URMC begins 7-year, $18M study of prenatal inflammation and child health

Wednesday, September 21, 2016


Over the past several decades, researchers have shown that an array of conditions in pregnant women, such as anxiety, stress, and obesity, are associated with a large and common cluster of behavioral and physical health conditions in the child. Now, researchers at the University of Rochester Medical Center (URMC) are embarking on a seven-year mission to study one factor that may explain the link: prenatal inflammation.

The research, supported by a grant from the National Institutes of Health that could total more than $18 million, is the first detailed longitudinal investigation of how inflammation — part of the body’s immune response — during pregnancy can affect a child’s neurodevelopment as well as the metabolic systems for processing nutrients and energy. Should the study reach its seven-year maturity, it will be one of the largest grants in URMC history.

“Obesity, stress, anxiety, and a history of trauma have all been linked with elevated levels of pro-inflammatory cytokines, which are chemicals that are part of the body’s immune response. This seems to be generally the case in adults and, of particular concern to us, in pregnant women,” said Thomas O’Connor, Ph.D., Professor of Psychiatry and Director of the Wynne Center for Family Research at URMC. “Inflammation underlies a number of health conditions which may all be connected, and that makes it a very compelling target for developmental health research starting in the prenatal period.”

Thomas O'Connor, Ph.D.

Past research seeking to explain how and why maternal psychological states and physiology may have a long-term impact on child health focused on stress physiology, and especially the stress hormone cortisol, as a likely explanation. But the implications for human health were only modest, underscoring the need for further research.

Clinical scientists have known for some time that proinflammatory cytokines can be measured in the blood at varying levels among individuals. If URMC researchers find that prenatal immune activation does alter child growth and development, then that would open up new targets for intervention.

“In addition to providing new basic knowledge, our study is also positioned to identify additional mechanisms that may guide clinical treatment and improve child health outcomes and ultimately population health,” said O’Connor, the study director.

The grant is part of $157 million in funding announced today by the National Institutes of Health as it launches its Environmental influences on Child Health Outcomes (ECHO) program. The ECHO program will investigate how exposure to a range of environmental factors in early development — from conception through early childhood — influences the health of children and adolescents.

Working with collaborators at the University of Pittsburgh Medical Center, researchers will follow 500 families from the first trimester of pregnancy through the child’s fourth birthday. Researchers will administer prenatal assessments to examine social and family factors, psychological symptoms such as depression and anxiety, and clinical measures such as diet and nutrition. Biological samples including blood, urine, and saliva will also be collected from the mothers in each trimester, and regularly from babies starting at birth.

At birth, cord blood and placenta samples will be collected through a process developed by co-investigator Richard K. Miller, Ph.D., Professor of Obstetrics and Gynecology, and colleagues at URMC. Then, throughout the first four years of life, the child will undergo behavioral and developmental assessments, brain imaging, and dual energy X-ray absorptiometry, a non-invasive scan that quantifies body composition. Children’s immune, endocrine, and metabolic system development will also be tracked from samples collected throughout the child’s first 4 years.

“Every baby should have the best opportunity to remain healthy and thrive throughout childhood,” said Francis S. Collins, M.D., Ph.D., National Institutes of Health Director. “ECHO will help us better understand the factors that contribute to optimal health in children.”

The study builds on previous URMC research and will involve a wide range of university specialists including experts from the Departments of Psychiatry, Neurology, Pediatrics, Obstetrics and Gynecology, and Biostatistics and Computational Biology. The study will capitalize on a range of medical research infrastructure already present at the university, including the Rochester Center for Brain Imaging, the Rochester Human Immunology Center, the UR Genomics Research Center, and the Ernest J. Del Monte Neuromedicine Institute.

In addition to O’Connor and Miller, the URMC team includes Sanjiv Amin, M.B.B.S., Richard Aslin, Ph.D., Emily Barrett, Ph.D., Mary Caserta, M.D., John Foxe, Ph.D., Philip Katzman, M.D., Jan Moynihan, Ph.D., Shawn Murphy, Ph.D., Eva Pressman, M.D., Kristin Scheible, M.D., Chris Stodgell, Ph.D., and Xin Tu, Ph.D. They are assisted by Carrie Salafia, M.D., of Placental Analytics, LLC. The team at the University of Pittsburgh and Magee’s Women’s Hospital is led by Hyagriv Simhan, M.D., with Pathik Wadhwa, M.D., Ph.D., and Claudia Buss Ph.D., of the University of California-Irvine; and Damien Fair, Ph.D., and Alice Graham, Ph.D., of Oregon Health and Science University.

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Neurology Celebrates 50 Years of Leadership in Research, Care, and Education

Wednesday, September 21, 2016


Department of Neurology faculty in 1966 and today

The University of Rochester Medical Center (URMC) Department of Neurology is honoring the 50th anniversary of its founding. The occasion will be marked with four day-long celebration of the department’s history, achievements, alumni, and vision for the future.

“The history of the department is ultimately a human story of relationships, inspiring leadership, and how a rare combination of great intellect, common sense, humility, wit, and charm can move the neurological needle on a global scale,” said Robert Holloway, M.D., M.P.H., the chair of the Department of Neurology. “From its humble beginnings 50 years ago, this department has shaped the careers of hundreds of caregivers and, through its care and research, impacted the lives of millions of patients.”

The URMC Department of Neurology was founded by Bob Joynt, M.D. in 1966 who served as its chair until 1986. The department has been subsequently led by Robert Griggs (1986-2008) Steve Goldman (2008-2012), and Holloway (2012-present).

Over the past five decades, the department has grown from its original six faculty members and is now comprised of more than 260 physicians, nurses, residents, fellows, and support staff. The department is among the top in the nation in research funding and has been a pioneer in experimental therapeutics, its clinical programs are regularly recognized among the best in the country, and its education and training programs are considered national models.

The celebration will take place September 22-24, 2016 and will include the Annual Goldberg Lecture, a gala banquet at the Monroe Golf Club, and a scientific session including posters and research updates by current faculty and alumni.

A Pioneer in Research

The Department of Neurology has consistently ranked among the top 10 in the nation in the amount of research funding it receives from NIH. Total funding for the department in 2015 exceeded $20 million.

The department’s basic research ranges from efforts to understand the fundamental biology of the central nervous system to identifying the mechanisms of neurological disorders. Much of the Neurology’s basic research activity is concentrated in the Center for Neural Development and Disease and the Center for Translational Neuromedicine, the latter operates labs in both Rochester and at the University of Copenhagen.

Neurology is also home to several leading centers that focus on muscular dystrophy research, including the Fields Center for FSHD & Neuromuscular Research, the Wellstone Muscular Dystrophy Cooperative Research Center , and the department maintains a national registry of patients with muscular dystrophy that is used by clinicians and scientists across the country to better understand the complex symptoms of the disease and recruit study participants.

The department is widely recognized as a pioneer in experimental therapies and clinical research. In the mid-1980’s, Joynt tapped Ira Shoulson, M.D., and Karl Kieburtz M.D., M.P.H., to create what would eventually be called the Clinical Trials Coordination Center, a unique academic-based enterprise with the scientific expertise and infrastructure necessary to work with the pharmaceutical and biotech industry, foundations, and the NIH to design and run multi-center clinical trials. Since its inception, the CTCC, which was renamed the Center for Human Experimental Therapeutics in 2012, has conducted 120 clinical trials and is responsible for bringing six FDA-approved drugs to market to treat Parkinson’s disease, Huntington’s disease, and periodic paralysis.

URMC neurologists have also been instrumental in organizing the international networks of clinicians and researchers necessary to carry out multi-center clinical trials. These efforts led to the creation of the Parkinson’s Study Group, the Huntington’s Study Group, and the Muscle Study Group. The department is also one of the inaugural members of the NIH-sponsored NeuroNEXT research network and has recently established a program in global neurology.

Excellence in Clinical Care

The URMC Department of Neurology’s clinical enterprise is one the largest and most sophisticated of its kind in the country and its expertise across the sub-specialties of neurological care attracts patients from across the globe. The department is currently ranked among the top programs in the nation by US News & World Report.

URMC is home to upstate New York’s largest, most advanced, and multi-disciplinary care programs for Parkinson’s disease and movement disorders, muscular dystrophy and neuromuscular disorders, multiple sclerosis, neuro-oncology, and epilepsy.

In recent years, the department has launched a neurohospitalist program, opened the region’s only NeuroMedicine Critical Care Unit, was designated a Comprehensive Stroke Center by the Joint Commission and the American Heart Association/American Stroke Association, and opened the URMC Headache Center.

URMC neurologists have also been pioneers in expanding access to specialized care via technologies such as telemedicine and mobile applications.

A National Model in Education

Rochester is a national magnet for medical students, resident, and fellows. Since 2001, eight percent of the graduates of the School of Medicine and Dentistry have matched into either adult or child neurology residency programs, compared to a national average of one percent. The department’s adult residency program is considered to be one of the top programs nationally and is highly sought after by medical graduates. This year the department received 574 applications for 6 adult residency positions.

The department’s NIH-sponsored training grant in Experimental Therapeutics is in its 26th year and is one of the longest continually-funded NIH training programs in the country. URMC neurologists have also helped develop and oversee neuromedicine education programs in Poland, China, Zambia, Malawi, and Spain.

Ralph Jozefowicz, M.D., who has overseen the department’s education programs for more than 20 years, has been honored by the Association of American Medical Colleges and the American Association of Neurology for enhancing the education of neurologists nationwide.

Alumni of department’s training programs have or are currently practicing neurology in more than 20 countries and 35 states and have gone on to hold various academic, government, and industry leadership positions.

“Over the next 50 years, the field of neurology will be profoundly transformed, from our concept of disease, to our ability to diagnose with more precision, to the impact of our therapies, to the way we teach our trainees,” said Holloway. “But some things will not change. The patient will remain at the center of all we do, guiding our way and reminding us that the most important things we do with our lives we do for others.”

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UR Medicine Launches Outpatient Lactation Medicine/Breastfeeding Practice

Wednesday, September 21, 2016


UR Medicine is launching the area’s first physician-led outpatient practice dedicated to lactation medicine and breastfeeding. The practice will provide women with medical care and support for breastfeeding issues before conception, during pregnancy, and after childbirth.

Casey Rosen-Carole, M.D., M.P.H., MSEd, is Medical Director of UR Medicine’s Lactation Services and Programs and will lead the new UR Medicine Breastfeeding practice. Two office locations will be offered for outpatient breastfeeding consultations: University OB/GYN at 125 Lattimore Road and Strong Perinatal Associates, 500 Red Creek Drive. Rosen-Carole also provides inpatient consultations at Strong Memorial Hospital for mothers and newborns.

“Establishing this practice fills a need for patients who require breastfeeding help after their hospital discharge,” said Rosen-Carole, who specializes in breastfeeding medicine and pediatrics. “Rochester hospitals do a good job of helping mothers establish breastfeeding, but often issues surface later, when mom and baby are in the home environment. Growing a robust outpatient support community in Rochester is critical to help these women.”

The practice also provides essential medical supervision and support for complex medical issues that can make breastfeeding challenging. Some of these include babies born prematurely, or with cleft palate or ankyloglossia (“tongue-tie”), and mothers undergoing treatment for chronic illnesses, including cancer, who still wish to breastfeed.

“We know the benefits of exclusive breastfeeding for the optimal health and well-being of babies, mothers, and communities,” Rosen-Carole said. “But each woman has her own unique goals and challenges for breastfeeding her child. My role is to provide the appropriate medical services and support to help her reach those goals.”

Rosen-Carole is the first physician to complete a formal fellowship in the still-evolving field of breastfeeding medicine. The specialized training was developed by Ruth A. Lawrence, M.D., the Northumberland Trust Professor of Pediatrics at the University of Rochester and an internationally recognized expert in breastfeeding medicine.

Rosen-Carole earned her joint medical degree and master’s degree in public health at New York Medical College School of Medicine and completed a residency in Pediatrics at Yale New Haven Children’s Hospital. She was a practicing community pediatrician and residency faculty from 2008-2009 at Yale, then directed a pediatric practice and served as Chair of Pediatrics in New York's Hudson Valley as faculty for the Mid-Hudson Family Medicine Residency program from 2009-2014. She relocated to Rochester to pursue the fellowship in Breastfeeding Medicine and General Academic Pediatrics.

Rosen-Carole’s research focus has been in systems change for breastfeeding education and support. Other areas of interest include community organizing to address social determinants of health, programming for diversity and equity, and obesity prevention and management. She is fluent in Spanish and French.

To schedule an appointment, call UR Medicine Breastfeeding at (585) 276-MILK (276-6455).

For more information, visit UR Medicine Breastfeeding’s web site: www.urmc.edu/breastfeeding.

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Nuclear Protein Causes Neuroblastoma to Become More Aggressive

Tuesday, September 27, 2016


Aggressive forms of neuroblastoma contain a specific protein in their cells’ nuclei that is not found in the nuclei of more benign forms of the cancer, and the discovery, made through research from the University of Rochester Medical Center (URMC), could lead to new forms of targeted therapy.

EYA1, a protein that contributes to ear development, is present in the cytoplasm of many neuroblastoma tumors, but this protein migrates to the nucleus in the cells of more aggressive forms of the disease. The research, recently published in two medical research journals, allows for the development of targeted drugs that will work to prevent the neuroblastoma from reaching this more aggressive stage; researchers at URMC and elsewhere have already begun testing some of these potential treatments in a laboratory setting.

“Neuroblastoma is one of the most common and deadly forms of childhood cancer, and this discovery allows us to identify drugs that prevent the change in EYA1 structure and potentially minimize the danger to a child who has this disease,” said Nina Schor, M.D., Ph.D., professor of Pediatrics and Neuroscience and the William H. Eilinger Chair of Pediatrics at URMC.

The EYA1 protein enters the cancer cell’s nucleus due to the presence of an enzyme called PRMT1. The presence of this enzyme also results in the increased hardiness of a second protein, N-MYC, which has long been known to increase the aggressiveness of neuroblastoma when it is present in higher-than-normal amounts.

So by limiting the effectiveness of the PRMT1 enzyme, researchers believe they can decrease the damage done by both proteins at once.

“Inhibitors of PRMT1 may deliver a ‘one-two punch’ to neuroblastomas before they become deadly,” said Schor.

The research was published in the Journal of Cancer Research & Therapy and Oncotarget. Schor’s collaborators include co-lead-author Xingguo Li, Ph.D., as well as Jeanne Hansen, Ph.D., Louis T. Lotta, Jr., and Allison Eberhart of URMC; Linda J. Valentijn, Ph.D., and Jan Koster, Ph.D., of the Academic Medical Center of the University of Amsterdam; and Yujun George Zheng, Ph.D., and Kun Qian, of the College of Pharmacy of the University of Georgia. The work was funded by Crosby's Fund for Pediatric Cancer Neuroblastoma Research, Strong Children's Research Center Small Grant Program, and the William H. Eilinger endowment of UR Medicine's Golisano Children's Hospital.

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Nelson Receives International Honor for HIV Disparities Research

Tuesday, September 27, 2016


LaRon Nelson was recognized for his work improving HIV care, being named the inaugural Research Chair in HIV Program Science for African, Caribbean and Black (ACB) Communities by the Ontario HIV Treatment Network.

The Ontario HIV Treatment Network (OHTN) has selected University of Rochester Assistant Professor of Nursing and UR Center for AIDS Research Associate Director of International Research LaRon E. Nelson, Ph.D., R.N., F.N.P. to be its inaugural OHTN Research Chair in HIV Program Science for African, Caribbean and Black (ACB) Communities.

In order to better provide integrated health services for populations most affected by HIV, the OHTN has launched a new program to promote health service innovation, naming three new applied HIV research chairs.

“Each of these research leaders has a unique vision for improved HIV care,” said Tony Di Pede, chair of the OHTN Board of Directors. “The review process identified leaders with the proven ability to work with people and communities across the health care system to investigate and implement solutions.”

Nelson will be appointed as a scientist with the Centre for Urban Health Solutions in the Li Ka Shing Knowledge Institute at St. Michael’s Hospital in Toronto, where he will build on his previous successful implementation of a self-determination-theory-based public health strategy to support HIV pre-exposure prophylaxis uptake and adherence among Black men who have sex with men in three U.S. cities (Los Angeles; Washington, D.C.; and Durham, N.C.). In Ontario, Nelson will lead research focused on reducing HIV disparities in ACB communities across the HIV continuum of care, from prevention to care outcomes, such as symptom management and viral suppression.

This is the second major honor for Nelson in Canada. In 2011, the Canadian government named him one of the nation’s Rising Stars in Global Health.

“I am excited for the opportunity to continue applying my expertise in public health nursing and HIV research to reduce racial and ethnic disparities in HIV infection and care outcomes in communities outside of the United States” said Nelson.

Sixty percent of all African, Caribbean and Black Canadians live in the province of Ontario, which is home to Toronto, the fourth largest metropolitan area in North America. ACB communities in the province are disproportionately affected by HIV. Although these communities make up less than 5 percent of Ontario’s population, they accounted for 25 percent of all new HIV diagnoses in 2015, according to the OHTN.

As the newly appointed OHTN Research Chair in HIV Program Science for African, Caribbean and Black Communities, Nelson will lead program science research on the design, evaluation, translation, and implementation of evidence-based interventions and public health strategies. He will work with regional health departments, community partners, policy makers, and an interdisciplinary team of scientists to implement multilevel prevention packages that are optimized to the needs of ACB communities in the Greater Toronto Area (GTA), which can then be replicated in other Ontario communities.

Nelson’s work in the GTA will start with ACB communities, individuals living with HIV, community service and public health providers in the Region of Peel. The team will help efforts to improve upon coordination and integration of HIV prevention, diagnosis and care for the rapidly growing ACB communities who are migrating west to the region. The new program will use customized mobile technology to address common barriers to prevention and care. Nelson will also develop and mentor a network of early-stage ACB Canadian researchers across Ontario.

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