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UD Disease Research

Alzheimer’s

Kelvin Lee

Kelvin Lee, Gore Professor of Chemical Engineering
at UD and director of DBI, is working to find a cure
for Alzheimer's disease.

Alzheimer's disease, the most prevalent form of dementia, affects some 4 million people in the United States. Not only is there no cure for Alzheimer's; there is no accurate pre-mortem diagnostic tool. Only an autopsy can indicate for sure that a patient had the disease.
Kelvin H. Lee (chemical engineering) is hoping that the work he and his research group are doing will contribute to the development of both an accurate diagnostic tool for Alzheimer's and a strategy that will protect against the ravages of the disease. They are attempting to come up with a “bar code” that can distinguish between patients with Alzheimer’s disease and those with similar neurodegenerative diseases. This is an important step to make sure that the proper treatment can be administered.

The next steps for the team include conducting additional clinical trials and moving towards obtaining FDA approval to treat Alzheimer's patients with IVIg. IVIg is essentially a cocktail of antibodies taken from a pool of healthy donors. Lee hopes that their work will lead not only to a noninvasive diagnostic tool and an effective treatment but also an understanding of the mechanisms underlying the development of the disease.

The Alzheimer's efforts of the lab of Dr. Lee have led to the first validated premortem test for the diagnosis of Alzheimer's disease. Using a "proteomics" approach to study changes in protein expression in cerebrospinal fluid, they identified a panel of biomarkers useful for the diagnosis of the disease in living individuals, a previously unmet challenge because a definitive diagnosis must await postmortem confirmation. In close collaboration with clinical collaborators, they have extended this approach to the assessment of a passive immunization strategy for the treatment of Alzheimer's disease which has resulted in the first human treatment to show clinical improvement in human subjects in a Phase I clinical trial.

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Arthritis

A grant awarded to the University of Delaware by the National Institutes of Health is aimed at addressing the mechanisms of osteoarthritis, its prevention and treatment by examining the disease from integrated perspective of tissue mechanics, biomechanics, physical therapy and clinical intervention. The wearing down of cartilage, the natural cushion between the bones and joints, causes osteoarthritis, the most common form of arthritis. The disease typically affects the knees, hips, back and hands.

The program involves 14 faculty members in three of UD’s seven colleges, with researchers from Alfred I. du Pont Hospital for Children and the Kessler Medical Rehabilitation Research and Education Corporation serving as collaborators. UD has a unique way of addressing osteoarthritis across multiple levels, by spanning a variety of disciplines.

The primary goals of the grant are to establish a new lab focusing on cytomechanics, or cell mechanics, and to advance five integrated research projects in osteoarthritis.

Mary C. Farach-Carson and Catherine Kirn-Safran (biological sciences) are leading a team to define the structural and functional roles of the biomolecule perlecan in cartilage biology. Liyun Wang (mechanical engineering) is exploring the pathway of communication between bone and cartilage. Lynn Snyder-Mackler (physical therapy) is leading a research team to determine whether rehabilitation that normalizes quadriceps strength between the limbs after total knee replacement will ultimately decrease the progression of osteoarthritis of the hip and knee. Jill Higginson (mechanical engineering) is investigating the muscle forces and coordination strategies used during walking in individuals with age-related osteoarthritis of the knee. Katherine Rudolph (physical therapy) is working to understand how quadriceps strength, knee stiffness, proprioception and instability contribute to osteoarthritis of the knee.

Ten million people in the United States are estimated to already have bone diseases, and almost 34 million more are estimated to have low bone mass, putting them at increased risk for osteoporosis, according to the National Osteoporosis Foundation.

Liyun Wang

Liyun Wang, UD assistant professor of mechanical
engineering, views osteocytes (bone cells) in her lab,
as graduate students Wen Li and Xiaozhou Zhou examine
the magnified images in the background.

Liyun Wang (mechanical engineering) is leading research that will shed light on how osteocytes--the cells encased inside bone--sense external stimuli and communicate with cells on the surface, signaling them to either build more bone or remove existing bone. The results may help scientists hone in on the cause of osteoporosis and arthritis as well as develop more effective drug therapies to treat debilitating bone and joint diseases.

Using a novel microscopic imaging method that Wang developed, which is based on fluorescence recovery after photobleaching (FRAP), the research team hopes to do what no one has done before: see inside living bone and determine how rapidly these signaling and nutrient molecules are transferred between the cells when a bone is at rest and when it is at work.

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Asthma

In Delaware, asthma affects almost 14,000 children. The American Lung Association of Delaware and the University of Delaware surveyed school nurses to identify the needs of children with asthma and the services and accommodations available to them. Findings from the study sparked development of a multidisciplinary Delaware Asthma Committee, an Asthma Education Center, and a statewide system for communicating with the parents of children with asthma.

Laurence Kalkstein (geography) contributed to an evaluation of the relationship between weather and asthma in New York City through a synoptic climatological methodology. The procedure isolates “air masses” that are homogeneous in meteorological character and relates them to daily counts of overnight asthma hospital admissions. If these results can be replicated at other locations in future studies, it may be possible to develop an asthma/weather watch-warning system based on the expected arrival of high-admissions masses.

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Autism

Michael Ferrari (human development and family studies) investigated the idea that a lack of self-awareness or a failure to distinguish self from nonself in autistic children is a characteristic of the syndrome. The study showed that the children who demonstrated clear self-recognition were those that were functioning at mental ages akin to developmental norms for self-recognition. Those who failed to show self-recognition had mental ages below the developmental norms for self-recognition. These results suggest that even when autistic children fail to recognize their self-images, this failure can be taken not as evidence for a syndrome-specific deficit, but as a reflection of a general developmental delay.

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Cancer

David Usher and Robert Sikes (biological sciences) have a grant to support minority undergraduate research in prostate cancer. The centerpiece of the program is a ten-week summer experience that will involve cutting-edge, hands-on research in the laboratories of UD faculty mentors with projects focused on prostate cancer. Select aspects of the research started at UD will continue at Delaware State University and Lincoln University under the joint direction of HBCU and UD research mentors during the following academic year.

A team that includes Paula Klemm and Veronica Rempusheski (nursing) has been awarded a two-year, $600,000 grant to conduct research aimed at supporting older adults affected by cancer and their caregivers in Delaware. The funding supports the development of an outreach program to inform the community about the resources available to those with cancer, specifically older adults. The goal of the project is to create a nationwide model for outreach to older adults in communities all over the United States. Ultimately, access to services through organizations like the Cancer Care Connection, an agency with a nationwide database of cancer resources, may reduce health care costs.

UD undergraduate researcher Kathryn Teixeria (biological sciences) was invited to present her cancer research to members of Congress through a program sponsored by the Council on Undergraduate Research. Her project focused on identifying a sensitive new model system based on chick embryos for studying the metastasis, or spread, of breast cancer cells to the brain. Using the new quantitative system, her research also showed that breast cancer cells preferentially target the brain.

Mary C. Farach-Carson (biological sciences) investigated the development of a biomimetic three-dimensional culture system for poorly adherent bone metastatic prostate cancer cells for use as an in vitro platform for anti-cancer drug screening. Unlike a 2D monolayer culture in which cells adopt atypical spread morphology, cells in the 3D culture system formed distinct clustered structures which grew and merged, reminiscent of real tumors. It was concluded that data obtained from the 3D systems is superior to that from conventional 2D monolayers, as the 3D system better reflects the bone metastatic microenvironment of the cancer cells.

Rajasekaran (biological sciences, materials science and engineering) investigated ways to develop drugs that target cancer stem cells (SC) by investigating changes in cellular mechanisms and kinetics that occur in stem cell populations during colorectal cancer (CRC) development. Computer modeling was used to determine which changes could give rise to exponential increases in both SC and non-SC populations in CRC. The results show that the only mechanism that can explain how these subpopulations increase exponentially in CRC development involves an increase in symmetric SC cell division. This finding suggests that any systemic therapies designed to effectively treat CRC and other cancers must act to control or eliminate symmetrical cancer SC division in tumors, while minimally affecting normal SC division in non-tumor tissues.

Kenneth van Golen (biological sciences) studied inflammatory breast cancer, a rapidly growing, distinct form of locally advanced breast cancer that carries a guarded prognosis. To identify the genes that contribute to this aggressive phenotype, the under- and overexpressed sequences were compared in an inflammatory breast tumor cell line with those of actively replicating normal human mammary epithelial cell lines using differential display. This study discovered two new possible molecular markers specific for inflammatory breast cancer.

Anja Nohe (biological sciences) participated in a study that reviewed current research findings in cell biology, epidemiology, preclinical, and clinical trials on the protective effects of vitamin D against the development of cancers of the breast, colon, prostate, lung, and ovary. The researchers found that efforts to improve vitamin D status would have significant protective effects against the development of cancer. The clinical research community is currently revising recommendations for optimal serum levels and for sensible levels of sun exposure, to levels greater than previously thought.

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Cardiovascular Disease

David Edwards

Prof. David Edwards (right) is using ultrasound studies
of large arteries to investigate vascular dysfunction
in patients with chronic kidney disease.

David Edwards (kinesiology and applied physiology) is studying vascular function in chronic kidney disease and its relationship to cardiovascular disease. Patients with chronic kidney disease are at a very high risk for cardiovascular disease. Even a small loss of kidney function can double a person’s risk of developing cardiovascular disease. Investigations into the mechanisms of endothelial, or vascular, dysfunction have the potential to lead to the development of therapeutic measures aimed at maintaining renal function and reducing cardiovascular risk in chronic kidney disease.

Raelene Maser (medical technology) investigated the impact of surgically induced weight loss of cardiovascular autonomic function in subjects with severe obesity and examine whether the effect was comparable for persons with and without diabetes. It was discovered that surgically induced weight loss 12 months after surgery has a favorable effect on cardiovascular autonomic function in severely obese individuals with and without diabetes.

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Diabetes

Raelene Maser (medical technology) is co-directing a study that will evaluate a new treatment for nerve dysfunction with the Christiana Care Health System. Approximately 60 percent of individuals with diabetes have some form of damage to the nervous system which results in impaired sensation of the lower extremities and can lead to amputation. Diabetes can also cause damage to nerves that innervate the heart and blood vessels, leading to an increased risk of death. Therefore, it is vital to find new therapies to stop the development and progression of nerve dysfunction in order to reduce both morbidity and mortality.

To download a PDF of the brochure, please click here.

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Down Syndrome

James C. Galloway (physical therapy) and Sunil Agrawal (mechanical engineering) have developed kid-size robots to provide mobility to children who are unable to fully explore the world on their own. The work is important because much of infant development of the brain and behavior emerges from the thousands of experiences each day that arise as babies independently move and explore their world. Infants with Down Syndrome, cerebral palsy, autism, and other disorders can have mobility limitations that disconnect them from the ongoing exploration that their peers enjoy. Currently, children with mobility impairments are not offered power mobility until they are 5-6 years old. This can have serious effects on brain development, as environmental interactions are a major part of shaping a child’s brain. With these robots, children as young as seven months are capable of learning to operate the simple joystick controls and maneuver around their environment.

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Hepatitis

Pei Chiu

Pei Chiu (left), and Yan Jin have developed an
inexpensive, nonchlorine-based technology that can
remove harmful microorganisms from drinking water,
including viruses.

Pei Chiu (civil and environmental engineering) and Yan Jin (plant and soil sciences) have developed a method of removing viruses from drinking water by using elemental iron in the filtration process. This technology has also been proven effective against human pathogens in drinking water, including hepatitis A and E. coli 0157.

Kalmia Kniel and Viviana Fino (animal and food sciences) have investigated the use of UV light as a means of inactivation of viruses in raw produce was investigated. The tested viruses included hepatitis A, Aichi virus, and feline calicivirus. This means of inactivation was most effective on the surface of lettuce, with lower results on strawberries and green onions.

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HIV/AIDS

Kathleen Brewer-Smyth (nursing) is exploring the relationship between neurological impairment and HIV in high-risk females. One study consisted of a test population of female inmates. It was discovered that neurological abnormalities were significantly associated with violent and HIV risk behaviors. One risk factor was determined to be a lack of regard for self and others, which is a possible explanation for why education alone has not been an effective tool in combating the spread of HIV. Female inmates tend to receive shorter sentences than males, and so they should be a major target of HIV risk reduction programs.

The use of antiretroviral drugs in HIV therapy is limited by the sequential development of multi-drug-resistant strains. Ryan Zurakowski (electrical and computer engineering) is developing a predictive model to estimate the likely genetic distribution of HIV variants in patients with a known history of antiretroviral use and virological failure. Such a model would work hand-in-hand with treatment-switching techniques to extend the lifespan of HIV patients.

Through the UD Center for Drug and Alcohol Studies, a project was developed to establish HIV/AIDS surveillance and monitoring systems in Rio de Janeiro, Brazil, and to develop, implement, and evaluate a community-based HIV/AIDS prevention/intervention program for drug users. The cooperative effort also involved the Comprehensive Drug Research Center at the University of Miami School of Medicine and a non-profit drug treatment and research center affiliated with the State University of Rio de Janeiro.

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Infectious Disease Vaccinations

Jack Gelb (animal and food sciences) is researching pathogenesis and epidemiology of avian/poultry infections caused by avian coronaviruses, avian influenza virus, and avian herpes viruses. Of particular interest is control of viral diseases through the development and evaluation of vaccines.

Michelle Parent (medical technology) is investigating the protective mechanism required to survive a pneumonic plague infection. Using an attenuated Yersinia pestis she and her research group hope to produce a more successful vaccine.

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Influenza

Serguei Golovan (animal and food sciences) is exploring a leading-edge molecular technique known as RNA interference (RNAi) to thwart the influenza virus across its many strains, including human, avian, and swine influenza. He is testing several approaches to overcome the ability of the virus to mutate and avoid suppression at the target RNAi site. The ultimate goal is to develop a human antiviral drug and virus-resistant poultry and swine.

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Parkinson’s Disease

The work of Ingrid Pretzer-Aboff (nursing) addresses restorative care of neurologically compromised older adults and their caregivers, specifically individuals with Parkinson’s Disease. Even with reasonable control of symptoms through medical and surgical treatments, individuals with PD still experience progressive disability due to disease progression, sedentary lifestyle and resultant deconditioning. Over time, individuals with PD may lose their ability to navigate through their environment, communicate, and perform self-care tasks such as eating, dressing, and bathing. This in turn leads to increased dependence on family caregivers, who are often untrained and unsure of what type of care or how much care they should provide to their family member, leaving them frustrated and burdened. To optimize function and quality of life of these individuals it logical to employ a restorative care intervention specifically designed for individuals with PD and their caregivers (Res-Care-PD) that focuses on education of the dyad to the benefits of participating in self-care activities, physical activities, and exercise.

Chris Knight (kinesiology and applied physiology) is studying the control of muscular force and movement at the most fundamental level of force control: a single motoneuron and the muscle fibers that it innervates, known collectively as a motor unit. It is hoped that the recordings of individual motor units will provide valuable new insights into what is occurring in the brains of individuals suffering from movement disorders such as stroke, Parkinson's Disease, and tremor.

Numerous disease states, including Alzheimer’s disease and Parkinson’s disease are characterized by protein misfolding and precipitation that is central to the observed pathology. Neal Zondlo (chemistry and biochemistry) is studying the molecular mechanisms leading from the soluble, monomeric to the insoluble, polymeric protein forms. To address these issues, the determinants of thermodynamic stability of postulated intermediate structures are examined, including systematic and high-throughput analyses and synthesis of novel amino acids to test mechanistic hypotheses.

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Spinal Cord Injury

A study investigating the effects of SCI on the contractile properties and force-frequency relationship of the paralyzed human quadriceps femoris muscle of adolescents and young adults was undertaken by members of the University of Delaware faculty. The quadriceps femoris muscle is often stimulated during functional electrical stimulation for important tasks such as standing or walking. The implications of this study may be useful in designing stimulation strategies to reduce the rapid fatigue that limits the clinical efficacy of functional electrical stimulation.

Jun Ding (physical therapy) is developing mathematical models that can predict human skeletal muscle forces in response to electrical stimulation. Better stimulation strategies can then be identified and individualized for patients, specifically those with spinal cord injuries.

A team of UD researchers has developed a Passive-Swing-Assist device for gait training of spinal-cord injury patients. The device will allow physical therapy professionals to aid gait training in patients more effectively than existing methods. Through simulation of a swinging leg, spring parameters on an externally applied device are optimized to provide the propulsion force required during walking. The University is currently in the process of obtaining a patent.

The laboratory of Jeffery Twiss (biological sciences) is focusing its research efforts on how the nervous system responds to injury. After an injury, there is a loss of function, such as paralysis after a spinal cord injury. Topics that are of particular interest include gene regulation after a spinal cord injury, specifically how the injured neuron knows which mRNAs it needs to translate after injury.

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