Dysregulated transcriptional responses to SARS-CoV-2 in the periphery.

My research at Duke has focused on understanding the dynamic between host and pathogen so as to discover and develop host-response markers that can diagnose and predict health and disease.  This new and evolving approach to diagnosing illness has the potential to significantly impact individual as well as public health considering the rise of antibiotic resistance.

With any potential infectious disease diagnosis, it is difficult, if not impossible, to determine at the time of presentation what the underlying cause of illness is.  For example, acute respiratory illness is among the most frequent reasons for patients to seek care. These symptoms, such as cough, sore throat, and fever may be due to a bacterial infection, viral infection, both, or a non-infectious condition such as asthma or allergies.  Given the difficulties in making the diagnosis, most patients are inappropriately given antibacterials.  However, each of these etiologies (bacteria, virus, or something else entirely) leaves a fingerprint embedded in the host’s response. We are very interested in finding those fingerprints and exploiting them to generate new approaches to understand, diagnose, and manage disease.

These principles also apply to sepsis, defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Just as with acute respiratory illness, it is often difficult to identify whether infection is responsible for a patient’s critical illness.  We have embarked on a number of research programs that aim to better identify sepsis; define sepsis subtypes that can be used to guide future clinical research; and to better predict sepsis outcomes.  These efforts have focused on many systems biology modalities including transcriptomics, miRNA, metabolomics, and proteomics.  Consequently, our Data Science team has utilized these highly complex data to develop new statistical methods, furthering both the clinical and statistical research communities.

These examples are just a small sampling of the breadth of research Dr. Tsalik and his colleagues have conducted.  

In April 2022, Dr. Tsalik has joined Danaher Diagnostics as the VP and Chief Scientific Officer for Infectious Disease, where he is applying this experience in biomarkers and diagnostics to shape the future of diagnostics in ID. 

I am a transplant infectious diseases physician. My clinical care focuses on the management of infections in immunocompromised patients, including solid organ and bone marrow transplant recipients, as well as cancer patients. My research focuses on developing noninvasive biomarker diagnostics and severity prognostic tools for infectious diseases in immunocompromised patients.

Dr. Kraft has a wide variety of clinical and research interests, including sepsis, pneumonia, and acute respiratory distress syndrome (ARDS), and has special expertise in rare lung diseases such as pulmonary fibrosis and pulmonary alveolar proteinosis (PAP). PAP can be congenital, hereditary, autoimmune, or due to occupational exposures (e.g. dusts, fibers, silica).

Dr. Kraft performs whole lung lavage (WLL) at Duke in a state-of-the art hyperbaric chamber within the Duke Center for Hyperbaric Medicine and Environmental Physiology. Performing WLL with hyperbaric oxygen (when necessary) augments oxygen delivery during the procedure, meaning both lungs can be lavaged on the same day, during a single episode of anesthesia.

Dr. Kraft’s research laboratory is devoted to understanding mechanisms of acute lung injury resolution, and uses translational models and clinical patient samples to identify novel pathways of recovery. Dr. Kraft is also an active investigator in clinical trials to develop new therapies for patients with lung diseases.

My research is broadly focused on elucidating the complex interactions that exist between the host microbiome and exogenous pathogens that cause infections in children. We have several ongoing projects evaluating: 1) the impact of the upper respiratory microbiome on the risk of colonization and invasion by bacterial respiratory pathogens among infants in Botswana; 2) associations between the gut microbiome of pediatric stem cell transplant recipients and the risk of infections (bloodstream infection, C. difficile infection) and graft-versus-host disease; and 3) the role of the gut and respiratory microbiomes in mediating COVID-19 infection susceptibility and disease severity in children. Ultimately, I aim to develop strategies that use targeted modification of the microbiome for the prevention of infections in children.

My broad research interests are the cellular and molecular mechanisms that contribute to pathogenic immunity in ophthalmic disease and vision loss. My studies are currently focused on dendritic cells (DC), a unique leukocyte population of antigen presenting cells required for both initiating and determining the type of immune response generated. These cells contribute to the maintenance of health versus immunity in ocular disease.

I am currently investigating the role of DCs in allergic immune responses in the eye. We have developed a robust experimental mouse model that allows us to engraft ex vivo manipulated DCs into the ocular surface tissues prior to allergen challenge. This has allowed us to address very precise mechanistic pathways regarding DC function in allergy, such as identifying the pathogenic subset(s) of DCs required to trigger allergic immunity, and the factors drive the recruitment versus homing of these cells to the lymphoid organs.

I am also interested in examining the role of antigen presenting cells in other clinically relevant models of immune-associated ophthalmic disease. It is now widely appreciated that immunity and inflammation contributes to the pathogenesis of very prevalent conditions, including dry eye disease, glaucoma, and age-related macular degeneration. Elucidating a possible role(s) for antigen presenting cells such as DCs in these conditions may be an important step in furthering our understanding and possibly in identifying novel targets for treatments.

Dr. Shen’s research interests lie at precision medicine and systems biology. His lab integrates engineering, computational and biological techniques to study cancer, stem cells, microbiota and the nervous system in the gut. This multidisciplinary work has been instrumental in initiating several translational clinical trials in precision therapy. He is the director of the Woo Center for Big Data and Precision Health (DAP) and a core member of the Center for Genomics and Computational Biology (GCB).