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Erectile Dysfunction Drugs Could Protect Liver from Sepsis-Induced Damage, Says Pitt Team

PITTSBURGH, Jan. 29, 2015 – Drugs that are on the market to treat erectile dysfunction (ED) could have another use—they might be able to protect the liver from damage caused by sepsis, a systemic inflammatory response to infection, say researchers at the University of Pittsburgh School of Medicine. They recently published their findings in Science Signaling.

Infection can lead to the release of chemicals that cause whole-body inflammation, which can cause life-threatening damage to organs including the liver and kidneys, explained senior investigator Timothy Billiar, M.D., professor and chair of surgery, Pitt School of Medicine. Sepsis is a leading cause of death in the intensive care unit.

“Sepsis is a very challenging problem, so the possibility that we might be able to repurpose a drug that is in use and well understood is very exciting,” Dr. Billiar said.

Sepsis triggers production of a protein called tumor necrosis factor, or TNF, which helps fight infection but is harmful at sustained high levels. The researchers found in a mouse model of sepsis that sildenafil, more commonly known as Viagra, induced the liver to produce greater amounts of a protein called cyclic GMP, which in turn led cells to shed surface proteins called TNF receptor, reducing TNF signaling in the cells and preventing  liver damage. Experiments with human liver cells also showed the protective effects of the drug.

“Our study suggests that increasing the bioavailability of cyclic GMP might be beneficial in ameliorating the inflammation associated with sepsis,” Dr. Billiar said. “Sildenafil and other ED drugs might be a good approach to try early in the course of the illness to forestall organ damage.”

The research team plans to verify their findings in a large animal model of sepsis.

Other investigators include lead author Meihong Deng, Ph.D., Patricia A. Loughran, Ph.D., Liyong Zhang, Ph.D., and Melanie J. Scott, M.D., Ph.D., all of the University of Pittsburgh. The project was funded by National Institutes of Health grants GM044100 and GM050441.

Dementia Expert Invited to Attend Young Leaders in Dementia Event at British Embassy

PITTSBURGH, Jan. 26, 2015 – Eric McDade, DO, assistant professor in the University of Pittsburgh Department of Neurology, has been invited to attend the U.S. Young Leaders Discussion Series for Innovative Ideas to Address Dementia on Feb. 9, 2015 at the British Embassy in Washington, D.C. The UK Science and Innovation Network organized the event as part of a series of young leaders events in parallel with the Global Action Against Dementia (GAAD) Legacy Events to raise awareness of the UK G8 Dementia Summit and create a network of young leaders who can contribute to the work of the UK-initiated World Dementia Council (WDC).

The discussion series will give young leaders the opportunity to develop innovative ideas to support the ongoing work of the WDC, and to create a sustainable global network, which will continue to address the challenges presented by dementia.

The goals of the events are to:

  • Create a virtual global network of future young leaders in dementia
  • Establish a ‘Young Innovators Declaration’ to address issues in dementia for the future
  • Contribute to GAAD and WDC strategies

Dr. McDade’s clinical focus is on dementia with interests in frontotemporal dementia, Alzheimer dementia, Lewy body dementia, and young-age onset dementias, as well as familial dementia syndromes. He also evaluates patients at the University of Pittsburgh Alzheimer’s Disease Research Center (ADRC), and contributes to clinical trials in Alzheimer’s disease.

Through his interest in familial dementia syndromes, Dr. McDade serves as the University of Pittsburgh’s principal investigator for the Dominantly Inherited Alzheimer Network (DIAN), an international, multi-site study of autosomal dominant Alzheimer’s.

For more information about the discussion series, please visit the UK Science & Innovation Network webpage.

Pitt Effort Seeks to Combat ‘Sitting Disease,’ Diabetes with $3M NIH Grant

PITTSBURGH, Jan. 26, 2015 University of Pittsburgh Graduate School of Public Health researchers are flipping conventional thought on its head regarding how to improve the health of sedentary people at risk for diabetes and heart disease in a new study designed to combat a condition popularly called “sitting disease.”

Armed with a $3 million grant from the National Institutes of Health (NIH), physical activity epidemiologist Andrea Kriska, Ph.D., and her team will investigate whether they can improve the health of sedentary, overweight people with a program initially focusing on decreasing the amount of time they spend sitting – rather than starting with an emphasis on increasing the amount of time they spend exercising. This current study will test the concept that sitting less may be as important as participating in planned bouts of moderate intensity physical activity in sedentary people.

“To maintain a healthy lifestyle,  national recommendations are that you get a minimum of about two-and-a-half hours of moderate to vigorous physical activity every week – but we know that there are a lot of people who do little, if any, physical activity on a regular basis,” said Dr. Kriska, professor in Pitt Public Health’s Department of Epidemiology. “For those people, getting them to exercise might not be as initially effective as working at the other end of the activity spectrum by trying to decrease the amount of time they spend sitting.”

The grant will be used to create a new, alternate version of the Group Lifestyle Balance™ (GLB) program, a lifestyle program designed for overweight and inactive individuals who want to improve their health. The GLB program was modified for use in public health from the highly successful lifestyle intervention utilized in the U.S. Diabetes Prevention Program clinical research trial, which demonstrated for the first time – in sites across the U.S. – that people at risk for diabetes who lost weight and increased their physical activity levels sharply reduced their risk for diabetes and heart disease, outperforming people who took a diabetes drug instead. Developed here in Pittsburgh by faculty from Pitt Public Health’s Diabetes Prevention Support Center, the GLB has been shown to be effective in a variety of diverse community settings, ranging from the worksite and the military to community senior centers and primary care facilities.

The GLB program involves 22 sessions delivered over the course of one year that focus on healthy lifestyle changes, including encouraging people to slowly and safely increase their levels of physical activity. The program introduces the idea of reducing sedentary behavior toward the end of the sessions, with the major emphasis on increasing physical activity levels throughout the program.

The new grant will put the concept of sitting less right up front as the primary movement goal.

“So at the beginning, participants are not going to start tracking how much walking and biking they do. Instead, they’re going to think about how much time they spend sitting – and then start decreasing that time,” said co-investigator M. Kaye Kramer, Dr.P.H., assistant professor in Pitt Public Health’s Department of Epidemiology and director of the school’s Diabetes Prevention Support Center.

The program will seek to enroll more than 300 people age 50 and older in the Pittsburgh region. Participants will be screened to ensure that they are at risk for diabetes or metabolic syndrome in order to test the program on those most likely to benefit from it. The research team will track participants’ weight, waist circumference, blood glucose and fat levels, blood pressure, physical function, quality of life and, of course, changes in sedentary behavior and physical activity.

“We believe that we’re going to see an increase in overall movement by encouraging people to sit less,” said Dr. Kriska. “And that will lead to a whole host of health improvements, from weight loss to decreasing risk factors for diabetes and heart disease.”

Additional investigators on this project are Bonny Rockette-Wagner, Ph.D., Vincent Arena, Ph.D., Elizabeth Venditti, Ph.D., Rachel Miller, M.S., Tom Songer, Ph.D., and Jennifer Brach, Ph.D., P.T., all of Pitt.

People interested in learning more about the new study can visit Pitt’s Diabetes Prevention Support Center at www.diabetesprevention.pitt.edu.

Pitt Researcher Receives Innovation Award for Parkinson’s Research

PITTSBURGH, Jan. 23, 2015 – Laurie Sanders, Ph.D., assistant professor of neurology in the Pittsburgh Institute of Neurodegenerative Diseases, University of Pittsburgh Department of Neurology, will receive the William N. & Bernice E. Bumpus Foundation Innovation Award. The Innovation Award is designed to provide support for the next generation of exceptionally creative thinkers with “high risk/high reward” ideas that have the potential to significantly impact the understanding of the cause and prevention of Parkinson’s disease.

The $300,000 award will enable Dr. Sanders to further investigate the underlying mechanisms of neurodegeneration in Parkinson’s disease. There is strong evidence that oxidative damage to proteins and lipids are a contributing factor to the development of Parkinson’s, but very little is known about unrepaired mtDNA damage, which has been shown to lead to cell death. Dr. Sanders’ research will focus on the events that lead to mtDNA damage and could lead to crucial advances in the understanding of Parkinson’s disease and experimental therapeutics.

UPMC Approved to Perform Kidney Transplants at UPMC Hamot

ERIE, Pa., Jan. 22, 2015 – The private organization that manages the nation’s organ sharing network has given approval for UPMC surgeons to start performing kidney transplants at UPMC Hamot. The decision by the United Network for Organ Sharing (UNOS) means kidney recipients in northwestern Pennsylvania will have access to the same world-class care offered at UPMC hospitals in Pittsburgh, where organ transplantation was pioneered and perfected.

UPMC officials expect to begin performing  kidney transplant surgeries, with organs from both living and deceased donors, at Hamot starting this summer. It will mark the first time that UPMC has performed transplant surgeries outside of Pittsburgh.

“This is a really exciting time for the UPMC transplant program. Over the last several years, we’ve expanded our clinics across western Pennsylvania and are seeing more patients for clinic visits where they live, instead of having them travel to Pittsburgh,” said Abhinav Humar, M.D., UPMC’s chief of transplantation. “Now we have our first opportunity to perform transplant surgeries outside of Pittsburgh, and hopefully offer this lifesaving procedure to many more people living with kidney disease.”

Officials estimate that about 250 patients who are currently being evaluated for transplants, are on the waiting list, or are post-transplant will have their care transferred from Pittsburgh to Hamot.  Over the next few months, officials at UPMC Hamot plan to spread the word about the new program through community outreach and town hall meetings. Dates for the meetings are still being determined.

“UPMC has led the way in organ transplantation, from performing first-of-its kind procedures to developing drug regimens that made it possible for transplant survivors to thrive. Now patients can stay here in our community to get the benefit of these amazing innovations,” said David P. Gibbons, M.H.A., R.N., UPMC Hamot’s chief operating officer.

The transplant team at Hamot is currently being assembled and will consist of individuals based at Hamot as well as individuals from the transplant program at Pittsburgh, allowing for a close partnership with the University of Pittsburgh’s Thomas E. Starzl Transplantation Institute. The institute’s namesake, Dr. Starzl, is considered by many to be the father of transplantation.

Since 1981, UPMC has performed more than 17,000 organ transplants, and has developed some of the most extensive clinical expertise in the field, giving hope to patients across the country and around the world.

New Machine-Perfusion Organ Preservation System Keeps Livers Healthier for Transplant

PITTSBURGH, Jan. 22, 2015 – A new preservation system that pumps cooled, oxygen-rich fluid into donor livers not only keeps the organs in excellent condition for as long as nine hours before transplantation, but also leads to dramatically better liver function and increases survival of recipients, according to a series of animal studies by researchers at the University of Pittsburgh School of Medicine and the McGowan Institute for Regenerative Medicine. The system could be tested with transplant patients at UPMC later this year.

The findings, which were published online in the American Journal of Transplantation, suggest that it’s possible to use the technique of “machine perfusion” with a newly created cell-free oxygenated solution to expand the number of high-quality livers available for transplant, thereby shortening waiting times and reducing patient mortality.

Currently, 20 to 40 percent of donor livers cannot be transplanted into recipients because oxygen deprivation during storage and transport in conventional containers can make pre-existing tissue damage worse, explained senior investigator Paulo Fontes, M.D., UPMC transplant surgeon, associate professor, Starzl Transplantation Institute, Department of Surgery, Pitt School of Medicine, and a deputy director of the McGowan Institute. If the damage is too extensive, the organ cannot be safely transplanted into a patient.

“Standard practice is to use a method called cold static preservation, which uses tissue cooling to slow down metabolism with the aim of reducing the demand for oxygen and thus protecting cells from death,” Dr. Fontes explained. “In our new system, we pump a special fluid designed to deliver oxygen to the liver, creating an environment that supports normal function. The integrity of the cells and vital metabolic activity is sustained for eventual transplantation of the organ.”

The research team optimized a machine-perfusion (MP) device that was developed by Organ Assist, a company in the Netherlands, and added a fluid with a hemoglobin-oxygen carrier component to deliver high concentrations of oxygen to the tissue. The liver is immersed in chilled fluid, which is also pumped through tubes inserted into the organ’s large blood vessels to effectively oxygenate the tissue.

The team transplanted six pigs with livers that had been kept for nine hours, roughly the average time between recovery of the organ and transplantation into a recipient, in the MP system and another six with organs placed in the standard container.

They found that 100 percent of the pigs who got MP livers survived, compared to 33 percent of those who received conventionally preserved organs. The MP livers functioned better, produced more bile and had higher oxygen levels than their conventional counterparts, and analyses of multiple biomarkers including inflammatory mediators indicated that the MP livers had been better preserved.

Also, “it was immediately obvious to us that the pigs who received MP livers looked much healthier and easily moved around their pens just hours after they woke up from the surgery,” Dr. Fontes said. “They didn’t look as ill as the animals treated with standard cold preservation. It was amazing.”

The data from the studies have been shared with federal regulators, he added, with the aim of launching a clinical trial to test the system at UPMC this year.

“This system has great potential to enhance our current standards for organ preservation, which should translate into more patients getting a life-saving procedure with potentially better outcomes,” Dr. Fontes said. “Not only that, we have hopes of a faster recovery because the liver could be less likely to become injured due to a lack of oxygen.”

Co-investigators include Roberto Lopez, M.D., Yoram Vodovotz, Ph.D., Marta Minervini, Ph.D., Victor Scott, M.D., Kyle Soltys, M,D., Sruti Shiva, Ph.D., Shirish Paranjpe, Ph.D., David Sadowsky, Derek Barclay, Ruben Zamora, Ph.D., Donna Stolz, Ph.D., Anthony Demetris, M.D., George Michalopoulos, M.D., Ph.D., and James Wallis Marsh, M.D., all of the University of Pittsburgh; and Arjan van der Plaats, Ph.D., of Organ Assist, Groningen, Netherlands.

The study was funded by a charitable gift from Mr. and Mrs. Garcia de Souza, as well as grant DK072146 from the National Institutes of Health.

UPMC Sports Medicine Concussion Program Releases Research Review

PITTSBURGH, Jan. 21, 2015 – The UPMC Sports Medicine Concussion Program has released its 2014 summary of concussion research trends, new research initiatives, publications, and ongoing collaborations from their Research Laboratory.

The UPMC Sports Medicine Concussion Program is under the leadership of director Michael Collins, PhD, associate professor of orthopaedic surgery in the Division of Sports Medicine, and assistant research director Anthony Kontos, PhD, associate professor of orthopaedic surgery in the Division of Sports Medicine.

Research initiatives of the Concussion Program continue to center on advances in empirically based assessment, neuroimaging, targeted treatments, and the effects of concussion in youth sport populations. Much of this research continues to focus on advancing the current clinical standard of care for assessing and treating this injury.

Key research and collaborations featured in the report include,

  • “Targeted Evaluation, Action, and Monitoring for TBI (TEAM-TBI),” a $4.4 million project funded by the United States Department of Defense that focuses on providing veterans and active duty military personnel with a comprehensive assessment and targeted clinical interventions for mild traumatic brain injuries (mTBI).
  • The NFL-GE Head Health Initiative grant to identify concussion and track recovery in athletes using high definition fiber tracking (HDFT) and other clinical measures.
  • Select published papers from UPMC and University of Pittsburgh faculty that were featured in peer-reviewed journals such as the American Journal of Sports Medicine, Pediatrics, and Brain Imaging and Behavior.
  • An ongoing, first-of-its-kind initiative funded by the National Collegiate Athletic Association (NCAA) and the Department of Defense Grand Alliance, and in partnership with Indiana University, the Medical College of Wisconsin, and the University of Michigan, to collect data on NCAA athletes from all sports and military personnel to gain understanding into the multidimensional predictors and outcomes associated with sports-related concussion.
  • President Barack Obama’s selection of Dr. Collins and Dr. Kontos to be among the few chosen clinical and research experts on concussion invited to attend the Healthy Kids and Safe Sports Concussion Summit at the White House where $86 million in funding from various stakeholders was announced.

For more information, please read the full Research Review.

Robert P. Edwards, MD, Named Chair of the Department of Obstetrics, Gynecology, and Reproductive Sciences

PITTSBURGH, Jan. 21, 2015 – The University of Pittsburgh School of Medicine and UPMC are proud to announce the appointment of Robert P. Edwards, MD, as chair of the Department of Obstetrics, Gynecology, and Reproductive Sciences, effective Jan. 1, 2015. Dr. Edwards is succeeding W. Allen Hogge, MD, who retired at the end of December 2014 after 22 years of distinguished service.

Dr. Edwards received his medical degree from the University of Pittsburgh School of Medicine and completed an internship in surgery at the University of California, San Francisco. He also completed a residency in obstetrics and gynecology at Magee-Womens Hospital of UPMC, and two postdoctoral fellowships at the University of Alabama; one in immunology and microbiology, and another in gynecologic oncology.

His first independent appointment was in 1993 as an assistant professor of Obstetrics, Gynecology, and Reproductive Sciences at the University of Pittsburgh with a secondary appointment in the UPMC Department of Surgery. In 2000, Dr. Edwards was promoted to associate professor. From 1993 through 2001, he was director of the Division of Gynecologic Oncology at Magee, and he was a clinical investigator in the Magee-Womens Research Institute (MWRI). Starting in 2002, Dr. Edwards spent three years at the University of Louisville School of Medicine in the Departments of Microbiology and Immunology, and Obstetrics, Gynecology, and Women’s Health. In 2005, Dr. Edwards returned to Pitt as vice chair for Clinical Affairs in the Department of Obstetrics, Gynecology, and Reproductive Sciences, a senior investigator in MWRI, and director of Gynecologic Oncology Research and Outreach at Magee. In 2008, tenure was conferred, and he was appointed full professor. In 2010, Dr. Edwards was appointed executive vice chair of Gynecologic Services and co-director of the Ovarian Cancer Center of Excellence at Magee.

Dr. Edwards is a member of several professional and scientific societies, including the American Association for Cancer Research, the American Association for the Advancement of Science, the American Society for Clinical Oncology, the International Gynecologic Cancer Society, and the Society of Gynecologic Oncologists. He also is a fellow of the American College of Obstetricians and Gynecologists and the American College of Surgeons.

He has received various awards and honors throughout his career including two National Faculty Awards from the Council on Resident Education in Obstetrics and Gynecology (CREOG) of the American Congress of Obstetricians and Gynecologists. Dr. Edwards also has authored or co-authored 177 peer-reviewed research reports published in obstetrics and oncology literature, as well as PLOS ONE, Human Genetics, Nature Genetics, and The New England Journal of Medicine, and he is a member of the editorial board of Gynecology. His prominence is reflected in frequent invitations to lecture in such venues as the Roswell Park Cancer Institute, as well as annual meetings of the Society of Surgical Oncology and the Society of Gynecologic Oncologists.

Dr. Edwards’ research is very well supported and has been since the inception of his independent academic career. Currently, he is co-principal investigator of an ovarian cancer NIH SPORE grant, and he is co-investigator on grants from the United States Army and the Ovarian Cancer Research Foundation.

Dr. Edwards’ research focuses on the diagnosis, pathogenesis, and management of gynecologic cancers. He investigates therapies for cervical and ovarian cancer, combining biologic and immunologic strategies. Clinical trials that he designed and implemented include studies on intraperitoneal interleukin-2 therapy for ovarian cancer, and he was involved in early trials of the human papillomavirus (HPV) vaccine. In his current work, Dr. Edwards is investigating vaccines to treat ovarian cancer, and he is studying the impact of cytoxin on T regulatory cell populations, which are associated with the induction of vaccine responses in ovarian cancer patients. In collaboration with the radiation oncology group, he has also worked to advance radiotherapeutic treatments for vulvar and cervical cancers. In addition to his own research, Dr. Edwards will be a member of the MWRI Board, while Yoel Sadovsky, MD, continues to serve as vice chair of the Department for Research, MWRI’s executive director, and associate dean for Women’s Health and Reproductive Sciences Research.

In addition to his clinical and research activities, Dr. Edwards is a committed teacher and mentor for University of Pittsburgh medical students, residents, and fellows. He is a member of many internal committees at UPMC and Magee. He also has been an ad hoc member of the Ovarian Cancer Research Program Integrated Panel NIH study section and a member of various advisory boards, as well as industry working groups.

Statins Inhibit Spread of Some Cancers in Laboratory Tests

PITTSBURGH, January 15, 2015 – Cholesterol-lowering drugs appear to be a promising, cost-effective way to reduce the risk of metastases in some cancers, according to laboratory research led by the University of Pittsburgh School of Medicine. Metastases, rather than the original tumor, are what usually kill people with cancer.

The discovery, published in the open-access journal Scientific Reports, part of the Nature Publishing Group, reveals the mechanism by which statins may impede the process that cancerous tumor cells need in order to split off from the primary tumor and cause cancer elsewhere in the body.

“We didn’t plan to discover this – we were actually modeling metabolism of tumor cells and looking at the response of various tumor cells to existing drugs, including statins,” said senior author Zoltán Oltvai, M.D., associate professor of pathology at Pitt. “But, sure enough, we were able to show that these cholesterol-lowering drugs interrupt the growth of some cancer cell lines that are very similar to those cancer cells that leave the primary tumor and eventually colonize other organs.”

When a tumor metastasizes, it spreads cancer cells through the body using the blood stream. The cells then come to rest at another site in the body, eventually forming new tumors. Sometimes these cells lie dormant, and a person can appear cancer-free after the primary tumor is removed, only to have his or her cancer reappear years later in another organ.

Scientists have known for several years that statins sometimes seem to fight cancer; however, the mechanism wasn’t clear, and previous clinical trials have yielded mixed results regarding statins as anti-cancer drugs.

Cancer cells require the synthesis of cholesterol and cholesterol precursor molecules to reprogram themselves from an adherent, or “epithelial” state, to a mobile, or “mesenchymal” state, in order to leave or “shed” from the primary tumor and recolonize elsewhere in the body. Statins, which are routinely used to lower lipid levels, could potentially block cancer cell spread by inhibiting an enzyme that catalyzes a key step in the cholesterol synthesis process, Dr. Oltvai said.

His team found that slower-growing, mesenchymal-like cancer cell lines that contain the protein vimentin inside the cell, but do not display the protein E-cadherin on their surface, are particularly sensitive to statins. Knowing this, doctors eventually may be able to test biopsies from cancerous tumors for these markers to determine if statins may be effective.

“While statins probably aren’t going to be effective against a patient’s primary tumor, they could work to block the tumor’s ability to metastasize,” said Dr. Oltvai. “And that is very important because most cancer patients die because of the metastases.”

Dr. Oltvai noted that coupling treatment of the primary tumor – which can involve chemotherapy, surgical removal of the tumor and radiation – with statins might be a way to prevent the primary tumor from shedding cells, and also prevent those cells from surviving their journey through the body or reactivating elsewhere in the body later on.

These are preliminary results, and people should not start taking statins as an anti-cancer drug, Dr. Oltvai stressed. His team tested the cancer cells’ reaction to statins in the laboratory, and the process could be different in the human body. The researchers are pursuing funding for additional studies on how exactly statins can interfere with the process that leads to metastases and whether combining statins with other drugs may be even more potent than using statins alone.

Additional researchers on this study are Katsuhiko Warita, Ph.D., Tomoko Warita, Ph.D., Colin Beckwitt, B.S., Mark Schurdak, Ph.D., and Alan Wells, M.D., D.M.S., all of Pitt; and Alexei Vazquez, Ph.D., of Rutgers Cancer Institute of New Jersey. Dr. Wells is also part of the Pittsburgh VA Health System, and Drs. Wells and Schurdak also are affiliated with the University of Pittsburgh Cancer Institute.

This research was supported by a U.S. Department of Veterans Affairs Merit grant, a National Center for Advancing Translational Sciences grant and a grant from the National Science Foundation.

Smoking, Alcohol, Gene Variant Interact to Increase Risk of Chronic Pancreatitis, Says Pitt Team

PITTSBURGH, January 14, 2015 – Genetic mutations may link smoking and alcohol consumption to destruction of the pancreas observed in chronic pancreatitis, according to a 12-year study led by researchers at the University of Pittsburgh School of Medicine. The findings, published today in Nature Publishing Group’s online, open-access journal Clinical and Translational Gastroenterology, provides insight into why some people develop this painful and debilitating inflammatory condition while most heavy smokers or drinkers do not appear to suffer any problems with it.

The process appears to begin with acute pancreatitis, which is the sudden onset of inflammation causing nausea, vomiting and severe pain in the upper abdomen that may radiate to the back, and is typically triggered by excessive drinking or gallbladder problems, explained senior investigator David Whitcomb, M.D., Ph.D., chief of gastroenterology, hepatology and nutrition, Pitt School of Medicine. Up to a third of those patients will have recurrent episodes of acute pancreatitis, and up to a third of that group develops chronic disease, in which the organ becomes scarred from inflammation.

“Smoking and drinking are known to be strong risk factors for chronic pancreatitis, but not everyone who smokes or drinks damages their pancreas,” Dr. Whitcomb said. “Our new study identifies gene variants that when combined with these lifestyle factors make people susceptible to chronic pancreatitis and may be useful  to prevent patients from developing it.”

In the North American Pancreatitis Study II consortium, researchers evaluated gene profiles and alcohol and smoking habits of more than 1,000 people with either chronic pancreatitis or recurrent acute pancreatitis and an equivalent number of healthy volunteers. The researchers took a closer look at a gene called CTRC, which can protect pancreatic cells from injury caused by premature activation of trypsin, a digestive enzyme inside the pancreas instead of the intestine, a problem that has already been associated with pancreatitis.

They found that a certain variant of the CTRC gene, which is thought to be carried by about 10 percent of Caucasians, was a strong risk factor for alcohol- or smoking-associated chronic pancreatitis. It’s possible that the variant fails to protect the pancreas from trypsin, leaving the carrier vulnerable to ongoing pancreatic inflammation and scarring.

“This finding presents us with a window of opportunity to intervene in the diseases process,” Dr. Whitcomb said. “When people come to the hospital with acute pancreatitis, we could screen for this gene variant and  do everything possible to help those who have it quit smoking and drinking alcohol, as well as test new treatments, because they have the greatest risk of progressing to end-stage chronic pancreatitis.”

Whitcomb’s team has been implementing more personalized approaches to pancreatic diseases in the Pancreas Center of Excellence within the Digestive Disorders Center at UPMC and hopes to learn whether use of genetic information can, in fact, reduce the chances of chronic disease in high-risk patients.

The study team includes Jessica LaRusch, Ph.D., Antonio Lozano-Leon, Ph.D., Kimberly Stello, Amanda Moore, Venkata Muddana, M.D., Michael O’Connell, Ph.D., Brenda Diergaarde, Ph.D., and Dhiraj Yadav, M.D., all of the University of Pittsburgh.

The project was funded by National Institutes of Health grants DK061451, DK077906 and DK063922, and the Conselleria de Industria e Innovación, Xunta de Galicia, Spain.

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