McGowan Institute?
March 2009 | VOL.8, NO. 3 | www.McGowan.pitt.edu
Distinguished Lecture Update: Dr. Marie Csete to speak in April
Marie Csete, MD, PhD, of the California Institute for Regenerative Medicine (CIRM), is the next speaker in the McGowan Institute Distinguished Lecturer Series. Dr. Csete’s lecture is scheduled for April 9, 2009 at 4:00 pm in Scaife Auditorium 5 on the fourth floor of Scaife Hall. A Moleculart Reception with art and light refreshments will follow in the Scaife Conference Center 1105 A&B.
Dr. Csete’s lecture is entitled, “Roadblocks to Translation of hES Cell-Derived Therapies.” Dr. Csete is the Chief Scientific Officer of CIRM, where her work focuses on the role of physiologic gases in stem cell fate. Prior to this, Dr. Csete was John E. Steinhaus Professor of Anesthesiology at Emory University, with adjunct appointment in Cell Biology, and program faculty appointments in Biochemistry, Cell and Developmental Biology, Neurosciences, and the Emory/Georgia Tech Biomedical Engineering Program. She was also the director of Liver Transplant Anesthesiology at the Emory University Hospital in Atlanta and director of the Emory/Georgia Tech Human Embryonic Stem Cell Core, and co-Director of the Emory MD/PhD Program.
The Moleculart Exhibition will feature the works of the Center for Biological Imaging. Under the direction of Dr. Simon Watkins, the Center for Biological Imaging is a leading center in the application of cellular imaging from the single molecule to the whole animal.
The McGowan Institute for Regenerative Medicine held its 2009 Retreat March 9-11, 2009. The focus was on peer-to-peer networking, and the forum provided many chances to explore collaborative opportunities with other researchers and participating industrial partners who are working to bring regenerative medicine technologies to clinical use.
The participation and contributions of the commercial leaders - along with McGowan Institute faculty and trainees - provided for insightful discussions and identification of opportunities for collaboration.
Highlights of the meeting included the McGowan Distinguished Lecture by Jeffrey A. Hubbell, PhD, Regenerative Medicine and Pharmacobiology Laboratory, Ecole Polytechnique Fédérale de Lausanne, Switzerland: “Biofunctional Materials in Regenerative Medicine and Immunotherapeutics”
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Annually, McGowan Institute for Regenerative Medicine faculty member Rory Cooper, PhD, director of the University of Pittsburgh/Veterans Administration (VA) Medical Center Human Engineering Research Laboratories, participates in a multi-event sports and rehabilitation program for military service veterans who use wheelchairs for sports competition due to spinal cord injuries, amputations, or certain neurological problems. Attracting more than 500 athletes each year, the National Veterans Wheelchair Games is the largest annual wheelchair sports event in the world. Competitive events at the Wheelchair Games include swimming, table tennis, weightlifting, archery, air guns, basketball, nine-ball, softball, quad rugby, bowling, handcycling, wheelchair slalom, power soccer, a motorized wheelchair rally, and track and field. Athletes compete in all events against others with similar athletic ability, competitive experience, or age.
As part of a national campaign organized by the VA, VA Canteen Services, and General Mills, veteran athletes from the 28th National Veterans Wheelchair Games, including Dr. Cooper, appeared on Cheerios cereal boxes available through the VA Canteen Services and Bases Exchanges. Dr. Cooper was the only veteran from Pennsylvania featured on the boxes. The availability of the veteran-covered Cheerios coincided with a major fund raising announcement for VA-affiliated Fischer Houses.
Sponsors of the Wheelchair Games are committed to improving the quality of life for veterans with disabilities and fostering better health through sports competition. While past Games have produced a number of national and world-class champions, the Games also provide opportunities for newly disabled veterans to gain sports skills and be exposed to other wheelchair athletes. Usually, one quarter of the competitors have never participated before in any type of organized wheelchair sports competition. Spokane, Washington will host the 29th National Veterans Wheelchair Games, July 13-18, 2009.
Dr. Rory Cooper is chair and professor of rehabilitation science and technology, School of Health and Rehabilitation Sciences, and professor of Bioengineering and Mechanical Engineering, at the University of Pittsburgh. Dr. Cooper is a professor in the Division of Physical Medicine and Rehabilitation within the Department of Orthopaedic Surgery. Dr. Cooper also remains actively involved in industry as the director and VA Senior Research Career Scientist of the Center of Excellence for Wheelchairs and Related Technology, a VA Rehabilitation Research and Development Center.
Photographs: General Mills, Inc.
Per McGowan Institute for Regenerative Medicine faculty member Joel Schuman, MD, director of the UPMC Eye Center and chairman of the Department of Ophthalmology at the University of Pittsburgh School of Medicine, “Glaucoma can be treated, and sight can be preserved – if the disease is detected early and treatment follows.” Glaucoma is the leading cause of blindness worldwide and usually has no symptoms until it’s too late – leaving about half of people with the disease unaware of having it until they experience vision loss. Dr. Schuman recommends regular screenings for glaucoma to detect the disease early. Since damage caused by glaucoma cannot be reversed, these screenings are vital – especially for those at high risk of developing the disease. If treatment is necessary, there are two new surgery options now available in Pittsburgh: Canaloplasty and ab interno trabeculectomy (AIT). Unlike earlier treatment options, these are minimally invasive.
A clear fluid, called aqueous humor, fills the front of your eye and provides nourishment to the tissues. Like the air in a balloon, the aqueous humor also provides pressure to help maintain the shape of the eye. In most types of glaucoma, the eye’s natural drainage system loses function and the fluid inside the eye cannot drain. This lack of drainage causes an elevation of pressure within the eye. This increase in intraocular pressure (IOP) exerts pressure on the optic nerve and results in vision loss. To prevent this from happening, it is essential to lower your IOP.
Canaloplasty is proven to safely lower IOP and dependence on medications. And unlike traditional procedures, canaloplasty is minimally invasive and has fewer complications and less follow-up. Canaloplasty uses breakthrough microcatheter technology in a simple and minimally invasive procedure. To perform canaloplasty, a tiny incision to gain access to a canal in the eye is created. A microcatheter circumnavigates the canal around your iris, enlarging the main drainage channel and its smaller collector channels through the injection of a sterile, gel-like material called viscoelastic. The catheter is then removed and a suture is placed within the canal and tightened. This tightened suture ensures that the canal remains open. By opening the canal, the pressure inside the eye is relieved.
AIT is the removal of diseased tissue using an electrosurgical pulse. Continuous irrigation and aspiration removes debris and regulates temperatures. The NeoMedix technology, Trabectome, works to help the body help itself. Designed to improve fluid drainage from the eye and balance intraocular pressure, this minimally invasive procedure stabilizes the optic nerve to minimize further visual field damage. Trabectome safely ablates and removes a 60°-120° strip of trabecular meshwork using a focused electrosurgical pulse and re-establishes access to the eye’s natural drainage pathway.
Since there is no cure for glaucoma, Dr. Schuman says, “With glaucoma surgery, the purpose is to protect your vision, and to preserve the vision you have remaining.”
“Being examined by an ophthalmologist at least every 2 years after turning 40 is key to preventing blindness,” said Dr. Schuman.
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McGowan Institute for Regenerative Medicine faculty member James Kang, MD, vice chairman of the University of Pittsburgh School of Medicine’s Department of Orthopaedic Surgery and director of the Ferguson Laboratory for Orthopaedic and Spine Research, is an international leader in the basic science and clinical treatment of intervertebral disc degeneration. Currently, Dr. Kang is actively involved with an accomplished University of Pittsburgh research team focusing on the biomechanics of the spine. In an ongoing study, embedded metal beads in a patient serve to help researchers develop computer models that predict the precise movements of joints post surgery. The computational, clinical tool may one day enable doctors to predict how individuals’ bones and soft tissue move. Such a tool would help doctors predict who would benefit from surgery, and would help doctors perform surgery more precisely, Dr. Kang said.
As reported in the Pittsburgh Tribune-Review, 1-millimeter tantalum metal beads embedded in a patient’s spine are being measured in her neck and back following separate surgeries. Through 3 D modeling techniques of the bones and soft tissue, the team of researchers will watch what happens in the body during motion. The scientists will track the range of motion in the patient’s spine by using stereo X-ray imaging to determine how the beads are moving. The patient will perform tasks such as turning her head from side to side and flexing and extending her neck while machines capture images of her, Dr. Kang said. The patient said she cannot feel the beads, which are smaller than the head of a pin.
Members of the team have used computer models that simulate bone and soft tissue movement to further understand how wrists and forearms move. Advanced imaging technology has also been used to create a sharper picture of the anterior-cruciate ligament (ACL) to improve ACL surgery. This latter procedure is now used by Freddie Fu, MD, David Silver Professor of Orthopaedic Surgery and chairman of the Department of Orthopaedic Surgery at the University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, when evaluating each of his ACL surgical patients.
Hand transplantation, like all tissue and organ transplantation requires the administration of strong immunosupression drugs to ensure that the transplant is not rejected by the recipient. The number of hand transplants to date around the world is limited. The UPMC recently became the second U.S. facility to perform a hand transplant, and the doctors at UPMC are relying on the use of the “Pittsburgh Protocol” to achieve immunosuppression while avoiding the side effects of the traditional immunosuppression drugs.
The Pittsburgh Protocol is composed of two elements: treating the patient with antibodies on the day of transplant, followed by a donor bone marrow infusion several days later. In the past, rejection of a new hand following a transplant has been a major concern for the team of specialists who performed the transplant. Typically, induction therapy with antibodies, together with multi-drug maintenance therapy represents the standard employed around the world in human hand transplantation. Such drug regimens, while effective, have caused complications like infection and drug toxicity, jeopardizing the benefits gained from an otherwise successful hand transplantation. The transplantation specialists at UPMC believe that the “Pittsburgh Protocol” will greatly reduce these complications. When used in solid organ transplants at UPMC, this protocol allows patients to be treated with low doses of a single maintenance drug.
The two-day hand transplant surgery was led by McGowan Institute faculty member W.P. Andrew Lee, MD, director of the Division of Plastic and Reconstructive Surgery. The surgical procedure was started on March 14, 2009, and was performed on a former Marine, who was injured in a training accident. Within days, the patient was able to move the fingers of his new hand. The goal now is the successful avoidance of the risks of high-dose multiple drug therapy to prevent rejection, through the utilization of the “Pittsburgh Protocol”.
Strategies like the “Pittsburgh Protocol” that aim to minimize maintenance of immunosuppression have the potential to improve quality of life of transplant recipients. Realization of such protocols will herald a new era of reconstructive transplant surgery to treat complex and major tissue defects.
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Several McGowan Institute for Regenerative Medicine faculty members agree: Consuming nourishing foods, using self-discipline, and incorporating healthy eating habits into our lives can be easy, fun, and delicious! Blair Jobe, MD, associate professor of surgery in the Heart, Lung and Esophageal Surgery Institute at the University of Pittsburgh and UPMC, and David Whitcomb, MD, PhD, professor of Medicine, Cell Biology and Physiology, and Human Genetics at the University of Pittsburgh, chief of the Division of Gastroenterology, Hepatology, and Nutrition, and founder and director of the Center for Genomic Sciences, recently reviewed the book, “The Anti-Cancer Cookbook,” subtitled “How to Cut Your Risk With the Most Powerful, Cancer-Fighting Foods.” The book was written by Julia Greer, MD, MPH—a UPMC physician, cancer researcher, and food enthusiast.
In the book Dr. Greer explains what cancer is and how antioxidants work to prevent pre-cancerous mutations in your body's cells, and then describes in detail which foods have been scientifically shown to help prevent which types of cancer. She then shares her collection of more than 250 scrumptious recipes for soups, sauces, main courses, vegetarian dishes, sandwiches, breads, desserts, and beverages, all loaded with nutritious ingredients chock-full of powerful antioxidants that may significantly slash your risk of a broad range of cancer types, including lung, colon, breast, prostate, pancreatic, bladder, stomach, leukemia, and others. Dr. Greer even includes tips on how to cook foods to protect their valuable antioxidants and nutrients and how to make healthy anti-cancer choices when eating out.
“This resource will be particularly useful to patients who have a very strong family history and, thus, a genetic predisposition to a certain type of cancer,” Dr. Jobe says. “It enables them to 'do something,' even though the cards are stacked against them genetically.”
"Some people have a higher risk of getting cancers because of a combination of genetics and environmental factors," says Dr. Whitcomb. "We can't change the genetics," he says, "so one other thing we can do is change the environment," which includes what people eat. "If you're eating right, chances are, you'll have a lower chance of something bad happening."
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McGowan Institute for Regenerative Medicine faculty member James Antaki, PhD, professor of biomedical engineering, Carnegie Mellon University, and University of Pittsburgh adjunct professor, Departments of Surgery and Bioengineering, is the recipient of the 2009 Steven J. Fenves Award for Systems Research. This recognition was recently announced by Carnegie Mellon University’s Director for the Institute for Complex Engineered Systems (ICES). The Steven J. Fenves Award for Systems Research is presented annually to individuals for their contributions to systems research in areas that are relevant to Carnegie Mellon University’s College of Engineering and ICES.
Dr. Antaki received this award in recognition of his applications of systems engineering to the design and optimization of medical devices in general, and cardiovascular devices in particular. Professor Antaki is responsible for a paradigm shift in the design of blood pumps by replacing trial-and-error approaches with rigorous systems engineering that integrates biomedical engineering, computational fluid dynamics, electromagnetics, control system design, and software engineering. He is a world leader in systems engineering of medical devices, and his contributions have led to life-extending artificial hearts and left ventricular assist devices for adults, toddlers, and infants with cardiac deficiencies.
The innovative work of Dr. Antaki is being applied to the development of the PediaFlow-- a novel pediatric ventricular assist device. The goal of the project is to develop a miniature centrifugal pump utilizing suspended magnetic levitation technology for use in babies between 5 and 35 pounds. It's conceived that the device could be used for up to 6 months as a bridge to heart transplantation. In some babies, the device may allow the heart to recover. As such, plans are to develop a smart control system that will indicate patterns consistent with a recovering heart. Since the device will be fully implantable with a small lead to an external power supply, children supported by the device will be able to be mobile and active.
Congratulations, Dr. Antaki!
McGowan Institute for Regenerative Medicine faculty member Raman Venkataramanan, PhD, professor of pharmaceutical sciences, University of Pittsburgh School of Pharmacy, and professor of pathology within the School of Medicine, recently received the 2009 Bristol-Myers Squibb Mentorship in Clinical Pharmacology Award from the American College of Clinical Pharmacology. This bi-yearly award recognizes sustained excellence in clinical pharmacology mentorship in an academic, regulatory, and/or industrial setting. Dr. Venkataramanan’s efforts exhibited a demonstrated promotion of the field of clinical pharmacology with an emphasis on the training/guidance of junior scientists and/or colleagues.
The American College of Clinical Pharmacology was founded on September 11, 1969. Today, the College consists of almost 1,000 professionals who remain dedicated to the founders' objectives: To advance the science of clinical pharmacology in all its phases and to engage in appropriate educational efforts in the public interest. These goals are to be attained in a manner consistent with the highest ethical and scientific standards. Membership of the College ranges from physicians (39%) to PhDs and PharmDs (48%) and to other professionals actively engaged in the teaching and conduct of clinical pharmacology.
Congratulations, Dr. Venkataramanan!
McGowan Institute for Regenerative Medicine faculty member Mark Roberts, MD, medical school professor, is a winner of the 2009 University of Pittsburgh chancellor’s award for distinguished teaching. Dr. Roberts is director of degree-granting programs at the Institute for Clinical Research Education, and chief of the section of decision sciences and clinical systems modeling in the Division of General Internal Medicine. He will be recognized during Pitt’s 33rd annual honors convocation and his name will be inscribed on a plaque displayed in the William Pitt Union.
“The very existence of this award underscores the high institutional priority that we assign to our teaching responsibilities, and your individual efforts stand as an inspiring example of excellence in the role of University teacher,” Pitt Chancellor Mark Nordenberg wrote to Dr. Roberts.
Dr. Roberts was honored by the chancellor as “an inspiring example of excellence in the role of University teacher. Your ability to motivate your students is noteworthy, as is your dedication to advising master’s and PhD-level students in clinical research and in industrial engineering. The clinical research courses that you have developed and continue to teach serve to strengthen the degree-granting programs within the Institute for Clinical Research Education. Your efforts do honor to the title of ‘teacher.’ The University is proud to reward your many contributions by granting you its highest teaching award.”
“I was really pleased to win this award, but I think this is really an award for our program. There are so many great people and in particular, great students. That combination helped,” Dr. Roberts said.
Dr. Roberts will receive a $2,000 cash prize. In addition, he will receive a $3,000 grant, administered by his department, to support his teaching.
Congratulations, Dr. Roberts!
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McGowan Institute for Regenerative Medicine faculty members Paul Robbins, PhD (top), and Theresa Whiteside, PhD (bottom), were members of a research team that has reported the first clinical evidence that gene therapy reduces symptoms in patients with rheumatoid arthritis (RA), an important milestone for this promising treatment. Originally conceived as a means of treating genetic diseases, such as cystic fibrosis and hemophilia, gene therapy involves implanting a normal gene to compensate for a defective gene in the patient. The first clinical trial to test gene therapy was launched in 1990 for the treatment of a rare, genetic immunodeficiency disease.
A classic autoimmune disease, RA develops when, for unknown reasons, the body’s immune system turns against itself, causing joints to become swollen and inflamed. If the disease is inadequately controlled, the tissues of the joint are eventually destroyed. Although anti-inflammatory agents and biologics can help to mitigate symptoms, there is no cure for the condition, estimated to affect more than 2 million individuals in the U.S. alone.
The study’s principal investigator is Christopher Evans, PhD, Director of the Center for Advanced Orthopaedic Studies at Beth Israel Deaconess Medical Center, a teaching hospital of Harvard Medical School. Dr. Evans has spent many years studying the molecules responsible for the breakdown of cartilage in patients with arthritis, identifying interleukin-1 as a good target for the gene therapy. By implanting a gene in the affected joint, he and his team were able to stimulate production of a human interleukin-1 receptor antagonist protein, which serves to block actions of the interleukin-1 protein.
This study, conducted in Germany, was to prove that the therapy was not only safe, but that it was of therapeutic benefit. Two study subjects were recruited. Both subjects were postmenopausal females under the age of 75 with a diagnosis of advanced RA. After tissue was removed from the subjects’ knuckle joints, a harmless retrovirus was inserted into the tissue cells, in order to serve as a “vector” to transport the gene into the patients’ joints. After being placed in culture to grow and replicate, the cells were injected back into the afflicted joints
After 4 weeks, patients reported reduced pain and swelling. It was reported that one of the patients experienced dramatic effects—the gene-treated joints remained pain-free even though other joints flared. Subsequent laboratory tests showed that tissues removed from the subject’s joint tissue synthesized lower amounts of disease-related proteins, confirming that the reduction in pain and swelling resulted from the actions of the implanted gene. This is the first real evidence that the painful symptoms of RA can indeed be lessened through gene therapy.
Dr. Robbins is a Professor of Molecular Genetics and Biochemistry at the University of Pittsburgh School of Medicine. Dr. Whiteside is the Director of the Immunologic Monitoring and Cellular Products Laboratory at the University of Pittsburgh Cancer Institute, and a Professor of Pathology, Otolaryngology, and Immunology at the University of Pittsburgh.
Dr. Burhan Gharaibeh represented the Stem Cell Research Center SCRC, at a meeting on the use of Growth Factors in Sports Medicine in Doha, Qatar Feb 7-10 2009. The symposium was held at Qatar Orthopaedic and Sports Medicine Hospital (ASPETAR) with presentations by Dr. Gharaibeh and Dr. Johnny Huard. The delegates discussed over a two day symposium both the rationale and the current level of evidence for the use of Growth Factors (GF) in the management of soft tissue injuries. Recognition of the increasing international utilization of (GF) technology in sports medicine in the absence of high level clinical evidence, resulted in this attempt to formulate a clear consensus on both the clinical utility of this technology and future directions for research.
Numerous international researchers and clinicians with expertise in the area of muscle injury, as well as representatives of organizations with particular interests in the state of this research including the International Olympic Committee and the World Anti-Doping Agency were invited. With a focus on muscle injury, key areas for consideration of this symposium were the indications, efficacy and safety of GF use, in conjunction with the anti-doping implications faced by practitioners working in with elite athletes.
Speaking and listening are instrumental for effective communication. McGowan Institute for Regenerative Medicine faculty members Barry Hirsch, MD (top), professor of otolaryngology and communication sciences and disorders and neurological surgery at the University of Pittsburgh School of Medicine, director of UPMC’s Ear and Hearing Center, and chairman of the hearing committee for the American Academy of Otolaryngology-Head and Neck Surgery, and Clark Rosen, MD (bottom), director of the UPMC Voice Center and associate professor of otolaryngology, University of Pittsburgh School of Medicine, offer several reminders for protecting your hearing and your voice from damage.
Every day, we experience sound in our environment, such as the sounds from television and radio, household appliances, and traffic. Normally, we hear these sounds at safe levels that do not affect our hearing. However, when we are exposed to harmful noise—sounds that are too loud or loud sounds that last a long time—sensitive structures in our inner ear can be damaged, causing noise-induced hearing loss. These sensitive structures, called hair cells, are small sensory cells that convert sound energy into electrical signals that travel to the brain. Once damaged, our hair cells cannot grow back. To protect these hair cells, a good rule of thumb is to avoid noises that are “too loud” and “too close” or that last “too long.”
Ear protection safeguards your hearing. Wear earplugs or other hearing protective devices when involved in a loud activity (special earplugs and earmuffs are available at hardware and sporting goods stores). Hearing protection needn't be dorky; small foam earplugs, when rolled tightly and inserted snugly, can provide 15 to 20 decibels of protection. Forget sticking cotton in your ears, Dr. Hirsch says; it doesn't work at all.
A last caution: Some medications—including intravenous antibiotics, chemotherapy drugs, and narcotics such as hydrocodone—can permanently damage hearing. People who have lost hearing in one ear should be sure to let their doctor know, says Dr. Hirsch, so that they minimize risk to the remaining good ear.
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On Wednesday, April 29, 2009, the Wine Loft Wine Bar, located in the South Side Works, has generously offered to donate all revenue from the evening (5-9 PM) to the McGowan Institute for Regenerative Medicine. We invite you to treat yourself to an evening out and support groundbreaking medical research.
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The Regenerative Medicine Podcasts continue to gain listeners and explore pertinent topics. Remember to tune in and keep abreast of new interviews. The most recent podcasts are:
#66 – Peter Wearden, MD, PhD – Dr. Wearden is an Assistant Professor-Pediatric Cardiac Surgery, Director Pediatric Mechanical Cardiopulmonary Support at the Children's Hospital of Pittsburgh, and a faculty member at the McGowan Institute for Regenerative Medicine. Joining Dr. Wearden is Dr. Joel Gradowski and Cindy Gradowski, who discuss their son’s recent cardiac treatment and recovery through the use of a Ventricular Assist Device.
Visit www.regenerativemedicinetoday.com to keep abreast of the new interviews.
| Authors: | Scott MJ, Liu S, Shapiro RA, Vodovotz Y, Billiar TR. |
| Title: | Endotoxin uptake in mouse liver is blocked by endotoxin pretreatment through a suppressor of cytokine signaling-1-dependent mechanism. |
| Summary: | The liver is the main organ that clears lipopolysaccharide (LPS) and hepatocytes are a major cell-type involved in LPS uptake. LPS tolerance, or desensitization, is important in negative regulation of responses to LPS, but little is known about its mechanisms in hepatocytes. Primary isolated C57BL/6 hepatocytes, and liver in vivo, internalized fluorescent LPS, and this was dependent on Toll-like receptor 4 (TLR4) at the cell surface but not on TLR4-TIR signaling through MyD88. LPS clearance from plasma was also TLR4-dependent. Pretreatment of C57BL/6 hepatocytes with LPS prevented uptake of LPS 24 hours later and this LPS-mediated suppression was dependent on TLR4 signaling through MyD88. Many regulators of TLR4 signaling have been identified and implicated in LPS desensitization, including suppressor of cytokine signaling 1 (SOCS1). SOCS1 mRNA and protein expression increased after LPS stimulation in hepatocytes and in whole liver. LPS uptake in hepatocytes and liver was significantly reduced following infection with adenoviral vectors overexpressing SOCS1. Similarly, inhibition of SOCS1 using small interfering (si)RNA-mediated knockdown prevented LPS desensitization in hepatocytes. SOCS1 is known to interact with Toll/IL-1 receptor associated protein (TIRAP) and cause TIRAP ubiquitination and degradation, which regulates TLR signaling. We have also shown previously that TIRAP regulates LPS uptake in hepatocytes. SOCS1 coimmunoprecipitated with TIRAP in wild type hepatocyte cell lysates up to 8 hours after LPS stimulation, but not at later times. In the same samples, ubiquitinated TIRAP was detected after 4 hours and up to 8 hours after LPS stimulation, but not at later times. Conclusion: These data indicate hepatocytes are desensitized by LPS in a TLR4 signaling-dependent manner. LPS-induced SOCS1 upregulation increases degradation of TIRAP and prevents subsequent LPS uptake. The exploitation of these mechanisms of LPS desensitization in the liver may be important in future sepsis therapies. |
| Source: | Hepatology. 2009 Feb. 9 [Epub ahead of print]. |
PI |
Steven Belle and Kyong-Mi Chang |
Co-Investigators |
Robert Carithers, Adrian Di Bisceglie, Michael Fried, Marc Ghany, Steven Han, E. Jenny Heathcote, W. Ray Kim, Daryl Lau, William Lee, Anna Lok, Mitchell Shiffman, KathleenSchwarz, and Norah Terrault |
Title |
Multi-Center Clinical Trials of Novel Therapies and Diagnostics for Patients with Chronic Hepatitis B |
Description |
In establishing the Hepatitis B Research Network, the NIDDK wishes to consider the potential application of diagnostics and therapeutics for patients of all ages with chronic hepatitis B. The overall goal of the Hepatitis B Network will be to perform clinical, epidemiological and therapeutic research in patients with chronic hepatitis B using a standardized and coordinated approach to the evaluation and therapy of chronic hepatitis B and to provide sufficient numbers of patients for the research. This will be done by development of a database on chronic hepatitis B patients including clinical information as well as liver, serum and DNA samples. |
Source |
National Institute of Diabetes and Digestive and Kidney Diseases |
Term |
2009 - 2016 |
| Amount: | $11 million |
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