Scientific Symposia

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

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

Speakers:

Deena Iskander
Imperial
London, United Kingdom
The Role of Ribosome Dysregulation in Erythropoiesis

Luis Batista
Washington University in St. Louis
St. Louis, United States
The Connections Between Telomere Biology and Hematopoiesis

Meng Wang
Cornell University
Ithaca, NY, United States
Genotoxic Aldehydes, DNA Repair, and Premature Aging in Fanconi Anemia

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

The role of chronological age as predisposition for disease development is undebated. However, in depth understanding of genetic, epigenetic, metabolic and other mechanisms causing age-induced alterations that increase the predisposition for the development of blood-born disease are unresolved. High-dimensional analysis are broadly used in the context of aging and disease addressing fundamental alterations in hematopoiesis and clonal contributions to benign and malignant hematopoiesis.

This session will focus on recent advances in understanding the regulation of hematopoiesis in response to the stem cell microenvironment but also more broadly to systemic factors and it will also address approaches to reverse potentially harmful molecular alterations. Attendees will be exposed to recent advances in the field of hematopoietic stem cell regulation with the context of its native environment.

Chair:

Stephanie Halene
Yale University School of Medicine
New Haven, CT, United States

Speakers:

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

Leif Ludwig
Berlin Institute of Health at Charité Universitätsmedizin Berlin
Berlin, Germany
Tic, Toc: Cell Intrinsic Regul

Eirini Trompouki
Institute for Research on Cancer and Aging of Nice (IRCAN), CNRS UMR7284, INSERM U1081, Université Cote d'Azur, 06107, Nice, France.
Nice, France
Preventing Fires: Targeting Strategies to Mitigate Clonal Evolution

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

The understanding and treatment of pain in many genetically inherited red blood cell disorders such as sickle cell disease (SCD) and hemophilia remain understudied, while individuals with these rare diseases continue to suffer and lead a poor quality of life since childhood. Individuals with SCD suffer with debilitating and often life-threatening and unpredictable episodes of acute pain of “crises,” in addition to lifelong chronic pain. Opioids are the mainstay of pain therapy but remain challenging due to side effects and stigma. A critical unmet need is to identify how organ damage, sickle cell pathobiology, social determinants of health, and curative therapies influence SCD pain?

This session will present the current understanding of mechanisms underlying sickle cell pain, revealing treatable targets for the development of novel interventions to prevent/treat pain. It 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.

Chair:

Hyacinth Hyacinth
University of Cincinnati College of Medicine
Cincinnati, OH, United States

Speakers:

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

Bin He
Carnegie Mellon University
Pittsburgh, PA, United States
Treat the Pain in My Brain: Understanding Neuromodulation and Technology Enhanced Interventions for Sickle Cell Disease Pain

Manisha Madkaikar
ICMR-National Institute of Immunohaematology
Mumbai, Maharashtra, India
It Refuses to Leave: The Challenging Bone Pain in Sickle Cell Disease

Special Symposium on the Basic Science in Hemostasis and Thrombosis

Wound healing is a highly coordinated process composed of distinct but interdependent phases: hemostasis, inflammation, proliferation, and tissue remodeling. The precise timing of each phase is essential for effective tissue repair and the prevention of excessive scarring. This session will highlight the critical contributions of platelets, the coagulation cascade, and the fibrinolytic system in promoting optimal cutaneous wound healing.

The session will also explore the intricate mechanisms that regulate clot structure and influence wound healing at the intersection of hemostasis, vascular biology, and platelet function.

Speakers:

Ashley Brown
North Carolina State University
Raleigh, NC, United States
Clots, Cuts, and Healing: The Dynamic trio of Coagulation, Platelets, and Fibrinolysis

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

Oliver Borst
University of Tuebingen
Tübingen, Germany
Lipoprotein(a) and Venous Thromboembolism: A Silent Culprit or Innocent Bystander?

Targeting Cancer Metabolism – Innovative Methods to Translation

Cancer cells exhibit heightened context-specific metabolism, driven in part by specific genetic lesions (translocations/mutations) and microenvironmental constraints. Intrinsic tumor metabolism has profound implications on therapy sensitivity and resistance. Despite identification of small molecule metabolic inhibitors, targeting metabolism has been challenging given the plasticity of cellular metabolism and toxicity in normal cells. Testing metabolic inhibitors more comprehensively in immune competent models and identification of synthetically lethal strategies can overcome barriers to targeting cancer metabolism. A re-interest in tumor metabolism has emerged from a better understanding of why cells engage aerobic glycolysis i.e. the Warburg effect and identification of oncometabolites like 2-HG. Serum metabolites including 2-HG have aided in stratifying AML prognosis. Diet and microbial derived metabolites also are emerging as important regulators of therapy sensitivity.

This session will review mechanisms of tumor-specific metabolism, and insights on how extrinsic metabolites impact therapy sensitivity and resistance will be highlighted. The session will also shed light on approaches that have informed researchers’ understanding of cancer metabolism including the identification of therapeutic strategies for heme malignancies.

Chair:

Mala Shanmugam
Winship Cancer Institute, Emory University
Atlanta, GA, United States

Speakers:

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

Jeffrey C Rathmell
University of Chicago
Chicago, IL, United States
Metabolic Sources of Immune Cell Dysfunction

Andrew Intlekofer
Memorial Sloan Kettering Cancer Center
New York, NY, United States
Enzyme Hyperactivation to Target Oncometabolism