Objective 5: Develop and optimize novel diagnostic and therapeutic strategies to prevent, treat, and cure HLBS diseases

Recent scientific and technological developments offer especially promising opportunities to prevent disease, manage and treat illness, and promote resilience. These wide-ranging developments include, but are not limited to, new gene editing techniques that could safely treat and prevent  heart, lung, blood, and sleep (HLBS) diseases, “smart” tools that could monitor and adjust biological processes, techniques that modulate stem cell or immune system signaling to reduce disease risk, and advances in materials science that could yield vastly improved implant devices. Other technologies and bioengineering developments may further facilitate diagnostic capabilities, and new lifestyle interventions may improve the maintenance of continued health and wellness and facilitate behavioral modification to prevent disease. Many of these advances, which are the results of past investments in basic research, are critical to developing and optimizing novel diagnostics and therapeutics strategies.

Envision a future in which we are able to...
  • Develop surgical grafts (using stem cells, 3-D printing, and nanotechnologies) for children born with heart defects, such that the grafts grow as the child grows into adulthood, thereby avoiding multiple operations.
  • Transform the safety and availability of the nation’s blood supply by using genetically engineered stem cells to eliminate histo-incompatibility antigens and generate universal donor red blood cells that are available off the shelf by a high-throughput process.

Related Priorities

Compelling Question
Would reduction of known cardiac and vascular risk factors during childhood and adolescence translate into the prevention or delayed development of atherosclerosis and other heart diseases? (5.CQ.01)
Compelling Question
Would interventions in pregnancy or early childhood designed to modulate immune development result in primary prevention of asthma? (5.CQ.02)
Compelling Question
How should the management of diseases that typically develop in childhood (including childhood interstitial lung disease, hemoglobinopathies, congenital heart disease, cystic fibrosis, and asthma) be modified as affected individuals mature into adulthood? (5.CQ.03)
Compelling Question
Would using multidisciplinary teams (e.g., nutritionists, exercise physiologists, social workers, psychologists, nurses) be an effective approach to developing, testing, and ultimately applying lifestyle interventions as part of routine patient care in a variety of contexts from community to patient care settings? (5.CQ.04)
Compelling Question
Would circadian-based strategies (e.g., sleep, timing of medication, meals) improve the efficacy of treatments for HLBS diseases (e.g., hypertension, asthma, thrombosis, obesity/diabetes)? (5.CQ.05)
Compelling Question
What technical improvements in the collection, preparation, storage, and processing of blood products would improve their potency, safety, and lifetime? What biomarkers or other characteristics predict stability during storage and successful transfusion? (5.CQ.06)
Compelling Question
What effective and implementable practices (e.g., recognition and initial response by the community, emergency medical response, hospital-based care) would reduce the rate of mortality associated with out-of-hospital cardiac arrest? (5.CQ.07)
Compelling Question
How can real-time, individual-level monitoring be used to detect and predict electrical instability of the heart and reduce risk for sudden cardiac death in low-risk patients? (5.CQ.08)
Compelling Question
What is the optimal clinical management approach for patients with severe calcific aortic stenosis but with minimal symptoms? (5.CQ.09)
Compelling Question
What is the best strategy for reducing cardiac and vascular morbidity and mortality in cancer survivors who are at enhanced risk of cardiac and vascular events and whose clinical care may be complicated by both comorbidities and drug toxicity? (5.CQ.10)
Compelling Question
In patients with enhanced cardiovascular risk due to comorbidities from chronic diseases (e.g., HLBS disorders, diabetes) and multiple drug therapy, what is the best strategy for reducing cardiac and vascular morbidity and mortality? (5.CQ.11)
Compelling Question
What are the optimal red blood cell transfusion thresholds and optimal plasma transfusion strategies in both pediatric and adult patients? (5.CQ.12)
Compelling Question
How can we optimize the effectiveness and safety of allogeneic hematopoietic stem cell transplantation in the treatment of nonmalignant blood and immune disorders and prevent both short-term and long-term complications? (5.CQ.13)
Compelling Question
What are the mechanisms for the late development of complications after hematopoietic stem cell transplantation ? How can these consequences be predicted and prevented to reduce the high rates of mortality following HSCT? (5.CQ.14)
Compelling Question
How can we "reprogram" the immune system to improve outcomes of allogeneic cell therapies, tissue and organ transplants, and regenerative strategies and to diminish allogeneic responses to essential biologic replacement therapies? (5.CQ.15)
Compelling Question
How can improved methods for hematopoietic cell transplantation or gene therapy approaches be used to cure certain hemoglobinopathies (e.g., sickle cell disease)? (5.CQ.16)
Compelling Question
How do we develop and implement novel strategies to prevent and treat minor and major hemorrhagic complications in males and females affected by acquired and inherited disorders? (5.CQ.17)
Compelling Question
Is targeted manipulation of epigenetic modifications (distinct from global suppression of histone acetylation or DNA methylation) a useful strategy for therapeutic intervention in chronic cardiopulmonary or blood diseases? (5.CQ.18)
Compelling Question
With increasing use of direct-acting oral anticoagulants for stroke prevention in atrial fibrillation and treatment of venous thromboembolism, what is the role of laboratory monitoring, and can the use of new technologies help better define those at risk of bleeding or thrombosis with use of direct-acting oral anticoagulants or warfarin? (5.CQ.19)
Compelling Question
How can imaging technology be leveraged to identify clinically useful markers of metabolic syndrome and cardiopulmonary disease? (5.CQ.20)
Compelling Question
Do interventions to improve ventilation during sleep decrease morbidity and mortality in individuals with either heart failure (or other diseases associated with chronic hypoxemia) and sleep-disordered breathing? (5.CQ.21)
Compelling Question
How can alterations of stem cell cycles and other therapies, as well as endogenous mechanisms, be harnessed to promote repair and regeneration of the heart, lung, and blood systems? (5.CQ.22)
Compelling Question
How can we better integrate palliative care concepts, such as respect for personal values, goals, and treatment preferences, in the management of patients with HLBS diseases? (5.CQ.23)
Critical Challenge
A better understanding of the factors governing the safety and efficacy of therapeutic hemoglobin-based extracellular oxygen carriers (HBOCs) and improved animal models for HBOC studies are needed. (5.CC.01)
Critical Challenge
An understanding of the immune system from a systems biology perspective is needed to design more efficacious treatment strategies for chronic inflammatory and autoimmune HLBS diseases. (5.CC.02)
Critical Challenge
Improved capabilities for responding rapidly and effectively to emerging infectious threats to the safety and availability of the nation's blood supply are needed. (5.CC.03)
Critical Challenge
Robust tools and algorithms are needed to evaluate objective biomarkers of sleep health and dysfunction. (5.CC.04)
Critical Challenge
New materials and constructs that are electrically, chemically, and mechanically active are needed to enable the development of self-adjusting bioengineered implants (e.g., self-regenerating protective layers, biologics like vein grafts, glucose-responsive polymers that release insulin). (5.CC.05)
Critical Challenge
Development of safe, well-functioning designer platelets and red blood cells from stem or progenitor cells, as well as the large-scale production of these products, is needed for therapeutic and diagnostic uses. (5.CC.06)
Critical Challenge
Expanded research on bleeding risk in elderly patients with atrial fibrillation is needed to develop more accurate risk stratification that would enhance anticoagulation decision-making for the elderly population and reduce stroke incidence. (5.CC.07)

Overarching Objectives

  1. Understand normal biological function and resilience
  2. Investigate newly discovered pathobiological mechanisms important to the onset and progression of HLBS diseases
  3. Investigate factors that account for differences in health among populations
  4. Identify factors that account for individual differences in pathobiology and in responses to treatments
  5. Develop and optimize novel diagnostic and therapeutic strategies to prevent, treat, and cure HLBS diseases
  6. Optimize clinical and implementation research to improve health and reduce disease
  7. Leverage emerging opportunities in data science to open new frontiers in HLBS research
  8. Further develop, diversify, and sustain a scientific workforce capable of accomplishing the NHLBI’s mission