About

Charles S. Abrams, M.D., is the Francis C. Wood Professor and Chief of Non-Malignant Hematology at the University of Pennsylvania School of Medicine. He also serves as the Director of the Blood Center at PENN/CHOP and is the Vice Chair for Research & Chief Scientific Officer at the University of Pennsylvania School of Medicine. His research focuses on phospholipid signaling in platelets and its contribution to inappropriate platelet activation, which is involved in vascular diseases including stroke and myocardial ischemia. Abrams's laboratory investigates the roles of pleckstrin and lipid kinases in blood cells, employing molecular and cellular biological techniques such as expression mutagenesis, single cell microinjection, genetic library screening, and murine homologous gene targeting. His work has contributed to understanding how phospholipid signaling pathways regulate cytoskeletal reorganization in platelets and lymphocytes, with particular emphasis on the functions of pleckstrin, lipid kinases, and small GTP-binding proteins like Rac.

Research topics

• Internal medicine
• Medicine
• Immunology
• Computer Science
• Cancer research
• Genetics
• Economic growth
• Data science
• Biology
• Economics

Selected publications

• PITPβ Drives JAK2 V617F-Mediated Myeloproliferative Neoplasms by Promoting PtdIns(3,4)P _₂ -Dependent AKT Hyperactivation

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-03-30

  articleOpen access

  ABSTRACT JAK2 is a key regulator of cytokine-mediated proliferative signaling in hematopoietic stem and progenitor cells. Activating mutations, most commonly JAK2 V617F, trigger aberrant cytokine signaling driving the pathogenesis of myeloproliferative neoplasms (MPNs). Phosphatidylinositol transfer proteins (PITPs) facilitate phosphoinositide synthesis by delivering phosphatidylinositol to lipid kinases, though their roles in oncogenic signaling have remained poorly defined. Here we show that PITPβ is critical for the development of JAK2V617F-driven MPN in mice. Deleting Pitp β across the hematopoietic system, but not Pitp α, prolonged 25-week survival of Jak2V617F mice from 10% to 85%. Loss of Pitp β attenuated disease-associated splenomegaly and curtailed erythroid progenitors expansion both in vivo and in vitro . Mechanistically, PITPβ is necessary for AKT hyperactivation in hematopoietic progenitors, while STAT5 and ERK signaling remain unaffected. In alignment with this role, PITPβ promotes the production of PtdIns(3,4)P ₂ , a phosphoinositide that sustains aberrant AKT signaling in Jak2V617F progenitors. Pharmacologic inhibition of AKT with the FDA-approved inhibitor capivasertib in Jak2V617F-transplanted mice similarly reduced splenomegaly and erythroid proliferation, mimicking the effects of Pitp β loss. Collectively, these results identify a novel PITPβ-PtdIns(3,4)P ₂ signaling axis that selectively maintains pathological AKT activation in JAK2V617F-driven MPN, revealing a promising therapeutic vulnerability.

  PublisherOA PDFDOI

• Novel use of a privacy-preserving hashed identifier to match individuals in different sickle cell disease registries and assess acute care utilization

  Blood · 2025-11-03

  articleOpen access

  Abstract Introduction: Sickle cell disease (SCD) is the most common inherited clinically relevant blood disorder resulting in several complications including organ dysfunction, fatigue and pain. These issues contribute to high acute care utilization and reduced quality of life. To better understand SCD, several registries have been developed but are not always maintained due to insufficient funding. Further, these registries do not use common data elements, are poorly coordinated and fall short of the comprehensive insights provided by well-structured, longitudinal registries used in other diseases. To overcome the lack of a single robust clinical registry in SCD, we implemented a privacy preserving technique for linking individuals across 3 of the larger multi-site SCD registries using a hashed identifier token. This proof-of-concept project was done to enhance our understanding of SCD to demonstrate how combining information across the registries is more accurate than using one data source alone. The findings also highlight the errors seen when relying on a single dataset when measuring acute care utilization. Methods: The study was conducted at the University of Alabama Birmingham (UAB). We have IRB approval for three SCD data collections: the Alabama SCD surveillance database (part of the CDC Sickle Cell Data Collection Project) called ALSTATE, the American Society of Hematology Research Collaborative (ASH RC) Data Hub for people with SCD seen at a UAB hospital, and the Globin Research Network for Data and Discovery (GRNDaD) registry. For each database, we internally create a set of identity tokens based on a selected set of identifiers and then used hashing (SHA-256) to create a hashed token to enable data linkage without compromising participant privacy. First, we proved that the hashed token could be used to link individuals across all 3 registries. Second, we quantified the acute care use within each dataset. As people with SCD may obtain care for acute pain crisis in the emergency department (ED), hospital, or a day hospital (DH), each data collection system may include different information from different sources. ALSTATE includes ED and hospital use from multiple hospitals, the ASH RC Data Hub only includes ED and hospital data from UAB hospitals and GRNDaD includes acute care data from DH, ED, and hospitals if that data is available within the patient's chart. Results: The first part of the project included 8026 records across the 3 registries. With the hashed identifier token, we identified 1080 unique individuals with records in at least two data sets. There were 340 individuals (93% of the 365 individuals enrolled in GRNDaD) were successfully matched and linked across all data sets. Second, we evaluated the information on acute care use in each database from a sub-set of 253 individuals that had acute care data from 2023 available for comparison. Within this cohort, we identified if people had zero, 1-3, 4-6 or >6 acute care visits in 2023. ALSTATE identified 69 people with zero acute care visits while the ASH RC data hub identified 118 people with no acute care visits but GRNDaD showed that only 77 (30.4% of 253) actually had no acute care visits. Similarly, ALSTATE showed that 64 people had >6 acute care visits, while the ASH RC data hub identified 21 people and GRNDaD showed only 36 people had >6 acute care visits. Conclusion: This is the first SCD project to implement a privacy preserving technique for linking individuals across multiple registries. This approach can leverage unique data elements from each source while ensuring that PHI is protected. Each data set provides key information on people with SCD. However, in isolation, the data from each data set may be misleading as shown with the acute care use information here. GRNDaD is the only source that includes DH visits for acute pain crisis as neither ALSTATE nor the ASH RC data hub can distinguish these visits from outpatient clinic. At the same time, ALSTATE includes data from multiple hospitals providing a wider view. However, by linking registries, we can triangulate the information for the most accurate data compared to using any of the data sets alone. Enhancing data interoperability is essential to increase our longitudinal understanding of SCD, improve our ability to identify and personalize treatments for affected individuals and ensure we can bring more treatments to the forefront for this at-risk population.

  PublisherOA PDFDOI

• The ASH Research Collaborative Sickle Cell Disease Research Network: past, present, and future

  Blood Advances · 2025-09-03 · 1 citations

  articleOpen accessSenior author

  ABSTRACT: Historically, sickle cell disease (SCD) has been overshadowed by progress in other hematologic disorders, but recent advances are reshaping its clinical and research landscape. Despite SCD reducing life expectancy by >20 years even with optimal care, transformative initiatives are fostering hope for improved outcomes. The American Society of Hematology (ASH) established the ASH Research Collaborative Sickle Cell Disease Research Network as a comprehensive program to revolutionize SCD research in the United States. This Network comprises a collection of innovative, research-focused cooperative sites and a robust Data Hub that aggregates extensive real-world data sets to enhance clinical insights and streamline research designs. Community advisory boards at both local and national levels ensure that the perspectives of individuals living with SCD guide research priorities. This report includes an overview of the initial demographics, such as the number of records, encounters, laboratory data, prescriptions, years of follow-up, and comorbidities per patient, within the context of the ASH Research Collaborative Sickle Cell Disease Research Network. These coordinated efforts are poised to significantly transform the landscape of SCD care, and this report details the initiative's mission, history, achievements to date, and its promising trajectory toward improving the lives of individuals affected by this chronic condition.

  PublisherOA PDFDOI

• Novel use of a Hashed Identifier Token for Sharing Sickle Cell Disease Data Without Sharing PHI (Preprint)

  2025-08-17

  article

  <sec> <title>BACKGROUND</title> Background: Sickle cell disease (SCD) is the most common inherited clinically relevant blood disorder. Anemia and progressive organ injury ultimately results in significant debility, health care utilization and reduced quality of life. As efforts continue to improve care for people living with SCD, several new registries have been developed but are often reliant on specific grants/contracts resulting in their early termination. Current ongoing medical registry initiatives lack coordination, leading to fragmented datasets that fall short of the comprehensive insights provided by well-structured, longitudinal registries. Although much of the data elements of interest are technically available in the separate electronic medical record systems of various hospitals; they are difficult to aggregate due to minimal interoperability within these systems, insufficient use of common data elements, and poor translation of natural language reports into codified data elements. These barriers to data collection prevent researchers from accessing the comprehensive needed to advance understanding of the illness at the population level. This lack of robust data creates significant gaps in our knowledge of how SCD progresses longitudinally throughout a person’s life. Efforts to create a common data system are being considered but this may result in the loss of years of data and knowledge that is needed in SCD. A better way to optimize existing data collections requires a data linkage system that connects datasets while de-duplicating and linking individuals within each database. </sec> <sec> <title>OBJECTIVE</title> Objective: The primary objective of this project is to develop a privacy-preserving approach for securely linking three of the largest data collection efforts in SCD in the United States. </sec> <sec> <title>METHODS</title> Methods: The study was conducted at the University of Alabama (UAB) Lifespan Sickle Cell Center (LSCCC). The LSCCC currently holds IRB approval to access three of the SCD data collection systems: the Sickle Cell Data Collection (SCDC) project, the American Society of Hematology Research Collaborative (ASH RC) Data Hub for people with SCD seen at a UAB hospital, and the Globin Research Network for Data and Discovery (GRNDaD) registry. For each of the data sources, we internally create a set of identity tokens based on our selected set of identifiers and then used hashing (SHA-256) to create a hashed token that enables data sharing without compromising participant privacy. </sec> <sec> <title>RESULTS</title> Results: A total of 8026 records were combined across the three registries. Through deterministic matching of the hashed identifier token, we were able to identify 1080 unique individuals with records in at least two of the registries. </sec> <sec> <title>CONCLUSIONS</title> Conclusion: This is the first project in SCD to implement a privacy preserving technique for linking individuals across multiple registries. By securely connecting data from each registry, the approach leverages unique data elements from each source while ensuring that PHI is protected. Enhancing data interoperability is essential to deepening our longitudinal understanding of SCD, improving our ability to study and personalize treatments for affected individuals and to ensure we can bring more treatments to the forefront for this at-risk population. </sec>

  PublisherDOI

• PITPβ loss disrupts malignant pAKT activation to ameliorate Jak2 V617F-induced myeloproliferative neoplasms (MPN) in mice

  Blood · 2025-11-03 · 1 citations

  article

  Abstract Myeloproliferative Neoplasms (MPN) is a group of phenotypically defined blood cancers that affect thousands of people around the world. A driving mutation in JAK2 kinase (most commonly Jak2 V617F) is frequently found in MPN patients, occurring in over 99% of polycythemia vera cases as well as over 50% of essential thrombocythemia and primary myelofibrosis patients. JAK2 inhibitors have been clinically used to reduce disease burden, but they are not curative, highlighting the need for new therapeutic strategies. The mouse model endogenously expressing Jak2 V617F mutation develops lethal MPN with 100% penetrance, and is characterized by erythrocythemia, elevated hematocrit, and splenomegaly (Mullally et. al. Cancer Cell 2010). Previously, we found that phosphatidylinositol transfer proteins (PITP) indirectly modulate hematopoietic stem cell (HSC) function in mice. Megakaryocytes deficient in both PITPα and PITPβ oversecrete TGF-β1, leading to suppression of HSC proliferation. (Capitano &amp; Zhao et. al. Blood 2018). Besides PITP primary function to shuttle lipids between submembranes in a cell (Carvou et. al. J. Cell Sci. 2010), they also play a role as a cofactor in phosphoinositide synthesis (Zhao et. al. Blood Adv. 2023). Given their impact on hematopoiesis, we hypothesized that PITPs might influence signaling and disease progression in Jak2 V617F-driven MPN. Following a pan-hematopoietic vavCre knockout of either PITPα or PITPβ in Jak2 V617F mutant mice, we found that PITPβ deficiency dramatically improved survival: 85% of double transgenic mice survived beyond 50 weeks, compared to only 10% of Jak2 V617F mice surviving past 25 weeks. Furthermore, Jak2 V617F mice with PITPβ KO exhibited normalized red blood cell count, hematocrit, reticulocyte count, and alleviated splenomegaly. This was specific to PITPβ loss and was not observed with deletion of the paralog PITPα. We evaluated these mice for erythroid lineage expansion associated with the Jak2 V617F mutation and found that PITPβ deficiency reduced the number proerythroblasts (Ery I) in the bone marrow and spleens of JAK2 V617F mice to the wildtype level. Furthermore, the level of early erythroid progenitors (CFU-e and BFU-e), as well as myeloid- (MPP3) and erythroid-biased (MPP2) multipotent progenitors was reduced by the PITPβ KO. In contrast, PITPα deficiency did not rescue erythroid expansion in Jak2 V617F mice. To evaluate the effect of PITPβ deficiency on stem cell function in Jak2 V617F MPN, we utilized methylcellulose colony forming assay for erythroid progenitors. We found that PITPβ KO reduced EPO hypersensitivity of Jak2 V617F bone marrow cells, reducing CFU-e colony formation to the wildtype level. Furthermore, preliminary data from the bone marrow transplantation suggests that PITPβ KO improved engraftment of transplanted stem and progenitor cells (Lineage- cKit+ Sca-1+) from JAK2 V617F bone marrow and mildly reduced myeloid reconstitution bias. To investigate the mechanism behind the rescue, we adapted flow cytometry panels to study signaling in rare hematopoietic progenitor populations at a single cell level. We observed JAK2 V617F driven hyperactivation of pSTAT5, pAKT, and pERK throughout the hematopoietic lineage in spleen, from early multipotent progenitors to more differentiated erythroid and myeloid progenitors in response to erythropoietin and stem cell factor. Importantly, we found that PITPβ deficiency selectively reduced pAKT across all populations tested, while leaving pSTAT5 or pERK unaffected. These findings suggest that reducing pAKT alone is sufficient to alleviate MPN symptoms and improve survival in mice. To validate these finding, we are currently testing if pharmacological AKT inhibition is sufficient to attenuate MPN in Jak2 V617F mice. In parallel, we are investigating if PITPβ deficiency impairs the production of phosphatidylinositol (3,4,5)-trisphosphate (PIP3), a key secondary messenger in the AKT pathway. The results of both experiments will be ready by the ASH meeting. While these experiments are ongoing, our work has already revealed an unrecognized role for PITPβ in promoting Jak2 V617F-driven MPN through dysregulation of malignant pAKT activation. This discovery not only highlights a new therapeutic target for MPN, but also underscores the critical role of AKT signaling in MPN progression.

  PublisherDOI

• β-actin function in platelets and red blood cells can be performed by γ-actin and is therefore independent of actin isoform protein sequence

  Molecular Biology of the Cell · 2024-12-20 · 1 citations

  articleOpen access

  Actin is an essential component of the cytoskeleton in every eukaryotic cell. β-and γ-nonmuscle actin are over 99% identical to each other at the protein level but are encoded by different genes and play distinct roles in vivo. Blood cells, especially red blood cells (RBC), contain almost exclusively β-actin, and it has been generally assumed that this bias is dictated by the unique suitability of β-actin for RBC cytoskeleton function due to its specific amino acid sequence. Here we tested this assumption by analyzing the "β-coded γ-actin" (Actbcg) mouse model, in which the β-actin gene is edited by five-point mutations to produce γ-actin protein. Strikingly, despite lacking β-actin protein, Actbcg mice had no detectable phenotypes in RBCs, and no changes in the RBC shape, integrity, deformability, and molecular composition of their spectrin-based membrane skeleton. No actin-dependent changes were observed in platelets, another anucleate cell type enriched for β-actin. Our data show that, contrary to expectations, β-actin function in mature RBCs and platelets is independent of its protein sequence and therefore its enrichment in hematopoiesis and mature blood cells is likely driven entirely by its nucleotide-dependent functions.

  PublisherOA PDFDOI

• COVID-19 mRNA vaccination responses in individuals with sickle cell disease: an ASH RC Sickle Cell Research Network Study

  Blood Advances · 2024-07-11 · 3 citations

  articleOpen accessSenior author

  ABSTRACT: Children and adults with sickle cell disease (SCD) have increases in morbidity and mortality with COVID-19 infections. The American Society of Hematology Research Collaborative Sickle Cell Disease Research Network performed a prospective COVID-19 vaccine study to assess antibody responses and analyze whether messenger RNA (mRNA) vaccination precipitated any adverse effects unique to individuals with SCD. Forty-one participants received 2 doses of the Pfizer-BioNTech vaccine and provided baseline blood samples before vaccination and 2 months after the initial vaccination for analysis of immunoglobulin G (IgG) reactivity against the receptor binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 spike protein. Six-month IgG reactivity against the viral RBD was also available in 37 patients. Postvaccination reactogenicity was common and similar to the general population. There were no fevers that required inpatient admission. Vaso-occlusive pain within 2 to 3 days of first or second vaccination was reported by 5 participants (12%) including 4 (10%) who sought medical care. Twenty-seven participants (66%) were seropositive at baseline, and all 14 initially seronegative participants (34%) converted to seropositive after vaccination. Overall, mRNA vaccination had a good risk-benefit profile in individuals with SCD. This mRNA vaccine study also marks the first evaluation of vaccine safety and antibody response in very young children with SCD. This trial was registered at www.ClinicalTrials.gov as #NCT05139992.

  PublisherDOI

• TARGETED DRUG DELIVERY OF LEUKOMIMETIC NANOPARTICLES TO ALLEVIATE PERIPHERAL NEUROPATHY IN CHARCOT-MARIE-TOOTH 1X

  Journal of Pharmacology and Experimental Therapeutics · 2024-05-13

  articleSenior author
  PublisherDOI

• Pitpβ Loss Ameliorates Jak2 V617F-Induced Myeloproliferative Neoplasms (MPN) in Mice

  Blood · 2024-11-05

  articleOpen access

  Myeloproliferative Neoplasms (MPN) is a blood disorder that affects ~300,000 people in the US. Mutations in the JAK/STAT pathway, which is responsible for essential cytokine signaling in blood development, are a common cause of MPN. One of the most common mutations, JAK2 V617F is present in 50-60% of all MPN cases. Although JAK inhibitors are shown to improve patient outcomes, they are not curative, suggesting the need for new therapeutic avenues. The mouse model bearing the Jak2 V617F mutation at the endogenous locus develops lethal MPN with 100% penetrance. MPN is characterized by elevated hematocrit, splenomegaly, and erythroid expansion in the spleen and bone marrow (Mullally et. al. Cancer Cell 2010). Previously, we showed that phosphatidylinositol transfer protein α (PITPα) is essential for platelet-mediated tumor metastasis (Zhao et. al. Nat Commun 2017). Furthermore, Pf4-Cre conditional knockout (CKO) in mice of PITPα, or both PITPα and PITPβ, results in defective megakaryocytes with abnormal α-granule morphology that indirectly affects hematopoiesis. These mice exhibit moderately reduced hematopoietic stem cell (HSC) numbers with reduced competitive reconstitution ability, attributed to over-secretion of TGF-β1 (Capitano &amp; Zhao et. al. Blood 2018). PITPs are known to regulate phosphoinositide synthesis by transferring phosphatidylinositol and phosphatidylcholine from the ER to other membrane compartments in the cell (Carvou et. al. J. Cell Sci. 2010). They have also been implicated in vesicular synthesis and exocytosis, and involved in cellular signaling as a carrier of metabolic precursors to inositol triphosphates (IP3) and diacylglycerol (Ile et. al. Nat Chem Biol 2006). However, their role in MPN or JAK2 signaling has not been explored. Due to the effect of PITP family proteins on hematopoiesis, we set out to determine the role of PITP in Jak2 V617F-mediated MPN. We generated pan-hematopoietic Jak2 V617F knock-in mice combined with PITPα or PITPβ KO using vavCre. We found that PITPβ KO, but not PITPα KO, significantly improved survival of Jak2 V617F mutant mice. Importantly, PITPβ deficiency normalized red blood cell count, hematocrit, reticulocyte count, and alleviated splenomegaly of Jak2 V617F MPN mice. We further evaluated the effect of PITP KO on erythroid populations in Jak2 V617F mice using flow cytometry. Jak2V617F markedly elevated the level of proerythroblasts (Ery I) and orthochromatic erythroblasts (Ery IV) in the bone marrow. In the spleen, Jak2 V617F elevated proerythroblasts (Ery I), and basophilic and polychromatic erythroblasts (Ery II). PITPβ deficiency significantly reduced all affected populations, whereas PITPα deficiency did not have an effect. Furthermore, PITPβ deficiency reduced erythroid precursor expansion in Jak2 V617F mutant mice. The Jak2 V617F mice exhibited a markedly expanded population of colony-forming progenitors (CFU-e) in the bone marrow and spleen. PITPβ, but not PITPα, deficiency completely normalized CFU-e population in Jak2 V617F mice to WT level. We next analyzed the HSPC populations in these mice. Jak2 V617F mice have a 2-fold increase in Lineage-Sca-1+cKit+ (LSK) compartment in their bone marrow. We found that LSK expansion is largely due to an increase in erythroid/megakaryocyte-biased multipotent progenitors (MPP2) and myeloid-biased MPP3. LT-HSC as well as lymphoid-biased MPP4 were not affected. PITPβ deficiency restored both MPP2 and MPP3 populations to WT level. Furthermore, we analyzed the effect of PITPβ knockout on erythropoietin (EPO)-mediated progenitor cell growth. PITPβ deficiency significantly reduced EPO-dependent and cytokine-independent erythroid colony formation (CFU-E) of Jak2 V617F bone marrow. We then examined EPO-mediated JAK/STAT signaling in primary erythroid progenitors. Jak2 V617F conferred cytokine-independent phosphorylation of Stat5 in proerythroblasts (Ery I) and early basophilic erythroblasts (EryA), which was abrogated by PITPβ deficiency. Our findings revealed a previously unappreciated interaction between JAK2 V617F and the phosphatidylinositol transfer protein β. PITPβ KO mice have a normal survival rate and display normal hematopoiesis and erythropoiesis, indicating that PITPβ does not impact wildtype JAK2 signaling. Hence, our work points to a potential novel therapeutic avenue for the treatment of JAK2 V617F-mediated polycythemia vera or MPN in general.

  PublisherOA PDFDOI

• PB1503 Significant Effect of Hormonal Contraception on Venous Thromboembolism Risk in Women with Sickle Cell Disease, but is Estrogen the Culprit?

  Research and Practice in Thrombosis and Haemostasis · 2023-10-01

  articleOpen access

  Conclusion(s):Estrogen use in this transgender cohort was frequent, and although not significantly associated with CTE, a trend towards higher risk was observed.Even in young transgender women, addressing modifiable cardiovascular risk factors should be a critical priority.Prospective studies are needed to better understand the intrinsic risks of this population and risk reduction strategies.

  PublisherDOI

Recent grants

• NIH Grant R01HL110110

  NIH · $834k · 2016

• NIH Grant K11HL002464

  NIH · $460k · 1995

• NIH Grant P01HL120846

  NIH · $24.3M · 2019

• NIH Grant R29HL053545

  NIH · $428k · 1998

• NIH Grant R01HL083392

  NIH · $3.2M · 2015

Frequent coauthors

• Louise Lucast

  Yale University

  51 shared

• Laura A. Volpicelli‐Daley

  University of Alabama at Birmingham

  51 shared

• Laura E. Swan

  University of Liverpool

  49 shared

• Yuanbo Qin

  49 shared

• Cynthia Khoo

  Colorado State University

  49 shared

• He Wang

  49 shared

• Weijun Pan

  49 shared

• Sun‐Cheol Choi

  University of Ulsan

  49 shared

Labs

• Charles S. Abrams LaboratoryPI

Education

• Other, Bioengineering

  The Johns Hopkins University

  1980

• M.D., Medicine

  Yale University School of Medicine

  1984

Awards & honors

• Francis C. Wood Professor
• Chief, Non-Malignant Hematology, University of Pennsylvania…
• Director, Blood Center at PENN/CHOP
• Vice Chair for Research & Chief Scientific Officer, Universi…