RESEARCH

Everything is connected

Omics technologies, especially metabolomics and proteomics, have helped us revealing emerging patterns in systemic responses to acute or chronic hypoxia. By focusing on cancer metabolism and (red) blood cell biology, we are increasingly appreciating shared molecular mechanisms driving systemic responses to trauma/ hemorrhagic shock, I/R injury, sickle cell disease, ageing and inflammation, mammalian hibernation and pulmonary hypertension.

High-Throughput Metabolomics

Mass spectrometry-based metabolomics has recently contributed great strides in biomedical research, influencing the most diverse fields from pulmonology to immunology, from cancer research to intensive care medicine and sports physiology. Technological advancements in the field of mass spectrometry (MS)-based metabolomics have made it cost affordable for small/middle-sized metabolomics centers to serve hundreds of investigators on a yearly basis, fostering a new era in the field of omics disciplines and their translational relevance to basic science and clinical applications.

 

Check out our exploratory method paper here.

Deep Red

Red blood cells (RBCs) are the most abundant host cell in the human body, accounting for ~83% of the 30 trillion total host cells in an adult individual. Despite the lack of nuclei and organelles, the RBC proteome is complex enough (~2800 proteins) to include a variety of receptors and transporters, which allow RBCs to uptake exogenous (e.g. drugs) or endogenous metabolites as they circulate for ~120 days in the bloodstream. RBC metabolism thus mirrors systemic metabolic homeostasis and its pathological derangements beyond traditional RBC-specific pathologies such as sickle cell disease (e.g. HbA1c and diabetes). Through the use of state of the art Omics tools, our Lab focuses on the characterization of RBCs in health and disease.

Check out a recent review of our ongoing projects here.

Red Blood Cell Storage

Transfusion of packed red blood cells is a life-saving treatment for approximately 4-5 million Americans every year (108 million units donated yearly worldwide). At an average cost of ~220-300$ per unit, the estimated economic burden of transfusion services to the US economy averages around 3.3-4.5 billion dollars per year in the US alone. Improved RBC storage quality can be achieved through the omics-driven testing and implementation of blood processing and storage strategies that mitigate the storage lesion, a series of biochemical and morphological alterations RBCs undergo when stored in the blood bank for up to 42 days.

Check out our review in Transfusion (Most cited paper in 2015 of the Journal!!!)

Trauma & Hemorrhagic Shock

Trauma is the global leading cause of mortality under the age of 45, the major cause of total life years lost, more than cancer and cardiovascular disease combined. While immediate death by trauma is not preventable, early or late (hours to day) causes of preventable death in trauma with or without severe hemorrhage have been identified, including multiple organ failure, metabolic acidosis, coagulopathy and acute lung injury. Our research addresses the molecular underpinnings of these phenomena and ways to prevent/intervene in the critically ill patient.

Check out our recent paper in Blood Advances

Hypoxia, Inflammation and Aging

From high altitude hypoxia to ischemia and reperfusion, from hibernation to underwater mammals... From sickle cell disease to pulmonary hypertension, from immune cell activation to aging: emerging "metabolic theories" suggest that cellular and mitochondrial metabolic dysfunction underlies the pathology of these disease. Through collaborative work we investigate these phenomena and test pharmaceutical targets to tackle metabolic dependencies.

Check out our recent review summarizing the collaborative papers with the Stenmark lab.

Down Syndrome

Trisomy 21 (T21) is the etiological factor of Down syndrome (DS), the most common chromosomal abnormality in the human population occurring in 1 in ~700 live births in the United States. Individuals with DS display an altered disease spectrum, whereby they are protected from some medical conditions but highly predisposed to others. For example, rates of most solid malignancies are lower among people with DS, yet they are highly predisposed to develop Alzheimer’s disease, several autoimmune disorders, leukemia, pulmonary hypertension, and various hearing and vision problems.

Check out our seminal paper on RBC metabolism in Down Syndrome.

 
 
 

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