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Glen N. Barber, Ph.D., professor of medicine and the Eugenia J. Dodson Chair in Cancer Research, and Hiroki Ishikawa, Ph.D., post-doctoral fellow.
Glen N. Barber, Ph.D., professor of medicine and the Eugenia J. Dodson Chair in Cancer Research, and Hiroki Ishikawa, Ph.D., post-doctoral fellow.
Sylvester Cancer Researcher Expands Breakthrough Immune System Findings

A prominent researcher at the Sylvester Comprehensive Cancer Center at the Miller School has taken another major step in understanding the mechanisms of the immune system. For the second year in a row, Glen N. Barber, Ph.D., professor of medicine and the Eugenia J. Dodson Chair in Cancer Research, and Hiroki Ishikawa, Ph.D., a post-doctoral fellow, have published their findings in the prestigious journal Nature (online edition September, print October).

In their previous study, Barber and Ishikawa identified a molecule, STING (STimulator of INterferon Genes), which activates the body's innate immune system by triggering the production of interferon. That study focused on fibroblast cells, the most common cells, in vitro. When a virus invades a cell, interferon production is triggered, which then alerts other cells that there is a virus infection. This activates the immune response by creating hundreds of antiviral genes which protect uninfected cells from infection. Without interferon, the body has no early antiviral defense.

In this latest research, Barber and his team expanded their work to examine more specific cell types, including macrophages and dendritic cells which are responsible for activating anti-pathogen B and T cell responses. They also evaluated the importance of STING in an animal model. They found that STING is a "vital element," said Barber.

This NIH-funded study by Barber and Ishikawa further solidifies the importance of STING's role in activating the pathway to begin production of interferon.

STING, as Barber and Ishikawa discovered, initiates a sequence of events that unleashes interferon against viruses. What scientists did not know is how the innate immune system is propelled to react to DNA-based microbes. Armed with the knowledge that STING triggers interferon in basic cells, Barber and Ishikawa took a closer look at STING's role in attacking DNA pathogens such as herpes simplex virus, and the bacteria Listeria, among others. Mice lacking STING were found to be extremely sensitive to virus infection. "What we found," said Barber, "is that STING is absolutely essential to the body's defense against a variety of different DNA pathogen types."

This becomes an especially critical finding in gauging the immune system's reaction to plasmid DNA-based vaccines, such as those being used to develop new types of flu vaccines. Working with animal models, the scientists found that STING was a critical factor in facilitating DNA-mediated immune responses. Vaccines are meant to trigger the body to make antiviral or anti-bacterial antibodies and T cells.

"We think the human innate immune system reacts the same way," says Barber. The theory is that without STING, a DNA-based vaccine wouldn't be effective because the body would not create interferon and other cytokines which are essential for stimulating adaptive immune responses.

W. Jarrard Goodwin, M.D., director of Sylvester, describes the discovery of STING "of fundamental importance to our understanding of innate immunity." Goodwin says Barber's continued work in this area "is likely to be of direct benefit to patients dealing with the 20 percent of human malignancies that are known to be caused by viruses. I am very proud that Sylvester has supported this work along with the National Institutes of Health and other funding agencies."

The finding in this study is leading Barber to the next step in this critical research path. After the initial discovery of STING and its role in triggering the production of interferon in response to DNA and RNA viruses, the team will turn to other DNA-based pathogens. Barber and Ishikawa intend to examine STING's effect on parasites, such as malaria, and fungi. They'll also further evaluate the importance of this molecule in regulating T-cell response to DNA-based vaccines. Better understanding of that relationship, explains Barber, "could lead to improved and safer vaccines to combat cancer and other serious illnesses."

Grand Rounds
Thursday, September 30, 2010 7 a.m. Orthopaedic Grand Rounds: “Cartilage Injuries in the Talus”
Thursday, September 30, 2010 8 a.m. Otolaryngology Grand Rounds: “An Electrophysiological Intra-Operative Monitoring of Hearing During Ossiculoplasty"
Thursday, September 30, 2010 8 a.m. Neurological Surgery Grand Rounds: “Advances and Controversies in the Management of Pituitary Tumors"
Friday, October 1, 2010 1 p.m. Neurology Grand Rounds:  “Assessment of Rapidly Progressive Dementia and Early Diagnosis of Prion Disease"
Tuesday, October 5, 2010 12 p.m. Pathology Grand Rounds: “HPV Carcinogenesis in Head and Neck Tumors”
Wednesday, October 6, 2010 8 a.m. Family Medicine and Community Health Grand Rounds: “Global Health—The Haiti Experience”
Wednesday, October 6, 2010 12 p.m. Medicine Grand Rounds: “How Statisticians Think and Why it Annoys Doctors”
Thursday, October 7, 2010 7 a.m. Orthopaedic Grand Rounds: “Reverse Shoulder Replacement for Fractures and Their Sequelae”
Thursday, October 7, 2010 12 p.m. Department of Medicine Chair Dr. Marc Lippman Presents Pathology Grand Rounds
Thursday, October 7, 2010 12 p.m. Hospital Medicine Grand Rounds: “Providing Quality End-of-Life Care”
Thursday, October 7, 2010 1 p.m. Endocrinology, Diabetes and Metabolism Grand Rounds: “Molecular Regulation of RAGE: Implications for Diabetes and Beyond"
Friday, October 8, 2010 1 p.m. Neurology Grand Rounds: “Dense Array EEG”
Friday, October 8, 2010 2 p.m. Neurology Clinicopathological Conference: “A 61-Year-Old Male with Acute Onset Facial Diplegia, Diplopia and Dysphagia"
Tuesday, October 12, 2010 12 p.m. Cardiovascular Grand Rounds: “Contemporary Management of Paravalvular Leaks”
Wednesday, October 13, 2010 8 a.m. Family Medicine and Community Health Grand Rounds: “The Handoff of Hospitalized Patients”
Thursday, October 14, 2010 7 a.m. Orthopaedic Grand Rounds: “Doing Right and Avoiding Wrong in Orthopaedics Today”
Thursday, October 14, 2010 7:30 a.m. Surgical Grand Rounds: “Preparing for a Terrorist Threat: Defining the Role of the Surgeon”
Thursday, October 14, 2010 12 p.m. Hospital Medicine Grand Rounds: “Update in Obstructive Sleep Apnea”
Friday, October 15, 2010 1 p.m. Neurology Grand Rounds: “Creativity and the Brain”
Tuesday, October 19, 2010 12 p.m. Cardiovascular Grand Rounds: “Diagnosis and Therapy for Vulnerable Plaque”
Wednesday, October 20, 2010 12 p.m. Pathology Grand Rounds: “Thyroid FNA Cytology: Bethesda and Beyond”
Wednesday, October 20, 2010 12 p.m. Epidemiology and Public Health Grand Rounds: “A Randomized Controlled Trial of Structural Ecosystems Therapy for HIV+ Women in Drug Recovery and Their Families"
Wednesday, October 20, 2010 12 p.m. Psychiatry Grand Rounds: “Developmental Factors Underlying the Risk to Develop Anxiety and Depression"
Wednesday, October 20, 2010 12 p.m. Medicine Grand Rounds: “Management of HIV—Beyond HAART”
Wednesday, October 20, 2010 4 p.m. Special Miami Transplant Institute Grand Rounds Presentation and Celebration of 40 Years of Excellence
Thursday, October 21, 2010 7 a.m. Orthopaedic Grand Rounds: “The Biomechanical Rationale for Interosseous Ligament Reconstruction in Essex-Lopresti Injuries"
Thursday, October 21, 2010 7 a.m. Neurological Surgery Grand Rounds: “Surgical Management of Spine Tumors”
Thursday, October 21, 2010 8 a.m. Neurological Surgery Grand Rounds: “Neuropathology”
Thursday, October 21, 2010 8 a.m. Otolaryngology Grand Rounds: “Assessing the Levels of Obstruction in Sleep Apnea”
Thursday, October 21, 2010 12 p.m. Division of Hospital Medicine Grand Rounds: “A Man with Abdominal Pain and Jaundice”
Thursday, October 21, 2010 1:30 p.m. Endocrinology Grand Rounds: “Growth Hormone in Aging”
Tuesday, October 26, 2010 12 p.m. Cardiovascular Grand Rounds: “Carotid Stenting vs. Endarterectomy”
Wednesday, October 27, 2010 7:30 a.m. Plastic Surgery Grand Rounds: “Avoidance and Management of Complications in Lower Eyelid Surgery”
Wednesday, October 27, 2010 8 a.m. Family Medicine and Community Health Grand Rounds: “Promoting Smoking Cessation: Role of the Physician"
Wednesday, October 27, 2010 12 p.m. Department of Medicine Grand Rounds: “Clinical Empathy”
Thursday, October 28, 2010 7 a.m. Neurological Surgery Grand Rounds: “Biomarkers for CNS Injuries: From Benchside to Bedside”
Thursday, October 28, 2010 8 a.m. Otolaryngology Grand Rounds: “Nasal Osteotomy Techniques and Treatment of the Crooked Nose”
Thursday, October 28, 2010 8 a.m. Neurological Surgery/Neurology Grand Rounds: “Collateral Perfusion in Acute Ischemic Stroke”
Friday, October 29, 2010 1 p.m. Neurology Grand Rounds: “What Have We Learned From ADNI?”
Thursday, November 4, 2010 6:45 a.m. Anesthesiology Grand Rounds: “Postoperative Nausea and Vomiting: Can We Ever Get Rid of It?”
Events
Wednesday, September 29, 2010 9 a.m. The Miami Project Wednesday Morning Seminar: “Do Additional Inputs Change Maximal Voluntary Motor Unit Firing Rates After Spinal Cord Injury?"
Wednesday, September 29, 2010 12 p.m. Healthy Steps Presentation: “Clingy Children Who Won’t Let Go: Strategies to Help Your Child Overcome Separation Anxiety"
Thursday, September 30, 2010 12 p.m. Pediatric Clinical Research Forum: “The Incompatibility of Clinical Research and the Common Malady of P Value Neurosis"
Monday, October 4, 2010 12 p.m. Sylvester Comprehensive Cancer Center Seminar: “Target Identification and Inhibition in the Chronic Myeloproliferative Neoplasms"
Thursday, October 7, 2010 12 p.m. Research Roundtable: “Reporting System Overview”
Friday, October 8, 2010 12 p.m. Biochemistry and Molecular Biology Seminar: “Androgen Receptor Coregulators as Biomarkers and Therapeutic Targets in Prostate Cancer"
Friday, October 8, 2010 12 p.m. Ethics Seminar: “Getting to the Good Society—U.S. Research Priorities 2010-2020”
Friday, October 8, 2010 12 p.m. Friday Noon Interdisciplinary Lecture Series
Friday, October 8, 2010 1 p.m. Sylvester Distinguished Lecture: “The Role of Ubiquitination in Signaling Pathways in Inflammation and Cancer"
Tuesday, October 12, 2010 12 p.m. Cell Biology and Anatomy Seminar: “Basic Concepts in Cancer Histopathology”
Wednesday, October 13, 2010 9 a.m. Miami Project Wednesday Morning Seminar: “Recombinant Inhibitory Neuronal Progenitors in Models of Chronic Pain"
Wednesday, October 13, 2010 12 p.m. Pediatric Clinical Research Forum: “Early Detection of Kidney Disease in Preterm Infants”
Thursday, October 14, 2010 12 p.m. Molecular and Cellular Pharmacology Seminar: “Understanding the Molecular Basis of Angiogenesis for Therapy Design"
Thursday, October 14, 2010 12 p.m. Pathology Journal Club Meeting
Thursday, October 14, 2010 7 p.m. The Buoniconti Fund and the Miami Heat’s Chris Bosh Team Up with Neiman Marcus Coral Gables
Friday, October 15, 2010 12 p.m. Friday Noon Interdisciplinary Lecture Series: “Fragile X: A Family of Genetic Disorders”
Friday, October 15, 2010 1 p.m. Neuroscience Center Seminar: “Out on a Limb: Roles for EphA4 and SMN”
Monday, October 18, 2010 12 p.m. Microbiology and Immunology Seminar: “NF-kB Activation and Function: An Alternative View and New Insights Into NF-kB Function in the Nervous System"
Tuesday, October 19, 2010 12 p.m. Developmental Center for AIDS Research Seminar: “Mucosal Immune Responses in HIV Controllers: Location, Location, Location"
Tuesday, October 19, 2010 4 p.m. Genetics/Genomics Seminar: “Emerging Therapeutic Approaches to Mitochondrial Diseases”
Wednesday, October 20, 2010 7:30 a.m. Endocrinology Core Lecture: “Etiopathogenesis and Prevention of Type 2 Diabetes”
Wednesday, October 20, 2010 9 a.m. New Oral and Maxillofacial Surgery Office Opens at University of Miami Hospital
Wednesday, October 20, 2010 12 p.m. Pediatric Clinical Research Forum: “mAKAP and Cardiac Hypertrophy”
Thursday, October 21, 2010 1 p.m. Biochemistry and Molecular Biology Seminar: “Nutritional Modulation of Environmental Toxicity: Implications in Atherosclerosis"
Thursday, October 21, 2010 1 p.m. Endocrinology Fellows Clinical Case Conference: “The Diagnostic Challenges of Growth Hormone Deficiency"
Thursday, October 21, 2010 2:45 p.m. Endocrinology Research Conference: “Role of Type 3 Deiodinase (D3) in Pancreatic Islet Function”
Friday, October 22, 2010 12 p.m. Biochemistry and Molecular Biology Seminar: “Astroglial-NF-kB is an Important Regulator of Learning and Memory and Neurogenesis in Female Mice"
Saturday, October 23, 2010 3 p.m. Cancelled: Bike to the BankAtlantic Center
Sunday, October 24, 2010 10 a.m. 2010 Miami-Dade County “Out of the Darkness” 5K Walk for Suicide Prevention
Monday, October 25, 2010 10 a.m. Sylvester Comprehensive Cancer Center Seminar: “Bayesian Statistical Methods for the Design of Early Phase Cancer Trials and Analysis of Longitudinal Cancer Data"
Tuesday, October 26, 2010 12 p.m. Cell Biology and Anatomy Seminar: “ROS-Sensitive Association of Respiratory Complexes into Supercomplexes"
Tuesday, October 26, 2010 3:30 p.m. Anesthesiology Seminar: “Bedside to Bench: What Can We Learn About Migraine by Studying the Mechanisms of Action of Triptans?"
Wednesday, October 27, 2010 9 a.m. Miami Project Wednesday Morning Seminar: “Axon Formation”
Wednesday, October 27, 2010 12 p.m. Sylvester Distinguished Lecture: “Intracellular Antibodies as Inhibitors of Hepatitis C Virus Replication"
Wednesday, October 27, 2010 12 p.m. Healthy Steps Seminar: “School Readiness: Is Your Child Ready? Are You Ready?”
Wednesday, October 27, 2010 12 p.m. Pediatric Clinical Research Forum: “History of Whole Body Periodic Acceleration (WBPA) 1996-”
Wednesday, October 27, 2010 4 p.m. McKnight Research Seminar: “Deiminated REF Mediated mRNA Transport to Mitochondrial Surface in a Transgenic Mice Model of Multiple Sclerosis"
Thursday, October 28, 2010 8:30 a.m. Sylvester and University of Miami/Jackson Town Hall Meeting
Thursday, October 28, 2010 12 p.m. Brown Bag Lunch-and-Learn Seminar: “IRB 101”
Thursday, October 28, 2010 1:30 p.m. Molecular and Cellular Pharmacology and Division of Endocrinology to Host Seminar
Friday, October 29, 2010 9 a.m. The Miami Project to Cure Paralysis Seminar: “Brain-Machine Interfaces in Neuromedicine: Harnessing the Coding of Behavior from Neural Ensembles"
Friday, October 29, 2010 12 p.m. Biochemistry and Molecular Biology Seminar: “Structure and Function of Insect Odorant Receptors”
Friday, October 29, 2010 2 p.m. Neurology Clinicopathological Conference: “57-Year-Old Female with Progressive Lower Extremity Numbness"
Saturday, October 30, 2010 9 a.m. DOCS Little Haiti Health Fair
Saturday, October 30, 2010 10 a.m. 2010 Start! Heart Walk
Tuesday, November 2, 2010 12 p.m. Cell Biology and Anatomy Seminar: “Tissue Specific Control of Thyroid Hormone Action”
Wednesday, November 3, 2010 12 p.m. Gail F. Beach Memorial Visiting Lectureship: “Microglial Activation, Neuronal Death and Glial Regeneration After SCI"
Wednesday, November 3, 2010 12 p.m. Monthly Networking Meeting for Clinical Research Professionals
Friday, November 5, 2010 1 p.m. Neuroscience Center Seminar: “The Brain’s Logic for Storing Memories”
Monday, November 8, 2010 11 a.m. United Way Raffle Features Travel Prizes
Monday, November 8, 2010 4 p.m. Genetics/Genomics Seminar: “Genome Structure and Expression”
Friday, November 12, 2010 1 p.m. Sylvester Distinguished Lecture: “Cellular Phenotyping of Breast Tumors”
Saturday, November 13, 2010 8:30 a.m. College of Engineering and SEEDS Writing Workshop
Thursday, November 18, 2010 12 p.m. Office of Finance and Treasury 2010 United Way Silent Auction

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