American Society of Hematology

Special Scientific Symposia

These sessions will take place from Saturday through Monday and will feature transformative research with implications for scientific investigation and clinical practice across the field of hematology.

View Symposia Highlights From the 2017 Meeting

Challenging the Paradigms in Hematopoiesis

Saturday, December 1, 2018, 2:00 p.m. - 3:30 p.m.
San Diego Convention Center, Room 29C

Hematopoietic stem and progenitor cells proliferate and undergo lineage commitment to produce all types of white blood cells, red blood cells, and platelets. In the classic hierarchical model, hematopoiesis is maintained by self-renewing hematopoietic stem cells (HSCs) that proceed through a series of multipotent, oligopotent, and unipotent progenitors to make blood. This session will focus on the latest research in the field of hematopoiesis with an emphasis on challenges to this paradigm of gradual loss of potency in lineage fate decisions. Using data obtained through emerging technologies (e.g., single cell RNA sequencing, ATAC seq, and mass spectrometry to interrogate transcriptional profiles, epigenetic states, proteomes, and metabolomics), each speaker will challenge the classical dogma. Reaching a final all-inclusive model of hematopoiesis is complicated by the variety of species, cell sources, and analytical approaches used along with the inherent challenge in the continuum of hematopoiesis, where hematopoietic progenitors do not stop at discrete steps on single paths as classically drawn in hematopoietic hierarchy models. While controversies will likely remain, the novel discoveries that will be presented open exciting new avenues of basic science and clinical research.

Dr. John Dick will present data obtained from highly sensitive single cell assays, which bring into question the understanding of gradual loss of potency from multipotent and bipotent lineage progenitors. He will also discuss epigenetic and metabolomic data that define a unique quiescent HSC state as well as the potential for using this new understanding to define improved conditions for ex vivo maintenance and expansion of HSC.

Dr. Sten Eirik Jacobsen will discuss single cell transplantation data leading to a novel understanding of the functional potentials of hierarchically related but lineage-restricted fates of multipotent self-renewing HSCs.

Dr. Ana Cvejic will address novel lineage fate trajectories based on single cell transcriptome analysis in zebrafish. She will discuss how these findings parallel hematopoiesis in higher vertebrates including humans.

Chair:

Diane S. Krause, MD, PhD
Yale University
New Haven, CT

Speakers:

John E. Dick, PhD
University Health Network
Toronto, ON, Canada
Distinct Models of Hematopoiesis During Ontogeny

Sten Eirik W Jacobsen, MD,PhD
University of Oxford
Oxford, United Kingdom
Lineage Restriction of Multipotent Hematopoietic Stem Cells

Ana Cvejic, BSc, PhD
University of Cambridge
Cambridge, United Kingdom
Single Cell RNA Sequencing Provides Insights Into Fate Decisions in Hematopoiesis

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Glycobiology in Hematology: The New Frontier

Sunday, December 2, 2018, 9:30 a.m. - 11:00 a.m.
San Diego Convention Center, Room 29C

While scientists and clinicians have successfully applied new and precision-driven treatments to fundamental building blocks of life (nucleic acids, lipids, and proteins), the science of glycans (carbohydrates) has received the least attention. This session will focus on diverse glycan functions and their potential as therapeutic targets in multiple blood lineages.

Dr. Sean Stowell will discuss a novel mechanism which shows that the formation of anti-ABO(H) antibodies is dependent upon individual gut bacteria expressing ABO-like glycans. Anti-ABO(H) antibodies, a major barrier to effective transfusion and transplantation, were described more than a century ago. However, mechanisms for anti-ABO(H) antibody formation remain elusive. Remarkably, animals exposed to a single strain of microbe isolated from anti-blood group positive animals developed robust causing hemolytic transfusion reaction following incompatible RBC transfusion. Thus, manipulation of microbial flora may provide a novel and unique precision approach to prevent anti-ABO(H) antibody development in patients requiring transplantation or chronic transfusion. Dr. Stowell will address how gut microbiota with distinct ABO-like decoration promotes the development of anti-ABO antibodies and how the relative abundance of microbes decorated with blood group-like antigens predicts the level of anti-blood group antibodies.

Dr. Karin Hoffmeister will discuss how aberrant megakaryocytes' sialylation affects the bone marrow niche and immune cell regulation of platelet production. Circulating platelet numbers are tightly regulated to avoid bleeding or thrombosis. Glycans have been intimately linked with platelet count regulation. Aberrant platelet glycans bind to the Ashwell-Morell receptor on hepatocytes and hepatic macrophages lectins leading to their clearance. However, little interest has been directed to the role of glycans in thrombopoiesis and in the bone marrow environment. Dr. Hoffmeister will discuss how aberrant terminal glycan structures (loss of sialic acid) on megakaryocytes affect thrombopoiesis and the bone marrow niche environment. She will elucidate the role of specific subsets of immune cells in regulating late stage thrombopoiesis of megakaryocytes expressing tumor-associated antigens, such as the Thomsen-Friedenreich antigen (O-linked glycans lacking sialic acid).

Dr. Robert Sackstein will review how cell-surface glycoengineering to enforce E-selectin ligand expression may improve efficacy and safety for cell-based therapeutics. Culture-expanded immunoregulatory cells and genetically altered cells are currently used to treat hematologic diseases. While great attention has been given to cell collection and propagation as well as genetic cell manipulation, little interest is directed to cell trafficking and targeted cell delivery to sites of therapeutic need. Improved cell delivery would ameliorate the incidence and severity of treatment-related adverse events and dramatically curtail cell acquisition/expansion costs. Cell migration depends on the ability of circulating cells to fasten with target tissue endothelial cells. Blood cells express potent “homing receptors” (E-selectin ligands) with discreet glycan determinants that mediate this process by engaging with endothelial E-selectin, which is constitutively displayed on marrow microvascular endothelial cells and which is inducibly expressed in tumor endothelial beds and upon inflammation/tissue injury. Dr. Sackstein will also discuss the structural biology of E-selectin ligands and current data on their expression on culture-expanded T cells and stem cells.

Chair:

Karin M. Hoffmeister, MD
BloodCenter of Wisconsin
Milwaukee, WI

Speakers:

Sean R. Stowell, MD, PhD
Emory University
Atlanta, GA
Exposure to Bacterial Glycans Underlies the Development of Anti-ABO Antibodies

Karin M. Hoffmeister, MD
BloodCenter of Wisconsin
Milwaukee, WI
Novel Roles of Megakaryocyte and Platelet Glycans in Regulating the Bone Marrow Niche

Robert Sackstein, MD
Harvard Medical School
Boston, MA
Glycoengineering and Optimization of CAR T Cells, Regulatory T Cells, and Human Stem Cells

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RNA Modifications in Hematology

Saturday, December 1, 2018, 2:00 p.m. - 3:30 p.m.
San Diego Convention Center, Room 28D

RNA modifications are emerging as important novel mechanisms of molecular regulation in normal and malignant hematopoiesis. This session will focus on the latest research on the roles of RNA methylation and RNA editing in leukemia pathogenesis.

Dr. Chuan He will discuss recent advances in the biology of RNA methylation, with a focus on reversible RNA methylation in tuning gene expression regulation. RNA modifications have been shown to be dynamic and have critical regulatory roles that affect a wide range of biological processes. The internal N6-methyladenosine (m6A) modification in messenger RNA is one of the most prevalent RNA modifications in eukaryotes. Dr. He will present recent discoveries on how m6A affects mRNA stability and translation. He will also discuss aberrant RNA m6A methylation in the context of human leukemia.

Dr. Michael Kharas will review the latest functional and mechanistic insights of m6A methylation in normal hematopoiesis and myeloid leukemia. The m6A RNA methylation writer complex is responsible for placing m6A marks on mRNAs, and several components have recently been demonstrated to be required for myeloid leukemia. Additionally, RNA methylation and m6A modifications have been demonstrated to be critical for controlling the differentiation state. Dr. Kharas will discuss the importance of RNA methylation regulators in leukemia and will further explore how RNA methylation can alter hematopoietic stem cell self-renewal and cellular identity.  

Dr. Catriona Jamieson will discuss recent developments in the biology of RNA editing. While seminal studies show that somatic DNA mutations promote clonal evolution of cancer, the concept of the “epitranscriptome” suggests that post-transcriptional adenosine-to-inosine (A-to-I) RNA modifications, which are governed by adenosine deaminase associated with RNA (ADAR), dynamically determine gene expression diversity in response to environmental inputs during cancer progression. Dr. Jamieson will address the role of direct inhibition of ADAR1 in malignant microenvironments and review current studies of RNA editing in pre-cancer stem cell evolution to fully potent self-renewing cancer stem cells.

Chair:

Ulrich G. Steidl, MD, PhD
Albert Einstein College of Medicine
New York, NY

Speakers:

Chuan He, PhD
The University of Chicago/HHMI
Chicago, IL
The Biology of RNA Methylation

Michael G. Kharas, PhD
Memorial Sloan Kettering Cancer Center
New York, NY
RNA Methylation in Normal and Malignant Hematopoiesis

Catriona Jamieson, MD, PhD
University of California, San Diego
La Jolla, CA
Biology of RNA Editing

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Special Symposium on the Basic Science of Hemostasis and Thrombosis

Monday, December 3, 2018, 4:30 p.m. - 6:30 p.m.
San Diego Convention Center, Room 30D

This session will focus on the role of inflammation in the pathophysiologic events surrounding abnormal hemostasis and pathologic thrombosis. Speakers will discuss the unique mechanisms by which different components of the hemostatic system influence the development and progression of inflammatory disorders.

Dr. Katerina Akassoglou will discuss the role of fibrinogen in neuroinflammation, neurodegeneration, and inhibition of neural repair. She will emphasize novel studies focused on imaging fibrinogen in the inflammatory milieu.

Dr. Samir Parikh will discuss the role of the endothelial receptor and tyrosine kinase TIE2 in the regulation of inflammatory thrombus formation. TIE2, the physiologic receptors for angiopoietins 1 and 2, is highly expressed in the vascular endothelium, where its tonic activation maintains vascular homeostasis. Dr. Parikh will discuss how dysregulation of this system in patients with vascular inflammation contributes to disseminated intravascular coagulation and thrombus formation.

Dr. Steffen Massberg will discuss the ability of platelets to collect and bundle bacteria during infection. Platelets are recruited to sites of inflammation and infection to have immunologic function. There, they directly neutralize pathogens by releasing anti-microbial mediators and/or physically trapping and encapsulating microorganisms, thus preventing their dissemination. Dr. Massberg will also discuss a novel autonomous single platelet function, which is to migrate, collect, and bundle bacteria in order to stimulate neutrophil activation.

Moua Yang will present the Mary Rodes Gibson Memorial Award-winning abstract, as the trainee with the highest-scoring abstract submitted in the field of hemostasis and thrombosis for the ASH annual meeting (Abstract #867).

Immediately following this session, you are invited to attend the ASH Hemostasis and Thrombosis Community Reception!  It will take place across the hall, outside on the East Terrace.  Network with your colleagues from the hemostasis and thrombosis community while you enjoy specialty cocktails, hors d’oeuvres, and beautiful views of San Diego Bay and Coronado Island.  Your meeting badge is required to attend.

Co-Chairs:

Karin M. Hoffmeister, MD
BloodCenter of Wisconsin
Milwaukee, WI

Keith R. McCrae, MD
Cleveland Clinic
Cleveland, OH

Alvin H. Schmaier, MD
Case Western Reserve University
Cleveland, OH

Speakers:

Steffen Massberg
Ludwig Maximilians University of Munich
Munich, Germany
Platelet and Immunology: Migrating Platelets Collect and Bundle Bacteria

Samir Parikh, MD
Beth Israel Deaconess Medical Center
Boston, MA
TIE2 Modulates Vascular Inflammation and Thrombus Formation

Katerina Akassoglou, PhD
University of California – San Francisco
San Francisco, CA
Fibrinogen in Neurologic Diseases: Mechanism, Imaging, and Therapeutics

Moua Yang, PhD
Vascular Pathobiology
Milwaukee, WI
Platelet CD36 Promotes ERK5 and Caspase-Dependent Procoagulant Phosphatidylserine Externalization and In Vivo Fibrin Formation in Dyslipidemia

Alvin H. Schmaier, MD
Case Western Reserve University
Cleveland, OH
Best of ASH in Hemostasis and Thrombosis 1

Keith R. McCrae, MD
Cleveland Clinic
Cleveland, OH
Best of ASH in Hemostasis and Thrombosis 2

Karin M. Hoffmeister, MD
Blood Research Center Institute, Blood Center of Wisconsin
Milwaukee, WI
Best of ASH in Hemostasis and Thrombosis 3

Other Scientific Sessions

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