We need to understand sleep and circadian disorders at a more mechanistic level. This applies to both the pathogenesis of these disorders and to their impact on health. New neurobiological and molecular tools facilitate this research. The focus needs to be not only in brain but also the impact of these disorders on future of peripheral organs. The elucidation of the fundamental functions of sleep and the impact of... more »

What triggers decompensation of cellular and molecular pathways during exacerbations of chronic lung diseases?

Critical challenges in the assessment of aortic aneurysms are: (1) Availability of reliable animal models that simulate the human pathology, (2) Availability of molecular imaging resources – identification of biomarkers, development of targeted imaging probes and pre-clinical imaging methods, and plasma markers that predict whether an aneurysm is prone to rupture or dissection, (3) Bringing together a wide array of multi-disciplinary... more »

Critical Challenge

Respiratory failure in sepsis is almost universal and leads to worse clinical outcomes, yet it is poorly understood. Recent epidemics of pulmonary failure from respiratory viruses (e.g. influenza, SARS, MERS, etc) makes understanding molecular determinants of respiratory failure and the associated inflammatory and physiologic responses, critical for improving the health of our nation and potentially mitigating future... more »

Critical Challenge

It is essential to develop clinically viable, non-invasive, less expensive technologies for the surveillance of allograft rejection in heart transplant patients. Critical challenges that exist in the near term or long term surveillance after transplant is the unavailability of molecular and cellular level markers that can be non-invasively imaged and quantified detect rejection and thus improve patient survival. Development... more »

What are the molecular phenotypic differences in blood and tissue of IPF ILD and how do they relate to disease course and potential response to therapy. There is a need to gain understanding in humans of the differences and similarities in iPF and iLD in general to eliminate the idiopathic nature and establish human targets. The challenge is coupling such research to longer term studies/outcomes and potentially clinical... more »

Natural genetic variation between individuals can influence the outcome of carrying an HHT mutation. Some gene variants may be protective while others may increase the risk of AVM or telangiectasis. By identifying the variant genes that alter risk of AVM may give clues to the molecular mechanisms of AVM formation and provide new drug targets

What is the sequence and time course of molecular events that cause irreversible cardiovascular and neurologic dysfunction during and after cardiac arrest?