School of Medicine

Wayne State University School of Medicine
Resident wins grant to explore antibody to provide greater protection against pertussis
In Headlines on April 10, 2014
Jacqueline Guterman, M.D., Ph.D.

Jacqueline Guterman, M.D., Ph.D.

A first-year resident with the Wayne State University School of Medicine’s Department of Obstetrics and Gynecology has received a grant to explore whether a different antibody in the bodies of pregnant mothers holds the possibility of greater protection against pertussis for newborns.

Jacqueline Guterman, M.D., Ph.D., has secured a one-year, $20,000 grant from the American College of Obstetricians and Gynecologists’ Research Fellowship Program for her study, “Immunoglobulin D response to antepartum pertussis vaccination and its role in neonatal protection.”

Despite routine vaccinations against pertussis since the 1940s, whooping cough, as it is commonly known, has made a comeback in the United States. Cases have been steadily increasing, causing significant illness and death in infants younger than 1 year.

The disease is more common in infants and young children, according to the U.S. Centers for Disease Control and Prevention. Of U.S. infants infected before the age of 1, about half are hospitalized. One in four of those will develop pneumonia, and between one and two in every 100 infected will die.

Health officials report that worldwide an estimated 300,000 annual deaths can be traced to whooping cough. The CDC received 48,000 reports of cases nationwide in 2013, the largest single-year number since vaccinations became available.

The Michigan Department of Community Health has previously reported a “worrisome steady increase” in pertussis cases in the state. In 2010, the department recorded 1,500 reported cases. In just the first six months of 2012, the department received 847 reports of pertussis cases,  including one death – a 21 percent increase over the 691 cases in 2011. A provisional report by the CDC showed Michigan with 858 reported cases in 2013.

“I am very excited to start on the project,” said Dr. Guterman, an ACOG junior fellow who received her medical degree from State University of New York, Upstate Medical University. “This study will provide novel insights into the mechanisms underlying the immune protection against pertussis induced by antepartum vaccination and direct the design of more efficient maternal vaccines for pertussis and other respiratory pathogens.”

In an effort to reduce infant pertussis infection, Dr. Guterman said, the ACOG recommends tetanus, diphtheria and acellular pertussis vaccinations during every pregnancy. The rationale behind that recommendation is the belief that the maternal antibody isotope Immunoglobulin G, or IgG, developed by the vaccinations provides passive immunity in infants until they can receive routine childhood vaccinations.

However, the mechanism of pre-birth vaccine-induced protection again pertussis is not completely understood, Dr. Guterman said. Experiments with animal models have shown that pertussis-specific IgG is only detectable in the serum when the infection is cleared from the respiratory tract, a finding that argues against the role of IgG in preventing a primary infection.

Dr. Guterman and her colleagues recently found that another antibody known as Immunoglobulin D, or IgD, present in large amounts in the human upper respiratory system, displays “potent functions” in respiratory immune defense. The IgD activates antimicrobial, pro-inflammatory and antibody-inducing functions of basophils, a type of white blood cell. The antibody also binds to respiratory pathogens, and could transfer across the placenta, providing an early form of protection against pertussis in newborns.

The study will set out to determine maternal IgD response to pre-birth pertussis vaccination and its role in newborn protection. Dr. Guterman hypothesizes that pre-birth pertussis vaccination in mothers induces maternal IgD, which can be transferred to their infants, contributing to protection against neonatal infection.

In the study, Dr. Guterman will work with her mentors, Kang Chen, Ph.D, assistant professor of obstetrics and gynecology, whose lab developed the preliminary research on IgD; and Bernard Gonik, M.D., professor of obstetrics and gynecology and the Frann S. Srere chair of Perinatal Medicine, who will oversee the clinical/patient aspect of the project.

Pertussis made national headlines in 2010 when a spike in cases was reported in California. That outbreak – which affected more than 9,000 people and killed 10 infants – rated as the Golden State’s worst outbreak in 60 years. Closer to home, in 2013 Washtenaw County recorded almost 200 cases of pertussis. Washtenaw County Public Health reports that this year as many as two new cases are being reported each week.

Among the reasons for the outbreaks and the resurgence of the disease, researchers say, is the fact that pertussis strikes cyclically every five years or so, and a newer vaccine decreases in potency faster than previous versions. New findings also point to a philosophical factor as well: the movement among some parents to refuse to have their children vaccinated.

National Academy of Sciences selects Dr. Noa Ofen as Kavli Frontiers Fellow
In Headlines on April 9, 2014
Noa Ofen, Ph.D., presented her research as a Kavli Frontiers Fellow at a recent symposium in California.

Noa Ofen, Ph.D., presented her research as a Kavli Frontiers Fellow at a recent symposium in California.

Dr. Ofen discusses her work with an attendee.

Dr. Ofen discusses her work with an attendee.

A Wayne State University faculty member presented her research on capturing episodic memory development at the 19th German-American Kavli Frontiers of Science Symposium, a prestigious biannual meeting held April 4-6 in Irvine, Calif.

Noa Ofen, Ph.D., an assistant professor in the School of Medicine’s Department of Pediatrics and WSU’s Institute of Gerontology, was among the 70 researchers competitively selected and invited to present as Kavli Frontiers Fellows, a scholarship co-sponsored by the Alexander von Humboldt Foundation and the National Academy of Sciences.

Attendees are selected by academy members from a pool of young researchers who have already made recognized contributions to science and have been identified as future leaders in science.

“The Frontiers of Science experience was incredible,” Dr. Ofen said. “It is a great honor to be recognized as one of the top young scientists in my field. The opportunity to discuss major scientific issues across a broad range of disciplines with bright scientists who work in the frontiers of each discipline was extremely energizing. The symposium reminded me how exciting science exploration is, not only within my field, and motivated me to look more broadly at conducting impactful research.”

The meeting allowed participants like Dr. Ofen to explore innovative research ideas across a wide variety of fields and develop new networks that will serve them as they progress in their careers.

“This meeting took me back to my high school days, when I was selected to represent Israel -- where I then lived -- at the International Youth Science Meeting in the United Kingdom. It was wonderful experience then and a good reminder now of how fascinating science is,” she added. “It was a great opportunity to represent Wayne State University and our strength as a research university.”

She presented “Development of Memory Systems in the Human Brain” in a poster as part of the meeting’s formal session on neuroplasticity and development.

“Episodic memory – the ability to encode, maintain and retrieve information – is critical for everyday functioning at all ages, yet little is known about the development of episodic memory systems and their brain substrates,” Dr. Ofen said. “The use of neuroimaging methodologies, including MRI, in the study of episodic memory development is providing new insights into the neural underpinnings that support improvements in episodic memory.”

She presented data on these neural mechanisms, highlighting evidence that demonstrates how functional and structural brain development underlies changes in memory functioning throughout childhood and adolescence. She leads the Ofen Lab for Cognitive and Brain Development, which investigates structural and functional brain development across a wide age range of typically developing children and adults. Using tests of cognitive abilities combined with neuroimaging techniques, she probes how brain structure and function shape human cognitive functioning across development. She has worked to explore the structure and function with a neurodevelopmental basis of the hippocampus, a crucial brain structure for learning and memory that is altered in a number of psychiatric disorders.

Michigan AHEC launches Upper Peninsula Regional Center
In Headlines on April 8, 2014
The Michigan Area Health Education Center has announced the launch of its Upper Peninsula Regional Center, partnering with Northern Michigan University. Located in Marquette, the center will be responsible for implementing AHEC goals in 15 counties: Alger, Baraga, Chippewa, Delta, Dickinson, Gogebic, Houghton, Iron, Keweenaw, Luce, Mackinac, Marquette, Menominee, Ontonagon and Schoolcraft.

Established by Wayne State University in 2010, Michigan AHEC seeks to enhance access to quality health care, particularly primary and preventive care, by improving the supply and distribution of health care professionals through community and educational partnerships. Through a statewide network of regional centers, Michigan AHEC prepares underrepresented and disadvantaged youth for health care careers, promotes clinical training opportunities for students in shortage areas and provides continuing education programs for health professionals.

“We are very happy to have Northern Michigan University serve as our host partner in the state’s AHEC network,” said Valerie M. Parisi, M.D., M.P.H., M.B.A., dean of the WSU School of Medicine and co-principal investigator of the Michigan AHEC program. “The northern regions of our great state also are underserved areas in terms of access to health care. Having NMU join us in this effort will be crucial to further addressing this issue.”

Northern Michigan University is the host partner for the Upper Peninsula Regional Center. The university offers medical pre-professional programs as well as certificate, bachelor’s and master’s degree programs in nursing, clinical lab sciences and allied health. Students also have the opportunity to participate in the Early Assurance Program, an initiative that targets students from underserved rural or urban areas, first-generation college students, graduates from low-income high schools, students who are Pell grant-eligible or those interested in practicing medicine in a high-need specialty in areas where there are health care shortages.

“Michigan AHEC is excited about extending our reach and resources to the Upper Peninsula,” said Dr. Ramona Benkert, Ph.D., A.N.P.-B.C., F.A.A.N.P., associate dean for Clinical and Academic Affairs for the WSU College of Nursing and co-principal investigator of the Michigan AHEC program. “The Upper Peninsula has a severe shortage of primary care and other health professionals. We are pleased Northern Michigan University has joined the Michigan AHEC team and look forward to working with the university and the community to identify and address northern Michigan’s health care workforce needs.”

The Upper Peninsula Regional Center is the fourth of Michigan AHEC’s five regional centers. The Southeast Regional Center, established in 2011, is located in Detroit and hosted by the Greater Detroit Area Health Council. Opened in 2012, the Mid-Central Regional Center is hosted by Central Michigan University. The Western Regional Center, launched in 2013 and located in Grand Rapids, is hosted by Western Michigan University. The Northern Lower Regional Center is expected to open in 2015.

Mary Jane Tremethick, Ph.D., R.N., assistant dean and director of the NMU School of Health and Human Performance, was appointed interim executive director of the Upper Peninsula Regional Center. In this role, she will plan, organize, direct and evaluate all aspects of the center, including financial administration, program planning and development, personnel management, fundraising, and public relations and marketing. Before becoming a professor at NMU in 2000, she served as assistant professor in the department of Health Education and Promotion at Western Illinois State University, and she worked for several years as a registered nurse at Marquette (Mich.) General Hospital.

Cindy Noble was named program manager for the Upper Peninsula Regional Center. She will manage programs, coordinate data collection, and develop public relations, marketing and community engagement strategies. Noble previously served as parks and recreation coordinator for the city of Marquette. She taught courses in health promotion and personal training as an adjunct instructor at NMU, where she earned her master’s degree.

Michigan AHEC is funded by the U.S. Health Resources and Services Administration, the Kresge Foundation and Wayne State University. Academic partners include Wayne State University’s College of Nursing, College of Pharmacy and Health Sciences, School of Medicine and School of Social Work; the University of Detroit Mercy School of Dentistry; Central Michigan University; Western Michigan University; and Northern Michigan University.
Dr. Ledgerwood named first female president of American Surgical Association
In Headlines on April 8, 2014
Anna Ledgerwood, M.D.

Anna Ledgerwood, M.D.

Anna Ledgerwood, M.D., F.A.C.S., professor of surgery for the Wayne State University School of Medicine, will be inducted as president of the American Surgical Association this week.

Dr. Ledgerwood will become the association’s first female president April 11 at the ASA’s 134th meeting in Boston.

The ASA is the nation’s oldest – and considered by many the most prestigious – surgical organization. Members include the country’s most prominent surgeons from leading academic medical schools. Its primary mission is to be the premier organization for surgical science and scholarship, provide a national forum for presenting state-of-the-art science of general and sub-specialty surgery and elevate the standards of the profession.

Dr. Ledgerwood will serve as president-elect through 2014, and will deliver her presidential address at the association’s 135th meeting, which will be held in San Diego in April 2015.

The Grosse Pointe Farms resident, a School of Medicine faculty member since 1972, said that among the issues she plans to address during her term as president are those “related to the resident work hours and their training, and how to increase research productivity of the young faculty.”

The trauma director for Detroit Receiving Hospital, Dr. Ledgerwood serves as a trauma site visitor to verify hospitals as trauma centers for the American College of Surgeons.

She continues to give small teaching sessions to groups of WSU residents and medical students twice a week and makes rounds daily with them to educate and mentor at the bedside. She is a frequent guest lecturer at other medical schools and has a special interest in promoting women in the field of surgery.

She has been recognized locally, nationally and internationally for her achievements. She served as president of the Detroit and Michigan surgical associations, and as president of the Midwest Surgical Association, the Michigan chapter of the American College of Surgeons, the American Association for the Surgery of Trauma, and as vice president for the ACS and the American Surgical Association.

Other WSU faculty members who belong to the ASA include Charles Lucas, M.D., F.A.C.S.; Larry Stephenson, M.D.; Choichi Sugawa, M.D.; Robert Wilson, M.D.; Lawrence Diebel, M.D.; Scott Dulchavsky, M.D., Ph.D.; and Robert Mentzer Jr., M.D.
Dr. Juhasz receives $1.6 million R01 renewal to better diagnose brain, eye and skin disorder
In Headlines on April 7, 2014
Csaba Juhasz, M.D., Ph.D.

Csaba Juhasz, M.D., Ph.D.

The National Institute of Neurological Disorders and Stroke has renewed a five-year, $1,662,500 million grant to Wayne State University School of Medicine faculty member Csaba Juhasz, M.D. Ph.D., to develop better diagnostic tools for a rare disorder present at birth that affects the brain, eye and skin in the form of venous blood vessel malformations.

The malformations, a skin lesion called port-wine stain, commonly appears on the face. The facial marker allows early diagnosis, often before neurological symptoms begin.

“This opens a unique, early window for intervention to prevent or diminish neurological symptoms; however, current imaging techniques often miss early brain involvement and no effective preventive treatments exist,” said Dr. Juhasz, professor of pediatrics and neurology, and the principal investigator on “Longitudinal neuroimaging in Sturge-Weber syndrome.”

“The overall aim of our research is to develop better diagnostic tools to detect brain involvement early and uncover new treatment paradigms to fundamentally alter neurocognitive outcome. For this, we study children affected by the disease in a prospective, longitudinal fashion using advanced multimodal imaging techniques, such as magnetic resonance imaging and positron emission tomography,” Dr. Juhasz said.

More than 75 percent of children with Sturge-Weber will develop seizures. They also have a 60 percent risk of developing a learning disability and variable motor deficits such as weakness in the arms and legs.

The renewed grant phase will build upon results from the previous funding period and collect data for preventive antiepileptic treatment guided by advanced neuroimaging for children with the disorder who are at risk for severe epilepsy.

They also will study feasibility of a new treatment approach to block abnormal vessel proliferation in the affected brain vessels, utilizing imaging and surgical tissue data and the recent discovery of a somatic gene mutation in the syndrome.

“Finally, we will determine how surgical brain resection – applied in SWS children with drug-resistant seizures – alters long-term disease trajectory and improves neurocognitive outcome, thus reversing the devastating effects of the disease on brain development,” he said.

Dr. Juhasz works with co-investigators from Children’s Hospital of Michigan, Pediatric Neurology; in the PET Center; and in WSU MR Research Facility, as well as with representatives of the Sturge-Weber Foundation. He also is the WSU site leader of the Brain Vascular Malformation Consortium, a collaborative network involving several Sturge-Weber centers across the country. They have already built, together with Professor Harry Chugani, M.D., chief of Pediatric Neurology and director of the PET Center at Children’s Hospital of Michigan, an internationally recognized clinical research and imaging program for children with SWS.

“We recruit patients from the United States and Canada. Families travel to Detroit for testing, which typically lasts two days to complete,” he said.

Imaging studies are performed at the PET Center and Translational Imaging Laboratory at Children’s Hospital of Michigan and at WSU’s MR Research Facility.

The grant, R01NS041922, has been funded continuously by the National Institutes of Health since July 1, 2003.

Since the initial grant cycle, the researchers have determined the natural disease course, identified a critical age window (younger than 4 years) for progressive brain damage in affected children and identified potential mechanisms related to early epileptogenesis, a process in the brain that leads to clinical seizures and as potential drivers of disease progression.

They hope to identify and validate new imaging markers of epileptogenesis and abnormal angiogenesis (the process of new blood vessels forming from pre-existing vessels), providing targets for novel drug treatments during the early disease course. The imaging markers could be applied to children with epilepsy caused by other underlying etiologies.

“We will also understand the effects of early brain surgery on brain plasticity and functional reorganization, leading to better neurological and cognitive outcomes. These latter results can be translated to other focal pediatric brain disorders amenable for surgical resection,” Dr. Juhasz said.

Tissue studies will be carried out at the Translational Neuro-Oncology Research Laboratory at the Barbara Ann Karmanos Cancer Institute, led by Associate Professor of Neurosurgery and Oncology Sandeep Mittal, M.D., along with co-investigator and Professor of Pathology William Kupsky, M.D.

For more information on Sturge-Weber syndrome, visit the National Institute of Neurological Disorders and Stroke or The Sturge-Weber Foundation.
WSU researchers secure grant to study newborn hearing loss in West Bank
In Headlines on April 7, 2014
William Lyman, Ph.D.

William Lyman, Ph.D.

James Coticchia, M.D.

James Coticchia, M.D.

Two Wayne State University School of Medicine researchers will team with colleagues in the West Bank to study the cause of the prevalence of hearing loss among newborns in the West Bank region.

James Coticchia, M.D., professor of otolaryngology, and William Lyman, Ph.D., professor of pediatrics, have secured a $264,200 grant (1R21DC014238-01) from the National Institute on Deafness and Other Communication Disorders for the two-year study. They will collaborate with geneticists at Bethlehem University, research staff at Caritas Baby Hospital in Bethlehem, and the maternity services staff at Holy Family Hospital in Bethlehem and Al Ahli Hospital in Hebron.

“This award will support a research study focused on the epidemiology and etiology of newborn hearing loss on the West Bank, Palestine,” Dr. Lyman said. “Although it is known that hearing loss is common on the West Bank, there are only limited and inconclusive data about the precise incidence and causes of congenital deafness in Palestine.”

He noted that in addition to helping improve public health efforts on the West Bank, the outcome of the study, titled “Epidemiology of Newborn Hearing Loss on the West Bank,” may benefit children and families served by Wayne State University School of Medicine and the Detroit Medical Center, many of whom have origins in the Middle East.

Dr. Coticchia and Dr. Lyman will establish a newborn hearing-screening program in the southern West Bank, recruiting a statistically significant study population from area birthing hospitals. Before they are discharged, the newborns will undergo a risk factor survey and otoacoustic testing for hearing loss. If the babies fail the tests, they will be referred to a local children's hospital, where a diagnostic algorithm will be incorporated that includes auditory brain response testing and, if indicated, tympanometry, infectious disease and imaging studies. If the tests find a genetic basis for sensorineural hearing loss, or SNL, the parents will receive genetic counseling and the infant will be further tested for known and potential new genes that can impact hearing.

Dr. Lyman said possible reasons for the prevalence of hearing loss in newborns in the West Bank include infection and consanguinity – intermarriage among families – contributing to a host of genetic diseases. Higher rates of diseases and disorders are more common in the offspring of consanguineous relationships.

Estimates of consanguinity in Palestine range up to approximately 40 percent of marriages in the West Bank, Dr. Lyman said. When this approximation is considered against the backdrop of its multigenerational nature, the potential effect of genetic inbreeding on SNL increases.

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