Dr. Juhasz will use the imaging technique positron emission tomography, or PET, to track the movement of the tracer AMT, a modified form of tryptophan, to areas of the brain where the enzyme IDO is expressed. IDO, which is present in many kinds of tumors, can remove tryptophan from the tumor tissue, causing tolerance to immune rejection. AMT-PET can detect tryptophan uptake and conversion to its metabolites by IDO, contributing to escape from tumor rejection.

What IDO detection means for brain cancer patients, Dr. Juhasz said, is earlier, more accurate detection of tumors, especially in those who have already undergone therapy or tumor removal. "Lots of times patients come back after surgery, radiation or chemotherapy, and something shows up on the follow-up MRI," Dr. Juhasz said. "And it's very difficult to tell, in some cases, whether you're seeing a recurrent tumor or just some damage from the radiation, which is called radiation necrosis."

In addition to distinguishing tumors from non-tumorous lesions, the tracer may also be able to identify tumor type and severity based on the kinetics of AMT uptake observed on the PET scan and the degree of IDO expression in removed tumor tissue.

"It may have a very high prognostic value in determining how severe the tumor is or the likelihood of survival," Dr. Juhasz said. "But we are not that far right now; we're just trying to figure out how IDO is expressed in brain tumors and how we can detect it with PET."

Usha Sethuraman, M.D., has secured a Blue Cross Blue Shield of Michigan Foundation Investigator Initiated Program Grant to research a screening method that could detect childhood health problems earlier.

Dr. Sethuraman, an assistant professor in the Division of Emergency Medicine, Caman & Ann Adams Department of Pediatrics, at the Wayne State University School of Medicine, will use the $70,130 grant to study the efficacy of waist circumference to Body Mass Index in screening for metabolic syndrome in children seen in the emergency department. If the study is successful, children could then receive early treatment to curtail future health problems.

“Adult studies have shown that the waist circumference is a better predictor of presence of metabolic syndrome – the constellation of risk factors for heart disease that includes hypertension, high cholesterol and impaired glucose metabolism,” said Dr. Sethuraman. “We hope to find that waist circumference is a better and more accurate tool for screening for metabolic syndrome in children too. If we find that the waist circumference is indeed more accurate, we hope to introduce its routine measurement in the emergency department, screen the children, and then refer those children with a high waist circumference to a multidisciplinary center for early intervention and treatment.”

This is Dr. Sethuraman’s first grant for this study.

Zhe Yang, Ph.D., assistant professor of Biochemistry and Molecular Biology with the Wayne State University School of Medicine, has been awarded a four-year Scientist Development Grant from the National American Heart Association to further his research of an enzyme that could lead to new treatments to combat heart arrhythmia and cardiac failure.

The $308,000 award will fund research to develop a detailed structural and functional understanding of SmyD1, a histone methyltransferase specifically expressed in cardiac and skeletal muscles.  Histone modifications are now widely recognized as a vital epigenetic mechanism that controls diverse cellular processes, such as gene expression, chromatin remodeling, DNA repairing and cell division. However, the molecular details of the roles of histone modifications in cardiovascular biology remain poorly understood.

Dr. Yang said he is interested in researching this area to provide a structural basis of histone methylation in heart development and cardiovascular diseases. Dr. Yang hopes studying the enzyme at the atomic level may lead to stylized drug treatments to prevent abnormal heart beat and heart failure.

“The protein we are focusing on is a histone methylation enzyme that is recently identified – the only one to date -- specifically expressed in heart and skeletal muscle,” Dr. Yang said. “More importantly, this enzyme is related to fatal cardiovascular diseases and has been implicated in end-stage heart failure and arrhythmia, a disease characterized by abnormal heartbeat rhythm.”

The long-term goal of Dr. Yang’s research is to understand, both at the molecular and structural level, how heart failure happens and how abnormal heartbeat rhythm develops. The research involves developing a detailed understanding of the biochemical function of this enzyme while simultaneously providing an atomic “picture” of its interactions with other factors associated with heart failure.

“The results of this work will be significant because the project will provide high-resolution three-dimensional images of this enzyme, which not only help us better understand the role of this enzyme in cardiovascular functions but also potentially have direct applications to the development of new therapeutic agents -- structure-based drug design -- against cardiac arrhythmias, sudden death and heart failure,” Dr. Yang explained. “Since this enzyme participates in a novel pathway that appears to be highly specific to heart, the greatest advantage of targeting this pathway is the potentially more specific and effective therapies, which may overcome side effects seen with conventional therapeutics in arrhythmias.”

By investigating a novel approach to the treatment of prostate cancer, a Wayne State University School of Medicine researcher hopes to uncover a better way to fight the deadliest forms of the disease.

Zhiwei Wang, Ph.D., a postdoctoral fellow in the Department of Pathology, received a $106,121 award from the U.S. Department of Defense for his research on the genes involved in the proliferation, migration and invasion of prostate cancer cells.

Dr. Wang is investigating Jagged-1, a gene believed to be associated with Hormone Refractory Prostate Cancer (HRPC) - a state the disease sometimes reaches when hormone treatment is no longer affective - and metastatic prostate cancer, the condition in which the disease spreads from the prostate to other parts of the body.

While most cases of prostate cancer are treatable, the instances in which the disease progresses to hormone refractory prostate cancer or metastatic disease usually end in death, Dr. Wang said.

"There is a dire need for the development of novel strategies by which HRPC and metastatic disease could be treated with a better outcome," he said.

Wang may have one such novel strategy with his work involving Jagged-1. In his preliminary studies, he has found that a natural product he has been testing decreases Jagged-1 expression.

Before its impact can be assessed, however, Dr. Wang will first investigate whether the heightened expression of Jagged-1 causes the progression to more severe stages in prostate cancer, as past studies have suggested. If a connection is found between Jagged-1 and the spread of prostate cancer, Dr. Wang will test whether this natural product can help keep prostate cancer in the more treatable forms.

The results, Dr. Wang said, could be an alternative treatment for prostate cancer - used in conjunction with more traditional forms of cancer treatment - in the form of a pill. It could also lead to patients needing lower doses of chemotherapy and radiotherapies. Most importantly, HRPC and metastatic disease may finally have effective treatments.

"Dr. Wang's research reflects the type of ingenuity and vigor needed for fighting the most commonly diagnosed cancer and second leading cause of cancer death in the United States," said Dr. Joe Dunbar, associate vice president for Research at Wayne State. "With no practical methods for treating either Hormone Refractory Prostate Cancer or Metastatic Prostate Cancer currently in existence, Dr. Wang's work gives new hope to those battling this devastating disease, and exemplifies Wayne State's dedication to cutting edge research that will change people's lives."

Diane Chugani, Ph.D., professor of Pediatrics and Radiology at the Wayne State University School of Medicine, was recently awarded a $5.79 million grant from the National Institute of Neurological Disorders and Stroke of the National Institutes of Health for a study that may open doors to finding a treatment for improving those afflicted with autism.

The grant, “Early Pharmacotherapy Guided by Biomarkers in Autism,” will continue earlier research that showed that the brain serotonergic system is abnormal during critical periods of brain development in children with autism.

In this study, Dr. Chugani and her team demonstrated that serotonin synthesis capacity in children younger than 6 was significantly altered when compared to non-autistic children.

Serotonin, an important factor involved in postnatal synaptogenesis -- or specialized junctions through which neurons signal to each other and other non-neuronal cells to form interconnected circuits within the central nervous system that are crucial to the biological processes that underlie perception and thought -- is thought to be one potential target to treatment of autism. Through the use of the 5hT1A serotonin agonist, buspirone, in children younger than 6, Dr. Chugani hopes to uncover a new and safe treatment in groups or subgroups of autistic children.

Phillip D. Levy, M.D., M.P.H., an assistant professor in the School of Medicine’s Department of Emergency Medicine, has received a prestigious award that will assist him in continuing his work to identify preemptive signs of congestive heart failure.

Dr. Levy, who also serves as associate director of clinical research in the department, has been selected as a recipient of a Robert Wood Johnson Physician Faculty Scholar Award. The award, which includes a grant of $300,000 over three years, was one of 15 awarded. Sixty medical schools submitted applications for consideration.

"Dr. Levy is truly an exceptional faculty member, and the Robert Wood Johnson Foundation Physician Faculty Scholar Award is well-deserved,” said Suzanne White, M.D., Chair of the Department of Emergency Medicine. “This accolade, along with his many other accomplishments, reflect his inner commitment to improve the prognosis and quality of life for patients at risk for heart failure through research."

Levy received the award for his research in screening asymptomatic hypertensive patients identified in the emergency department at DetroitReceiving Hospital for early cardiac dysfunction via echocardiography. The patients are randomized to two levels of blood pressure control: “usual,” consistent with current guideline-based recommendations, and “aggressive,” which seeks to lower blood pressure to optimal levels.

The project is an extension of his previous work, funded by the Blue Cross Blue Shield of Michigan Foundation in 2005, which sought to define the prevalence of early yet asymptomatic cardiac disease in the same patient population. Although Dr. Levy initially estimated a symptom prevalence of no more than 10 percent, the actual results discovered that 95 percent of patients screened showed evidence of disease through echocardiography. The work is in the final stages of analysis, said Dr. Levy, and the preliminary results will be presented at the Society of Academic Emergency Medicine Annual Meeting this month.

Dr. Levy believes his work will contribute significantly to the practice of medicine. “Heart failure is an issue of significant societal importance, imparting debilitating morbidity and progressive demise on those who are afflicted and tremendous financial burden on the healthcare system. Hypertension is the primary population attributable risk for development of heart failure, triggering a pressure-dependent continuum of structural cardiac damage that eventually culminates in overt disease. Detection of morphological changes in the heart prior to the onset of symptoms offers the opportunity to intercede in the process and, with appropriately aggressive therapy, potentially prevent clinically apparent heart failure.”

The rates of the condition, Dr. Levy explained, are far greater among African-Americans compared to whites and Hispanics. Blood pressure control among African-Americans is much poorer, leading to premature onset of conditions such as heart failure.

“Despite the increased risk which blacks experience, few programs have been developed to target pre-clinical hypertensive cardiac disease detection or treatment in this specific population,” Dr. Levy said. “Not surprisingly, predominantly black urban areas such as Detroit experience an excessive burden of hypertensive heart disease. Socio-economic factors contribute and increase reliance on emergency departments as a usual source of care.”

Focused efforts in emergency departments could have “profound” downstream effects on disease prevention, said Dr. Levy, but this has yet to be investigated.

As he pursues his research, Dr. Levy will work with his primary mentor, John Flack, M.D., M.P.H., chair of the Department of Internal Medicine.

“Dr. Phil Levy is an outstanding faculty member, and is justly deserving of the Robert Wood Johnson Award,” said Robert Zalenski, M.D., M.A., the Brooks F. Bock Professor of Emergency Medicine, director of the Division of Palliative Emergency Medicine at the School of Medicine and director of the Center to Advance Palliative-Care Excellence for Wayne State University. Dr. Zalenski served as a mentor to Dr. Levy. “His passion is to use the patients' visits to the Emergency Department for other problems to identify those who are succumbing to the effects of high blood pressure and heart failure and don't even know it. By screening them for heart damage with an echo at a point very much earlier in the disease (than they would normally be assessed), he may be able to prevent decades of disability and years of life lost to heart failure and kidney failure. A more worthy or innovative project you will not find in medicine today.”

In 2006, Dr. Levy received a Faculty Research Excellence Award from the School of Medicine, and was named Distinguished Faculty Teacher of the Year by Wayne State and the Detroit Receiving Hospital Department of Emergency Medicine for 2002, 2003 and 2007. In 2004 he received the Medical Student Teaching Award from Wayne State University and in 2005 the WSU College Teaching Award. In 2003, he was awarded the Commander’s Award for Excellence in Service from the Darnall Army Community Hospital in Fort Hood. And from 2005 to 2008, Dr. Levy has held a fellowship in the American College of Emergency Physicians.

“This project will have a profound effect on my career development, enabling development of further content expertise in my chosen area of focused research,” said Dr. Levy. “The team of mentors that will be supporting my application offer unparalleled knowledge and, by way of this grant, I will be able to learn from them in a concentrated fashion. Of particular importance, this grant will provide specific data to help formulate the next phase of investigation for a planned National Institutes of Health R01 submission to track longitudinal outcomes associated with early cardiac dysfunction identified in asymptomatic hypertensive urban emergency department patients.”