Featured Publications in the Collaboratory

graphical respresentation of how chlamydia can evade immunityThe bacterial effector GarD shields Chlamydia trachomatis inclusions from RNF213-mediated ubiquitylation and destruction

Jörn Coers, Raphael Valdivia, Dennis Ko and colleagues ran a large genetic screen of chlamydia that identified its cloaking mechanism, which has allowed the disease to evade detection.

Read more in Cell Press

Large-scale genome-wide association study of coronary artery disease in genetically diverse populations

Elizabeth Hauser was part of a large, international collaboration that conducted a genome-wide association study (GWAS) of coronary artery disease (CAD) incorporating nearly a quarter of a million cases, in which existing studies are integrated with data from cohorts of white, Black and Hispanic individuals from the Million Veteran Program. This study highlights the value of diverse populations in further characterizing the genetic architecture of CAD.

Read full text in Nature Medicine


Evaluating immune response and metabolic related biomarkers pre-allogenic hematopoietic stem cell transplant in acute myeloid leukemia

Anthony Sung, Virginia Kraus, James Bain, Jichun Xie, and team have identified several inflammatory and metabolomic biomarkers that differentiate young and old hematopoietic stem cell transplantation (HCT) patients and are associated with survival and clinical outcomes in HCT. A combination of biomarkers could guide interventions, personalized immune-modulatory therapeutics post-HCT, and could help improve clinical outcomes in acute myeloid leukemia.

Read full text in Plos One


An antiplatelet response gene expression signature is associated with bleeding

Deepak Voora, William Kraus, Svati Shah and colleagues developed a gene expression based score, the Antiplatelet Response Signature (ARS), measured in whole blood samples that is increased by aspirin and ticagrelor. ARS and other similar gene expression scores may inform future strategies to personalize antithrombotic therapy to balance bleeding and ischemic risk.

Read full text in Cardiovascular Research


Single Cell RNA-Seq Analysis of Human Red Cells

Ashley Chi, Simon Gregory and team performed single red cell RNA-seq of circulating red blood cells from three healthy donors that had been storied for one or 15 days and found that the expression pattern of single red blood cells separates into distinct cellular clusters. Their results show new insights into gene expression regulation and heterogeneity among red blood cells.

Read full text in Frontiers in Physiology


Myoblast deactivation within engineered human skeletal muscle creates a transcriptionally heterogeneous population of quiescent satellite-like cells

Nenad Bursac, Yarui Diao and colleagues investigated the specific roles that muscle fibers, a critical niche constituent, have in human satellite cell maintenance and injury-induced activation by utilizing human myobundles made from purified myogenic cells.

Read full text in Biomaterials


Serum metabolomic analysis of men on a low-carbohydrate diet for biochemically recurrent prostate cancer reveals the potential role of ketogenesis to slow tumor growth: A secondary analysis of the CAPS2 diet trial

Ashley Chi and colleagues investigated the effect a low-carbohydrate diet had on prostate cancer growth using both animal models and participants in the Carbohydrate and Prostate Study 2 (CAPS2) clinical study.

Read full text in Nature


Modulation of microbial community dynamics by spatial partitioning

Lingchong You, Lawrence David and team investigated spatial partitioning of microbial communities and its effects on biodiversity. Their results reveal a general mechanism underlying the maintenance of microbial diversity and have implications for natural and engineered communities.

Read full text in Nature Chemical Biology


The preference for sugar over sweetener depends on a gut sensor cell

Diego Bohorquez and colleagues discovered that cholecystokinin (CCK)-labeled duodenal neuropod cells can tell the difference between sugars and artificial sweeteners. They showed that preference for sugar over sweetener in mice depends on neuropod cell glutamatergic signaling. By swiftly discerning the precise identity of nutrient stimuli, gut neuropod cells serve as the entry point to guide nutritive choices.

Read full text in Nature Neuroscience          Read article in Duke Today


Steroid-sensitive nephrotic syndrome candidate gene CLVS1 regulates podocyte oxidative stress and endocytosis

Rasheed Gbadegesin, Gentzon Hall, Alejandro Ochoa and colleagues performed next generation sequencing in patients with familiar steroid sensitive nephrotic syndrome, a common pediatric kidney disease that is responsive to steroids. They identified a homozygous segregating variant in the gene encoding clavesin-1 in a family with three affected individuals.

Read full text in JCI Insight


Role of DNA methylation on the association between physical activity and cardiovascular diseases: Results from the longitudinal multi-ethnic study of atherosclerosis (MESA) cohort

Yongmei Liu and colleagues used the Multi-Ethnic Study of Atherosclerosis (MESA) cohort to examine the role of DNA methylation on the association between physical activity and cardiovascular disease.

Read full text in BMC Genomics


Repurposing cancer drugs identifies kenpaullone which ameliorates pathologic pain in preclinical models via normalization of inhibitory neurotransmission

Ru-Rong Ji and colleagues surveyed the "junkyard of cancer drugs" that might have the potential to be repurposed to aid in chronic pain and discovered that kenpaullone and similarly-acting kinase-inhibitory compounds, as well as delta-CAT gene therapy, have the potential to become new tools in our toolbox against chronic refractory pain, including nerve injury pain and cancer bone pain, and likely against other forms of chronic pain.

Read the news release on Eureka Alerts          Read full text in Nature


Bevacizumab-induced hypertension and proteinuria: a genome-wide study of 1000+ patients

Kouros Owzar was part of a team that conducted a GWAS meta-analysis on 1039 patients of European ancestry who have been treated with bevacizumab, a medication used to treat a number of types of cancers. This is the largest study of bevacizumab toxicity and it provides new markers of drug safety for further evaluation.

Read full text in Nature


Predictions of primate–parasite coextinction

Charlie Nunn worked with Duke professors James Herrera and James Moody to analyze potential effects on parasite existence and biodiversity if primates threatened with extinction go extinct.

Read full text in Phil. Trans. R. Soc.          Read article in Duke Today


Non-diphtheriae Corynebacterium species are associated with decreased risk of pneumococcal colonization during infancy

Matthew Kelly, Sweta Patel, John Rawls and colleagues studied the nasopharyngeal microbiomes of 179 mother-infant dyads in Botswana. They examined changes in microbiome diversity and composition during infancy, evaluated associations  between the nasopharyngeal microbiome and pneumococcal colonization risk, and identified environmental factors that influence nasopharyngeal microbiome composition during infancy. 

Read full text in The ISME Journal


Circadian clock, carcinogenesis, chronochemotherapy connections

David Hsu collaborated with UNC Chapel Hill to investigate sites of DNA damage and repair following anti-cancer drug treatments. They mapped these sites genome wide at single nucleotide resolution and as a function of circadian time. This data might help provide valuable information for creating rational chronochemotherapy regimens.

Read full text in the Journal of Biological Chemistry


Circulating long chain acylcarnitines and outcomes in diabetic heart failure

James Bain, Chris Newgard, William Kraus, Robert McGarrah, Svati and team used metabolomic profiling to identify biomarkers that report on exercise capacity, clinical outcomes and differential response to exercise in heart failure patients with and without diabetes mellitus.

Read full text in Cardiovascular Diabetology


Altered skeletal muscle metabolic pathways, age, systemic inflammation, and low cardiorespiratory fitness associate with improvements in disease activity following HIIT in persons with RA

William Kraus, David Bartlett, Kim Huffman and team identified connections between skeletal muscle molecular pathways, rheumatoid arthritis (RA) disease activity, and RA disease activity improvements following high intensity interval training.

Read full text in Arthritis Research & Therapy 


Sequencing of 640,000 exomes identifies GPR75 variants associated with protection from obesity

William Kraus and Svati Shah were part of a large collaboration that sequenced over 640,000 exomes from people in the US, UK and Mexico to estimate associations of rare coding variants with body mass index (BMI). They found that inhibiting GPR75 may be a therapeutic strategy for obesity.

Read full text in Science


Genome-Wide Variants Associated With Longitudinal Survival Outcomes Among Individuals With Coronary Artery Disease

William Kraus, Elizabeth Hauser, Carol Haynes and team used a genome-wide screening approach to identify gene variants associated with all-cause mortality among individuals with clinically phenotyped coronary artery disease.

Read full text in Frontiers in Genetics 


Metabolomic profiling identifies complex lipid species and amino acid analogues associated with response to weight loss interventions

Laura Svetkey, Chris Newgard, William Kraus and Svati Shah worked to identify metabolic biomarkers associated with beneficial metabolic changes to weight loss that identify individuals with obesity who would most benefit from a given type of intervention.

Read full text in Plos One


An atlas connecting shared genetic architecture of human diseases and molecular phenotypes provides insight into COVID-19 susceptibility

A team at Duke featuring Ricardo Henao, Micah McClain, Ephraim Tsalik, Geoff Ginsburg, Xiling Shen, Chris Woods, Beth Hauser and Dennis Ko created an interactive web database that helps explore and quickly analyze user-uploaded GWAS summary statistics. The database generated novel hypotheses to explain the pathophysiology of common diseases. 

Read full text in Genome Medicine


Three-dimensional tissue-engineered human skeletal muscle model of Pompe disease

Nenad Bursac, Dwight Koeberl, Priya Kishnani and team developed a 3-D model of infantile-onset Pompe disease that demonstrates the signature pathological features of the disease.

Read the full text in Nature


Mucosal Associated Invariant T Cell Responses Differ by Sex in COVID-1

A collaboration including Ephraim Tsalik, Micah McClain, Chris Woods, Xilng Shen and other Duke faculty carried out sex-balanced sampling of peripheral blood mononuclear cells from confirmed 30 COVID-19 inpatients and outpatients, uninfected close contacts, and healthy controls for 36- 31 color flow cytometry and single cell RNA-sequencing.

Read full text in Med


A Rare Autosomal Dominant Variant in Regulator of Calcineurin Type 1 (RCAN1) Gene Confers Enhanced Calcineurin Activity and May Cause FSGS

Nephrotic syndrome (NS) is a kidney disorder that causes the body to pass too much protein in its urine. Rasheed Gbadegesin and team conducted whole-genome sequencing on 320 individuals of unclear genetic etiology and analyzed data from several patient cohorts to gain insight into the genetic architecture of the condition. 

Read full text in JASN


CHG Bathing Reduces Number of Bloodstream Infections in Adults Undergoing Inpatient Hematopoietic Cell Transplantation

Anthony Sung, Julia Messina, Sin-Ho Jung, Li Ma and team conducted a prospective cohort study with historical controls to assess the impact of chlorhexidine gluconate bathing on the rate of bloodstream infections and gut microbiota composition among adults undergoing inpatient HCT at the Duke University Medical Center. 

Read full text in Transcriptional and Cell Therapy


Clinical implementation of an oncology‐specific family health history risk assessment tool

Ryanne Wu, Geoff Ginsburg, Lori Orlando and colleagues used MeTree, a patient-facing family health history risk assessment platform, in a pilot study to test its impact in an oncology setting.

Read full text in Hereditary Cancer in Clinical Practice


In vivo proximity labeling identifies cardiomyocyte protein networks during zebrafish heart regeneration

Ken Poss and team used a transgenic BioID2 strategy to capture cell-specific proteome changes in cardiomyocytes during heart regeneration in adult zebrafish. 

Read full text in eLife


Benchmarking DNA isolation kits used in analyses of the urinary microbiome

Cindy Amundsen and Nazema Siddiqui collaborated with Oregon Health and Science University and the University of Alabama in Huntsville to compare the performance of several DNA isolation kits used in microbiome studies to see if recovered microbes identified by 16S rRNA sequencing differ based on the DNA isolation protocol.

Read the full text in Scientific Reports


Alterations in acylcarnitines, amines, and lipids inform about the mechanism of action of citalopram/escitalopram in major depression

The Proteomics & Metabolomics Core Facility and Jessica Tennenbaum were part of a large collaboration that used a targeted metabolomics approach utilizing a panel of 180 metabolites to gain insights into mechanisms of action and response to certain SSRIs used to treat major depressive disorder.

Read full text in Translational Psychiatry


The Pediatric Obesity Microbiome and Metabolism Study (POMMS): Methods, Baseline Data, and Early Insights

Raphael Valdivia, Lawrence David, Holly Dressman, Christopher Newgard, Svati Shah and John Rawls and team analyzed clinical, metabolomic and microbiome samples from adolescents with obesity as they undergo lifestyle modifications.  

Read full text in Obesity


Efficacy of metformin and fermentable fiber combination therapy in adolescents with severe obesity and insulin resistance

Christopher Newgard and Michael Freemark are part of an international team that is comparing metabolic effects of metformin and fermentable fibers in combination with those of metformin or fiber alone in adolescents with obesity. They will also determine if therapeutic responses correlate with compositional and functional features of the gut microbiome.

Read the study protocol in Trials


Mutational processes in cancer preferentially affect binding of particular transcription factors

Raluca Gordan collaborated with Duke-NUS to develop the "Signature-QBiC" model that integrates signature profiles of mutational processes with the QBiC estimates of changes in binding affinity to investigate the effect of mutational signatures on the binding of 582 human transcription factors.

Read full text in PMC


Genome-wide analysis identifies novel susceptibility loci for myocardial infarction

William Kraus and Beth Hauser were part of a large international team that performed GWAS studies for myocardial infarction to see if genetic factors that establish atherosclerosis may be distinct from those that predispose to vulnerable plaques and thrombus formation.

Read full text in European Heart Journal


Pleiotropy and epistasis within and between signaling pathways defines the genetic architecture of fungal virulence

Paul Magwene, Joseph Heitman and team describe the genetic architecture of six traits in C. deneoformans and then used GWAS function-valued QTL mapping to identify genetic differences that underlie variation in those six traits. Their work illustrates the complex effects that variants may have with respect to virulence potential.

Read full text in PLOS Genetics


Validation of a host gene expression test for bacterial/viral discrimination in immunocompromised hosts

Several members from the Duke Center for Applied Genomics and Precision Medicine collaborated on a study that evaluated the performance of a host gene expression test to discriminate bacterial, viral, and noninfectious illness in immunocompromised patients. Although test performance was marginally lower than in immunocompetent patients, this approach may provide useful diagnostic information in this high-risk population.

Read full text in Clinical Infectious Diseases


Investigating the genetic architecture of noncognitive skills using GWAS-by-subtraction

Avshalom Caspi and Terrie Moffitt were part of a large, international team that used genetic correlation and polygenic score analysis to test if noncognitive skills influence educational and economic attainments and longevity and to investigate traits and behaviors that constitute noncognitive skills. They also conducted hypothesis-free bioinformatic annotation analysis with help from the Genomic Analysis & Bioinformatic core facility to explore the tissues, cell types and brain structures that might distinguish the biology of noncognitive skills from the biology mediating cognitive influences on educational attainment.

Read full text in Nature


Digital Health—The Need to Assess Benefits, Risks, and Value

Geoff Ginsburg, along with Eric Perakslis, published a viewpoint in JAMA about the potential for digital health -- wearable and internal devices, sensors in people, homes, communities and more -- to improve health management. However, the current state of technology development and deployment requires a "buyer beware" cautionary note. Ginsburg was also interviewed by JAMA editor-in-chief Dr. Howard Bauchner.

Read full text in JAMA          Listen to the interview


Air Pollution May Hasten Aging

A collaboration with DMPI, the departments of Biostatistics and Bioinformatics and Psychiatry and Behavorial Sciences, the division of Cardiology, UNC Chapel Hill, Georgia Tech, Durham VA, and EPA found that epigenetic age acceleration may be a biomarker of sensitivity to air pollution, especially traffic-related air pollution in urban cohorts. This research shows a new way to understand sensitivity to air pollution and provides a molecular measure of environmental sensitivity.

Read full text in Aging


Modeling statin myopathy in a human skeletal muscle microphysiological system

Deepak Voora led a collaboration between the Center for Applied Genomics and Precision Medicine and the Department of Biomedical Engineering that developed a "muscle on a chip" platform to study the effects of statin associated musculoskeletal symptoms.

Read full text in Plos One


CRISPR dCas9 used to program pluripotent stem cells into adult neuronal cells

A team of researchers at Duke University led by Dr. Charlie Gersbach has developed a new method to discover gene regulatory networks for programming stem cells to become any cell type. Their work, published today in Cell Reports, demonstrates the potential of the approach in making mature adult neuronal cells, but is broadly applicable.

Read full text on Cell Reports


RT-PCR-based 36-gene signature performance over time

Researchers in the Center for Applied Genomics and Precision Medicine assessed the ability of transcriptomic biomarkers to identify naturally acquired respiratory viral infection before symptoms appear.

Read full text in The Lancet


Novel Murine Models of Cerebral Cavernous Malformations

Doug Marchuk and team developed a genetic mouse model of cerebral cavernous malformations. 

Read full text in Angiogenesis


Identification of Undetected Monogenic Cardiovascular Disorders

A collaboration between DMPI, Division of Cardiology, Center for Applied Genomics and Precision Medicine as well as Regeneron Genetics Center and Vanderbilt Medical Center shows the large burden of undetected monogenetic cardiovascular disorders.

Read full text in the Journal of the American College of Cardiology