Scientific Program

The Scientific Program will be held Saturday, December 7, and Sunday, December 8, with each session being offered twice. A question-and-answer period will occur at the end of each individual speaker presentation.

Invited abstracts of these sessions will be available in the annual meeting app and in the online meeting planner.

2019 Scientific Program Co-Chairs

The Scientific Program will be held Saturday, December 7, and Sunday, December 8, with each session being offered twice. A question-and-answer period will occur at the end of each individual speaker presentation.

Invited abstracts of these sessions will be available in the annual meeting app and in the online meeting planner.

Ad Hoc Scientific Committee on Epigenetics and Genomics

Chromatin Structure in Development and Disease

Sessions Offered Twice:
Sunday, December 8, 2019 9:30 a.m. - 11:00 a.m. Orange County Convention Center, Tangerine 3 (WF3-4), Level 2	Sunday, December 8, 2019 4:30 p.m. - 6:00 p.m. Orange County Convention Center, Tangerine 3 (WF3-4), Level 2

The three-dimensional state of the genome is dynamic and critical in the regulation of gene expression. Recent technological advances have provided an unprecedented view of how the genome is interconnected and how this process changes as cells differentiate or undergo malignant transformation. This session will discuss cutting-edge genomic techniques for understanding the three-dimensional state of the genome and how genome organization and nuclear architecture are important in normal hematopoiesis as well as malignant hematopoietic cells.

Dr. Gerd Blobel will provide an overview of the organizing principles of chromatin in the nucleus of the cell and how their understanding can be useful in the context of clinically relevant questions such as the regulation of the globin locus. This will be accompanied by a brief introduction to the technologies that are being used in the field, including methods based on chromosome conformation capture.

Dr. Elisa Oricchio will discuss how genomic lesions modify the chromatin tridimensional organization and their contribution to lymphoma development and progression. Recently, her lab has demonstrated that in non-Hodgkin lymphoma, a significant interplay exists between the compartmentalization of the genome into topologically associating domains (TADs) and the epigenetic and transcriptional changes mediated by mutated EZH2. Indeed, EZH2 mutations drive the aberrant increase of H3K27me3 within specific TADs, resulting in loss of promoter-promoter interactions, synergistic silencing of multiple tumor suppressors and, thus, increased B-cell proliferation and tumor aggressiveness. She will present recent analyses in which her lab combined high-throughput chromatin conformation capture data (Hi-C) in lymphoma cells with whole genome sequencing and transcriptional profiles of primary patient samples to uncover new oncogenic mechanisms that can represent the stepping stone for the design of new therapeutic approaches.

Dr. Erez Lieberman Aiden will discuss his work mapping the three-dimensional architecture of the human genome. Stretched out from end-to-end, the human genome-a sequence of three billion chemical letters inscribed in a molecule called DNA-is over two meters long. Famously, short stretches of DNA fold into a double helix, which wind around histone proteins to form the 10nm fiber. But what about longer pieces? Does the genome's fold influence function? How does the information contained in such an ultra-dense packing even remain accessible? Dr. Aiden will describe his work developing Hi-C and more recently in-situ Hi-C, which use proximity ligation to transform pairs of physically adjacent DNA loci into chimeric DNA sequences. Sequencing a library of such chimeras makes it possible to create genome-wide maps of physical contacts between pairs of loci, thus revealing three-dimensional features of genome folding. Dr. Aiden will also discuss the biophysical mechanisms that underlie chromatin looping.

Chair:

Kathrin M. Bernt, MD
Children's Hospital of Philadelphia
Philadelphia, PA

Speakers:

Gerd A. Blobel, MD, PhD
University of Pennsylvania
Philadelphia, PA
Chromatin Architecture Through the Lens of the Cell Cycle

Elisa Oricchio, DPhil
Ecole Polytechnique Federale de Lausanne
Lausanne, Switzerland
Histone Modifications in Development and Malignancy

Erez Lieberman Aiden, PhD
Baylor College of Medicine
Houston, TX
Three-D Codes in the Human Genome

 

Joint Session: Scientific Committee on Bone Marrow Failure & Scientific Committee on Blood Disorders in Childhood

Molecular Mechanisms of Bone Marrow Failure

Sessions Offered Twice:
Saturday, December 7, 2019 9:30 a.m. - 11:30 a.m. Orange County Convention Center, W331, Level 3	Sunday, December 8, 2019 9:30 a.m. - 11:30 a.m. Orange County Convention Center, W331, Level 3

Our understanding of the mechanisms driving bone marrow failure has increased substantially over time. While these are rare disorders, these insights are critical for patient management and for understanding bone marrow pathophysiology in general. In this session, we will highlight some of the latest discoveries in the field.

Dr. Agata Smogorzewska will review the genetics of Fanconi anemia and the mechanism of DNA repair that fails in the disease. She will also discuss new insights into the endogenous sources of DNA damage associated with DNA replication that when left un-repaired lead to bone marrow failure and leukemia.

Dr. Jeffery Klco will discuss germline mutations in two interferon-inducible genes located on human chromosome 7 (SAMD9 and SAMD9L), which have been reported in pediatric, as well as adult myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) and bone marrow failure syndromes. The mechanisms of how these mutations result in abnormal hematopoiesis and potentially lead to MDS/AML are currently under investigation and will be discussed.

Dr. Katherine MacNamara will discuss novel mechanisms through which interferons contribute to bone marrow failure and aplastic anemia. Interferons are protective during many infections by driving expression of antimicrobial effector molecules, but also contribute to hematopoietic suppression through direct effects on hematopoietic cells as well as alterations to the bone marrow microenvironment.

Dr. Jennifer Trowbridge will highlight the discovery of novel factors and mechanisms causing HSC aging. She will address the relevance of these processes and mechanisms to bone marrow failure development as well as how they may be manipulated to prevent physiological aging and disease.

Co-Chairs:

Anupama Narla, MD
Stanford University
Stanford, CA

Alison A. Bertuch, MD, PhD
Baylor College of Medicine
Houston, TX

Speakers:

Agata Smogorzewska
The Rockefeller University
New York, NY
Fanconi Anemia: A Paradigm for Understanding DNA Repair During Replication.

Jeffery M. Klco, MD, PhD
St. Jude Children's Research Hospital
Memphis, TN
Role of Genetic Evolution and Germline Mutations in SAMD9 and SAMD9L Genes

Katherine C. MacNamara, PhD
Albany Medical College
Albany, NY
The Role of Interferon, Inflammation and Infection in Aplastic Anemia

Jennifer Trowbridge, PhD
The Jackson Laboratory
Bar Harbor, ME
Intrinsic and Extrinsic Factors Driving Hematopoietic Stem Cell Aging and Bone Marrow Failure

Joint Session: Scientific Committee on Hematopathology and Clinical Laboratory Hematology & Scientific Committee on Stem Cells and Regenerative Medicine

Insights into Hematopoietic Stem Cell Origin, Differentiation and Malignancy Provided by Single Cell Approaches

Sessions Offered Twice:
Saturday, December 7, 2019 9:30 a.m. - 11:30 a.m. Orange County Convention Center, W224, Level 2	Sunday, December 8, 2019 4:30 p.m. - 6:30 p.m. Orange County Convention Center, W224, Level 2

Cellular hierarchies, function, and evolution to malignancy of the hematopoietic system have been studied in bulk or purified cell populations. The complex heterogeneity of the hematopoietic system can now be resolved by single cell genomics. This session will present cutting-edge applications of single cell analyses focusing on hematopoietic stem cell (HSC) origin, deconstruction of the immune system, and cancer evolution.

Dr. Dan Landau will describe a single-cell multi-modality toolkit and apply it to chart the evolutionary history and developmental topographies of normal and malignant blood cells. Vast intra-tumoral genetic diversity provides the critical substrate for cancer to evolve and adapt to the selective pressures provided by effective therapy. In addition, epigenetic changes in cancer may be similar to the process of genetic diversification, in which stochastic trial and error leads to rare fitness enhancing events. These studies demonstrate the need to integrate genetic, epigenetic, and transcriptional information in the study of cancer evolution.

Dr. Nancy Speck will discuss HSC and progenitor cell emergence from hemogenic endothelial cells in the embryo. Specifically, she will describe lessons learned from the analysis of HSC formation in the mouse embryo using scRNA-seq. Once formed, progenitor cells and HSCs are released into the circulation, where they colonize the fetal liver, and immature (pre-HSCs) mature into fetal liver HSCs. Given the rarity of pre-HSCs and their precursors in the embryo, scRNA-seq is a powerful approach for identifying these rare cells, and for characterizing the developmental trajectory leading from endothelial cells to hematopoietic progenitors and fetal HSCs.

Dr. Ido Amit will discuss the immune system as a complex, dynamic, and plastic network composed of various interacting cell types that are constantly sensing and responding to environmental cues. Accumulating evidence indicates that current technologies and classification schemes are limited in their ability to account for the functional heterogeneity of immune processes. To that end, Dr. Amit will discuss how single cell genomics holds the potential to revolutionize the way complex immune cell assemblies are characterized including their spatial organization, dynamics, clonal distribution, pathways, and crosstalk. He will also address the impact of forthcoming technological and analytical advances in single cell genomics.

Dr. Adam Mead will discuss the intratumoral heterogeneity challenges in cancer medicine, including therapy-resistance, disease progression/evolution, and relapse after seemingly effective treatments. This heterogeneity is driven not only by tumor genetics, but also by other cell states, such as rare cancer stem cells (CSCs). Single cell genomic techniques are ideally placed to unravel such multi-layered heterogeneity and provide entirely new insights into cancer biology. Arguably, the best characterized CSC-propagated malignancies are chronic myeloid neoplasms, which are excellent tractable disease models for cancer biology. Dr. Mead will specifically review new insights that have been gained through single cell multi-omic analysis of CSC populations in chronic myeloid neoplasms and address how this might be applied to improve precision medicine approaches and outcomes for patients.

Co-Chairs:

James Palis, MD
University of Rochester Medical Center
Rochester, NY

Peter Valk, PhD
Erasmus University Medical Center
Rotterdam, Netherlands

Speakers:

Dan A. Landau, MD
New York Genome Center
New York, NY
Single Cell Approaches - Drilling Down Deeper Using Technology and Integrated Data Analyses

Nancy Speck, PhD
University of Pennsylvania
Philadelphia, PA
Developmental Biology of the Blood System

Ido Amit
Weizmann Institute of Science
Rehovot, Israel
The Power of ONE: Immunology in the Age of Single Cell Genomics

Adam J. Mead, MBBChir
University of Oxford
Oxford, United Kingdom
Unravelling Heterogeneity of Stem and Progenitor Cells in Myeloid Neoplasms Through Single Cell Multi-omics

Scientific Committee on Hematopoiesis

Dynamic Change of the Hematopoietic Stem Cell Niche

Sessions Offered Twice:
Saturday, December 7, 2019 7:30 a.m. - 9:00 a.m. Orange County Convention Center, W314, Level 3	Saturday, December 7, 2019 2:00 p.m. - 3:30 p.m. Orange County Convention Center, W314, Level 3

Ever since the conceptualization of the hematopoietic stem cell (HSC) niche by Schofield in 1978, much of niche research has focused on the identification of the most potent and influential niche cells within the bone marrow (BM). However, given that different hematopoietic stress factors dramatically impact the HSC niche, much is still to be learned about the heterogeneity, dynamics, function, and interactions of niche cells. To that end, this session will examine novel methods (e.g., in vivo live imaging, and mass spectrometry-based analyses of soluble factors or single cell niche dissection), that allow for the detection of minute changes on reserve and active HSCs and niche cells under short and long-term hematopoietic stress.

Dr. Hitoshi Takizawa will discuss how dormant HSCs are activated to self-renew and differentiate to increase blood production upon enhanced hematopoietic need. It remains unclear how HSCs and progenitor cells (HSPCs) integrate the peripheral demand signal to facilitate hematopoietic production and what the biological consequence of HSPCs activation is on cell fate decision. To that end, he will also discuss the mechanistic insights on how HSPCs sense pathogen insult through innate immune receptors and orchestrate hematopoiesis for host defense and tissue homeostasis.

Dr. Marieke Essers will discuss infections associated with extensive consumption of differentiated hematopoietic cells, representing a high risk for health. The mechanisms coordinating the rapid and efficient regeneration of these differentiated cells during such stress conditions remain unclear. In addition to identifying how HSCs respond under inflammatory conditions, she will also focus on investigating the response of the BM niche to inflammatory stress and how different components of the BM niche support the response of quiescent HSCs to inflammatory stress in vivo.

Dr. Tannishtha Reya will address how high-resolution in vivo imaging can be used to map normal stem cell behavior and interactions within living animals. She will describe how these interactions are driven by adhesive signals, and how they change during cancer formation. She will also highlight mechanisms that drive therapy resistance in the treatment of cancers. Dr. Reya's research focuses on the signals that control stem cell self-renewal and how these signals are hijacked in cancer. Using a series of genetic models, she has studied how classic developmental signaling pathways influence hematopoietic stem cell growth and regeneration as well as leukemia development when such pathways are dysregulated. Through this work she has determined that the cell fate determinant Musashi, plays a critical role in driving progression of hematologic malignancies and solid cancer and can be potential target for diagnostics and therapy.

Chair:

Toshio Suda, MD, PhD
National University of Singapore
Singapore, Singapore

Speakers:

Hitoshi Takizawa, PhD
Kumamoto University
Kumamoto City, Japan
Innate Immune Signal-Regulated Hematopoiesis

Marieke A. G. Essers, PhD
German Cancer Research Center
Heidelberg, Germany
Inflammation Mediated Bone Marrow Remodeling

Tannishtha Reya, PhD
University of California-San Diego
La Jolla, CA
Mapping Stem Cell Dependencies in Cancer Heterogeneity and Therapy Resistance

Scientific Committee on Hemostasis

Blood Coagulation: From Structure and Function to Therapeutics

Sessions Offered Twice:
Saturday, December 7, 2019 9:30 a.m. - 11:00 a.m. Orange County Convention Center, W311, Level 3	Sunday, December 8, 2019 7:30 a.m. - 9:00 a.m. Orange County Convention Center, W308, Level 3

The past two decades have seen major advances in the reactions of coagulation from the perspective of novel insights into mechanisms and the uncovering of new regulatory pathways or strategies. These advances bear on the next generation of approaches to modulate the reactions of coagulation for therapeutic gain. This session will focus on new insights into structure and function of the coagulation reactions as well as translation into novel therapeutic strategies.

Dr. Bruce Sullenger will describe how properties of nucleic acids can be employed to generate RNA aptamers that function as rapidly reversible inhibitors of coagulation factors and platelet proteins. He will discuss combinatorial chemistry methods that have been employed to generate nucleic acid ligands that can act as specific inhibitors of many proteins involved in hemostasis and thrombosis. The mechanism(s) of such inhibition will be addressed as well as how this understanding is guiding the development of the next generation of such inhibitors. Finally, Dr. Sullenger will present preclinical and clinical studies evaluating such therapeutics and their reversal agents.

Dr. Peter Lenting will discuss how the proteases that act in the coagulation cascade differ in catalytic capacity and how they frequently need cofactors to achieve physiologically relevant function. He will focus on factor IXa and the increased bleeding associated with the functional absence of its cofactor factor VIIIa. Whereas cofactor deficiency can be corrected via replacement therapy, the use of purified cofactor concentrates is associated with several limitations. Some of these limitations have been resolved by the development of alternate molecules with cofactor-like activities. Dr. Lenting will also discuss the similarities and dissimilarities between the original cofactor and cofactor-mimetics.

Dr. Nicola Mutch will focus on the relatively recent advances engendered by the discoveries of polyphosphate (polyP) as a modulator of the coagulation reactions. PolyP is a biopolymer of negatively charged phosphate residues that is ubiquitous in nature and varies in chain length according to the organism and tissue in which it is synthesized. PolyP with a defined chain length of 80-100 phosphates is contained within the dense granules of platelets and is released following agonist stimulation. Dr. Mutch will discuss how platelet-derived polyP affects the coagulation cascade at several distinct points to promote clot formation. She will also discuss recent finding suggesting that polyP retained on the activated platelet membrane further modifies the function of this biopolymer in coagulation.

Co-Chairs:

Sriram M. Krishnaswamy, PhD
Children's Hosp. of Phila.
Philadelphia, PA

Shannon L. Meeks, MD
Emory University
Atlanta, GA

Speakers:

Bruce A. Sullenger
Duke University
Durham, NC
Aptamers as Rapid Onset and Rapidly Reversible Antithrombotic Agents

Peter J. Lenting, PhD
Inserm U 1176, Université Paris-Saclay, Université Paris-Saclay
Le-Kremlin-Bicetre, France
Cofactor and Cofactor Mimetics

Nicola J. Mutch, BSc, PhD
University of Aberdeen
Aberdeen, United Kingdom
Regulation of Coagulation by Polyphosphate

Scientific Committee on Immunology and Host Defense

Stromal Cell Immune Regulation in the Microenvironment

Sessions Offered Twice:
Sunday, December 8, 2019 7:30 a.m. - 9:00 a.m. Orange County Convention Center, Tangerine 1 (WF1), Level 2	Sunday, December 8, 2019 4:30 p.m. - 6:00 p.m. Orange County Convention Center, W230, Level 2

Until recently, effective immunotherapy for the treatment of hematologic malignancies has been observed largely within the context of graft-versus-leukemia effects after allogeneic stem cell transplantation. The introduction of checkpoint inhibitors and chimeric antigen receptor T cells to the treatment of hematologic malignancies have resulted in remarkable responses in some patients but therapy still fails in a significant proportion. It is becoming increasingly clear that tumors and their stromal microenvironment possess an array of mechanisms to subvert effective immune responses. This session will discuss recent advances fostering the understanding of how tumor and stromal cells act to regulate immunity and how therapeutic interventions targeting these suppressive pathways may be harnessed to improve immunotherapy outcomes.

Dr. Kai Wucherpfennig will discuss therapeutic approaches to deal with resistance to cancer immunotherapy. In particular, the presentation will focus on a novel mAb his lab has developed that inhibits an escape pathway from natural killer (NK) cell-mediated tumor immunity. Tumor cells express the stress ligands MICA and MICB that are recognized by the NKG2D receptor on NK cells and CD8 T cells. Escape is mediated through proteolytic shedding of MICA and MICB by tumor cells. His research has found that inhibition of proteolytic shedding of MICA and MICB with a mAb induces anti-tumor immunity against metastases.

Dr. Melody Swartz will discuss lymphatic activation in the tumor microenvironment and its role on overall immunity. She will also describe how knowledge gained from understanding lymphatic control could influence the development of novel immunotherapeutic approaches and in vitro model systems that could serve as the platform for studying the perfused tumor microenvironment.

Dr. Ivan Maillard will review emerging evidence supporting a critical role for Notch ligands expressed by specialized subsets of non-hematopoietic stromal cells in secondary lymphoid organs, both during T and B cell immune responses and in lymphoma pathogenesis. Stromal Notch ligands play an essential role to prime pathogenic T cells through Notch signaling at the onset of graft-versus-host disease. Alloreactive T cells interact with Notch ligands in stromal cell niches within days after bone marrow transplantation, a finding of major immunobiological and translational significance. Moreover, many mature B and T cell lymphomas demonstrate oncogenic Notch activation as a result of lymphoma cell interactions with microenvironmental Notch ligands in secondary lymphoid organs, borrowing from the playbook of normal lymphocytes. Thus, stromal Notch ligands represent a new regulatory input relevant to multiple disease conditions in hematology.

Chair:

Geoffrey R. Hill, MD
Fred Hutchinson Cancer Research Center
Seattle, WA

Speakers:

Kai W. Wucherpfennig
Dana-Farber Cancer Institute
Boston, MA
Immune-Tumor Interactions in Resistance to Cancer Immunotherapy

Melody A. Swartz
University of Chicago
Chicago, IL
Lymphatic Control of the Tumor Immune Microenvironment

Ivan Maillard, MD,PhD
University of Pennsylvania
Philadelphia, PA
From Graft-Versus-Host Disease to Lymphoma Pathogenesis: Emerging Roles for Stromal Notch Ligands in Hematology

Scientific Committee on Iron and Heme

Pumping Iron, Handling Heme: Forging New Links in Health and Disease

Sessions Offered Twice:
Saturday, December 7, 2019 9:30 a.m. - 11:00 a.m. Orange County Convention Center, Valencia D (W415D), Level 4	Sunday, December 8, 2019 7:30 a.m. - 9:00 a.m. Orange County Convention Center, W331, Level 3

The major portion of iron in the body is found in hemoglobin, reflecting the intimate connection between iron metabolism and heme synthesis. Beyond the traditional area of erythropoiesis, proper pumping of iron and handling of heme is essential for a variety of biological processes such as mitochondrial respiration, cell proliferation, and DNA synthesis and repair. This session will present new insights into iron homeostasis and heme utilization pathways as well as demonstrate the importance of iron restriction for infection control.

Dr. Emanuela Tolosano will explain heme's pivotal role in cell energy metabolism, including its role as a cofactor for respiratory chain complexes and interactions with translocases responsible for the ADP/ATP exchange between mitochondria and cytosol. She will describe heme biosynthesis and the mechanisms of heme trafficking at the cellular level. In addition, Dr. Tolosano will highlight data demonstrating the existence of a heme biosynthesis/heme export axis that contributes to the regulation of the tricarboxylic acid (TCA) cycle as well as oxidative metabolism and discuss the implications for cell proliferation and survival. Finally, she will emphasize that heme synthesis is a major cellular iron-consuming process, competing for iron with the mitochondrial assembly of iron-sulfur clusters, which are crucial cofactors for electron transport chain complexes and some TCA cycle enzymes.

Dr. Jodie Babitt will discuss how the liver orchestrates systemic iron homeostasis by producing the iron hormone hepcidin, which regulates expression and function of the iron exporter ferroportin to control iron entry into circulation from the gut, iron recycling macrophages, and hepatocyte stores. Hepcidin production in the liver is regulated by a number of systemic cues that indicate the need for more or less iron, including serum and tissue iron levels, iron demand of erythropoietic cells, and inflammation. A pivotal pathway by which the liver regulates hepcidin transcription in response to these diverse signals is the bone morphogenetic protein (BMP)-Smad signaling pathway. This talk will focus on recent insights into how BMP-Smad signaling coordinates hepcidin production to control systemic iron homeostasis.

Dr. Tracey Rouault will address novel insights into molecular mechanisms of iron handling and illustrate the important link between iron homeostasis and infection control. Her research determined that mature red blood cells contain large amounts of the iron exporter, ferroportin, and she believes that this iron exporter transfers iron released from oxidation of heme to protect the red blood cells from iron-related oxidative damage. There is a mutation in ferroportin, Q248H, which leads to increased ferroportin mediated iron export relative to controls. It appears to confer a selective advantage in malaria endemic areas because low levels of free iron in red blood cells protects from malaria by preventing the parasites from acquiring enough iron to grow and divide.

Co-Chairs:

Elizabeta Nemeth, PhD
University of California-Los Angeles
Los Angeles, CA

Norbert Gattermann, MD
Heinrich-Heine-Universitat
Dusseldorf, Germany

Speakers:

Emanuela Tolosano, PhD
University of Torino
Turin, Italy
New Insights into Heme Utilization Pathways

Jodie L. Babitt, MD
Massachusetts General Hospital
Boston, MA
Paracrine Bone Morphogenetic Protein Signaling in Iron Homeostasis

Elizabeta Nemeth, PhD
University of California, Los Angeles
Los Angeles, CA
Role of Iron and Hepcidin in Infections

Scientific Committee on Lymphoid Neoplasia

Hodgkin Lymphoma: Genes to Microenvironment to Immunotherapy

Sessions Offered Twice:
Saturday, December 7, 2019 7:30 a.m. - 9:00 a.m. Orange County Convention Center, W224, Level 2	Saturday, December 7, 2019 4:00 p.m. - 5:30 p.m. Orange County Convention Center, Tangerine 1 (WF1), Level 2

Unique amongst lymphomas, classical Hodgkin lymphoma is characterized by a relatively rare population of malignant Hodgkin Reed-Sternberg cells surrounded by a dense tumor immune microenvironment (TME), the role of which remains undefined. The composition of the TME includes T and B lymphocytes, macrophages, plasma cells, eosinophils, and stroma, with the nature of the infiltrate varying by histological subtype.

Dr. Ralf Küppers will review how overcoming challenges of targeted deep sequencing or whole exome sequencing created by the rarity of Reed-Sternberg cells within tumor specimens has led to insights into the landscape of somatic mutations involved in the pathogenesis of Hodgkin lymphoma. Initial results have highlighted the importance of genetic dysregulation of the NF-?B and JAK/STAT pathways and various means of immune evasion. These genetic factors may directly and indirectly influence the TME. He will also outline additional work using exome sequencing that has elucidated the molecular pathogenesis and patterns of shared and distinct mutations in composite Hodgkin and B-cell non-Hodgkin lymphomas.

Dr. Maher Gandhi will summarize current knowledge of the Hodgkin TME and immune checkpoints in classical Hodgkin lymphoma in light of the reignited debate about the role of adaptive and innate immunity in this disease. He will also outline mechanisms by which Reed-Sternberg cells are able to evade host anti-tumor immunity and describe how this knowledge may lead to new insights in understanding prognosis and improving therapy.

Dr. Barbara Savoldo will highlight key aspects of innovations in immunotherapy that are relevant to the treatment of Hodgkin lymphoma including novel agents, combinations, and strategies to overcome treatment resistance. Engineering of chimeric antigen receptors (CARs) in T cells has propelled the clinical application of tumor specific cells in B cell malignancies, and this approach is now moving to Hodgkin lymphoma by targeting CD30. Given the unique biology of Hodgkin lymphoma, Dr. Savoldo will summarize early clinical data and describe CAR modifications which may enhance migration and trafficking to the tumor for greater therapeutic effect.

Co-Chairs:

Susan L. Slager, PhD
Mayo Clinic
Rochester, MN

John P. Leonard, MD
Weill Cornell Medical College
New York, NY

Speakers:

Ralf Küppers, PhD
University of Duisburg-Essen
Essen, Germany
Genomic Analysis of Hodgkin Lymphoma

Maher K. Gandhi, PhD,FRACP,FRCPath
University of Queensland
Brisbane, Australia
A Complicated Neighborhood: Insights into the Hodgkin Lymphoma Microenvironment

Barbara Savoldo, MD, PhD
University of North Carolina at Chapel Hill
Chapel Hill, NC
Novel Immunotherapeutic Approaches for Hodgkin Lymphoma

Scientific Committee on Megakaryocytes and Platelets

Filling a Clinical Void: Engineering Platelets In Vitro

Sessions Offered Twice:
Saturday, December 7, 2019 4:00 p.m. - 5:30 p.m. Orange County Convention Center, W315, Level 3	Sunday, December 8, 2019 4:30 p.m. - 6:00 p.m. Orange County Convention Center, W315, Level 3

Humans produce approximately 10¹¹ platelets daily, which are vital for hemostasis and a number of other essential biological processes. Platelet transfusions are a critical lifesaving therapy for thousands of patients every year, yet are plagued by chronic shortages, limited portability and shelf-life, and risk of contamination. There is an urgent need to develop technologies that will replace donor platelets with a more stable and reliable product. This session will present cutting-edge technologies with the potential to either reproduce thrombopoiesis in vitro or the function of platelets in vivo, thus reducing dependence on limited donation capacity.

Dr. Alessandra Balduini will discuss the use of a promising biomaterial for bone marrow tissue engineering, silk fibroin, derived from Bombyx mori silkworm cocoons. Silk fibroin possesses tunable architecture and mechanical properties. It has the capacity to incorporate labile compounds without loss of bioactivity (e.g., extracellular matrix components) and has a demonstrated ability to support platelet production without premature activation. Dr. Balduini's group has exploited these silk biomaterials to develop a series of three-D scalable systems that reproduce the structure of human bone marrow and support efficient platelet release from megakaryocytes. This novel model is a promising new technology for reproducing the bone marrow and studying thrombopoiesis in vitro under both physiologic and pathologic conditions.

Dr. Anirban Sen Gupta will present on the development of nanoparticle-based "synthetic platelet" technologies that modularly mimic and amplify platelet-mediated mechanisms of hemostasis. His work envisions that these technologies can allow large scale manufacture, reproducible quality control, and storage over months to years, with efficient hemostatic management of patients in both prophylactic and emergency settings. Due to their completely synthetic nature, these particles can be further engineered to act as "targeted drug delivery" vehicles for clot augmentation or clot stabilization or clot prevention/lysis depending on the therapeutic cargo. Application of these 'synthetic platelet' technologies have broad implications for the treatment of a variety of hematologic dysfunctions and vascular diseases.

Dr. Liangfang Zhang will discuss the latest development of platelet-mimicking nanoparticles for biomedical applications. Dr. Zhang's laboratory collects and translocates human platelet membranes onto the surface of synthetic nanoparticles; the resulting platelet-like nanoparticles faithfully present the entirety of surface antigens and their functions that are otherwise difficult to fabricate using bottom-up approaches. This technology aims to camouflage the nanoparticles with the platelet exterior for interfacing with biological systems, thereby enabling unique applications such as targeted drug delivery and removal of biological toxins/molecules.

Co-Chairs:

Jordan A. Shavit, MD,PhD
University of Michigan
Ann Arbor, MI

Kellie R. Machlus, PhD
Brigham and Women's Hospital, Harvard Medical School
Boston, MA

Speakers:

Alessandra Balduini, MD
University of Pavia
Pavia, Italy
Three-D Models for Megakaryopoiesis and Platelet Production

Anirban Sen Gupta, PhD
Case Western Reserve University
Cleveland, OH
Synthetic Platelets for Treatment of Traumatic Hemorrhage and Thrombocytopenia

Liangfang Zhang, PhD
University of California-San Diego
La Jolla, CA
Nanoparticles Mimicking Platelets and Platelet Cloaking

Scientific Committee on Myeloid Biology

My Metabolism and Myelopoiesis

Sessions Offered Twice:
Sunday, December 8, 2019 7:30 a.m. - 9:00 a.m. Orange County Convention Center, Valencia D (W415D), Level 4	Sunday, December 8, 2019 4:30 p.m. - 6:00 p.m. Orange County Convention Center, Valencia D (W415D), Level 4

Hematopoiesis is driven by a small group of cytokines acting on stem and progenitor cells within a complex bone marrow microenvironment. Within the myeloid stem and progenitor cells lies a far more complex metabolic circuitry that hematologists are just beginning to rediscover. Already, studies in myeloid metabolism have revealed the importance and interplay of metabolism and epigenetics yielding insights and therapies involving IDH1/2 and TET2. Myelopoiesis requires a prodigious amount of cell proliferation, which must emerge from a small pool of quiescent stem cells. This balance of quiescence and proliferation requires tight regulation of metabolic pathways that are common in stem cells neutrophil differentiation and monocytes. In this session, the mysteries of metabolic quiescence, reprogramming, and recycling will be explored.

Dr. Robert Signer will discuss how he determined that hematopoietic stem cells (HSCs) display lower rates of protein synthesis than other hematopoietic cells, which is necessary for stem cell maintenance. He will describe how cell-type specific differences in protein synthesis promote hematopoietic stem cell function. Dr. Signer determined that increasing protein synthesis reduces protein quality within HSCs and that these cells exhibited superior protein quality (e.g. less ubiquitylated and unfolded proteins) compared to restricted progenitors. He will elaborate on how low protein synthesis promotes stem cell function by enhancing protein homeostasis (proteostasis) and will conclude by discussing how defects in proteostasis contribute to age-related decline in stem cell function.

Dr. Hongbo Chi will discuss how rapidly dividing cells upregulate aerobic glycolysis (Warburg metabolism) and also reprogram mitochondrial oxidative phosphorylation to support the energy and growth demands. He will elaborate on how metabolic reprogramming occurs in myeloid cells, including monocytes and dendritic cells, by focusing on the functional significance and molecular regulation of the mTOR pathway, a central regulator of anabolic metabolism. Dr. Chi will conclude by identifying how a systems approach will be useful to dissect the multiple layers of interactions between metabolism and blood cell signaling and highlight new therapeutic opportunities.

Dr. Katja Simon will describe how autophagy plays a key role in the maintenance of metabolism and limits reactive oxygen species, thus keeping the genome and proteome healthy. She will also highlight how autophagy maintains healthy hematopoietic stem cells. Her laboratory demonstrated that hematopoietic stem cells require autophagy to repopulate a new hematopoietic system in order to survive and that erythroblasts rely on mitophagy as they differentiate into erythrocytes. Most recently, her studies indicate that autophagy provides free fatty acids for neutrophil differentiation by degrading lipid droplets. Genetic ablation of Atg7, which encodes a component of the autophagy system, resulted in a pre-leukemic phenotype, which predicted low autophagic flux found in blasts from patients with acute myeloid leukemia.

Chair:

Seth J. Corey, MD
Cleveland Clinic
Cleveland, OH

Speakers:

Robert Signer, PhD
University of California-San Diego
La Jolla, CA
Proteostasis and Myeloid Stem Cell Production

Hongbo Chi
St. Jude Children's Research Hospital
Memphis, TN
Metabolic Control and Systems Immunology in Blood Cell Development

Anna K. Simon, PhD
University of Oxford
Oxford, United Kingdom
Autophagy in the Hematopoietic System

Scientific Committee on Myeloid Neoplasia

Understanding and Targeting TP53 in Myeloid Malignancies

Sessions Offered Twice:
Saturday, December 7, 2019 7:30 a.m. - 9:00 a.m. Orange County Convention Center, Tangerine 1 (WF1), Level 2	Saturday, December 7, 2019 4:00 p.m. - 5:30 p.m. Orange County Convention Center, Valencia D (W415D), Level 4

TP53 mutations are common in myeloid malignancies and associated with poor outcomes. Functional inactivation of wild-type TP53 also occurs frequently and contributes to disease pathogenesis. How leukemia cells with mutant or dysregulated TP53 persist and ultimately expand likely depends on several variables, including the type of mutation, the hematopoietic cell of origin, and the presence of hematopoietic cell-intrinsic and cell-extrinsic stressors. A better understanding of the interplay between these variables is necessary to develop therapeutic strategies and improve patient outcomes. This session will highlight the diverse biology of TP53 mutations on the pathogenesis of myeloid malignancies and the benefits and potential risks of targeting regulators of TP53 function in the clinic.

Dr. Scott Lowe will address how TP53 mutations are common in therapy-related myeloid neoplasia and complex karyotype acute myeloid leukemia (CK-AML), including how they are associated with chemoresistance and poor prognosis in AML. To understand the impact of TP53 mutations on AML biology, his group has performed large-scale genomic analyses of TP53 mutant AML and generated a series of animal models that faithfully reflect molecular and biological features of the human disease. Their recent studies explored the biology of particular TP53 mutational configurations that drive AML initiation and maintenance as well as characterized the events that cooperate with TP53 mutations during leukemogenesis.

Dr. Ulrich Steidl will discuss how TP53 is often inactivated by mutations or other mechanisms in human cancers. Recent work has demonstrated that its endogenous inhibitor MDMX (or MDM4) is frequently overexpressed in patients with hematologic malignancies including AML, as well as other cancers. Pharmacological disruption of the interactions of TP53 with both its endogenous inhibitors (MDMX and MDM2) has long been sought after as an attractive strategy to restore TP53-dependent tumor suppressor activity. However, selective targeting of this pathway has previously been limited to MDM2-only small-molecule inhibitors, which lack affinity for MDMX. More recently, pharmacological dual targeting of MDMX/MDM2 has become feasible through stapled peptides and is currently being tested in clinical trials. This presentation will discuss such MDMX/MDM2 dual-targeting strategies as well as new insights into MDMX-mediated mechanisms of tumor progression at the stem cell level, which have emerged from recent studies.

Dr. Veronika Sexl will discuss the role of the cyclin dependent kinase CDK6 as a transcriptional regulator controlling hematopoietic stem cell quiescence and leukemogenesis. Results from her laboratory have shown that CDK6 counteracts TP53 induced function during transformation by inducing a complex transcriptional response co-regulated by nuclear transcription factor Y subunit alpha and SP1. In murine models, CDK6 deficiency requires functional TRP53 inactivation to allow for transformation.

Co-Chairs:

Matthew J. Walter, MD
Washington University in St. Louis
St. Louis, MO

Satu Mustjoki, MD, PhD
University of Helsinki
Helsinki, Finland

Speakers:

Scott W. Lowe
Memorial Sloan Kettering Cancer Center
New York, NY
TP53 Action and the Consequences of TP53 Mutation in Acute Myeloid Leukemia

Ulrich G. Steidl, MD,PhD
Albert Einstein College of Medicine, Montefiore Medical Center
New York, NY
Activating TP53 by Dual Inhibition of MDMX and MDM2

Veronika Sexl, MD, PhD
University of Veterinary Medicine
Vienna, Austria
CDK6 Antagonizes TP53-Induced Responses during Tumorigenesis

Scientific Committee on Plasma Cell Neoplasia

Targeting Apoptosis in Myeloma

Sessions Offered Twice:
Saturday, December 7, 2019 7:30 a.m. - 9:00 a.m. Orange County Convention Center, Tangerine 3 (WF3-4), Level 2	Sunday, December 8, 2019 9:30 a.m. - 11:00 a.m. Orange County Convention Center, W315, Level 3

Success in myeloma treatment in recent years has been built on a platform of immuno-modulatory drugs, proteasome inhibitors and more recently monoclonal antibodies targeting proteins expressed on myeloma cells. While effective, the repertoire of available agents is limited, and therapeutic resistance frequently arises. Targeting different aspects of myeloma biology may be an attractive way to increase our therapeutic armamentarium. In this regard, abnormalities in the cell death pathway (apoptosis) are common in B cell malignancies including multiple myeloma, and this is an area of cancer biology for which there is much interest in drug development. Targeting this pathway in myeloma patients has started in clinical trials.

Dr. Simone Fulda will describe the apoptosis pathway and machinery and discuss the mechanism by which this pathway is deregulated in myeloma. Novel opportunities to target the apoptosis pathway will also be discussed. How the pathway interacts with other important deregulated pathways in myeloma and how they can become an Achilles heel in myeloma where myeloma cells become dependent and therefore sensitive to the inhibition of the pathway will be discussed.

Dr. Martine Amiot will discuss the merits of targeting BCL2 proteins in myeloma. Both pre-clinical and clinical data will be critically evaluated. Different ways of stratifying patients for BCL2 inhibition will also be discussed. This is particularly relevant as these compounds are new the clinic and the ability to stratify and select patients will be key. BCL2 inhibition appears to benefit t(11;14) patients the most. Underlying reasons for this and how this can be further exploited will also be discussed.

Dr. Karin Vanderkerken will discuss the development of MCL1 inhibitors in myeloma and will present insights from pre-clinical studies and early results from clinical trials. Of note, potential rationale combinations and biomarkers arising from pre-clinical studies will be discuss and strategies for future us of these compounds in myeloma in the setting of current therapeutic armamentarium will be explored.

Chair:

Wee-Joo Chng, MBBS, PhD
National University Cancer Institute
Singapore, Singapore

Speakers:

Lawrence H. Boise, PhD
Emory University
Atlanta, GA
Mechanisms of Deregulation of Apoptosis in Myeloma (Replacement for Dr. Fulda)

Martine Amiot, PhD
Nantes University
Nantes, France
Targeting Bcl-2 Proteins in Myeloma

Karin Vanderkerken, PhD
Free University of Brussels
Brussels, Belgium
MCL1 Inhibitors in Multiple Myeloma

Scientific Committee on Red Cell Biology

From Blood to Single Cells: Emerging Concepts and Technologies

Sessions Offered Twice:
Saturday, December 7, 2019 9:30 a.m. - 11:00 a.m. Orange County Convention Center, W230, Level 2	Sunday, December 8, 2019 9:30 a.m. - 11:00 a.m. Orange County Convention Center, W230, Level 2

Differentiation from hematopoietic stem cells into the erythroid lineage ensures the generation of more than 200 billion red blood cells per day in a normal human. This session will highlight new insights in the molecular mechanisms of erythropoiesis revealed through the use of cutting-edge molecular, genetic, proteomic and functional methodologies at the single-cell level.

Dr. Bertie Gottgens will provide an overview of single cell technologies, and how they are advancing the understanding of multiple facets of hematology research. His presentation will focus on his lab’s multidisciplinary work combining single cell molecular profiling, bioinformatics analysis and experimental/functional validation. The overarching theme of his talk will highlight the fact that single cell landscapes allow researchers to move seamlessly between different scales of biological investigation, from the molecular to the cellular and whole tissue scale.

Dr. Merav Socolovsky will address how multipotent hematopoietic progenitors commit to the erythroid lineage and the subsequent processes that govern early erythroid progenitor development. Combining single-cell transcriptomics and functional assays, results from her studies reveal that hematopoietic progenitors form a continuous, hierarchical branching structure, in which the erythroid and basophil/mast cell fates are unexpectedly coupled. Novel growth factor signaling and specialized cell cycle remodeling in early erythroid progenitors will also be discussed.

Dr. Marjorie Brand will describe changes in the relative protein levels of transcription factors and cell surface markers during the course of human erythropoiesis. Using targeted mass spectrometry and single-cell mass cytometry, her data shows co-expression of transcription factors from antagonist lineages at the single-cell level in early progenitors. It also demonstrates that ectopic expression of non-erythroid transcription factors is enough to deviate the erythroid trajectory towards non-erythroid lineages. She will also discuss how relative levels of transcription factors drive cell fate decision.

Chair:

Lily Huang, PhD
UT Southwestern Medical Center
Dallas, TX

Speakers:

Bertie Gottgens, DPhil
University of Cambridge
Cambridge, United Kingdom
Application of Single Cell Technologies to the Study of Hematopoiesis

Merav Socolovsky, MBBS, PhD
University of Massachusetts Medical School
Worcester, MA
Blood Cell Fate Decisions: Insights from Single-cell RNA-seq

Marjorie Brand, PhD
Ottawa Hospital Research Institute
Ottawa, Canada
Understanding Erythropoiesis Using Quantitative Proteomics and Single Cell Mass Cytometry

Scientific Committee on Thrombosis and Vascular Biology

Hemolytic Disorders and Thrombosis: Mechanistic and Clinical Insights

Sessions Offered Twice:
Saturday, December 7, 2019 4:00 p.m. - 5:30 p.m. Orange County Convention Center, W311, Level 3	Sunday, December 8, 2019 9:30 a.m. - 11:00 a.m. Orange County Convention Center, Sunburst Room (W340)

Hemolytic disorders are associated with an increased risk of thrombotic complications but how is the destruction of erythrocytes linked to platelet activation or thrombin generation? This session will highlight emerging data regarding mechanisms underlying the hypercoagulable state in hemolytic anemia including the activation of platelets through reactive oxygen species (ROS) as well as complement-mediated activation of tissue factor. The session will also focus on the von Willebrand factor (VWF) cleaving enzyme, ADAMTS13, best known for its contribution in thrombotic thrombocytopenia purpura. Less appreciated is the physiologic role of ADAMTS13 in regulating arterial thrombus formation and resolution

Dr. Sruti Shiva will discuss the positive association between hemolysis and platelet activation, which is well established, yet the mechanisms underlying this phenomenon remain unclear. Platelet mitochondria traditionally are thought to contribute to platelet homeostasis predominantly through ATP production and energy maintenance. However, it is now recognized that platelet mitochondria also signal through their production of reactive oxygen species, which is closely linked to their energetic function. Dr. Shiva demonstrates that increased platelet mitochondrial ROS generation potentiates platelet activation ex vivo and in animal models. Altered platelet bioenergetic function is associated with hemolytic levels and platelet activation in patients with sickle cell disease. Elucidation of this pathway identifies the platelet mitochondrion as an important signaling hub linking hemolysis to platelet activation and its potential therapeutic modulation will be discussed.

Dr. Wolfram Ruf will provide an overview of the link between the complement cascade and thrombosis induction by the tissue factor (TF) pathway. The sequential steps of complement interacting with platelet activation and allosteric activation of TF will be delineated for thrombotic diseases. The presentation will also highlight new information on the contributions of complement to pathogenic signaling of the TF.

Dr. Simon De Meyer will discuss the crucial role VWF, a multimeric glycoprotein, plays in normal hemostasis. The activity of VWF is dependent on its size with activity increasing with multimer length. Ultra large, hyperactive VWF is cleaved in smaller less reactive VWF molecules by the VWF cleaving enzyme ADAMTS13. ADAMTS13's activity is essential to prevent the accumulation of ultra large, highly thrombogenic VWF, which can lead to thrombotic thrombocytopenic purpura (TTP). However, by cleaving VWF, ADAMTS13 can also exert an anti-thrombotic or even thrombolytic effect in various other thrombotic diseases such as stroke and myocardial infarction. During this talk, an overview of anti-thrombotic effects of ADAMTS13 outside of TTP will be presented.

Co-Chairs:

Ingrid Pabinger, MD
Medical University of Vienna
Vienna, Austria

Jeffrey I. Zwicker, MD
Beth Israel Deaconess Medical Center
Boston, MA

Speakers:

Sruti Shiva, PhD
University of Pittsburgh
Pittsburgh, PA
The Mitochondrion: A Link Between Hemolysis and Platelet Activation

Wolfram Ruf, MD
The Scripps Research Institute
La Jolla, CA
Links Between Complement Activation and Thrombosis

Simon De Meyer, PhD
University of Leuven
Leuven, Belgium
ADAMTS13, an Anti-thrombotic Protein: Evidence Outside of Thrombotic Thrombocytopenic Purpura

Scientific Committee on Transfusion Medicine

Ex Vivo Bioengineering of Blood Products for Transfusion

Sessions Offered Twice:
Saturday, December 7, 2019 7:30 a.m. - 9:00 a.m. Orange County Convention Center, Tangerine 2 (WF2), Level 2	Sunday, December 8, 2019 9:30 a.m. - 11:00 a.m. Orange County Convention Center, Hall E2, Level 2

Blood transfusions remain a life-saving treatment for millions worldwide. Major advances have been made in the development of alternative products for transfusions that bring us closer to having blood products that are pathogen-free, universally compatible, and can meet the demand. This session will present recent developments in manufacturing of bioengineered blood products focusing on development of novel blood substitutes as well as culture conditions to grow red blood and platelets from stem cells or immortalized cell lines.

Dr. Allan Doctor will discuss the challenges of successful oxygen carrier development. Classically, hemoglobin-based oxygen carriers (HBOCs) have failed in part due to ineffective oxygen release and over trapping of nitric oxide causing vasoconstriction. He will describe the design and features of bio-inspired design artificial red blood cells (ErythroMer), a novel HBOC which has overcome these weaknesses by controlling oxygen capture, release and attenuating nitric oxide uptake. Dr. Doctor will summarize pre-clinical results and discuss ongoing development, regulatory approaches, as well as potential novel indications enabled by this unique design.

Prof. Jan Frayne will discuss the development of progenitor cell lines for production of red blood cells. Various sources of stems cells from adult, cord blood, and induced pluripotent stem cells (iPSC) are currently used as ex vivo erythroid culture systems. As proof of principal of an alternative transfusion product, she will present data on the generation of immortalized erythroid lines which recapitulate adult erythropoiesis and provide a sustainable supply of red cells. Using a platform for CRISPR-Cas9 genome editing, sublines lacking one or more blood groups have also been created, thus generating more "universal' blood products and diagnostic tools. Data supporting additional applications will be presented. This will include highlighting the creation of cytokine independent lines for increasing the economic viability of ex vivo systems, lines as model cellular disease systems that can be used as research tools and drug screening platforms, and the use of lines for studying mechanisms of malaria parasite invasion.

Dr. Koji Eto will discuss the manufacturing of platelet like particle products from iPSC. Challenges remain in ex vivo manufacturing of the equivalent of one transfusion unit or roughly 200-300 billion functional platelets. He will describe the development of a megakaryocyte cell line as a master/working cell bank and present data demonstrating the production of clinical grade platelets. He will also discuss the use of a novel bioreactor, which applies turbulent energy with sheer stress to induce platelet biogenesis, and a process that incorporates steps in washing and concentrating the platelet preparations. Clinical applications of this design including the strategy of producing universal platelet products lacking human leukocyte antigens as well as next steps in industrial scale manufacturing will be discussed.

Chair:

Karina Yazdanbakhsh, PhD
New York Blood Center
New York, NY

Speakers:

Allan Doctor, MD
University of Maryland School of Medicine
Baltimore, MD
Bio-Inspired Artificial Red Blood Cell: Design, Pre-Clinical Results and Novel Indications

Jan Frayne
University of Bristol
Bristol, United Kingdom
Ex vivo Engineering of Red Blood Cells

Koji Eto, MD
Kyoto University
Kyoto, Japan
Ex vivo Engineering of Platelets

Scientific Committee on Transplantation Biology and Cellular Therapies

Genome Editing for Transplantation and Cellular Therapies

Sessions Offered Twice:
Saturday, December 7, 2019 9:30 a.m. - 11:00 a.m. Orange County Convention Center, Hall D, Level 2	Sunday, December 8, 2019 7:30 a.m. - 9:00 a.m. Orange County Convention Center, Hall D, Level 2

Hematopoietic transplantation and adoptive cellular therapies are expanding fields with increasingly established and experimental indications. Yet, even as the current approaches grow, the way these cellular therapies are developed and practiced may soon be strikingly different. Gene editing is poised to revolutionize hematopoietic transplantation and adoptive cell therapies, either through the editing of transplanted hematopoietic cells or editing the immune cells mediating curative and other protective responses. This session will present state-of-the-science advances in understanding the basic biology of genome editing, approaches to incorporate such editing into transplant and other cellular therapy settings, and efforts to utilize editing techniques to synthesize new biology that can enhance the efficacy and safety of cellular therapies.

Dr. Feng Zhang will discuss precision genome editing, which can be used to alter specific DNA sequences and can be utilized as a powerful tool for understanding the molecular circuitry underlying cellular processes. Over the past several years, his group and others have harnessed microbial CRISPR-Cas systems for use as platforms for investigating a range of genome and transcriptome manipulations. Dr. Zhang's talk will review the fundamentals of CRISPR-mediated technologies and highlight how further exploration of microbial diversity can contribute to the growing molecular toolbox and ultimately provide new therapeutic avenues for myriad diseases.

Dr. Giuliana Ferrari will discuss experimental gene therapy for hemoglobinopathies based on transplantation of autologous hematopoietic stem cells (HSCs) genetically modified to express therapeutic hemoglobin levels. Beta-thalassemia and sickle cell disease are congenital anemias caused by mutations in the beta-globin gene, resulting in either reduced production of globin chains or abnormal hemoglobin structure. Approaches to genetically modify HSCs for treatment of hemoglobinopathies include: the addition of globin genes by lentiviral vectors and gene editing by nucleases to reactivate fetal hemoglobin either through inhibiting repressors or through reproducing mutations associated with high fetal hemoglobin levels. Early clinical trials are promising, although hurdles limiting broader application remain. Dr. Ferrari will review these current challenges as well as improved strategies for HSC correction.

Dr. Wendell Lim will discuss synthetic biology approaches for engineering next-generation T cell therapies. Chimeric antigen receptor T cells have shown remarkable outcomes for certain malignancies, but targeting others, including solid tumors, has proven challenging. It is difficult to identify unique antigens, to ensure trafficking to tumor sites, and to mount strong anti-tumor responses in immunosuppressive tumor microenvironments. Dr. Lim's group is engineering cells that utilize new sets of sensors and modular control circuits that enable them to execute novel recognition and response programs with improved precision and robustness. These innovative capabilities may allow for development of therapeutic T cells that are far more effective and safer.

Co-Chairs:

Catherine J. Wu, MD
Dana-Farber Cancer Institute
Boston, MA

Alan M. Hanash, MD, PhD
Memorial Sloan Kettering Cancer Center
New York, NY

Speakers:

Feng Zhang
The Broad Institute
Cambridge, MA
Biology and Application of Genome Editing

Giuliana Ferrari, PhD
San Raffaele Telethon Institute for Gene Therapy
Milan, Italy
Genetic Engineering in Hematopoietic Stem Cells for Gene Therapy of Hemoglobinopathies

Wendell Lim, PhD
University of California-San Francisco
San Francisco, CA
Sensing and Sensibility: Programming Smarter Chimeric Antigen Receptor T Cells