Highlights of scientific papers published by Medical Research Program Grantees, organized chronologically
Study Identifies How Drug-Resistant Tuberculosis Cells Form
Clinical Scientist Development Awardee Sarah Fortune and colleagues at the Harvard School of Public Health have demonstrated how drug-resistant tuberculosis cells form. Researchers observed the growth of Mycobacterium smegmatis cells, which are similar to the Mycobacterium tuberculosis cells. They found that instead of evenly dividing into similar-sized daughter cells, the M. smegmatis cells divided into diverse daughter cells with variable sizes and growth rates, and, as further tests found, a difference in their susceptibility to various antibiotics. This finding suggests a new target for the treatment of drug-resistant tuberculosis by using combinations of antibiotics to target cells of varying susceptibility.
New Gene Targets Identified for Hypertension Treatment
Clinical Scientist Development Awardees Christopher Newton-Cheh (Massachusetts General Hospital) and Sekar Kathiresan (Broad Institute of MIT and Harvard) and Distinguished Clinical Scientist
David Altshuler (Broad Institute of MIT and Harvard) and their colleagues around the world who are part of the International Consortium for Blood Pressure Genome-Wide Association Studies have identified new gene targets for hypertension treatment, which could lead to new types of hypertension drugs.
Free Medications Not Enough to Address HIV in Africa
Operations Research on AIDS Care and Treatment in Africa grantee Gretchen Birbeck (Michigan State University) has published the results of her research looking at the impact that socioeconomic and psychiatric status has on antiretroviral (ART) adherence and mortality in rural Zambia. Dr. Birbeck found that factors such as travel time to the clinic, drug side effects and food access play a role in treatment adherence, demonstrating that provision of free medications alone will not be enough to address the morbidity and mortality of HIV in Africa.
- Am. J. of Tropical Medicine and Hygiene – October 2011
Abstract
Whole-Parasite Malaria Vaccine Shows Potential
A team of scientists that includes Clinical Scientist Development Awardee Kirsten Lyke and Distinguished Clinical Scientist Awardee
Christopher Plowe (both University of Maryland, Baltimore) has shown in a clinical trial that a malaria vaccine using the entire malaria parasite is safe and shows potential to produce an immune response in humans. This is the first time the entire malaria parasite has been used in an experimental vaccine against the disease, which infects 300 million people annually worldwide.
Natural Killer Cells Show Immune Response to HIV
Distinguished Clinical Scientist
Marcus Altfeld and colleagues at Massachusetts General Hospital and Harvard University demonstrated for the first time that natural killer cells, which are part of the body’s defense against infection, can contribute to the immune response against HIV. Previously only T cells have been shown to have an immune response to HIV in the human body. Researchers hope that this finding will eventually translate into new preventive or treatment strategies.
New Technique Developed for Human Tissue Regeneration
Clinical Scientist Development Awardee Christopher Breuer and colleagues at Yale University have developed a new method for engineering human tissue regeneration, representing a major shift in how scientists conceive of human tissue regeneration and engineering. Tissue engineering is used to repair damaged organs, bones or blood vessels. Previously it was believed that human cells added to a graft before implantation into a patient are the building blocks of the tissues that eventually grow. However, based on the results of this research, scientists now believe that engineered tissue grafts seeded with human cells work with the body’s innate healing capabilities to grow new tissue. This is an important shift because it shows that the body’s own repair mechanisms can be used to make new tissues through bioengineering. A clinical trial is underway to evaluate the safety and effectiveness of tissue-engineered vascular grafts in children undergoing surgery for congenital heart disease.
Medicare Part D Results in Savings
Clinical Scientist Development Awardee J. Michael McWilliams (Harvard Medical School) found that the creation of the Medicare Part D prescription drug benefit in 2006 has caused significant savings to other parts of the Medicare program. Medicare Part D resulted in increased medication use and adherence by seniors who previously could not afford prescription drugs for chronic conditions such as diabetes and high blood pressure. Due to improved disease management, fewer seniors needed a hospital or nursing home stay, resulting in substantial savings. These findings suggest that improved coordination of healthcare delivery is important for both improving seniors’ health and managing costs, which may inform future policymaking.
Controlling Movements with Thought
Clinical Scientist Development Awardee Leigh Hochberg and a team of researchers from Brown University and Massachusetts General Hospital reached a milestone in the pilot clinical trial of BrainGate, a brain-computer interface that harnesses electrical signals in the brain to allow people with paralysis to control external electronic devices. Researchers found that a tetraplegia patient implanted with the baby aspirin-sized BrainGate mechanism was still able to control a computer cursor accurately through neural activity alone more than two years after receiving the implant. This is the first demonstration that this technology can continue to be effective more than 1,000 days after it has been implanted.
Study Identifies Possible Keys to Natural Viral Suppression of HIV
Clinical Scientist Development Awardee Mathias Lichterfeld and colleagues at Massachusetts General Hospital may have found one of the keys to why some individuals are able to control HIV infection with their immune system alone. About one in 300 individuals with HIV are “elite controllers” and can naturally suppress viral replication without drugs. The team identified a cancer fighting protein known as p21 that may be involved in this phenomenon. The p21 protein blocks a cellular enzyme required for viral replication, and in elite controllers, its levels were 10 to 20 times higher than in individuals with progressive HIV infection. This study suggests that p21 may have an important role in producing greater resistance to HIV in a broader patient population.
Telomere Shortening May Be Linked to Age-Related Diabetes
Clinical Scientist Development Awardee Mary Armanios (Johns Hopkins University School of Medicine) reported in the journal PLoS One that short telomeres — the caps at the ends of chromosomes (pictured at left) — may predispose people to age-related diabetes. Telomeres are repetitive sequences of DNA that protect the ends of chromosomes, and they shorten with age. As telomeres shorten, cells lose the ability to divide normally and eventually die. Telomere shortening has been linked to cancer, lung disease and other age-related illnesses. Based on the observation that diabetes occurs more often in patients with dyskeratosis congenita, a rare inherited disease caused by short telomeres, Armanios surmised a possible link with telomere shortening and diabetes. Combining research in mice (not funded with the DDCF grant) and this observation, Armanios concluded that telomere length could serve as a biomarker for development of diabetes.
Genetic Mutations are Found to Trigger Severe Form of Hypertension
Clinical Scientist Development Awardee Tobias Carling and a team of researchers at Yale University have identified two novel genetic mutations that can trigger hypertension in up to a third of patients suffering from a common cause of severe high blood pressure. From 5% to 10% of patients with severe hypertension have tumors of the adrenal gland that produce the hormone aldosterone. Removing these tumors can cure this form of hypertension. Looking at the genes from these tumors, and comparing their sequences with the patients’ normal DNA, researchers found that either one of two mutations of a single gene were found in eight of the 22 tumors studied. The investigators discovered that these mutations cause both aldosterone release and tumor formation by allowing the encoded protein, a potassium channel, to conduct sodium rather than only allowing potassium through. In addition, inherited mutations in the same gene were found to be the cause of a rare familial form of severe hypertension. These findings may lead to new therapies for these forms of hypertension.
Genetic Mutations are Found to Trigger Severe Form of Hypertension
Clinical Scientist Development Awardee Tobias Carling and a team of researchers at Yale University have identified two novel genetic mutations that can trigger hypertension in up to a third of patients suffering from a common cause of severe high blood pressure. Five to ten percent of patients with severe hypertension have tumors of the adrenal gland that produce the hormone aldosterone. Removing these tumors can cure this form of hypertension. Looking at the genes from these tumors, and comparing their sequences with the patients’ normal DNA, researchers found that either one of two mutations of a single gene were found in 8 of the 22 tumors studied. The investigators discovered that these mutations cause both aldosterone release and tumor formation by allowing the encoded protein, a potassium channel, to conduct sodium rather than only allowing potassium through. In addition, inherited mutations in the same gene were found to be the cause of a rare familial form of severe hypertension. These findings may lead to new therapies for these forms of hypertension.
Science - February 2011
Abstract;
Press ReleaseHDL Function Better Measure of Protection Against Heart Disease
Distinguished Clinical Scientist
Daniel Rader and researchers at the University of Pennsylvania discovered that a measure of high density lipoprotein (HDL) function known as cholesterol efflux capacity is more closely associated with protection against heart disease than HDL levels by themselves. Previous research indicated that high levels of HDL (the “good cholesterol”), were linked to a reduced risk of cardiovascular disease. However, Rader’s research indicates that cholesterol efflux capacity is a more direct gauge of the efficiency by which a person’s HDL removes cholesterol from the blood cells that accumulate in arterial plaque and can lead to hardening of the arteries. The new findings could lead to additional therapeutic targets for heart disease.
Positive News for Treating Patients Co-Infected with HIV and Multidrug – Resistant Tuberculosis
Operations Research on AIDS Care and Treatment in Africa grantee Gerald Friedland, and Clinical Scientist Development Awardees Sarita Shah and Neel Gandhi continue their research into the growing problem of HIV and multidrug-resistant tuberculosis (MDR-TB) co-infection in patients in South Africa. Historically, patients co-infected with HIV and MDR-TB have poor outcomes. Friedland and colleagues found that combining treatment for MDR-TB with anti-retroviral medications for HIV led to interim cure rates in co-infected patients that were similar to those reported in HIV-negative patients. While future research is needed to examine whether similar cure rates are achieved at the conclusion of 2 years of MDR-TB treatment, these results provide welcome news for treatment of both diseases.