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<article  class="node node--type-objective node--view-mode-full"
        data-title="Investigate newly discovered pathobiological mechanisms important to the onset and progression of HLBS diseases"
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                <h1 class="objective-page-title">
                    Objective 2:  
<span>Investigate newly discovered pathobiological mechanisms important to the onset and progression of HLBS diseases</span>

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            <div class="field field--name-field-introduction field--type-text-long field--label-hidden field__item"><p>Discovering new pathobiological mechanisms and understanding them is critical for improving heart, lung, blood, and sleep (HLBS) health. Such discoveries and research can potentially lead to clinical and implementation studies, which in turn can inform new therapeutic strategies and clinical practice. Important areas to focus on, with the help of emerging technologies such as molecular imaging and nanotechnology, include mechanisms involved in the pathogenesis of rare and common diseases, disease-related structural and functional changes, and the clinical significance of these changes. In addition, tracking of disease onset and progression across the lifespan is essential because it has the potential to inform our understanding of the conversion of chronic conditions into acute disease and the effects of early exposures and interventions, including lifestyle changes.</p></div>
      
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            <div class="field field--name-field-future-goals-title field--type-string field--label-hidden field__item">Envision a future in which we are able to...</div>
      
                            
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              <li class="field__item">Preempt the transition from health to disease and enable primary and secondary prevention through an enhanced understanding of the pathobiological mechanisms underpinning HLBS disorders.</li>
              <li class="field__item">Leverage deep phenotyping and high-throughput “omic” technologies in NHLBI-supported cohort studies to define the functional significance of gain/loss-of-function genetic variants and gene knockouts on human pathobiology and the clinical outcomes of HLBS disorders. </li>
              <li class="field__item">Gain new insights into modifier genes and molecular pathways that influence the clinical manifestations and severity of monogenic disorders (e.g., sickle cell disease and cystic fibrosis) as well as structural defects such as congenital heart disease, and thereby catalyze new therapeutic strategies.</li>
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                        <h2>Related Priorities</h2>
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                                                                                                    What are the molecular mechanisms underlying dysregulation of homeostasis, and how do these mechanisms vary from individual to individual, leading to development of HLBS diseases in some but not in others? (2.CQ.01)
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                                                                                                    What are the roles of RNAs (e.g., microRNAs, long non-coding RNAs) in HLBS systems' growth, adaptation, and injury-repair responses? (2.CQ.02)
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                                                                                                    What biomarkers of acute and chronic environmental exposures (e.g., smoking) are predictive of disease onset or progression? What biologic effects measured by these biomarkers are irreversible responses and which are opportunities for intervention? (2.CQ.03)
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                                                                                                    How do endogenous stem/progenitor cells and defects in these cells contribute to the onset and progression of chronic HLBS diseases? (2.CQ.04)
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                                                                                                    What is the pathobiology of aberrant calcification of coronary arteries, heart valves, and peripheral arteries, and why is calcification associated with a poor prognosis? (2.CQ.05)
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                                <div class="objective-list-wrapper"><h2>Overarching Objectives</h2><div class="objective-list-container font-size-xl"><ol class="objective-list"><li class="objective-list-item inactive"><span>Understand normal biological function and resilience</span></li><li class="objective-list-item active"><span>Investigate newly discovered pathobiological mechanisms important to the onset and progression of HLBS diseases</span></li><li class="objective-list-item inactive"><span>Investigate factors that account for differences in health among populations</span></li><li class="objective-list-item inactive"><span>Identify factors that account for individual differences in pathobiology and in responses to treatments</span></li><li class="objective-list-item inactive"><span>Develop and optimize novel diagnostic and therapeutic strategies to prevent, treat, and cure HLBS diseases</span></li><li class="objective-list-item inactive"><span>Optimize clinical and implementation research to improve health and reduce disease</span></li><li class="objective-list-item inactive"><span>Leverage emerging opportunities in data science to open new frontiers in HLBS research</span></li><li class="objective-list-item inactive"><span>Further develop, diversify, and sustain a scientific workforce capable of accomplishing the NHLBI’s mission</span></li></ol>
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