UPMC Physician Resources

Pitt-Developed Drug Works Against ‘Superbug’ Biofilms and Respiratory Virus

A potential drug therapy developed at the University of Pittsburgh Center for Vaccine Research (CVR) has proven effective against tough bacterial biofilms and a deadly respiratory virus simultaneously. The drug outperforms traditional therapies in the laboratory setting.

The results, reported in the journal mSphere, build on a recent discovery from Pitt’s School of Medicine showing that the virus encourages biofilm growth and point to a new way to treat drug-resistant bacteria, including so-called “superbugs” that are resistant to almost all existing antibiotics and have become the focus of worldwide efforts to limit their spread.

“This is really unusual. To the best of our knowledge, no other antibiotics out there work on both the bacteria and the virus during a co-infection,” said senior author Jennifer M. Bomberger, PhD, assistant professor in Pitt’s Department of Microbiology and Molecular Genetics. “Antibiotic-resistant chronic infections are an urgent public health threat, and the development of new therapies has been painfully slow. So to see something work on a virus and the incredibly resistant biofilms that bacteria form is very exciting.”

Chronic infections, such as those that kill cystic fibrosis patients, resist the body’s efforts to clear them from the lungs, sinuses or other areas. Often these infections are characterized by biofilms, which are bacteria that stick together forming colonies that are as much as 400 times as resistant to antibiotics as a single bacterium.

The potential drug therapy relies on an engineered cationic antimicrobial peptide, or “eCAP,” which is a synthetic and more efficient version of naturally occurring antimicrobial peptides that form a first line of defense against infections in humans. Developed by co-author Ronald C. Montelaro, PhD, professor and co-director of Pitt’s CVR, the eCAP works by “punching into” bacteria and viruses, thereby destroying them.

Dr. Bomberger and her team tested the eCAP in the laboratory by growing biofilms of drug-resistant Pseudomonas aeruginosa bacteria on the cells that line the airway and then treating them for one hour with the eCAP. The eCAP was 50 times more effective at fighting the biofilm than traditional treatment, but did not harm the airway cells.

The team then did the same test, this time on airway cells first infected with respiratory syncytial virus (RSV), which causes serious infection in infants and older adults, as well as people with compromised lungs. In February, Dr. Bomberger reported in the journal Proceedings of the National Academy of Sciences that RSV helps Pseudomonas aeruginosa biofilms grow.

“When the body responds to fight the virus, it inadvertently leaves an Achilles heel by fostering an environment rich in the nutrient iron, which aids the bacteria in forming a biofilm,” said Dr. Bomberger.

The eCAP was 10 times more effective at fighting the biofilm in a virus-bacteria co-infection compared with traditional therapy. And when the eCAP was used on airway cells infected only with RSV, the number of viable virus particles was reduced by more than 150-fold.

The eCAP also worked against bacterial biofilms grown on plastic, indicating that it could be a good treatment for cleaning medical equipment, such as bronchoscopes, where biofilms sometimes grow.

“We’re incredibly encouraged by these results,” said Dr. Montelaro. “Again and again, eCAPS are performing well in laboratory tests and mouse models. They’re an exciting possibility to help solve the antimicrobial-resistant superbug crisis that our world increasingly faces.”

Additional researchers on this study are Jeffrey A. Melvin, PhD, Lauren P. Lashua, BS, Megan R. Kiedrowski, PhD, and Berthony Deslouches, MD, PhD, all of Pitt; and Guanyi Yang, BS, of Pitt and Tsinghua University in Beijing, China.

This research was funded by National Institutes of Health grants T32AI49820, R00HL098342, R01HL123771 and P30DK072506; and Cystic Fibrosis Foundation grants MELVIN15F0 and BOMBER14G0.

Pitt Nursing Earns Worldwide Recognition

The University of Pittsburgh School of Nursing’s outstanding reputation for excellence has been confirmed again with recent recognition as 12th in the world on the 2016 QS World University Rankings by subject, based on academic reputation, employer evaluation and research impact.

This international recognition is the most recent of accolades bestowed on Pitt Nursing with other exceptional rankings, including 5th on the 2016 U.S. News & World Report list of Best Graduate Schools, and 8th on the 2017 U.S. News & World Report list of Best Doctor of Nursing Practice Programs.

“It is an honor to be valued as a world-class nursing program based upon our faculty’s research impact, measured through citations, a wide desire for our graduates, and a strong academic reputation. We are pleased to join our peers across the U.S. and the globe in advancing the education and science underlying nursing in a time of transformation of nursing around the world,” said Jacqueline Dunbar-Jacob, PhD, RN, FAAN, dean of Pitt’s School of Nursing.

The School of Nursing has more than 960 students enrolled in its bachelor’s, master’s, Ph.D. and doctor of nursing practice programs.

Women with Cystic Fibrosis May Benefit from Specialized Sexual and Reproductive Health Care and Education, UPMC Study Shows

 

PrintFor female cystic fibrosis (CF) patients and providers, individual CF health care specialists have a significant role in helping patients gain access to educational resources that can help them improve sexual and   reproductive health, according to a study by researchers at Children’s Hospital of Pittsburgh of UPMC.

Women with CF face important disease-specific sexual and reproductive health concerns, including delays in puberty, increased risk of vaginal yeast infections, urinary incontinence, problems with sexual function, concerns regarding contraceptive choice, decreased fertility, and adverse effects of pregnancy on their lungs.

The study, published online this week in Pediatrics, led by Traci Kazmerski, MD, fellow, Division of Pulmonology, Children’s Hospital, sought to find the best ways to provide women with CF effective sexual and reproductive health care by interviewing CF center directors from a nationwide sample as well as young adult women with the disease and asked them about their experiences and preferences. The findings may help guide the development of educational resources around sexual and reproductive health for women with CF.

Both CF providers and patients agreed that the CF provider has a fundamental role in providing CF-specific sexual and reproductive health care. They also believed that educational resources and provider training on sexual and reproductive health topics would improve patient care in this area.

“Patients were clear that they want both sexual and reproductive health educational resources and for their CF providers to begin those discussions, early and routinely,” said Dr. Kazmerski. “Our next step is to figure out how to do this as we care for our patients with CF.”

“This study provides some critical guidance on how to better provide sexual and reproductive health education and care for adolescents with cystic fibrosis, and encourages us to consider how to integrate such care for all adolescents with chronic medical conditions,” said co-author Elizabeth Miller, MD, PhD, chief, Division of Adolescent and Young Adult Medicine, Children’s Hospital.

In addition to Drs. Kazmerski and Miller, other authors include David Orenstein, MD, and Daniel Weiner, MD, Joseph Pilewski, MD, and Sonya Borrero, MD, all of UPMC; and Lisa Tuchman, MD, of Children’s National Health System.

The study was supported by a grant from the Cystic Fibrosis Foundation (KAZMER13B0).

Jameson Health System and UPMC Merge to Officially Form UPMC Jameson

• As of May 1, 2016, UPMC Jameson is officially established.

• UPMC will invest $75 million to develop services and facilities in Lawrence County with an additional $10 million earmarked for strategic physician recruitment.

• Lawrence County will advance on the cutting edge in health care technology and quality assurance with local access to world-class UPMC.

• A regionally coordinated approach to health care for Lawrence and Mercer counties delivered through UPMC Jameson and UPMC Horizon will ensure local access to comprehensive services aligned to the needs of the region.

Jameson Health System (Jameson) and UPMC (University of Pittsburgh Medical Center) are pleased to announce that on May 1, 2016 Jameson merged into the UPMC network. UPMC Jameson now is officially established to deliver world-class health care for the residents of Lawrence County and its surrounding communities.

“The strongest solution for a healthy future for our communities has been achieved through our proud affiliation with UPMC,” said Doug Danko, president, UPMC Jameson. “After more than a year-long process requiring perseverance and commitment to the highest interests of area residents, this positive outcome is a credit to the determination of our Board of Directors and the support that we have received from our community.”

An arbitration decision in January paved the way by which Jameson and UPMC could merge following successful completion of a Consent Decree addressing the Pennsylvania Office of the Attorney General’s concerns about the transaction.

UPMC will invest $75 million to develop services and facilities in Lawrence County and provide an additional $10 million dedicated to physician recruitment for expansion of clinical advancements in the region.

Furthermore, the UPMC merger services all of Jameson’s debt, secures all employee pensions, and assures that it remains a vibrant acute care facility offering advanced services locally now and into the future.

“The outstanding clinical, educational and technological resources of UPMC will benefit health care outcomes throughout this entire region,” said Frank Mindicino, vice-chairman, UPMC Jameson and UPMC Horizon Boards of Directors. “UPMC, UPMC Horizon and UPMC Jameson will collaborate to grow and develop the best plan for services aligned to Mercer and Lawrence counties’ health care priorities and needs.”

UPMC is a world-class academic medical center and is consistently ranked in the prestigious U.S. News & World Report annual Honor Roll of America’s Best Hospitals.

“Our nationwide search proved that UPMC is the single best-qualified partner to fulfill all requirements set forth by Jameson’s Board of Directors,” said Steven Warner, chairman, UPMC Jameson and UPMC Horizon Boards of Directors. “We owe a debt of gratitude to Doug Danko for his vigilance in helping to achieve none other than the strongest outcome for Lawrence County. We are elated that a long-term future of world-class health care has been solidified for our region.”

Both Jameson and UPMC have a long history of providing high-quality, responsive and cost-effective care.

“We are pleased to begin executing our strategic vision for the region,” said Dave Martin, senior vice president, hospital division, UPMC. “A plan is being developed for both UPMC Jameson and UPMC Horizon to expand service offerings and it will incorporate results of physician manpower, community health needs and facilities studies to identify and prioritize developments to continually advance patient care services, access and outcomes within Lawrence and Mercer counties.”

The combined governance of UPMC Jameson and UPMC Horizon will result in a regionally coordinated approach to maximize efficiencies and align resources to deliver a comprehensive complement of specialized health care services locally for the Lawrence-Mercer region.

“We are excited to expand our physician and clinical care teams with new career opportunities resulting in job growth for the local economy,” said Danko. “I am proud of the dedication of our engaged medical staff and loyal employees who provide exceptional health care to our neighbors. Together, we celebrate this victory of preservation and growth of a vital community asset and our premier local health care delivery system—now with a new name: UPMC Jameson.”

Danko added, “We are now positioned to become stronger than ever.”

Pitt Computational Model Finds New Protein-Protein Interactions in Schizophrenia

Approach Can Shed New Light on Biological Processes Affected by the Mental Illness

Using a computational model they developed, researchers at the University of Pittsburgh School of Medicine have discovered more than 500 new protein-protein interactions (PPIs) associated with genes linked to schizophrenia. The findings, published online today in npj Schizophrenia, a Nature Publishing Group journal, could lead to greater understanding of the biological underpinnings of this mental illness, as well as point the way to treatments.

There have been many genome-wide association studies (GWAS) that have identified gene variants associated with an increased risk for schizophrenia, but in most cases there is little known about the proteins that these genes make, what they do and how they interact, said senior investigator Madhavi Ganapathiraju, PhD, assistant professor of biomedical informatics, Pitt School of Medicine.

“GWAS studies and other research efforts have shown us what genes might be relevant in schizophrenia,” she said. “What we have done is the next step. We are trying to understand how these genes relate to each other, which could show us the biological pathways that are important in the disease.”

Each gene makes proteins and proteins typically interact with each other in a biological process. Information about interacting partners can shed light on the role of a gene that has not been studied, revealing pathways and biological processes associated with the disease and also its relation to other complex diseases.

Dr. Ganapathiraju’s team developed a computational model called High-Precision Protein Interaction Prediction (HiPPIP) and applied it to discover PPIs of schizophrenia-linked genes identified through GWAS, as well as historically known risk genes. They found 504 never-before known PPIs, and noted also that while schizophrenia-linked genes identified historically and through GWAS had little overlap, the model showed they shared more than 100 common interactors.

“We can infer what the protein might do by checking out the company it keeps,” Dr. Ganapathiraju explained. “For example, if I know you have many friends who play hockey, it could mean that you are involved in hockey, too. Similarly, if we see that an unknown protein interacts with multiple proteins involved in neural signaling, for example, there is a high likelihood that the unknown entity also is involved in the same.”

Dr. Ganapathiraju and colleagues have drawn such inferences on protein function based on the PPIs of proteins, and made their findings available on a website Schizo-Pi that is publicly-accessible at http://severus.dbmi.pitt.edu/schizo-pi.

This information can be used by biologists to explore the schizophrenia interactome with the aim of understanding more about the disease or developing new treatment drugs.

The research team included Mohamed Thahir, MS, PhD, Adam Handen, MS, Saumendra N.  Sarkar, PhD, Robert A.  Sweet, M.D., PhD, Vishwajit L. Nimgaonkar, MD, PhD, Eileen M.  Bauer, PhD, and Srilakshmi Chaparala, MS, all of Pitt; and Christine E. Loscher, PhD, of Dublin City University, Ireland.

This project was funded by the Biobehavioral Research Awards for Innovative New Scientists (BRAINS) grant MH094564 awarded to Dr. Ganapathiraju by the National Institute of Mental Health, part of the National Institutes of Health.

Gwendolyn Sowa, MD, PhD, Named Chair of Pitt’s Department of Physical Medicine & Rehabilitation

The University of Pittsburgh School of Medicine has chosen one of its own renowned faculty members to be the next chair of the Department of Physical Medicine and Rehabilitation (PM&R). Gwendolyn Sowa, MD, PhD, who will assume her new role July 1, also holds joint appointments in the School of Medicine’s Department of Orthopaedic Surgery and the Swanson School of Engineering’s Department of Bioengineering. She also serves as associate dean for medical student research and medical director of UPMC Total Care-Musculoskeletal Health.

“Dr. Sowa’s many accomplishments demonstrate her ability to cross specialties and to collaborate effectively in the clinical, research and educational arenas,” noted Arthur S. Levine, MD, Pitt’s senior vice chancellor for the health sciences and John and Gertrude Petersen Dean of Medicine. “She is the definition of a committed teacher and mentor.”

The department of PM&R ranks among the nation’s top programs in research funding from the National Institutes of Health and includes a team of multidisciplinary faculty members who train and educate the next generation of rehabilitation physicians and researchers, specializing in the fields of traumatic brain injury, spinal cord injury, stroke, diseases and disorders of the musculoskeletal and peripheral nervous system, and many other conditions that affect function and mobility.

“We are fortunate to have had Dr. Sowa as an internal candidate,” said Steven D. Shapiro, MD, executive vice president, chief medical and scientific officer, and president, Health Services Division, UPMC. “Her extraordinary dedication to every aspect of her work will continue to strengthen the innovative mission of this program.”

Dr. Sowa’s research centers on molecular, laboratory-based translational and clinical research, investigating the effect of motion on inflammatory pathways and the beneficial effects of exercise. She is co-director of the Ferguson Laboratory for Orthopaedic and Spine Research, a 3,000-square-foot laboratory fully equipped to perform molecular assays, including gene expression analysis, protein analysis, cell and organ culture, histology, and cellular and spinal biomechanical testing. She also has an active research program investigating the role of serum biomarkers in guiding individualized treatment in intervertebral disc degeneration and back pain. She has received national recognition for her research.

Dr. Sowa completed her MD and PhD in biochemistry at the University of Wisconsin-Madison, followed by residency training at Northwestern University, Rehabilitation Institute of Chicago.

Pre-Surgical Exposure to Blue Light Reduces Organ Damage in Mice

A 24-hour exposure to bright blue light before surgery reduces inflammation and organ damage at the cellular level in a mouse model, according to new research from the University of Pittsburgh School of Medicine.

The finding, reported in today’s issue of the Proceedings of the National Academy of Sciences, suggests a potential pre-treatment light therapy that could improve outcomes in patients undergoing procedures characterized by a period of blood restriction, such as liver resection or organ transplantation. The research was funded by the National Institutes of Health (NIH).

“We were incredibly surprised by our results,” said senior author Matthew R. Rosengart, MD, MPH, associate professor in the Pitt School of Medicine’s departments of Surgery and Critical Care Medicine. “There’s long been evidence suggesting that light and circadian rhythms profoundly influence our biology, and specifically the physiological response to stress. So while we were expecting to find some correlation with light spectrum and the immune response, we were not expecting results quite so striking.”

Light is complex and consists of intensity, duration of exposure and wavelength. This study is one of the first that accounts for this complexity and derives results that could guide future clinical trials in humans.

Dr. Rosengart and his team compared what happened when mice were exposed to red light, ambient white fluorescent light similar to that in hospitals and high-intensity blue light 24 hours before kidney or liver surgery involving periods of blood restriction and restoration.

The high-intensity blue light outperformed the red and white light, attenuating cellular and organ injury through at least two cellular mechanisms. The blue light brought about a reduction in the influx of neutrophils, a type of white blood cell involved in inflammation, which can lead to organ damage and other problems. Additionally, blue light inhibited dying cells from releasing a protein called HMGB1 that triggers organ-damaging inflammation.

The team then tested whether the blue light was acting through the optic pathway or some other mechanism, like the skin. Blind mice had the same healing response regardless of whether they were exposed to blue or red light, indicating that the protective impact of blue light does, indeed, act through the optic pathway.

The team then looked at whether one color of light might disrupt the circadian rhythm, which is linked to immunity, more than another. Blood from mice exposed to red, white and blue light had similar concentrations of melatonin and corticosteroid hormones. Furthermore, the mice under each of the lights also had similar activity levels. These data indicate that the effects of blue light were not mediated by a disruption of sleep, activity or circadian rhythms.

Finally, Dr. Rosengart stresses that mice are nocturnal animals with visual, circadian and immune biology that is distinct from humans. Thus, the results of his study should not be broadly extended to patients or hospital settings until robust clinical trials have been performed to show whether or not pretreatment with intensive blue light is safe.

Additional researchers on this project are Du Yuan, MD, of Pitt and Central South University in Hunan, China; Richard D. Collage, Hai Huang, MD, Xianghong Zhang, PhD, Ben C. Kautza, MD, Anthony J. Lewis, MD, Brian S. Zuckerbraun, MD, Allan Tsung, MD, and Derek C. Angus, MD, MPH, all of Pitt’s School of Medicine.

This research was funded by NIH grant R01 GM082852.

Watercress Extract Detoxifies Carcinogens in Smokers, Clinical Trial Demonstrates

Watercress extract taken multiple times a day significantly inhibits the activation of a tobacco-derived carcinogen in cigarette smokers, researchers at the University of Pittsburgh Cancer Institute (UPCI), partner with UPMC CancerCenter, demonstrated in a phase II clinical trial presented today at the American Association for Cancer Research (AACR) Annual Meeting in New Orleans.

The trial also showed that the extract detoxifies environmental carcinogens and toxicants found in cigarette smoke, and that the effect is stronger in people who lack certain genes involved in processing carcinogens. This trial was supported by a grant from the National Cancer Institute (NCI).

“Cigarette smokers are at far greater risk than the general public for developing lung cancer, and helping smokers quit should be our top cancer prevention priority in these people,” said Jian-Min Yuan, MD, PhD, associate director of the UPCI’s Division of Cancer Control and Population Science and an epidemiologist with Pitt’s Graduate School of Public Health. “But nicotine is very addictive, and quitting can take time and multiple relapses. Having a tolerable, nontoxic treatment, like watercress extract, that can protect smokers against cancer would be an incredibly valuable tool in our cancer-fighting arsenal.”

Dr. Yuan, who also is Pitt’s Arnold Palmer Endowed Chair in Cancer Prevention, and his colleagues enrolled 82 cigarette smokers in the randomized clinical trial. The participants either took 10 milligrams of watercress extract mixed in 1 milliliter of olive oil four times a day for a week or they took a placebo. Each group of participants then had a one week “wash-out” period where they didn’t take anything and then switched so that those getting the placebo now received the extract. They all continued their regular smoking habits throughout the trial.

In one week, the watercress extract reduced activation of the carcinogen known as nicotine-derived nitrosamine ketone in the smokers by an average of 7.7 percent. It increased detoxification of benzene by 24.6 percent and acrolein by 15.1 percent, but had no effect on crotonaldehyde. All the substances are found in cigarette smoke.

Participants who lacked two genes involved in a genetic pathway that helps the antioxidant glutathione remove carcinogens and toxicants from the body saw an even bigger benefit to taking the watercress extract, which increased their detoxification of benzene by 95.4 percent, acrolein by 32.7 percent and crotonaldehyde by 29.8 percent.

A phase III clinical trial in hundreds of people must be performed before the treatment could be recommended for smokers, and Dr. Yuan warned that while eating cruciferous vegetables, such as watercress and broccoli, is good for people, they are unlikely to have the same pronounced effect as the extract.

Additional researchers on this project are Irina Stepanov, PhD, Sharon E. Murphy, PhD, Steven G. Carmella, BA, Heather H. Nelson, PhD, Dorothy Hatsukami, PhD, and Stephen S. Hecht, PhD, all of the University of Minnesota.

This research was funded by NCI grant R01CA122244.

Pitt Health Sciences Faculty Inducted into Prestigious Physician-Scientist Associations

Three University of Pittsburgh Health Sciences faculty members have been inducted into the Association of American Physicians (AAP), a nonprofit, professional organization founded in 1885 for the “advancement of scientific and practical medicine,” and three have been inducted into the American Society for Clinical Investigation (ASCI), which was founded in 1908 and is “dedicated to the advancement of research that extends our understanding and improves the treatment of human diseases.”
Election to AAP is an honor extended to individuals with outstanding credentials in biomedical science and/or translational biomedical research and is limited to 60 inductees per year. An association of the country’s most accomplished physician-scientists, AAP serves as a forum to create and disseminate knowledge and as a source of inspiring role models for upcoming generations of physicians and medical scientists.

Election to ASCI reflects early career accomplishment as new members must be 50 or younger. ASCI represents physician-scientists who are “at the bedside, at the research bench and at the blackboard.” Up to 80 new members are elected annually from hundreds of nominations.

“Endorsements from these respected societies further demonstrate the commitment to research and the impact of the work performed by the physicians, researchers, and staff at the University of Pittsburgh,” said Arthur S. Levine, MD, Pitt’s senior vice chancellor for the health sciences and John and Gertrude Petersen Dean of Medicine. “We are honored to work with such outstanding scientists who make such significant contributions to the future of science and medicine.”

AAP Inductees:

David A. Brent, MD, is the academic chief of Child and Adolescent Psychiatry at Western Psychiatric Institute and Clinic of UPMC, and professor of psychiatry, pediatrics and epidemiology, University of Pittsburgh School of Medicine and holds an endowed chair in suicide studies. Dr. Brent co-founded and now directs Services for Teens at Risk (STAR), a Commonwealth of Pennsylvania-funded program for suicide prevention, education of professionals, and the treatment of at-risk youths and their families. He has led work that has helped to established evidence based practices for assessing suicidal risk and for treating adolescent depression and suicidal behavior. Dr. Brent is a member of the National Academy of Medicine and has been recognized for his work by the American Psychiatric Association, the American Academy of Child and Adolescent Psychiatry, the American Foundation for Suicide Prevention, and the Brain and Behavior Foundation.

Anne B. Newman, MD, MPH, is the Katherine M. Detre Professor of Population Health Sciences, chair of the Department of Epidemiology at the University of Pittsburgh Graduate School of Public Health, and director of Pitt’s Center for Aging and Population Health. Dr. Newman’s research centers on the relationships between aging, longevity and disability. She currently is the principal investigator of several long-term cohort studies and clinical trials in older adults funded by the National Institute on Aging. Dr. Newman is an elected member of the American Epidemiology Society and the Delta Omega Honor Society in Public Health.

Brian Zuckerbraun, MD, is the Henry T. Bahnson Professor of Surgery and chief of Trauma and Acute Care Surgery at UPMC. Dr. Zuckerbraun’s research centers on how the body’s immune system responds to cell damage. His work investigates the inflammatory response in the liver and vasculature following injury from trauma/hemorrhagic shock, sepsis or direct vascular injury. Much of the work has focused on the development of therapeutic treatments with gaseous signaling molecules, including nitric oxide and carbon monoxide.

ASCI Inductees:

Caterina Rosano, MD, MPH, is a professor in Pitt Public Health’s Department of Epidemiology. Her research focuses on how the brain adapts to the “normal” processes of aging and disease and, specifically, in understanding the causes, biomarkers and consequences of brain aging.

Bernhard Kühn, MD, is a board-certified pediatric cardiologist at Children’s Hospital of Pittsburgh of UPMC, a scholar at the Richard King Mellon Institute for Pediatric Research, and director of research, Division of Pediatric Cardiology. Dr. Kühn’s work is focused on the cells of the heart muscle and discovering ways to make them replicate to enable the heart to heal itself in cases of heart failure or congenital defects.

Stephen Chan, MD, PhD, is an associate professor of medicine and director of the Center for Pulmonary Vascular Biology and Medicine at Pitt’s Vascular Medicine Institute. Dr. Chan studies the molecular mechanisms of pulmonary vascular disease and pulmonary hypertension (PH), with an intent to identify persons at risk for PH and to develop new therapies for this devastating disease.

Four Young Researchers from the Same UPCI Lab Receive AACR Scholar-in-Training Awards

Four young investigators from the same laboratory at the University of Pittsburgh Cancer Institute, partner with UPMC CancerCenter,  have been recognized with American Association for Cancer Research (AACR) scholar-in-training awards for AACR’s annual meeting in New Orleans, April 16 to 20.

“I am delighted the efforts of my students have been so successful and look forward to the next steps they take in their promising research careers,” said lab leader Shivendra Singh, PhD, professor of pharmacology and chemical biology, and UPMC Chair in Cancer Prevention Research, Pitt School of Medicine. His lab focuses on examining enzymes that play a role in drug metabolism and cellular defenses against environmental toxins, as well as exploring the anti-carcinogenic effects of certain natural agents found in edible plants.

Three researchers received scholar-in training awards in memory of Dr. Lee W. Wattenberg, a pioneer in cancer prevention research, who served as AACR president in 1992. According to AACR, these awards are presented to young investigators presenting high-quality papers relating to cancer prevention research.

Those awardees are:

Su Hyeong Kim, PhD: “Role of c-Myc in prostate cancer stem-like cell inhibition by sulforaphane” (Abstract 822).

In this project, Dr. Kim showed that sulforaphane, which naturally occurs in broccoli and other cruciferous vegetables, can inhibit prostate cancer in lab tests because it blocks the effects of c-Myc, a gene that regulates cancer growth. This investigation was supported by grant CA115498 of the National Cancer Institute (NCI), part of the National Institutes of Health.

Subrata K. Pore, PhD: “Benzyl isothiocyanate inhibits breast cancer-induced osteoclastogenesis” (Abstract 826).

Dr. Pore and colleagues built on previous work showing that benzyl isothiocyanate (BITC), found in edible cruciferous vegetables such as garden cress, inhibits breast cancer in a mouse model of the disease. In advanced breast cancer, bone loss can occur, which can be deadly with spreading disease. In this project, the team showed that BITC can limit bone breakdown by reducing the production of bone-resorbing cells called osteoclasts. This study was supported by NCI grant CA129347.

Krishna Beer Singh, PhD: “c-Myc is a novel target of prostate cancer cell growth inhibition by honokiol” (Abstract 831).

Dr. Singh led a project that showed honokiol, a naturally occurring agent derived from magnolia trees, suppressed activity of c-Myc and other genes that play key roles in prostate cancer growth. This study was supported by NCI grants CA101753 and CA115498.

In addition, a fourth researcher from the Singh Lab received a $1,500 AACR-Triple Negative Breast Cancer Foundation scholar-in-training award.

Ruchi Roy, PhD: “Benzyl isothiocyanate mediates glucose uptake through AKT activation in breast cancer cells” (Abstract 833).

Dr. Roy showed in animal models that BITC’s effects in suppressing Her-2-driven breast tumors could be enhanced with the addition of an agent that inhibits the protein AKT. This study was supported by NCI grant CA129347.

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