Area:
Cell Biology, Molecular Biology, Oncology
We are testing a new system for linking grants to scientists.
The funding information displayed below comes from the
NIH Research Portfolio Online Reporting Tools and the
NSF Award Database.
The grant data on this page is limited to grants awarded in the United States and is thus partial. It can nonetheless be used to understand how funding patterns influence mentorship networks and vice-versa, which has deep implications on how research is done.
You can help! If you notice any innacuracies, please
sign in and mark grants as correct or incorrect matches.
Sign in to see low-probability grants and correct any errors in linkage between grants and researchers.
High-probability grants
According to our matching algorithm, Stephan C. Lindsey is the likely recipient of the following grants.
Years |
Recipients |
Code |
Title / Keywords |
Matching score |
2009 — 2011 |
Lindsey, Stephan Cadet |
F32Activity Code Description: To provide postdoctoral research training to individuals to broaden their scientific background and extend their potential for research in specified health-related areas. |
Role of Ahr During Megakaryopoiesis
DESCRIPTION (provided by applicant): Understanding the fundamental molecular mechanisms underlying megakaryocytic differentiation and polyploidization is an essential first step to discovering novel therapeutic targets and approaches for treating Mk and platelet disorders such as essential thrombocytopenia, refractory thrombocytopenia in myelodysplastic syndromes, megakaryoblastic leukemia, and thrombocythemia. Myelodysplastic syndromes (MDS) are heterogeneous hematopoietic stem cell disorders often accompanied by defective megakaryocyte (Mk) development, decreased platelet counts, and often progress into leukemia. Most MDS patients have chronic thrombocytopenia, but platelet transfusion is complicated by the development of allogeneic antibodies and ca. 30% of MDS patients die of bleeding. Therefore, increased endogenous platelet production could extend the lifespan (and increase the quality of life) for a substantial fraction of MDS patients by rescue from and/or delayed onset of clinically significant thrombocytopenia. Unfortunately, little information is known about Mk (platelet precursors) or platelet production. Because the number of platelets released by a single Mk is directly proportional to how much DNA the cell contains, understanding the Mk cell cycle may provide crucial insights and allow for better platelet expansion. Well-known as a "toxic sensor," aryl hydrocarbon receptor (AhR) function is normally associated with the action mechanism of various environmental toxins, presumably by altering cell cycle regulation. Environmental exposure to high levels of AhR ligands has been associated with increased platelet counts and we hypothesize that as a cell cycle regulator, AhR may impact Mk polyploidization, a process known to involve a modified cell cycle. Our data indicate that AhR expression and activity increases during Mk differentiation of both cell lines and primary human CD34+ cells and coincides with increased target gene expression. Importantly, AhR RNAi knockdown results in decreased Mk polyploidization through unknown mechanisms. We propose to (1) test the hypothesis that AhR is required for the formation ofproplatelet extensions and in vivo platelet production and function, (2) further investigate if AhR is activated and necessary for megakaryopoiesis, leading to increased Mk polyploidization;(3) determine if AhR-mediated Hes1 expression regulates the level and localization of cyclin D3, cyclin E, and other key Mk genes during megakaryopoiesis;Our experiments could simultaneously provide important insights into megakaryopoiesis by identifying a novel thrombocytopenic event (reduced AhR), and guide new treatment options to increase platelet counts (drugs and/or treatments that increase AhR activity) in thrombocytopenic patients.
|
0.943 |