China’s Life Scientists
9. Scientists win $2 million to study new pathway in development and maintenance of lymphoma
10. UGA scientists reveal genetic mutation depicted in van Goghs sunflower paintings
11. Genetic mutation depicted in van Goghs sunflower paintings revealed by scientists
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/11/2017)... No two people are believed to ... York University Tandon School of Engineering and Michigan ... partial similarities between prints are common enough that ... and other electronic devices can be more vulnerable ... in the fact that fingerprint-based authentication systems feature ...
(Date:4/5/2017)... , April 5, 2017 Today HYPR ... that the server component of the HYPR platform is ... providing the end-to-end security architecture that empowers biometric authentication ... HYPR has already secured over 15 million users across ... manufacturers of connected home product suites and physical access ...
(Date:3/30/2017)...  On April 6-7, 2017, Sequencing.com will host the ... hackathon at Microsoft,s headquarters in Redmond, Washington ... developing health and wellness apps that provide a unique, ... is the first hackathon for personal genomics and ... in the genomics, tech and health industries are sending ...
Breaking Biology News(10 mins):
(Date:10/7/2017)... ... October 06, 2017 , ... ... instruments and applications consulting for microscopy and surface analysis, Nanoscience Instruments is ... Nanoscience Analytical offers a broad range of contract analysis services for advanced ...
(Date:10/7/2017)... , Oct. 6, 2017  The 2017 ... of three scientists, Jacques Dubochet, Joachim Frank ... developments in cryo-electron microscopy (cryo-EM) have ... within the structural biology community. The winners worked ... can now routinely produce highly resolved, three-dimensional images ...
(Date:10/6/2017)... ... 06, 2017 , ... On Tuesday, October 24th, ABC² (Accelerate ... first-ever adaptive clinical trial for glioblastoma (GBM). The featured speaker will be Dr. ... open to the public, but registration is required. , WHAT: ABC² Brain ...
(Date:10/5/2017)... (PRWEB) , ... October 05, 2017 , ... Understanding the ... newest frontiers in human health. Gut Love: You Are My Future, the newest exhibit ... artist’s perspective as it explores the human condition through the lens of the gut ...
Breaking Biology Technology: