Objective 4: Identify factors that account for individual differences in pathobiology and in responses to treatments

Research advances in areas such as genomics and other “omics” (e.g., proteomics, metabolomics) have provided new opportunities to deepen our understanding of heart, lung, blood, and sleep (HLBS) pathobiological processes and how these vary among individual patients. Accelerating progress toward precise, individualized prevention efforts and medical interventions will require research into biological factors, environmental exposures, and other influences that account for differences in pathobiology and unique responses to treatment (including drug reactions and other adverse events). This research will allow personal and clinical decisions, practices, and medical products to be tailored to the individual patient to help optimize outcomes.

Envision a future in which we are able to...
  • Develop precise clinical interventions based on individual environmental exposures, behaviors, genotypes, and molecular-cellular phenotypes.
  • Accelerate the incorporation of new imaging, omics, and sensor technologies with advanced data analytics to inform more precise clinical classification of chronic diseases (e.g., asthma, pulmonary fibrosis, chronic obstructive lung disease, heart failure) and thereby enable more accurate diagnosis and treatment.

Related Priorities

Compelling Question
Which phenotypic, biomarker, and molecular characteristics predict outcome and, when applied in clinical studies, predict differential responses to therapy in individuals and in different populations with HLBS diseases? (4.CQ.01)
Compelling Question
What factors render individuals or populations subjected to the same exposures (e.g., diet, smoking, other environmental and social exposures) resilient or susceptible to disease? (4.CQ.02)
Compelling Question
What underlies secondary resilience, such that some people are protected from the complications of HLBS diseases? (4.CQ.03)
Compelling Question
Which patients benefit from rehabilitation treatments (e.g., cardiac, vascular, and pulmonary), and how can the benefits of rehabilitation treatments be sustained long term? (4.CQ.04)
Compelling Question
How does the pathobiology that underlies nonobstructive ischemic heart disease and the associated risks for acute coronary syndrome and early mortality differ between subpopulations, and what are the targets for treatment and prevention? (4.CQ.05)
Compelling Question
What tests would identify individuals who are at high risk of venous thromboembolic events and would benefit from targeted risk factor modification and/or intensive prophylaxis? (4.CQ.06.)
Compelling Question
What are biomarkers of pulmonary hypertension that could better identify individuals at high risk, reveal underlying mechanisms, and guide treatment? (4.CQ.07)
Compelling Question
What are the major determinants of individual and sex differences in breathing patterns in sleep, susceptibility to insomnia, and other sleep behaviors? (4.CQ.08)
Compelling Question
What genetic, biomarker, and environmental predictors of risk and outcome would inform and improve management of sickle cell disease and secondary prevention of its progression and complications? (4.CQ.09)
Critical Challenge
Predictive modeling and prevention trials are needed in populations at high risk for highly prevalent HLBS diseases. (4.CC.01)
Critical Challenge
In patients with an aortic aneurysm, better tools are needed to determine which patient phenotypes and disease characteristics could best predict who would benefit from a repair. Examples of such tools include animal models that reflect human pathology and biomarkers/molecular imaging tools that are predictive of rupture or dissection. (4.CC.02)
Critical Challenge
Clinical evaluation tools are needed to differentiate patients with atherosclerotic heart disease who will progress to myocardial infarction or with sudden cardiac death from those with stable disease. (4.CC.03)

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