Scientific Symposia

Discovering the Biology of Hematopoiesis Through Studies of Bone Marrow Failure Syndromes

Saturday, December 6, 2025, 2:00 p.m. - 3:15 p.m.
Hyatt - Plaza Int'l HIJK

Studies exploring the germline genetic causes of inherited bone marrow failure syndromes (IBMFS) provide important opportunities to understand the mechanisms of normal and abnormal hematopoiesis. This session will feature the latest studies using IBMFS as models to identify the cellular and molecular underpinnings of hematopoiesis.

Fundamental insight into abnormal ribosome biogenesis and the tissue specific phenotypes of human ribosomopathies will be discussed, using the selective defects in erythropoiesis in Diamond-Blackfan anemia syndrome as a model. Attendees will be updated on the connections between aberrations in telomere biology genes associated with bone marrow failure and telomere function in hematopoiesis. Updates on new mechanisms by which genotoxic aldehydes contribute to aging phenotypes in Fanconi anemia will be presented, with implications for understanding the link between hematopoiesis and aging and its relevance to cancer development.

Taken together, this session will show how lessons from IBMFS can be translated to stem cell biology, aging and cancer.

Chair:

Austin G. Kulasekararaj, MD,MBBS,FRCPath,MRCP
King’s College Hospital

Speakers:

Deena Iskander

The Role of Ribosome Dysregulation in Erythropoiesis

Luis Batista

The Connections Between Telomere Biology and Hematopoiesis

Meng Wang

Aldehyde-Induced DNA Damage in HSC Exhaustion and Aging: Lessons from Fanconi Anemia

Hematopoiesis in the Golden Years: Aging, Epigenetic Landscapes, and Clonal Destiny

Monday, December 8, 2025, 10:30 a.m. - 11:45 a.m.
OCCC - W312

Chronological age is the strongest risk factor for blood-borne disease, yet the mechanisms that link aging to disordered hematopoiesis are only now coming into focus. This session brings together niche biology, cutting-edge single-cell technologies and innate immune signaling to illuminate how the hematopoietic system changes across the lifespan and how those changes might be reversed. Together, the talks chart a coherent path from niche-encoded cues to immune-metabolic checkpoints and quantitative clonal readouts, highlighting emerging therapeutic strategies to reset aging hematopoiesis. 

Dr. Marta Derecka will focus on the bone marrow microenvironment. Using EBF1 as an exemplar hematopoietic transcription factor expressed in stromal cells, she will dissect how mesenchymal niche programs shape steady-state hematopoiesis and how EBF1 dysregulation contributes to myeloproliferative neoplasm–associated fibrosis. These insights underscore that age-related hematopoietic decline is not solely cell-intrinsic but co-authored by the niche.

Dr. Leif Ludwig will explore clonal dynamics through the lens of mitochondrial DNA (mtDNA) mosaicism. Leveraging >1.25 million single-cell mutational profiles across age groups, longitudinal sampling, and post-transplant settings, mtDNA variants serve as natural barcodes to quantify human hematopoietic clones. Attendees will learn how clonally informative mtDNA mutations accumulate with age, how homeostatic clones remain largely stable yet regenerate dynamically after perturbation, and why apparent lineage “bias” often reflects immune expansions rather than fixed stem-cell programs until advanced age or clonal hematopoiesis tip the balance.

Dr. Eirini Trompouki will examine aging as an inflammatory and proteostatic phenotype governed by the innate RNA sensor MDA5. Genetic attenuation of MDA5 in mice preserves hematopoietic stem cell (HSC) quiescence, dampens inflammaging, improves metabolic fitness, and enhances repopulation capacity. Mechanistic data denote the master of proteostasis, HSF1, as an upstream node connecting MDA5 signaling to aging hallmarks, with small-molecule modulation of HSF1 reversing key phenotypes. This work positions antiviral sensing as actionable levers to delay HSC aging.

Chair:

Stephanie Halene

Speakers:

Marta Derecka, PhD
St. Jude Children's Research Hospital
Context Matters: HSC Regeneration in the Cellular Niche

Leif S. Ludwig

Mitochondrial DNA Mosaicism and Clonality in Human Hematopoiesis

Eirini Trompouki

Preventing Fires: Targeting Strategies to Mitigate Clonal Evolution

Ouch-it Hurts: Mechanisms of the Origin, Perception and Evolution of Pain in Sickle Cell Disease

Saturday, December 6, 2025, 2:00 p.m. - 3:15 p.m.
OCCC - W308

Recurrent and indeed chronic pain represents one of the most widely recognized complications of sickle cell disease (SCD). The complexity of SCD-associated pain has resulted in a limited understanding of its etiology and mechanism, despite several studies in this area. As a public health imperative, SCD-associated pain leads to poor overall quality of life from its impact on multiple aspects of daily living. Opioids, which are the mainstay of pain therapy in patients with SCD, present with multiple potential side-effects including opioid dependence. Understanding the mechanism that initiate, propagate and sustain pain, especially chronic pain in SCD represents a critical knowledge gap, given its impact on development of future and more effective preventative and therapeutic strategies. The goal of this session is therefore, to provide state-of-the-science information on SCD-associated pain complications and identify opportunities and gaps for future research.

Dr. Kalpna Gupta will present the current understanding of mechanisms underlying sickle cell pain, revealing treatable targets for the development of novel interventions to prevent and treat pain. She will highlight novel molecular and cellular mechanism based pharmacologic and integrative approaches and advancement in non-invasive technology to treat pain with potential for translation to the clinics.

Dr. Bin He will present on non-pharmacological approaches for treating pain and their potential application to SCD-associated pain. Dr. He will also discuss the neuroscience mechanisms underlying tFUS neuromodulation for non-invasive, circuit-specific brain stimulation in both animal models and human subjects.

Dr. Jahnavi Gollamudi will present on the contribution of SCD-associated bone disease, to the pathophysiology of chronic pain. First focusing on the mechanisms underlying bone complications in SCD and then moving to discuss the mechanisms by which bone cells interact with nociceptive nerves and contribute to bone pain and finally touch on bisphosphonates a potential non-opioid option for managing bone pain in SCD.

Chair:

Hyacinth Hyacinth

Speakers:

Kalpna Gupta, PhD
University of California, Irvine, CA
Two Sides of the Same Coin: Sickle Cell Pathobiology and Neural Mechanisms that Evoke, Maintain and Perceive Pain

Bin He

Treat the Pain in My Brain: Understanding Neuromodulation and Technology Enhanced Interventions for Sickle Cell Disease Pain

Jahnavi Gollamudi, MD
University of Cincinnati
It Refuses to Leave: The Challenging Bone Pain in Sickle Cell Disease

Special Symposium on the Basic Science in Hemostasis and Thrombosis

Monday, December 8, 2025, 4:30 p.m. - 6:00 p.m.
OCCC - Valencia Room W415D

Hemostasis is far more than the rapid sealing of a wound—it is a dynamic, finely tuned process that dictates whether injury leads to repair or pathology. This session explores the multifaceted roles of coagulation, platelets, and fibrinolysis in both physiological healing and disease states, highlighting how dysregulation in these pathways underlies organ damage and thrombotic disorders. Together, these talks will illuminate how the molecular choreography of clot formation, resolution, and repair shapes outcomes across bleeding and thrombotic disorders.

Dr. Ashley Brown will open the session by delineating the intricate crosstalk between coagulation, platelet activation, and fibrinolytic pathways in the orchestration of hemostasis and tissue repair. Her presentation will underscore how precise temporal control of clot formation and dissolution determines whether healing proceeds or fibrosis ensues. She will also highlight novel therapeutic strategies that harness this balance to promote regeneration while limiting scarring.

Dr. Tirthadipa Pradhan-Sundd will then extend this theme to the context of sickle cell disease, where chronic hemolysis disrupts vascular homeostasis. She will present compelling evidence that von Willebrand factor (vWF) serves not only as a hemostatic mediator but also as a biomarker and contributor to liver injury. Using preclinical models, she will illustrate how hemolysis-induced endothelial damage alters vWF cleavage and clearance, revealing a previously unrecognized regulatory role of cell-free hemoglobin independent of ADAMTS13.

Dr. Marlys Koschinsky will tackle the longstanding debate surrounding lipoprotein(a) [Lp(a)] and its potential role in venous thrombosis. Integrating mechanistic and translational data, she will describe how Lp(a) influences thrombin generation, fibrin architecture, and clot stability in both in vitro systems and transgenic models. These insights will help clarify whether Lp(a) acts as a silent culprit or an innocent bystander in thrombotic cardiovascular disease.

If you are attending the meeting in Orlando, following this session, please join ASH leadership and your colleagues at the ASH Networking Reception for the Hemostasis and Thrombosis Community, taking place just outside the room in the Valencia Lobby, from 6:00 p.m. - 7:30 p.m.

Speakers:

Ashley Brown

Clots, Cuts, and Healing: The Dynamic trio of Coagulation, Platelets, and Fibrinolysis

Tirthadipa Pradhan-Sundd, PhD
Versiti Blood Research Institute
Blood, Clots, and Scars: Unraveling the Hidden Links Between Coagulation and Liver Cirrhosis

Marlys Koschinsky, PhD
The University of Western Ontario
Lipoprotein(a) and Thrombosis: Insights from Basic and Clinical Science

Targeting Cancer Metabolism – Innovative Methods to Translation

Monday, December 8, 2025, 2:45 p.m. - 4:00 p.m.
OCCC - W312

This session explores how cancer metabolism shapes therapy response and resistance. It highlights advances in understanding the Warburg effect, metabolic dependencies, and oncometabolites such as 2-hydroxyglutarate (2HG), with a focus on their translational impact.

Dr. Matthew Vander Heiden will discuss how environmental nutrients constrain leukemia metabolism to impact therapy and suggest mechanisms by which metabolic adaptations might lead to changes in gene expression that could contribute to disease progression and therapy resistance. The nutrient environment creates constraints on how leukemia cells can acquire the biomass necessary to support proliferation.  This has implications for understanding the response to therapy, many of which target metabolism in a way that is impacted by the nutrient environment. 

Dr. Jeffrey Rathmell will discuss mechanisms by which metabolic pathways regulate immune cell function and highlight how mitochondria respond to stress to shape immunity. T cells experience metabolic and mitochondrial stress because of chronic inflammation and stimulation. Fever is a common stress that reflects a mild heat shock that can lead to mitochondrial dysfunction with implications on cell fate and ability to respond to cancer.

Dr. Andrew Intlekofer will describe mechanistic studies of an unusual drug resistance mutation in isocitrate dehydrogenase (IDH), which led to the surprising discovery that genetic or pharmacologic hyperactivation (rather than inhibition) of mutant IDH unleashes metabolic toxicity that selectively eliminates IDH-mutant leukemia cells. Mutant IDH enzymes drive cancer by producing a metabolite called 2HG that alters gene expression creating a stem-like state. Drugs that inhibit mutant IDH enzymes induce durable clinical responses in some patients with IDH-mutant acute myeloid leukemia. However, despite near universal suppression of oncometabolite 2HG, IDH inhibitors benefit less than half of patients with IDH-mutant AML, and drug resistance invariably develops.

Chair:

Mala Shanmugam

Speakers:

Matthew Vander Heiden, MD, PhD
Massachusetts Institute of Technology
Nutrient Environment Considerations for Understanding Leukemia Therapy

Jeffrey C Rathmell

Metabolic Sources of Immune Cell Dysfunction

Andrew Intlekofer

Enzyme Hyperactivation to Target Oncometabolism