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Gastroenterology Experts Present at AIBD 2014

PITTSBURGH, Dec. 8, 2014 – Faculty from the Division of Gastroenterology, Hepatology, and Nutrition were among the experts who presented at the recent 2014 Advances in Inflammatory Bowel Diseases, Crohn’s & Colitis Foundation’s Clinical & Research Conference in Orlando, Fla. Faculty research was presented in both oral and poster presentations, and covered a wide range of topics, including:

  • A Model Integrating Genetic and Environmental Factors Can Differentiate Crohn’s Disease from Ulcerative Colitis
    UPMC Co-Author: Richard Duerr, MD
  • The Patient-Centered IBD Medical Home: Will This Be the Future of IBD Healthcare Delivery?
    Presented by Miguel Regueiro, MD
  • E. Management of Psycho-Social Issues in IBD Patients: Case Studies
    Co-presented by Eva Szigethy, MD, PhD
  • Clinical Predictors of Moderate Depression and Suicidality in Adults with IBD
    UPMC co-Authors: Victor Chedid, MD, Jana Al Hashash, MD, Gregory Thorkelson, MD, Claudia Rivers-Ramos, MD, David Binion, MD, Miguel Regueiro,MD, Eva Szigethy, MD, PhD
  • What is the Optimal Medical Management of Post-Operative Crohn’s Disease?
    Presented by Miguel Regueiro, MD
  • Stop the Scanners! External Validation of Algorithms Predicting Complications in Patients with Crohn’s Disease Presenting to the Emergency Department
    UPMC Co-Author Jason Swoger, MD
  • Preventing and Treating Narcotic Dependence in Our IBD Patients
    Presented by Eva Szigethy, MD, PhD
  • IBD CONNECT: A Novel Inflammatory Bowel Disease Volunteer Program for Hospitalized Crohn’s Disease and Ulcerative Colitis Patients
    UPMC Co-Authors: Miguel Regueiro, MD, Eva Szigethy, MD, PhD

For more information on the conference, please visit AdvancesInIBD.com.

Physicians and Researchers Present at AASLD 2014

PITTSBURGH, Dec. 1, 2014 – Faculty from the Division of Gastroenterology, Hepatology, and Nutrition and the Thomas E. Starzl Transplantation Institute were well-represented at The Liver Meeting® held by the American Association for the Study of Liver Diseases in Boston. Experts from the division gave oral and poster presentations on topics such as:

  • BPAR (Biopsy Proven Acute Rejection) During Protocolized Immunosuppression Withdrawal (ISW) is Readily Reversed in Pediatric Liver Transplant (Tx) Recipients
    UPMC Contributors: Veena Venkat, MD, George Mazariegos, MD, Anthony Demetris, MD
  • Incremental Dose Model Identified GSK3β and β-catenin as Potential Targets for Regenerative Therapies for Acetaminophen-Induced Acute Liver Failure
    UPMC Contributor: Satdarshan (Paul) Singh Monga, MD
  • Cost-Effectiveness of Novel Hepatitis C Drug Regimens Among Treatment-Experiences U.S. Veterans
    UPMC Contributors: Cindy Bryce, PhD, Michael Fine, MD, MSc, Chester Good, MD, MPH, Larissa Myaskovsky, PhD, Vinod Rustgi, MD, MBA, Allan Tsung, MD, Kenneth Smith, MD, MS
  • Infection Challenges in the Cirrhotic Patient
    UPMC Contributor: Kapil Chopra, MD
  • The Economic Impact of Sofosbuvir-and Simeprevir-Based HCV Treatment in the Unites States
    UPMC Contributors: Mark Roberts, MD, and Michael Dunn, MD
  • Predictors of Mortality in Patients With Low MELD on the Liver Transplant Wait List
    UPMC Contributors: Swaytha Ganesh, MD, Chandraprakash Umapathy, MD, Abhinav Humar, MD, Christopher Hughes, MD, Mark Sturdevant, MD, Elizabeth Kallenborn, MSN, RN, Vinod Rustgi, MD, MBA, Shahid Malik, MD, Amit Tevar, MD
  • HCV Infection in Opiod-Using (OU) Pregnant Women
    UPMC Contributors: Elizabeth Krans, MD, MSc, Vinod Rustgi, MD, MBA
  • All Oral Treatment for Genotypr 4 Chronic Hepatitis C Infection With Sofosbuvir and Ledipasvir: Interim Results from the NIAID SYNERGY Trial
    UPMC Contributor: Vinod Rustgi, MD, MBA
  • Prevalence of Precore and Dual Basal Core Promoter HBV Variants in a Racially Diverse Cohort of Patients With Chronic HBV Infection in North America
    UPMC Contributors: Obaid Shaikh, MD, Abdus Wahed, PhD
  • ABT-450/r/Ombitasvir + Dasabuvir With or Without Ribavirin in HCV Genotype 1-Infected Patients Receiving Stable Opioid Substitution Treatment: Pooled Analysis of Efficacy and Safety in Phase 2 and Phase 3 Trials
    UPMC Contributor: Vinod Rustgi, MD, MBA
  • Safety of ABT-450/r/Ombitasvir + Dasabuvir With or Without Ribavirin in HCV Genotype 1-Infected Patients ≥65 Years of Age: Results From Phase 2 and 3 Trials
    UPMC Contributor: Vinod Rustgi, MD, MBA

For more information on The Liver Meeting, please visit the conference page.

Higher Risk of GI, Major Bleeding in Atrial Fibrillation Patients Taking Blood Thinner Dabigatran

PITTSBURGH, Nov. 3, 2014 – Patients with atrial fibrillation who take the blood thinner dabigatran are at greater risk for major bleeding and gastrointestinal bleeding than those who take warfarin, according to a new study by researchers at the University of Pittsburgh Graduate School of Public Health.

The findings, based on Medicare claims data and published today in JAMA Internal Medicine, indicate greater caution is needed when prescribing dabigatran to certain high-risk patients.

Atrial fibrillation, an arrhythmia in which the heart’s upper chambers irregularly contract, can send tiny clots from the heart to the blood vessels in the brain, explained the study’s senior author Yuting Zhang, Ph.D., associate professor and director of the Pharmaceutical Economics Research Group in Pitt Public Health’s Department of Health Policy and Management. For that reason, these patients often are prescribed a blood thinner to limit clot formation with the aim of preventing strokes.

“Dabigatran was introduced in 2010 and, at the time of approval, it was the only available alternative to warfarin,” Dr. Zhang said. “Warfarin dosing can be tricky and regular monitoring with blood tests is required, so doctors and patients were glad to have a drug that was easier to manage. But some recent studies suggest that dabigatran is associated with a higher risk of bleeding.”

To investigate that possibility, the study’s first author, Inmaculada Hernandez, Pharm.D., Pitt Public Health, and the team looked back at pharmacy and medical claims data, which employ a unique identifier code rather than patient names, from 2010 and 2011 of a random national sample of Medicare beneficiaries. They tracked 1,302 dabigatran users and 8,102 warfarin users to see whether they experienced bleeding episodes, classifying the events as major, such as intracranial bleeding or gastrointestinal bleeding requiring a hospital or emergency room stay, or minor, such as gastrointestinal bleeding that was treated on an outpatient basis, or nose bleeds.

They also looked more closely at bleeding episodes in four high-risk subgroups: those who were 75 and older; African-Americans; those with chronic kidney disease; and those with seven or more co-existing medical problems.

Medicare data showed that the incidence of major bleeding was 9 percent and of any bleeding was 32.7 percent in the dabigatran group and 5.9 percent and 26.6 percent, respectively, in the warfarin group. In other words, dabigatran users were 58 percent more likely to have a major bleed and 30 percent more likely to have any kind of bleed than those taking warfarin. African-Americans and patients with chronic kidney disease using dabigatran were about twice as likely to have a major bleed as those taking warfarin. In addition, dabigatran users were more likely than warfarin users to experience gastrointestinal or vaginal bleeding, or blood in the urine, joints or sputum. However, the dabigatran group had a lower risk for bleeding in the brain.

“These findings indicate that physicians should be cautious when prescribing dabigatran, particularly to African-Americans and patients with kidney impairments,” Dr. Hernandez said. “Also, the incidence of gastrointestinal bleeding was high in all the subgroups, so we recommend doctors explain to patients how to detect it so that it can be treated promptly.”

“We plan to examine 2012 data to monitor the risk of stroke for patients on dabigatran, which is the primary indication for taking the blood thinner,” Dr. Zhang said. “It’s possible that for some patients a greater reduction in the risk of stroke will outweigh the higher risk of bleeding with dabigatran compared to warfarin.”

Other co-authors are Seo Hyon Baik, Ph.D., of Pitt Public Health; and Antonio Piñera, M.D., of La Paz University Hospital, Madrid, Spain.

The project was funded by the Commonwealth Foundation for Public Policy Alternatives and the Agency for Healthcare Research and Quality.

Physicians and Researchers Present at 2014 American College of Gastroenterology Annual Meeting

PITTSBURGH, Oct. 31, 2014 – The University of Pittsburgh Division of Gastroenterology, Hepatology, and Nutrition was well-represented in Philadelphia at the recent American College of Gastroenterology (ACG) Annual Meeting. Faculty research was featured in both oral and poster presentations throughout the conference, including:

  • Pancreatic Cancer: The Genes You Need to Know
    Presented by Randall Brand, MD
  • Perceived Effectiveness of Endoscopic and Surgical Treatments Among North American Women With Complications of Chronic Pancreatitis (2014 ACG Presidential Poster Award winner)
    UPMC co-authors: Jyothsna Talluri, MD; Dhiraj Yadav, MD; David Whitcomb, MD, PhD
  • Antibiotic-Associated Microbiome Changes in Health Volunteers and Corrective Impact of the Probiotic Saccharomyces Boulardii (2014 ACG Presidential Poster Award winner)
    UPMC co-author: Toufic Kabbani, MD
  • Stratification of Crohn’s Disease Patients Using the Lemann Index to Quantify Gut Damage: A 5-Year Prospective Study (2014 ACG Presidential Poster Award winner and 2014 ACG Governor’s Award for Excellence in Clinical Research)
    UPMC co-authors: Claudia Rivers-Ramos, MD; Miguel Regueiro, MD; Jason Swoger, MD; Marc Schwartz, MD; Leonard Baidoo, MD; Jana Al Hashash, MD; Arthur Barrie III, MD; Michael Dunn, MD; David Binion, MD
  • Association of Mean Vitamin D Level With Clinical Status in Inflammatory Bowel Disease: A 5-Year Prospective Study
    UPMC co-presenters: Toufic Kabbani, MD; Claudia Rivers-Ramos, MD; Jason Swoger, MD; Miguel Regueiro, MD; Arthur Barrie III, MD; Marc Schwartz, MD; Jana Al Hashash, MD; Leonard Baidoo, MD; Michael Dunn, MD; David Binion, MD

For more information on ACG’s Annual Meeting, please visit the conference page.

UPMC Investigation into GI Scope-Related Infections Changes National Guidelines

PITTSBURGH, Oct. 9, 2014 – National guidelines for the cleaning of certain gastrointestinal (GI) scopes are likely to be updated due to findings from UPMC’s infection prevention team.

The research and updated disinfection technique will be shared Saturday in Philadelphia at ID Week 2014, an annual meeting of health professionals in infectious disease fields.

“Patient safety is our top priority,” said senior author Carlene Muto, M.D., M.S., director of infection prevention at UPMC Presbyterian Hospital. “We are confident that the change from disinfection to sterilization of GI scopes is necessary in preventing serious infections and we are glad to share our findings with hospitals nationwide.”

After tracking and monitoring  an uptick in antibiotic-resistant infections in 2012 in patients who had undergone an Endoscopic Retrograde Cholangiopancreatography (ERCP) procedure with flexible endoscopy scopes, UPMC began investigating the devices, which are equipped with an “elevator channel” used to deflect accessories passed through the biopsy channel and assist clinicians in examining a patient’s gastrointestinal tract. The elevator channel is most commonly found on ERCP and endoscopic ultrasound scopes.

UPMC took the scopes out of service, notified the manufacturer and began an investigation into the disinfecting process that takes place between each use. When it was ultimately determined that the normal process failed to eliminate all bacteria, UPMC switched to gas sterilization using ethylene oxide to ensure proper disinfection of the scopes.

“Throughout UPMC, no additional health care-associated infections have been linked to scopes since switching to sterilization,” said Dr. Muto.

The move from high-level disinfection of endoscopes to sterilization of them was foreshadowed earlier this year at the Association for Professionals in Infection Control and Epidemiology annual conference in Anaheim, Calif., by Bill Rutala, Ph.D., M.P.H., author of the Centers for Disease Control and Prevention Guideline for Disinfection and Sterilization in Healthcare Facilities. He said he believed the transition would take place in the next five years.

Approximately 11 million gastrointestinal endoscopies are performed annually in the U.S. and contaminated scopes have been linked to more hospital-acquired infections than any other type of medical device.

Pitt Drug Discovery Researchers Receive $5.8 Million Federal Grant to Build 3D Liver Model

PITTSBURGH, Sept. 23, 2014 – With a new $5.8 million, three-year award from the National Institutes of Health (NIH), researchers at the University of Pittsburgh School of Medicine will further develop a state-of-the-art, microfluidic 3D model system that mimics structure and function of the liver to better predict organ physiology, assess drug toxicity and build disease models.

The funding supports the next phase of the NIH’s Tissue Chip for Drug Screening program, which aims to improve ways of predicting drug safety and effectiveness. Researchers from 11 institutions will collaborate over three years to refine existing 3-D human tissue chips and combine them into an integrated system that can mimic the complex functions of the human body.

“We are very enthusiastic about the potential of these microphysiology systems to serve as powerful platforms for studying human diseases and identifying human toxic liabilities,” said the Pitt project’s principal investigator D. Lansing Taylor, Ph.D., Allegheny Foundation Professor of Computational and Systems Biology, Pitt School of Medicine, and director, University of Pittsburgh Drug Discovery Institute.

“The development of tissue chips is a remarkable marriage of biology and engineering, and has the potential to transform preclinical testing of candidate treatments, providing valuable tools for biomedical research,” said NIH Director Francis S. Collins, M.D., Ph.D.

The Pitt research team, along with additional collaborators, is creating models of the functional unit of the liver, called the acinus, using human liver cells and eventually liver cells derived from precursor cells known as induced pluripotent stem cells, as well as three additional cell types. The liver platform includes microfluidic devices, human cells, engineered matrix materials, fluorescence-based biosensors for real-time physiological read-outs, and biochemical and mass spectrometry measurements to determine acute and chronic toxicity effects. They also will build a “microphysiology database” to manage, analyze and model the data collected from the liver constructs.

With such a platform, biomedical scientists will be able to test treatment efficacy in conditions such as non-alcoholic fatty liver disease, liver cancer and breast cancer that has spread to the liver, as well as liver damage including immune-mediated toxicology and fibrosis.  Also, a team of institutions and investigators has been assembled to integrate the liver, kidney and gut models to recapitulate the organ system that is central to drug absorption and metabolism.

The integrated platform will involve the creation of a universal medium, the development of the proper “scaling” of the interacting organ constructs, physiologically relevant flow, incorporation of a micro-formulator to add factors from missing organs and micro-analyzers for monitoring parameters such as pH and oxygen.

Fifteen NIH Institutes and Centers are involved in the coordination of the tissue chip program. Current funding is being provided by the National Center for Advancing Translational Sciences, the National Institute for Biomedical Imaging and Bioengineering, the National Cancer Institute, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Environmental Health Sciences, NIH Common Fund and NIH Office of Research on Women’s Health.

Collaborators include Martin Yarmush, M.D., Ph.D., of Massachusetts General Hospital; John Wikswo, Ph.D., of Vanderbilt University; Jonathan Himmelfarb, M.D., of the University of Washington; Mark Donowitz, M.D., of Johns Hopkins University; and Mary Estes, Ph.D., of Baylor University.

Screening and Drug Therapy Predicted to Make Hepatitis C a Rare Disease

PITTSBURGH, Aug. 4, 2014 – Newly implemented screening guidelines and improved, highly effective drug therapies could make hepatitis C a rare disease in the United States by 2036, according to the results of a predictive model developed at the University of Pittsburgh Graduate School of Public Health.

The results of the analysis, funded by the National Institutes of Health (NIH) and performed with the University of Texas MD Anderson Cancer Center, are published in the Aug. 5 issue of the Annals of Internal Medicine.

A “rare” disease is one that affects at most one in every 1,500 people. Approximately one in every 100 people in the U.S. currently has chronic hepatitis C, a viral infection that compromises liver function.

“Making hepatitis C a rare disease would be a tremendous, life-saving accomplishment,” said lead author Mina Kabiri, M.S., a doctoral student in Pitt Public Health’s Department of Health Policy and Management. “However, to do this, we will need improved access to care and increased treatment capacity, primarily in the form of primary care physicians who can manage the care of infected people identified through increased screening.”

In the U.S., hepatitis C is the leading cause of chronic liver disease and the leading reason for liver transplantation. At 15,100 deaths annually, hepatitis C surpassed the annual number of deaths from HIV in 2007. The economic burden associated with chronic infection is estimated at $6.5 billion a year.

“This is, indeed, a very interesting time for hepatitis C patients and providers,” said senior author Jagpreet Chhatwal, Ph.D., now of the University of Texas MD Anderson Cancer Center, who performed most of the research while at Pitt Public Health. “Several changes have happened in the last two years, including screening policy updates and availability of highly effective therapies.”

In 2012, the Centers for Disease Control and Prevention and the U.S. Preventive Services Task Force recommended that anyone born between 1945 and 1965 — encompassing about 81 percent of chronically infected people — receive a one-time screening for hepatitis C. Hepatitis C often is asymptomatic, meaning that infected people do not know they have it until it is detected through a blood screening.

In early 2014, hepatitis C drug regimens that could be taken orally were introduced to the market, allowing primary care physicians and infectious disease specialists to take on the role of treating hepatitis C patients. The drugs have been shown to be highly effective in making the virus almost undetectable in the blood of patients previously found positive for hepatitis C.

The research team created a highly detailed computer model of the natural history and progression of hepatitis C, both with and without treatment. The model predicts the number of hepatitis C infections in the U.S. at any given time from 2001 to 2050, under multiple potential scenarios describing future treatment, while taking into consideration infection status awareness, stage of disease, treatment history and continued drug development, based on data from the National Health and Nutrition Examination Survey (NHANES) and published clinical studies.

To validate the prediction, the researchers ran the model for the years 2003 to 2010 and predicted 2.7 million cases of hepatitis C, which equaled the actual number of cases reported by NHANES.

The research team then considered what would happen if the guidelines were increased to include a one-time universal screening for hepatitis C among all U.S. citizens, not just baby boomers.

“In that scenario, nearly 1 million cases of hepatitis C would be identified in the next 10 years,” said Ms. Kabiri. “And that translates into making hepatitis C a rare disease by 2026, a decade earlier than we’d predicted with the current screening guidelines.”

The researchers note that such a measure would bring increased costs. The oral therapy regimen costs as much as $1,000 per day.

The model estimated that universal screening coupled with the new drug therapies would reduce liver-related deaths by 161,500 and liver transplants by 13,900 from 2014 to 2050.

“Though impactful, the new screening guidelines do not identity the large number of hepatitis C patients who would progress to advanced disease stages without treatment and could die,” said Dr. Chhatwal. “More aggressive screening recommendations are essential in further reducing the burden, preventing liver-related deaths and eventually eradicating hepatitis C.”

Future research will be needed to determine how the reduction in deaths and transplants offsets the increased costs of screening and drug therapy.

Additional researchers on this study are Alison B. Jazwinski, M.D.; Mark S. Roberts, M.D.; and Andrew J. Schaefer, Ph.D., all of Pitt.

This study was supported by the National Center for Advancing Translational Sciences of the NIH under award number KL2TR000146.

Surgical, Other Advances Made at UPMC Improve Graft Survival of Intestinal, Multi-Visceral Transplant Patients

SAN FRANCISCO, July 30, 2014 – Innovations in surgical techniques, drugs and immunosuppression have improved survival after intestinal and multi-visceral transplants, according to a retrospective analysis of more than 500 surgeries done at UPMC over nearly 25 years.

The study was led by Goutham Kumar, M.D., a transplant surgery fellow at UPMC’s Thomas E. Starzl Transplantation Institute. Dr. Kumar was recognized for his work with the Young Investigator Award by the 2014 World Transplant Congress and presented his findings at the group’s July 26 to 31 meeting in San Francisco.

“UPMC has led the way in the development of new surgical techniques and important research involving transplantation, and our analysis shows that our innovations have made a real difference to patients,” Dr. Kumar said.

The researchers examined 541 intestinal and multi-visceral transplants done at UPMC from 1990 to 2013. The total consisted of 228 pediatric transplants and 313 adult transplants; 252 were intestine-only transplants, 157 were liver-intestine, 89 were full multi-visceral, and 43 were modified multi-visceral. A majority of the pediatric patients suffered from gastroschisis, followed by volvulus and necrotizing entercolitis. The adult patients needed transplants because of thrombosis, Crohn’s disease or some kind of obstruction.

Researchers analyzed several outcomes and found that pre-conditioning with certain immunosuppressants, the time the graft is outside of the body, certain blood types and a disparity in the gender of donor and recipient were among the factors predicting graft survival.

Co-authors on the study are George Mazariegos, M.D., Guillerme Costa, M.D., Gaurav Gupta, M.D., Dolly Martin, Geoff Bond, M.D., Kyle Soltys, M.D., Rakesh Sindhi, M.D., Abhinav Humar, M.D., and Hiroshi Sogawa, M.D., all of either the Thomas E. Starzl Transplantation Institute, Children’s Hospital of Pittsburgh of UPMC or UPMC.

In addition to Dr. Kumar, six other UPMC and University of Pittsburgh Schools of the Health Sciences researchers were recognized this year with Young Investigator Awards by the World Transplant Congress. They and their presentations are:

Aravind Cherukuri, M.D., Ph.D.
“Transitional B Cell (TrB) T1/T2 Ratio is a Marker for Graft Dysfunction in Human Kidney Transplant Recipients (KTRs)”

Vinayak Rohan, M.D.
“Outcomes of Liver Transplantation for Unresectable Liver Malignancy in Children”

Qing Ding, Ph.D.
“TIM-1 Signaling is Required for Maintenance and Induction of Regulatory B Cells Through Apoptotic Cell Binding or TIM-1 Ligation”

Kanishka Mohib, Ph.D.
“TIM-4 Expression by C Cells Identifies an Inflammatory B Effector 1 Subset that Promotes Allograft Rejection and Inhibits Tumor Metastases”

Dalia Raich-Regue, Ph.D.
“Myeloid Dendritic Cell-Specific mTORC2 Deficiency Enhances Alloreactive Th1 and Th17 Cell Responses and Skin Graft Rejection”

Tripti Singh, M.D.
“B Cell Depletion of Naïve Recipients Enhances Graft Reactive T Cell Responses”

Pitt-led Study Suggests Cystic Fibrosis is Two Diseases, One Doesn’t Affect Lungs

PITTSBURGH, July 17, 2014 – Cystic fibrosis (CF) could be considered two diseases, one that affects multiple organs including the lungs, and one that doesn’t affect the lungs at all, according to a multicenter team led by researchers at the University of Pittsburgh School of Medicine. The research, published online today in PLOS Genetics, showed that nine variants in the gene associated with cystic fibrosis can lead to pancreatitis, sinusitis and male infertility, but leave the lungs unharmed.

People with CF inherit from each parent a severely mutated copy of a gene called CFTR, which makes a protein that forms a channel for the movement of chloride molecules in and out of cells that produce sweat, mucus, tears, semen and digestive enzymes, said co-senior investigator David Whitcomb, M.D., Ph.D., chief of gastroenterology, hepatology and nutrition, Pitt School of Medicine. Without functional CFTR channels, secretions become thick and sticky, causing problems such as the chronic lung congestion associated with CF.

“There are other kinds of mutations of CFTR, but these were deemed to be harmless because they didn’t cause lung problems,” Dr. Whitcomb said. “We examined whether these variants could be related to disorders of the pancreas and other organs that use CFTR channels.”

Co-senior author Min Goo Lee, M.D., Ph.D., of Yonsei University College of Medicine in Seoul, Korea, conducted careful tests of CFTR in pancreatic cell models and determined that a molecular switch inside the cell called WINK1 made CFTR channels secrete bicarbonate rather than chloride molecules.

“Pancreas cells use CFTR to secrete bicarbonate to neutralize gastric acids,” Dr. Whitcomb said. “When that doesn’t happen, the acids cause the inflammation, cyst formation and scarring of severe pancreatitis.”

The research team found nine CFTR gene variants associated with pancreatitis after testing nearly 1,000 patients with the disease and a comparable number of healthy volunteers. They also learned that each variant could impair the WINK1 switch to prevent CFTR from becoming a bicarbonate-secreting channel.

Co-senior author Ivet Bahar, Ph.D., Distinguished Professor and John K. Vries Chair of Computational Biology, Pitt School of Medicine, built a computer model of the CFTR protein’s structure and determined that all the nine variants alter the area that forms the bicarbonate transport channel, thus impairing secretion of the molecule.

“It turns out that CFTR-mediated bicarbonate transport is critical to thin mucus in the sinuses and for proper sperm function,” Dr. Whitcomb said. “When we surveyed pancreatitis patients, there was a subset who said they had problems with chronic sinusitis. Of men over 30 who said they had tried to have children and were infertile, nearly all had one of these nine CFTR mutations.”

He added that identification of the mechanisms that cause the conditions make it possible to develop treatments, as well as to launch trials to determine if medications that are used by CF patients might have some benefit for those who do not have lung disease, but who carry the other mutations.

The team includes researchers from the University of Pittsburgh, the Mayo Clinic, Brigham and Women’s Hospital, and many other institutions that are part of the North American Pancreatitis Study Group.

The study was supported by National Institutes of Health grants DK061451, DK062420, GM086238, DK063922, CA047904 and RR024153; the Ministry for Health & Welfare, Republic of Korea; and Brain Korea 21 Project for Medical Sciences, Seoul.

Jeffrey I. Gordon, M.D., Will Receive Pitt’s Dickson Prize at Science 2014—Sustain It!

PITTSBURGH, July 17, 2014 – A scientist who has explored how the tens of trillions of microbes that live in the gastrointestinal tract and their genes influence human physiology, metabolism and nutritional status will receive the University of Pittsburgh’s 2014 Dickson Prize in Medicine.

Jeffrey I. Gordon, M.D., will accept the University of Pittsburgh School of Medicine’s most prestigious honor during Science 2014—Sustain It!, a showcase of the region’s latest research in science, engineering, medicine and computation that will be held from Oct. 1 to 3 at Alumni Hall in Oakland. Dr. Gordon is the Dr. Robert J. Glaser Distinguished University Professor and director of the Center for Genome Sciences and Systems Biology at Washington University School of Medicine in St. Louis.

“Dr. Gordon’s work describes our species as a rich and meaningful ecosystem of interactions between human and microbial components,” said Arthur S. Levine, M.D., Pitt’s senior vice chancellor for the health sciences and John and Gertrude Petersen Dean of Medicine. “His fascinating work has broadened our understanding of obesity in the western world and malnutrition in developing countries and has the potential to stimulate new therapies directed at the microbiome.”

In the body, microbes, primarily bacteria, but also fungi and archaeons, and the viruses that infect them, outnumber an individual’s human cells by a factor of 10. The number of genes in the body’s indigenous microbial communities far exceeds the number of genes in the human genome. Most of these microorganisms reside in the gut. Through innovative experimental and computational methods, including studies of twins of different ages, geographic locales and cultural traditions, and the use of germ-free animal models colonized with gut microbial communities (microbiota) harvested from healthy and unhealthy humans, Dr. Gordon and his students have provided new insights about how the gut microbiota contribute to obesity and metabolic abnormalities, as well as to childhood undernutrition.

Their interdisciplinary studies have helped create a new field of research, altering ways to define the health benefits of foods being produced or that could be produced in response to the global challenges of population growth and sustainable agriculture. Also, Dr. Gordon’s lab is providing a microbial view of human development, including how functional maturation of the gut microbiota is related to healthy growth of infants and children, and helping to usher in a new era of microbiota-directed therapeutics.

At 11 a.m., Thursday, Oct. 2, Dr. Gordon will deliver the Dickson Prize in Medicine Lecture. His talk is titled “A Microbial View of Human Development: The Gut Microbiota and Childhood Undernutrition.”

Dr. Gordon earned his bachelor’s degree in biology at Oberlin College in 1969 and his medical degree at the University of Chicago Pritzker School of Medicine in 1973. He completed a residency in medicine at Barnes Hospital in St. Louis, a postdoctoral fellowship in biochemistry and molecular biology at the National Institutes of Health, and a fellowship in gastroenterology at Washington University in St. Louis. He is the recipient of the Danone International Prize for Nutrition, the Selman A. Waksman Award in Microbiology from the National Academy of Sciences, the Robert Koch Award, and many other honors. He is a member of the National Academy of Sciences, the Institute of Medicine of the National Academies, the American Academy of Arts and Sciences and the American Philosophical Society.

In addition to Dr. Gordon, other renowned researchers also will deliver plenary lectures at Science 2014. The Mellon Lecture will be given by Stuart Orkin, M.D., of Harvard Medical School; the Hofmann Lecture will be given by Jeannie T. Lee, M.D., Ph.D., also of Harvard Medical School; and the Provost Lecture will be given by Jonathan Rothberg, Ph.D., founder of Ion Torrent Systems, Inc., and a pioneer in the field of next-generation DNA sequencing.

Nominations for the 2015 Dickson Prize in Medicine are now being accepted.

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