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College of Medicine / Research / Areas of Focus


Research Highlights
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[Image: amd]  Two of the most prevalent ocular diseases, cataracts and age-related macular degeneration (AMD), afflict millions worldwide. More than half of all Americans either have a cataract or have had cataract surgery by the age of 80, and AMD is the number one cause of vision loss in older Americans. The goal of the Kantorow laboratory, under the leadership of Marc Kantorow, Ph.D. , Professor of Biomedical Science, is to discover ways to prevent and to treat age-related blinding diseases. Age-related eye diseases including macular degeneration and cataract are the leading cause of blindness in the United States and worldwide but, to date, no therapies against these diseases are available.
[Image: bed]  More than 1.6 million Americans  live in nursing homes, and about 60 percent are sent to emergency rooms and 25 percent are admitted to a hospital in a year. Although hospitalizations are often required for medical reasons, experts suggest that 28 percent to 40 percent of these admissions could be avoided with enhanced care in the skilled nursing facility. To help address the national imperative for innovative strategies to improve care and reduce costs, Joseph G. Ouslander, M.D., Senior Associate Dean of Geriatric Programs and  Chair of the Integrated Medical Science Department, developed a program called “Interventions to Reduce Acute Care Transfers” or INTERACT to facilitate the early identification, assessment, documentation and communication about changes in the status of residents in SNFs, and provide the necessary tools to manage conditions before they become serious enough to necessitate a hospital transfer.

[Image: breast_cancer]  Aside from non-melanoma skin cancer, breast cancer is the most common cancer among women in the United States. In 2009, 211,731 women in the U.S. were diagnosed with
 breast cancer and more than 40,000 women died from the disease. Metastasis is responsible for 90 percent of all cancer deaths despite significant improvements in diagnosis and treatments. The Iragavarapu-Charyulu lab, under the leadership of Vijaya Iragavarapu-Charyulu, Ph.D., Associate Professor of Biomedical Science, is focused on breast cancer research and the inflammation that promotes tumor growth and metastasis. She and her colleagues have shown that increased expression of the inflammatory molecule, chitinase-3-like-1 (CHI3L1) correlates with tumor growth and metastasis of breast tumors. She was the first to show that inhibition of CHI3L1 with chitin microparticles decreases tumor growth and metastasis. CH131L is a secreted glycoprotein in humans that is encoded by the CH131L gene and is implicated in inflammatory diseases such as asthma and cancer progression. Dr. Iragavarapu-Charyulu and her colleagues are focused on two specific aims in an NIH-funded project titled “Role of CH13L in Accelerating Breast Cancer Metastasis: a Mechanistic Approach” to determine if inflammation associated with CH13L1 in the lung alters the pulmonary environment to attract circulating breast tumor cells and accelerates metastatic growth; and to determine if inhibition of CH13L1 by either chitin microparticles, anti-CH13L1 neutralizing antibody or combination of these two decreases tumor metastasis. They hypothesize that CH13L1-induced pulmonary inflammation generates the proper environment for recruiting circulating breast cancer cells, thereby increasing the rate of metastasis to the lung. They anticipate that inhibiting CHI3L1 will reduce metastasis.
[Image: brain]  People with major mental health conditions are at increased risk for early death from cardiovascular disease and diabetes mellitus. However, this population often has modifiable risk factors such as obesity or high blood sugar. A range of evidence indicates that psychotropic medications, including antipsychotics, antidepressants and mood stabilizers, can adversely affect these risk factors.  Certain of these medications can affect insulin sensitivity and lipid profiles, increasing risk for diabetes and cardiovascular disease in an already at-risk population. Based on individual patient-level risk and medication-specific risk, working closely with patients in a shared decision-making process, clinicians can beneficially modify risk using behavioral and pharmacologic strategies.  The Newcomer laboratory, under the leadership of John W. Newcomer, M.D., has focused on understanding the effects of disease and pharmacological agents on physiology, substrate metabolism, behavior and cognition. 
[Image: bacteria]  Over 30 million adults and 2.5 million children are infected with the human immunodeficiency virus (HIV) that causes acquired immune deficiency syndrome (AIDS). HIV infection in humans is considered pandemic by the World Health Organization (WHO). Without treatment, HIV-infected individuals develop AIDS and have a life expectancy of less than five years. To date, more than 25 million people have died of AIDS, and two million more are expected to die this year. With recent setbacks in the development of vaccines, the high mutation rate of HIV and new multi-drug resistant strains of the disease appearing with growing frequency, there is an urgent need to develop new drugs. The Caputi laboratory, under the leadership of Massimo Caputi, Ph.D., Associate Professor of Biomedical Science, is identifying novel therapeutics for HIV. 
[Image: body]  Huntington’s disease (HD) is a highly complex genetic, neurological disorder that causes certain nerve cells in the brain to waste away, and the underlying molecular mechanism of this disease still remains elusive. HD is a fatal, inherited disease caused by abnormal repeats of a small segment in an individual's DNA or genetic code. The Wei laboratory, under the leadership of Jianning “Jenny” Wei, Ph.D. , Assistant Professor of Biomedical Research, has identified a novel mechanism and potential link between mutant huntingtin, cell loss and cell death or apoptosis in the brain, which is responsible for the devastating effects of this disease. Dr. Wei and her colleagues conducting research to identify the pathways in the brain that are altered in response to mutant proteins, as well as to understand the cellular processes impacted by the disease in order to facilitate the development of effective pharmacological interventions.
[Image: body]  Alzheimer's disease is a mind-robbing condition that affects nearly five million Americans, and is the seventh leading cause of death in the U.S. As the baby boom generation ages, these numbers are expected to surge. Current medications only temporarily ease the symptoms. For more than 10 years, Peter Holland, M.D., Associate Professor of Clinical Biomedical Science, has focused on better ways of treating and combatting this disease. Dr. Holland is conducting several different studies targeting various stages of illness from mild to moderate and using the latest technologies in AD diagnostics and treatments investigating novel medications that may have an effect on disease progression. An investigator-initiated study is researching the effects of treatment on delaying the progression of driving impairment in patients with AD. Additional clinical research includes a long-term observational study for treatment-resistant depression.
[Image: shot]  Vaccines are one of the most successful means of preventing communicable disease spread to humans, providing an important tool for protecting high risk groups such as the elderly, newborns or those who are immunocompromised. However, vaccines for these susceptible populations don’t always provide sufficient effectiveness, particularly in tobacco smokers where nicotine can degrade vaccine effectiveness. Vaccinations serve as a “firewall” in the spread of disease. The reduced efficacy and protection seen in smokers as compared to non-smokers following vaccination is therefore a significant hurdle in maintaining public health, particularly during an epidemic season, in a pandemic outbreak or in the event of biological warfare. The Nouri-Shirazi lab, under the leadership of Mahyar Nouri-Shirazi, D.V.M, Ph.D., Associate Professor of Clinical Biomedical Science, has identified an immunologic agent that shows promise for optimizing vaccines’ efficacy, particularly in smokers, and in children or adults exposed to environmental tobacco. 
[Image: arthritis]  Osteoarthritis is the most prevalent form of arthritis and afflicts more than 21 million people over the age of 25 in the U.S. The Brew laboratory, under the leadership of Keith Brew, Ph.D. , Chair of the Department of Biomedical Science, is spearheading an international project aimed at developing and evaluating a novel approach for OA treatment by employing engineered proteins and other molecules that specifically block the enzymes responsible for degrading cartilage in osteoarthritis. Dr. Brew and his colleagues are focused on developing and evaluating a novel approach for  treatment by developing and employing engineered proteins that block specific metalloproteinases. Using rodent models of the disease and human tissues derived from joint replacement surgery, they are investigating the mechanisms through which these inhibitors act and are assessing their effectiveness. Finding ways to specifically inhibit disease-related metalloproteinases may provide new opportunities for the development of therapeutics and treatments to prevent the joint destruction seen in OA.
[Image: cancer]  Other than skin cancer, prostate cancer is the most common cancer in American men. Novel targets aimed at blocking tumor metastasis for the development of future therapies are urgently needed. The Lu laboratory, under the leadership of Michael Lu, Ph.D. , Associate Professor of Biomedical Science, has identified a novel molecular regulator, a protein kinase enzyme named PAK6, to be a dominant factor in controlling androgen-regulated tumor metastasis in prostate cancer cells. Dr. Lu has designed a project to fully delineate the molecular process of how androgen influences the development of advanced metastatic prostate cancer, and is using state-of-the-art proteomic technology, including chromatography and mass spectrometry to identify cellular components that interact directly with PAK6 in this signal pathway. It is hoped that the results from Dr. Lu’s research study will open a new avenue to define various novel targets that are pivotal to the future development of treatment to prevent the spread of cancer.
Charles H. Hennekens, M.D., Dr.P.H., the first Sir Richard Doll professor and senior academic advisor to the dean, has has conducted seminal research on aspirin, statins,[Image: artery]   converting enzyme inhibitors, and beta adrenergic blockers, all drugs of lifesaving benefit in the treatment and prevention of heart attacks and stroke.   He was the founding principal investigator (PI) of the landmark Physician's Health Study of 22,071 dedicated and conscientious physicians. Hennekens was also a randomized subject in the trial and took a placebo for five years when his investigator-initiated research grant funded by the U.S. National Institutes of Health was terminated early by the independent and external Data and Safety Monitoring Board due principally to the emergence of a statistically extreme and clinically important reduction in a first heart attack among those assigned at random to aspirin. He was also the first to demonstrate that aspirin prevents heart attacks, strokes, and cardiovascular deaths when given within 24 hours after onset of symptoms of a heart attack as well as to a wide variety of patients who have survived an event associated with a blockage in the heart, brain, or legs.
[Image: cardiomyopathy]  For more than 10 years, Xupei Huang, M.D., Ph.D., Professor of Biomedical Science, has been investigating the mechanisms of restrictive cardiomyopathy, a disorder of the heart muscle in which the walls of the ventricles become stiff, and therefore resist normal filling of blood. Currently, there is no cure and few effective treatments. Some individuals with severe cases of the disease may require heart transplants. Dr. Huang’s investigation provides important clues on how a “normal” heart becomes an “abnormal” one in diseased mouse models, as well as how to prevent this rare, life-threatening condition, and develop optimal personalized treatments. Up until six or seven years ago, the cause of restrictive cardiomyopathy was unknown or “idiopathic.” 
[Image: malaria]  Severe malaria syndromes caused by Plasmodium falciparum kill about 1 million African children each year. Severe malaria is mainly due to adhesion of parasite-infected erythrocytes in deep vascular beds in various organs mediated by the PfEMP1 family of parasite proteins expressed on the erythrocyte surface. The Oleinikov laboratory, under the leadership Andrew Oleinikov, Ph.D., Associate Professor of Biomedical Science, studies malaria parasite biology and virulence factors, and anti-malarial defense mechanisms. Primary research objectives include understanding immunity to severe malaria in children and molecular mechanisms of pregnancy malaria, developing a pregnancy malaria vaccine, and developing various technologies for malaria research and treatment including identification of new anti-malarial drugs.

[Image: malaria]  Research in the Guthrie laboratory, under the leadership of Kathleen Guthrie, Ph.D. , Associate Professor of Biomedical Science, currently focuses on the role of survival/maturation signals in adult brain neurogenesis. The olfactory system is unique in its ability to continuously replace old CNS neurons with new neurons throughout an animal's lifetime. This turnover affords the system a high degree of plasticity as synapses and neural circuits are continually remodeled to incorporate new cells into adult networks. Using transgenic mice and viral-mediated gene transfer, we examine the role of trophic factors in controlling the survival and differentiation of adult-born neurons, as well as how such factors can protect new cells from death.



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