To maintain cardiac health and prevent disease, there is a need to decipher the cardiome of cells and genes and use this knowledge (1) to better understand cardiac structure and function and (2) to engineer systems on the level of organs, organ systems, and the entire individual.

Given that chronic diseases are 'Evolutionary Biology' in reverse, can we use developmental and phylogenetic principles to diagnose and treat them safely and effectively?

Redox imbalance as represented by alterations in oxidative versus reductive stresses are well appreciated to occur during nearly all forms of cardiovascular and lung diseases. However, specific molecular mechanisms responsible for these changes remain largely unknown and poorly organized. Study of redox biology principals has revealed that protein cysteine thiols are a unique target for redox posttranslational modifications... more »

How do we identify potential targets for therapy in the age of systems biology/genomics?

Can we define the developmental abnormalities leading to birth defects and extrapolate that knowledge to define strategies for regeneration?

 

How can we recognize initiation of disease earlier?

Precision medicine will provide unprecedented opportunities to tailor health care based on knowledge of personal patterns of genetic variations. These variations usually impact protein or RNA sequences, resulting in altered properties. These alterations can result in increased susceptibility to a particular disease or intolerance to common therapeutics. To take full advantage of knowing a patient’s set of gene variations,... more »

Microvascular ischemia is common, particularly in the setting of critical illness. We need better ways to evaluate, diagnose and treat these conditions, whether they relate to microvascular myocardial ischemia, as a primary diagnosis of complication of other acute illness, or non-myocardial ischemia during the course of surgery, injury, infection or acute illness.

Sepsis is the leading cause of death in hospitalized patients, the 3rd leading cause of death in all people in the US, the most common condition leading to widespread vascular collapse, among the most common causes of respiratory failure, and a frequent cause of acute cardiac dysfunction.

In the human failing heart, it is the systems biology that ultimately fails: electrical, mechanical, and chemical perturbations in their function do not manifest in isolation, but critically impact on each other in health and disease. Investigation of human myocardium, unlike inbred rodent models, is challenging since no two humans are identical. There is a need for the collection and assessment of clinical patient data,... more »

Unravel the cellular & molecular mechanisms related to the vascular biology of sepsis and related cardiovascular collapse. The goal is to develop a new scientific framework for the prevention of sepsis related morbidity and mortality by applying novel approaches to discover new targets for biomarkers and therapy by promoting multidisciplinary research required for scientific cross-talk between complementary research disciplines... more »

In the late 20th century, the NHLBI cohorts were created as separate entities with specific research goals. The NHLBI’s funding of GWAS served as a powerful incentive for collaboration among the NHLBI-funded cohort studies. The creation of a scientific commons would provide a major national resource comprising the participants, their deeply phenotyped data, their biological samples, and the investigator expertise to... more »

The challenge is to identify limitations in using data from non-human animal species for elucidation of human electromechanical function/activity and to identify what specific information and computational approaches need to be incorporated. To aid in achieving such a goal, it might be useful to convene a series of workshops to build consensus and improve communication among investigators working at the same horizontal... more »

How do growth, development, exposure, and behavior affect heart, lung, blood, sleep disease development and outcome throughout the lifespan?

 

How do you improve organ function/capacity during childhood?

Critical Challenge

Although many think of the vasculature as a lump sum of vessels that all react in a similar fashion to a certain stimulus, e.g., alpha-adrenergic activation, this is not the situation. For example, coronary resistance vessels show little to no direct response to alpha-adrenergic activation while resistance vessels in most organs show marked constriction. Another example is the response of different vessels to angioplasty... more »