Funding

The NIDDK Hematology Centers Program is providing a novel support mechanism for researchers to pursue new directions in non-malignant hematology. Applicants do not need to be U.S. citizens or Green card holders but must be from any registered, domestic (U.S.), eligible organization. However, those from institutions not currently part of the NIDDK Hematology Centers Program will be prioritized. Applications from investigators coming from other fields, bringing new perspectives or tools to address questions in nonmalignant hematology are also encouraged to apply.

P&F Type A

$5,000 – $12,000 worth of core credits to provide equal access to services and expertise offered by any core. Rolling deadlines, abbreviated application forms, and streamlined review by Core Directors all contribute to a rapid and equitable distribution of core credits. Type A support is ideally suited for trainees who want to master a new expertise or acquire a new skill to enhance their competitiveness.

Details and submission instructions

P&F Type B

$75,000 total award (grant) including F&A. Use of CCEH Core resources is not required but encouraged. The primary goal of Type B P&F grants is to support innovative pilot research projects in non-malignant hematology, including the generation of preliminary data for larger research grants.

Details and submission instructions

Application Process for Type A or Type B P&F Proposals

Check guidelines for eligibility
a. Priority will be given to Junior Investigators and Postdocs.
b. Established Investigators starting a new line of Research in nonmalignant hematology – cannot be focused on currently funded project.
Determine the type of grant you wish to apply for.a. Type A – Core Usage Funds Only (C-UFO) up to $12,000 (no F&A, funds made available only at Core proposed).
b. Type B – New Pilot Proposal (HCCC-P&F) up to $75,000 including recommended F&A (Use PHS 398 forms as detailed).
Contact the core director(s) of the core you will be using to initiate guidance on feasibility and costs associated with core use.
Write and submit proposals as a single PDF using the detailed guidelines on length and inclusions on the appropriate submission instruction page (Type A, Type B) prior to final due date and time.

No applications will be accepted after 5pm MST on the due date.

Submit Application Here

The CCEH program supports pilot and feasibility program grants funding small projects aimed at generating preliminary data for inclusion in larger grant applications. The grants will be awarded competitively and are designed to support collaborative research projects that utilize core resources at one of the five CCEH centers.

Please refer to the guidelines for writing and formatting applications (above) before submitting. Applications can be uploaded using the form to the right. You will receive rapid acknowledgement of receipt of your application via email. If you do not receive acknowledgement, please confirm the correct email address is provided and resubmit prior to the deadline. Please reach out to Lori Blake prior to the deadline to confirm that your application has been received or for assistance prior to the deadline.

No applications will be accepted after the due date.

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Publications Associated with P&F Funding

Is the erythropoietin-erythroferrone-hepcidin axis intact in human neonates?

Maternal prolactin or estrogen signaling in hepatocytes does not regulate iron homeostasis during pregnancy

Precision analysis of mutant U2AF1 activity reveals deployment of stress granules in myeloid malignancies.

P&F Recipients

Xia Xiao, PhD

Xia completed her PhD degree in Nutritional Sciences at the Pennsylvania State University, University Park. Under the mentorship of Dr. Matam Vijay-Kumar, she studied the roles of the innate immune proteins lipocalin 2 and myeloperoxidase in iron toxicity-induced liver damage, and the interplay among innate immune proteins, bacterial siderophores, and iron on innate immune function and gut health. For her postdoctoral training, Xia joined Dr. Jodie Babitt Lab at Massachusetts General Hospital/Harvard Medical School studying BMP-SMAD signaling, hepcidin regulation and iron homeostasis. This U24 CCEH Type B P&F award from NIDDK will provide her resources and experience to study the role of the hemochromatosis gene HFE in hepcidin regulation and iron homeostasis.

Emily Collins, PhD

Emily Collins, PhD, is a Postdoctoral Researcher in the lab of Anthony Rongvaux at Fred Hutchinson Cancer Center. With the support of CCEH, her research is focused on developing a CRISPR-based functional in vivo Screen of Human Hematopoiesis (C-FiSHH). This project proposes to combine CRISPR screen technology with the Rongvaux lab’s expertise in humanized mouse models to create a new tool to probe the essential mechanisms that maintain hematopoiesis and give rise to varied immune cell lineages. C-FiSHH will provide a necessary complement to the high-dimensional mapping of human hematopoiesis transcriptomes, adding a functional perspective to descriptive studies. The first goal is to deliver a protein-barcoded gRNA/CAS9 complex to human donor hematopoietic stem cells that will then successfully engraft in the MISTRG mouse model. We will then demonstrate the feasability of a multi-gene screen approach by delivering a CRISPR library of well-described genes involved in the development of the major hematopoietic lineages. Once developed, this approach intends to be highly versatile to accommodate any genes of interest and will help elucidate mechanisms underlying fundamental characteristics of hematopoiesis, such as the long-term maintenance of self-renewing HSCs, lineage commitment, or the role of cytokines.

Yagna Jarajapu, Type B P&F Recipient

Yagna is a vascular pharmacologist by training; received doctorate in vascular Physiology and Pharmacology from the Glasgow Caledonian University, Glasgow, Scotland. He had post-doctoral training in the field of ischemic vascular regeneration by adult stem/progenitor cells and the pharmacology of renin angiotensin system under the mentorship of Prof. Grant and Prof. Raizada at the University of Florida. As an independent investigator at the North Dakota State University he pursued research in ACE2 and Mas receptor pharmacology in the CD34+ stem/progenitor cells from diabetic adults. Collectively, his studies showed that activation of ACE2 or Mas receptor by pharmacological or molecular strategies is sufficient to enhance endothelialization or revascularization potential of the dysfunctional diabetic CD34+ cells in preclinical studies involving ischemic vascular injury. During the course of this research, his team identified that mitochondrial telomerase reverse transcriptase (mtTERT) is critical for restoring the reparative functions of diabetic CD34+ cells. Furthermore, the expression of dominant negative mutants of TERT, deletion splice variants, was higher in diabetic cells, which indeed impair the protective functions of mtTERT. The U24 CCEH type B P&F award will provide resources to study the pathological role of TERT-splice variants on the mitochondrial stress and bioenergetics, and hematopoietic functions in CD34+ cells.

Amy Medlock, PI University of Georgia Member Utah U54 CCEH

The CCEH Type B grant entitled “Erythroblastic Island Heme Synthesis under Normal and Inflammatory Conditions” in the Medlock laboratory is focused on understand the transcriptomics and proteomics at the single cell level of developing erythroid cells in erythroblastic islands under normal and disease states. The model we are using was developed in the Torok-Storb laboratory and allows the development of erythroblastic island from CD34+ cells. This systems allow us to probe the complex interaction of the central macrophage with the developing erythroid cells. Our first goal is to establish a time line for heme synthesis during erythropoiesis in this system that more closely resembles the bone marrow niche. Personnel from the Medlock laboratory traveled to the Fred Hutchinson Cancer Center to learn how to isolate CD34+ cells from adult bone marrow, grow, transform, and differentiate these cells. We also carried out flow analysis and single cell Western on the cells from these erythroblastic islands. Currently, we are continuing these experiments and starting single cell RNA-seq experiments. The second aim is to characterize the impact that the inflammatory response has on heme synthesis and differentiation of the erythroblasts within the erythroblastic island. These experiments will begin in the spring.

P&F recipient, James Ropa, PhD

James is currently a postdoctoral fellow at Indiana University School of Medicine where he has worked under the mentorship of first Dr. Hal Broxmeyer and now Dr. Mark Kaplan. He is in the process of transitioning to an independent position. James’s research is broadly focused on identifying the molecular machinery important for hematopoietic cell potency in various homeostatic/diseased/stressed states, with the overall goal of improving hematopoietic cell therapies. This CCEH supported study will identify gene programs that correlate with and/or drive hematopoietic stem and progenitor cell function by modeling the hematopoietic transcriptome against clinical readouts of potency and predicted potency. The objective of the project is to identify genes that are highly expressed in potent umbilical cord blood units and/or that drive better outcomes in hematopoietic transplantation. These data will have immediate translational implications for cord blood (and other donor sources) unit selection for use in cellular therapies, as well as for identifying molecular targets to improve cell function for other therapeutic utilities.

Radoslaw Omelianczyk, PhD

Radoslaw received his doctorate from the Nanyang Technological University in Singapore where he worked in the lab of Dr. Peter Preiser. He studied virulence genes of the human malaria parasite Plasmodium falciparum. He is receiving his postdoctoral training in the labs of Dr. Ellen Leffler and Dr. Paul Sigala (Utah CCEH) at the University of Utah. He is studying recently identified adaptations of Plasmodium falciparum that allow the parasite to thrive in otherwise resistant sickle disease patients. The Sickle allele provides near complete immunity to severe malaria, which caused allele frequencies to reach almost 20% in Sub-Saharan Africa. The spread of adapted parasites would therefore put large parts of the population at increased risk to get malaria. The U24 CCEH type B P&F grant is used to study the biological roles of these adaptations. Specifically, he hypothesizes that mutant parasites interfere with red blood cell metabolome and lipid composition.

Liang Zheng, PhD University of Kansas Medical Center

ANKRD26 (Ankyrin repeat domain-containing protein-26) is a highly conserved protein that is involved in platelet production. Mutations in the 5′ untranslated region (5’UTR) of ANKRD26 gene lead to ANKRD26 overexpression during megakaryocyte differentiation. resulting in impaired proplatelet formation. Point mutations and small size deletions in the 5’UTR of ANKRD26 have been identified in patients with inherited thrombocytopenia 2 (THC2), a life-long thrombocytopenia with a predispostion to developing hematological malignancies, However, little is known about the underlying mechanism of ANKRD26 mutation-associated thrombocytopenia. To explore the function of ANKRD26 and its role in magakaryopoiesis and thrombocytopenia, we established and characterized the first animal model of THC2. Our preliminary results demonstrated that zebrafish ankrd26 mutants with mutations in the 5’UTR of ankrd26 resulted in overexpression of Ankrd26 and reduction of thrombocyte count, similar to the clinical presentation of THC2 patients. Moreover, we found that the level of ANKRD26 was positively correlated with the level of PRMT1 in the megakaryoblastic leukemeia cells and in the platelets of immune thrombotic thrombocytopenic purpura patients. PRMT1 is an arginine methyl-transferase for RUNX1 (runt-related transcription factor 1), which is a negative regulator for ANKRD26 expression. We hypothesize that dysregulation of PRMT1-RUNX1-ANKRD26 pathway may affect both hereditary and acquired thrombocytopenia. Our study will further evaluate the role of this novel pathway in platelet development and production, providing a potential avenue for developing novel therapeutic strategies for patients with thrombocytopenia.

Type B P&F Recipient Audrey Belot

Audrey completed her BS degree in Physiology and Cell Biology at the University of Bretagne Occidental, Brest, France. She then joined the lab of Dr Delphine Meynard at the Paul Sabatier University, Toulouse, France to pursue her MS and PhD degrees. Her PhD work focused on understanding the role of iron in liver pathophysiology, specifically in NAFLD and NASH. In parallel, she also tested a new therapeutic strategy, LJ000328 an ALK2/3 kinase inhibitor, to treat Iron Deficiency Iron Refractory Anemia. In August 2021, Audrey started her post-doctoral research with Dr Iqbal Hamza at the University of Maryland, Center for Blood Oxygen Transport and Hemostasis where she studies heme transport and trafficking during erythropoiesis. The funding from the Type B P&F from the NIDDK CCEH will provide her with resources and experiences to support her long-term career goals of becoming an independent researcher.