- Doug Johnson, Justin Balko, Melissa Hicks, Jason Becker, David Slosky, Elizabeth Phillips, Mark Pilkinton, Dan Roden and Javid Moslehi described the first cases of fatal myocarditis, characterized by T-cell and macrophage infiltrates, in patients with melanoma after treatment with immune checkpoint inhibitors and identified this side effect in 0.27% of patients treated with ipilimumab and nivolumab based on pharmacovigilience.
- Nancy Cox Eric Gamazon of the Vanderbilt Genetics Institute and a team of others developed a robust methodology for imputing tissue-specific gene expression based on Genotype-Tissue Expression (GTEx) data.
- Sara Van Driest, Quinn Wells, Sarah Stallings, William Bush, Ben Shoemake, Josh Denny and Dan Roden demonstrated that the identification of rare functional variants in SCN5A and KCNH2 are not robustly associated with either arrhythmia or QT prolongation, suggesting notifying patients of incidental genetic findings may not always be appropriate.
- Tim Blackwell, Joy Cogan, Jonathan Kropski, William Lawson, Mark Steele, Lisa Lancaster, Lisa Young, James Loyd and team identified a rare variant in the gene encoding for telomere elongation helicase 1 (RTEL1) that is associated with familial interstitial pneumonia and short telomere length.
- Leora Horn,co-authored a pivotal trial demonstrating that nivolumab was superior to docetaxel in patients with advanced nonsquamous non-small cell lung cancer that have progressed during or after platinum-based chemotherapy.
- Eric Gamazon of the Vanderbilt Genetics Institute, Nancy Cox and collaborators developed a gene-based association method for mapping traits using reference transcriptome data, known as PrediXcan.
- Wei Zheng , Ben Zhang and colleagues carried out a large scale study of East Asians which identified six new loci associated with colorectal cancer risk.
- Ning Wei, Rupesh Chaturvedi, Keith T. Wilson, and collaborators found that peroxisome proliferator-activated receptor δ promoted colonic inflammation and tumor growth.
- Jin Chen, Shan Wang , Dana M. Brantley-Sieders and colleagues revealed that genetic and pharmacologic inhibition of EPHA2 promotes apoptosis in NSCLC.
- Robert J. Coffey, Cunxi Li, Yang Wang, Zheng Cao, Ramona Graves-Deal, Anne Powell and collaborators uncovered how excess PLAC8 promotes an unconventional ERK2-dependent EMT in colon cancer.
- David M. Aronoff and colleagues discovered that Prostaglandin E₂ suppresses allergic sensitization and lung inflammation by targeting the E prostanoid 2 receptor on T cells.
- Billy Hudson, Julie Hudson, Aaron Fidler, Roberto Vanacore, Sergei Chetyrkin, Vadim Pedchenko, Gautam Bhave, Dorin-Bogdan Borza and other researchers in the Aspirnauts Inititiative discovered that a unique covalent bond in basement membrane is a primordial innovation for tissue evolution.
- Dorin-Bogdan Borza’s research group uncovered how the neonatal Fc Receptor Promotes Immune Complex-Mediated Glomerular Disease.
- Wes Ely, Pratik P. Pandharipande, Robert S. Dittus. Gordon R. Bernard, Eduard E. Vasilevskis, Nathan E. Brummel, James C. Jackson, Timothy D. Girard other other BRAIN ICU investigators revealed how survivors of long-term illness often suffer from a disabling prolonged form of cognitive impairment.
- William Pao, Monica Red Brewer, Lai Darson and collaborators reported the mechanism for activation of mutated epidermal growth factor receptors in lung cancer.
- Mark Boothby , James W. Thomas and colleagues defined the requirement for Rictor in homeostasis and function of mature B lymphoid cells.
- Carlos Arteaga , Ariella Hanker, Justin M. Balko, Christian D. Young, Violetta Sanchez, Cammie R. Sutton, and collaborators discovered how mutations in PIK3CA accelerates HER2-driven transgenic mammary tumors and induces resistance to combinations of anti-HER2 therapies.
- Robert J. Coffey’s group elucidated the transformation of polarized epithelial cells by apical mistrafficking of epiregulin.
- Richard M. Peek Jr., Jennifer M. Noto, Jennifer Gaddy, Blanca Piazuelo, Judith Romero-Gallo, Giovanni Suarez, John Loh, Douglas Morgan, Keith Wilson, Pelayo Correa, Timothy Cover, and colleagues illuminated how iron deficiency accelerates Helicobacter pylori-induced carcinogenesis in rodents and humans.
- April Pettit and colleagues described the index case of fungal meningitis related to injection with contaminated steroids and triggered a public health response to prevent additional cases and deaths.
- Rick Peek and colleagues demonstrate that iron deficiency accelerates
H. pylori-induced carcinogenesis.
- Ray Harris’s group identifies a critical role for CSF-1 signaling in recovery from acute kidney injury.
- Volker Haase shows that hypoxia-inducible factor regulates hepcidin via erythropoietin-induced erythropoiesis.
- William Pao, and others identify BRAF gene mutations in some lung cancers with acquired resistance to EFR inhibitors.
- Sunil Kripalani and the Pharmacist Intervention for Low Literacy in Cardiovascular Disease Study Group find no beneficial effect of a pharmacist intervention on clinically important medication errors.
- Justin Balko , Carlos Arteaga, and others identify deficiency of dual specificity protein phosphatase 4 (DUSP4), an ERK phosphatase, as a mechanism of drug resistance in breast cancer.
- Takamune Takahashi’s group finds that thrombospondin-1 acts as a ligand for CD148 tyrosine phosphatase.
- Jeff Sosman, with Igor Puzanov, leads landmark trial studying the effect of vemurafenib on survival in BRAF V600-mutant advanced melanoma.
- Chris Williams reports that blood vessel epicardial substance prevents epithelial-mesenchymal transition, a critical step in the progression of epithelial colorectal carcinomas.
- William Pao and Mia Levy launch MyCancerGenome, the first internet-based decision support tool to help physicians and researchers track the latest developments in personalized cancer medicine and connect with clinical research trials for their patients.
- Harvey J. Murff, Theodore Speroff, and colleagues develop new methods using natural language processing to detect adverse events after surgery using an electronic medical record.
- Robert Miller, John Newman, and James Sheller identify bronchiolitis obliterans in men during military service in Iraq and Afghanistan.
- Josh Denney, Dan Roden and others demonstrate the feasibility of using a phenome-wide scan to discover gene-disease associations.
- Billy Hudson, Vadim Pedchenko, and others describe the molecular mechanism of Goodpasture's disease, in which conformational change in the alpha3NC1 and alpha5NC1 domain subunits of type IV collagen in the glomerular basement membrane elicits an autoimmune response.
- Tim Sterling and colleagues report results of an international clinical trial that supports a new, shorter, and more effective chemotherapeutic regimen for treatment of latent tuberculosis.
- Olivier Boutaud, John Oates, Jack Roberts and others report that Acetaminophen inhibits hemoprotein-catalyzed lipid peroxidation and attenuates rhabdomyolysis-induced renal failure.
- Dan Roden, Dawood Darbar and others identify genetic variants contributing to cardiac arrhythmias.
- Kathy Murray and Mike Stein, together with Wayne Ray, report the effect of antipsychotic medications on the risk of sudden death.
- Richard D'Aquila and colleagues indicate that the APOBEC3 defense system in lymphocytes can partially defend against HIV-1 at physiological levels of expression, even if HIV-1 expresses a countermeasure, highlighting the potential of attempting to increase expression of these defensive proteins.
- Keipp Talbot and colleagues report how immunization of school age children against influenza impacts older adults.
- Alfred George identified a genetic modifier of congenital long-QT syndrome.
- John Oates and Clinical Pharmacology fellow David Adler describe a patient with inherited phospholipase C2 deficiency characterized by impaired eicosanoid biosynthesis, small intestinal ulceration and platelet dysfunction.
- Mike Stein, Dan Roden and Ute Schwartz identify genetic determinants of the initial response to warfarin.
- Spryos Kalams, David Haas, and colleagues identify HIV-specific CD8+ T cells in CSF of HIV-infected subjects.
- Tom Talbot plays a prominent national leadership role to increase immunization of health care workers against influenza.
- Pingsheng Wu, Tina Hartert and colleagues demonstrate winter virus seasonality as a causal factor in asthma development.
- Alfred George discovered the functional basis for familial migraine associated with brain sodium channel mutations.
- Tim Sterling, ChristinaFiske and colleagues identify risk factors and immunogenetic predictors of extrapulmonary tuberculosis.
- Tim Sterling, Vlada Melekhin, and colleagues find that pregnancy slows HIV-1 immunodeficiency progression during antiretroviral therapy.
- Wonder Drake and colleagues demonstrate immune responses to specific mycobacterial antigens in sarcoidosis, strengthening support for a pathogenetic role identified by their earlier findings of an association of mycobacterial nucleic acids with sarcoidosis.
- Jeffrey Smith defined single nucleotide polymorphisms spanning the entire zebrafish genome.
- Alfred George elucidated functional consequences of heart sodium channel mutations that predispose to sudden infant death syndrome
- Tim Blackwell and colleagues report that NF-ÎºB pathway signaling is important for lung cancer development
- James Loyd and colleagues discovered that telomerase mutations cause disease in some families with idiopathic pulmonary fibrosis
- Bjorn Knollmann and others in the division identify a role for Casq2 deficiency in catecholamine-induced polymorphic ventricular tachycardia.
- David Haas and colleagues identify genomic predictors of response to, and toxicity of, antiretroviral drugs.
- Ela Knapik identified the gene encoding a secretory vesicle coat protein as essential for craniofacial development.
- Gordon Bernard, Art Wheeler and the ARDS network investigators report that a conservative strategy of fluid management reduces the duration of mechanical ventilation and intensive care without increasing nonpulmonary-organ failures in patients with Acute Lung Injury.
- Dan Roden and colleagues identify genetic factors that predispose to drug-induced cardiac arrhythmia.
- Todd Hulgan, Tim Sterling, Bryan Shepherd and colleagues are the first to identify that the percentage of CD4+ T lymphocytes independently adds to the absolute count for clinical prediction HIV disease progression during antiretroviral therapy.
- Tim Cover and colleagues define multi-functional effects of a Helicobacter pylori toxin, VacA.
- Guanqing Wu discovered the functional importance of the recessive polycystic kidney disease gene in morphogenesis of renal tubular. cells
- Michelle Southard-Smith discovered genetic modifiers of murine Hirschsprung disease using genome-wide linkage analysis
- Matt Breyer and colleagues demonstrate that thiazolidinediones expand body fluid volume through PPAR stimulation of ENaC-mediated renal salt absorption.
- Tom Talbot, Tina Hartert, William Schaffner, and Marie Griffin report that asthma is an independent risk factor for invasive pneumococcal disease.
- Wes Ely, Gordon Bernard, Robert Dittus and colleagues demonstrate that delirium in a critical determinant of ICU mortality.
- Spyros Kalams and colleagues determine that a limited T-cell receptor repertoire on virus-specific cytotoxic T cells is associated with escape from antiviral cytotoxic T lymphocyte responses.
- Neil Bhowmick, Eric Neilson, and Hal Moses demonstrate that stromal fibroblasts in interstitial tissues can regulate the oncogenicity of adjacent epithelium.
- David Carbone, Piere Maisson, Yu Shyr, Richard Caprioli, and colleagues identify the subset changes in the proteome in small cell lung cancer
- William Schaffner and colleagues investigate an outbreak of pseudomonas infections caused by defective bronchoscopes. This results in a global recall of these bronchoscopes.
- Dan Roden and colleagues identify genetic factors that predispose to drug-induced cardiac arrhythmia.
- Doug Vaughan and colleagues engineer the first transgenic animal model to develop spontaneous coronary arterial thrombosis and myocardial infarction.
- Munirathinam Sundaramoorthy and Billy Hudson describe the structure of the NC1 domain from type IV collagen and identify the putative quaternary structures of the Goodpasture antibody binding sites in the NC1 domain of alpha-3 (IV) collagen.
- Peggy Kendall and Tom Thomas demonstrate that the natural autoantibody repertoire of nonobese diabetic mice is highly active.
- Matt Breyer identifies mechanism of COX-2 selective inhibitors in development or exacerbation of hypertension.
- Wonder Drake and colleagues report that a novel mycobacterium is a possible etiologic agent of sarcoidosis based on molecular genetic evidence.
- David Johnson and colleagues demonstrate in a randomized study no current regimen was superior to cisplatin and paclitaxel in patients with advanced non-small-cell lung cancer.
- Eric Neilson and colleagues demonstrate that tissue fibroblasts derive locally from epithelium through epithelial-mesenchymal transition.
- Alfred George repairs a mutant chloride channel using a trans-splicing ribozyme.
- Wes Ely, Gordon Bernard, and Robert Dittus develop and validate first method of monitoring delirium in ICU patients, eventually translated into over 8 languages and now implemented by ICUs all over the world as routine ICU management.
- Jorge Capdevila reports novel P450 arachidonic acid metabolites are important regulators of blood pressure.
- Gordon Bernard, Wes Ely, and colleagues report on the efficacy and safety of recombinant human activated protein C for treatment of patients with severe sepsis for the Prowess Sepsis Study Group.
- Doug Kernodle and colleagues demonstrate that the secreted iron-cofactored superoxide dismutase of Mycobacterium tuberculosis inhibits host immune responses and apoptosis, and describe the prototype of a highly effective live-attenuated tuberculosis vaccine based on diminishing microbial immune-inhibitory capacity.
- Ray Harris describes the mechanism by which COX-2-derived prostaglandins regulate renal renin expression and secretion.
- Robert Coffey and colleagues report on the successful treatment of Menetrier's disease with a monoclonal antibody against the epidermal growth factor receptor.
- Mark Anderson and colleagues establish second messenger activation of calcium entry into heart cells by calmodulin kinase II.
- Gordon Bernard reports for the ARDS network that a lower tidal volume than used traditionally results in decreased mortality and increases the number of days without ventilator use.
- David Robertson, Italo Biaggioni, and colleagues demonstrate that orthostatic intolerance and orthostatic tachycardia in some patients is associated with a norepinephrine-transporter deficiency.
- Walter Smalley, Marie Griffin, and Wayne Ray report that FDA-mandated black box warnings on Cisapride do not significantly alter physician prescribing behavior, ultimately eventuating in Cisapride being withdrawn from the market.
- Richard D'Aquila and colleagues demonstrate that drug resistant HIV variants remain archived in CD4+ T lymphocytes for years after emergence, even when not detectable in actively replicating virus.
- John Newman, John Phillips, Jim Loyd, and colleagues discover the mutation in the bone morphogenic protein type II receptor underlying primary pulmonary hypertension.
- Richard Peek and colleagues report that activation of b-catenin in gastric epithelium by carcinogenic Helicobacter pylori contribute to the formation of gastric cancers.
Nancy Brown, Jason Morrow, and Jay Gainer demonstrate that bradykinin contributes to the short-term effects of ACE inhibition on blood pressure in normotensive and hypertensive persons.
David Johnson demonstrates that split-dose radiation improves small-cell lung cancer survival in association with cisplatinum.
Raymond Dubois describes the protective effects of cyclooygenase inhibitors on colon cancer.
Steven Hebert clones and identifies the ROMK potassium channel in the kidney.
Steve Davis demonstrates that increased plasma cortisol is the mechanism responsible for antecedent hypoglycemia causing hypoglycemia associated autonomic failure.
Jeffrey Smith and colleagues report the first major susceptibility gene for human prostate cancer.
William Schaffner and Steven Standaert, colleagues describe the ecology and epidemiology of tick-borne Ehrlichiosis.
Mac Linton and Sergio Fazio use bone marrow transplantation to study the effects of macrophages on atherosclerosis.
Alfred George, Dan Roden and colleagues define a molecular defect responsible for sudden death in the congenital long QT syndrome.
Alfred George and colleagues discover that mutations in the human skeletal muscle chloride channel gene cause dominant myotonia congenita.
Raymond Hakim identifies the critical importance of using biocompatible dialysis membranes in the treatment of patients with acute renal failure.
Stephen Raffanti and colleagues start an HIV care program (The Comprehensive Care Center) in Nashville and use an all-electronic medical record as a founding participant in a large multi-center observational cohort study to document outcomes of HIV infection and its treatment.
Martin Blaser and colleagues identify the Helicobacter pylori cytotoxin-associated gene (cagA) as a virulence marker, associated with increased risk for both gastric cancer and peptic ulcer disease.
Oscar Crofford leads 'The Diabetes Control and Complications Trial Research Group' showing the value of tight glucose control with insulin.
Sanford Krantz demonstrates that cytokines produce apoptosis in erythroid progenitors explaining the anemia of chronic disease.
Robert J. Coffey discovered that Menetrier's Disease is caused by overexpression of TNF-alpha, and eight years later that it could be treated with anti-EGF receptor antibody.
Debra Echt reports the landmark Cardiac Arrhythmia Suppression Trial (CAST) showing the pro-arrhythmic effects of encainide and flecainide in patients post-myocardial infarction.
Martin Blaser reports that colonization of the stomach with Helicobacter pylori is strongly associated with an increased risk of gastric carcinoma.
Doug Kernodle and Allen Kaiser demonstrate that in vivo hydrolysis of peri-operative antibiotic prophylaxis by staphylococcal beta-lactamase is a major mechanism leading to deep surgical wound infections.
Jack Roberts and Jason Morrow identify isoprostanes. These and other non-enzymatically-derived lipids are now recognized as markers of oxidant stress and potential mediators of oxidant injury.
Kamal Badr, Ray Harris, Matt Breyer, John Murray, and colleagues provided the first definitive description of the effect of endothelin on the renal microcirculation.
Doug Kernodle describes four kinetic variants of staphylococcal beta-lactamase.
Marie Griffin, Wayne Ray, and William Schaffner provide the first public alert that elderly users of non-steroidal anti-inflammatory drugs were at increased risk for death or serious gastrointestinal toxicity.
Billy Hudson reports the NC1 domain of the alpha-3 (IV) collagen chain is the target antigen of Goodpasture's disease.
Garret FitzGerald and John Oates define the molecular basis for the efficacy of low dose aspirin to prevent acute coronary events via selective inhibition of platelet thromboxane production.
William Stone identifies beta-2 microglobulin in dialysis-related amyloid.
William Stone and colleagues first describes the failure of antibodies in Goodpasture's disease to stain kidney tissue in Alport's syndrome, providing the first biochemical link between the two diseases.
Rose Robertson, John Oates, and colleagues describe the relationship between thromboxane A2 and coronary vasospasm.
Hal Moses describes a transforming growth factor in chemically-modified cell lines and helps to open the field of TGF-beta biology.
Dan Roden, Ray Woosley, Grant Wilkinson, and Alastair Wood identify instances of genetically-determined drug metabolism and effect, laying the groundwork for the field of pharmacogenetics.
Lloyd King, Graham Carpenter, and Stanley Cohen discover that epidermal growth factor stimulates receptor autophosphorylation.
Alastair Wood and Bob Vestal identify age as a key factor modulating heart rate response to catecholamines.
Zell McGee and colleagues define species-specific factors that allow Neisseria (gonoccoci and meningococci) to bind to epithelial cells.
John Oates and colleagues report the overproduction of prostaglandins in lung cancer, providing the first evidence that the inducible cyclooxygenase may play a role in certain malignancies.
Grant Wilkinson and David Shand describe first-pass metabolism, a common feature for the processing of many drugs.
Kenneth Brigham demonstrates that gram-negative bacteremia can cause increased lung permeability and acute respiratory distress syndrome.
William Schaffner, Marian Ann Melly, and Glenn Koenig perform ground-breaking investigations tracing sepsis in hospitalized patients to contaminated IV fluids.
Roger Des Prez and Robert Goodwin provide the first comprehensive description of mediastinal fibrosis from infection with histoplasmosis.
Glenn Koenig and Jay S. Goodman describe the immunologic detection of cryptococcal antigen for diagnosis of cryptococcal meningitis.
Anderson Spickard, Glenn Koenig, David Rogers and colleagues develop a regimen for using amphotericin B to treat histoplasmosis and other disseminated fungal infections.
Sanford Krantz describes the immune basis for pure red cell aplasia and later shows it response to immunosuppressive therapy.
Robert Hartmann describes the "sugar-water" test for paroxysmal nocturnal hemoglobinuria..
William Coppage and Grant Liddle describe a familial renal tubular disorder simulating primary aldosteronism, later known as Liddle's syndrome (pseudohyperaldosteronism) that is now recognized by a mutation in the apical sodium channel along the cortical collecting duct.
Sanford Krantz describes the effect of erythropoietin on hemoglobin synthesis by marrow cells and later describes its kinetic binding to a putative erythropoietin receptor.
Elliot Newman established one of the first General Clinical Research Centers at Vanderbilt and his notion of how it should operate became a model across the country.
Clifton Meador and Grant Liddle report the ectopic production of ACTH from a tumor producing Cushing's syndrome.
David Rogers, Marian Ann Melly, and M. Glenn Koenig publish landmark findings showing differences in phagocytosis and intracellular survival of pathogenic versus non-pathogenic staphylocci.
Grant Liddle demonstrates that Cushing's disease is primarily a pituitary disorder with increased levels of ACTH at any level of plasma cortisol..
Grant Liddle develops the dexamethesone suppression test to assess the pituitary-adrenal axis. Later Liddle and Clifton Meador show this is due to suppression of ACTH.
John Oates describes one of the early, important anti-hypertensive drugs that became alpha-methyldopa (Aldomet).
Alexander Townes and Grant Liddle develop the metyrapone stimulation test to assess pituitary reserve
David E. Rogers first reports that pneumonia from influenza by itself could be fatal.
Grant Liddle describes the inhibitory effects of spironolactone on aldosterone expression.
Elliot Newman reports the changes in solute excretion following alteration of posture and position.
Paul Teschan first delivers hemodialysis to patients in a war zone.
William Darby demonstrates salt excess as a basis for acquired hypertension.
Rudoph Kampmeier the leading authority on syphilis publishes his classic textbook Essentials of Syphilology.
Samuel Riven, Hugh Morgan, and Alfred Blalock report the first cure of myasthenia gravis by removal of a thymoma.
William Darby first describes protein M (folate) deficiency anemia. Later he went on to identify a number of other vitamin deficiency states and helped establish the minimal daily requirements for iron and vitamins in pregnancy.
Tinsley Harrison after a decade of fundamental research publishes his classic textbook entitled The Failure of the Circulation. Fifteen years later he published his now famous textbook Principles of Internal Medicine.
John Youmans provides the first comprehensive description of the causes of endemic nutritional edema.
John Youmans reports the first formula for estimating osmotic pressure from measurements of albumin and total protein in human blood.
Sidney Burwell measures the physiologic effects of digitalis on cardiac output.
Tinsley Harrison and Alfred Blalock describe the effect of oxygen deficiency on cardiac output.
Tinsley Harrison and William Dock report the effects of arteriovenous fistulas on cardiac output.
Hugh Morgan measures the changes in blood count and blood gases in patients with pneumonia.
Canby Robinson and Sidney Burwell describe methods for measuring PO2 and PCO2 in mixed venous blood