Kathy Griendling, PhD (in green), surrounded by members of her lab
On June 15, 2010, vascular biologist Kathy Griendling delivered the 2010 Dean’s Distinguished Faculty lecture at Emory University School of Medicine.
Some of Griendling’s publications have been cited thousands of times by fellow scientists around the world, making her the lead member of a small group of researchers at Emory called theÂ “Millipub Club.”
With her five children and one grandson watching in the back row, Griendling explained how she and her colleagues, over the course of more than two decades at Emory, have gradually revealed the functions of a family of enzymes called NADPH oxidases in vascular smooth muscle cells. Read more
A recent article in Nature describes the resurgence of interest in cancer cell metabolism. This means exploiting the unique metabolic dependencies of cancer cells, such as their increased demand for glucose.
Cancer cells' preference for glucose is named after 1931 Nobelist Otto Warburg
Otto Warburg, who won the Nobel Prize in Medicine in 1931, noticed that cancer cells have a “sweet tooth” decades ago, but only recently have researchers learned enough about cancer cells’ regulatory circuitry to possibly use this to their advantage.
AtÂ Winship Cancer Institute of Emory University, several scientists have been investigating aspects of this phenomenon. Jing Chen and his team have identified a switch, the enzyme pyruvate kinase, which many types of cancer use to control glucose metabolism, and that might be a good drug target.
Jing Chen, PhD, and Taro Hitosugi, PhD
Shi-Yong Sun, Wei Zhou and their colleagues have found that cancer cells are sneaky: blockade the front door (for glucose metabolism, this means hitting them with the chemical 2-deoxyglucose) and they escape out the back by turning on certain survival pathways. This means combination tactics or indirectly targeting glucose metabolism through the molecule mTOR might be more effective, the Nature article says.
A quote from the article:
Clearly, metabolic pathways are highly interconnected with pathways that govern the hallmarks of cancer, such as unrestrained proliferation and resistance to cell death. The many metabolic enzymes, intermediates and products involved could be fertile ground for improving cancer diagnostics and therapeutics.
B cells are workhorses of the immune system. Their main function is to produce antibodies against bacteria or viruses when they encounter something that they recognize.Â But recently researchers have been getting hints that certain kinds of B cells can also have a calming effect on the immune system. This property could come in handy with hard-to-treat conditions such as graft-vs-host disease, multiple sclerosis, or Crohn’s disease.
Hematologist Jacques Galipeau has found that B cells treated with an artificial hybrid molecule called GIFT15 turn into “peacemakers”. These specially treated B cells can tamp down the immune system in an experimental animal model of multiple sclerosis, suggesting that they could accomplish a similar task with the human disease.
Galipeau’s paper inÂ Nature Medicine from August 2009 says succinctly: “We propose that autologous GIFT15 B regulatory cells may serve as a new treatment for autoimmune ailments.”Â Galipeau, a recent arrival to Emory from McGill University in Montreal, explains this tactic and other aspects of personalized cell therapy in the video above. Read more
Former National Institutes of Health director Elias Zerhouni created a vivid label for a persistent problem. He noted there was a widening gap between basic and clinical research. The “valley of death” describes the gap between basic research, where the majority of NIH funding is directed and many insights into fundamental biology are gained, and patients who need these discoveries translated to the bedside and into the community in order to benefit human health. Thus, a chasm has opened up between biomedical researchers and the patients who would benefit from their discoveries.
Translational research seeks to move ideas from the laboratory into clinical practice
Translational research seeks to move ideas from the laboratory into clinical practice in order to improve human health.
A new certificate program in translational research is designed to empower PhD graduate students to bridge that gap. Participants (PhD graduate students) from Emory, Georgia Tech and Morehouse School of Medicine can take courses in epidemiology, biostatistics, bioethics, designing clinical trials and grant writing, and will have rotations with clinicians and clinical interaction network sites where clinical research studies are carried out to get a better sense of the impact and potential benefit of the research they are conducting.
View of MR/PET scanner from front, with Ciprian Catana of MGH and Larry Byars of Siemens
The scanner is one of four world-wide and one of two in the United States, and permits simultaneous MR (magnetic resonance) and PET (positron emission tomography) imaging in human subjects. This provides the advantage of being able to combine the anatomical information from MR with the biochemical/metabolic information from PET. Potential applications include functional brain mapping and the study of neurodegenerative diseases, drug addiction and brain cancer.
Thursday’s event brought together leaders of the three other MR/PET programs in Boston, JÃ¼lich and TÃ¼bingen, the Siemens engineers who designed the device, and the Atlanta research community to explore the possibilities of the technology.
The drugs now available to treat Alzheimer’s address the symptoms of the disease — memory problems — rather than the underlying mechanism of neurodegeneration.
But what if something could do both? Here’s a tantalizing prospect, hinted at by a long-running thread of brain research: compounds that boost the function of certain acetylcholine circuits in the brain might also modify production of toxic beta-amyloid protein.
The possibility grows out of the properties of certain receptors for the neurotransmitter acetylcholine, called “muscarinic acetylcholine receptors.” Acetylcholine is a major transmitter of signals in the brain, and there are several varieties of receptors, or receiver dishes for the signals, on brain cells.
Researchers at Emory studying lung transplantation have identified a marker of inflammation that may help predict primary graft dysfunction (PGD), an often fatal complication following a lung transplant.
â€œDespite major advances in surgical techniques and clinical management, serious lung transplant complications are common and often untreatable,â€ Pelaez says. â€œPGD is a severe lung injury appearing just a few days after transplantation. Unfortunately, predicting which lung transplant recipients go on to develop PGD has been so far unsuccessful. Therefore, our research has been directed towards identifying predictive markers in the donor lungs prior to transplantation.â€
Briefly, they found that increased appetite and insulin resistance can be transferred from one mouse to another via intestinal bacteria. The results were published online by Science magazine.
Previous research indicated intestinal bacteria could modify absorption of calories, but Gewirtz and his colleagues showed that they influence appetite and metabolism (in mice)
“It has been assumed that the obesity epidemic in the developed world is driven by an increasingly sedentary lifestyle and the abundance of low-cost high-calorie foods,” Gewirtz says. “However, our results suggest that excess caloric consumption is not only a result of undisciplined eating but that intestinal bacteria contribute to changes in appetite and metabolism.”
A related report in Nature illustrates how “next generation” gene sequencing is driving large advances in our understanding of all the things the bacteria in our intestines do to us.
Gewirtz’s laboratory’s discovery grew out of their study of mice with an altered immune system. The mice were engineered to lack a gene, Toll-like receptor 5 (TLR5), which helps cells sense the presence of bacteria.
Two researchers at Emory, Anita Corbett and Grace Pavlath, recently have combined their expertise to probe how a puzzling form of muscular dystrophy develops.
Oculopharyngeal muscular dystrophy (OPMD) is an inherited type of muscular dystrophy that primarily affects muscles of the face and throat. In the video below, Anita Corbett explains how this affects patients as they get older.
The mutations that cause the disease make a protein called PABPN1 longer and stickier than normal, and the mutated protein appears to form clumps in muscle cells.
The puzzle lies in that PABPN1 (poly A binding protein nuclear 1)Â can be found everywhere in the body, but it’s not clear why the mutated protein specifically affects muscle cells — or why the muscles in the face and throat are especially vulnerable.
In December 2009, Corbett, Pavlath and postdoctoral fellow Luciano Apponi published a paper where they suggest that the clumps of mutated protein, which some researchers have proposed to be toxic, might not be the whole story. A lack of functioning PABPN1 might be just as strong a factor in the disease, they’ve discovered.
What a cancer patient wants to know after surgery can be expressed succinctly: “Did you get everything?” Having a confident answer to that question can be difficult, because when they originate or metastasize, tumors are microscopic.
Considerable advances have been made in “targeted therapy” for cancer, but the wealth of information available on the molecular characteristics of cancer cells hasn’t given doctors good tools for detecting cancer during surgery – yet.
Even the much-heralded advent of robotic surgery has not led to clear benefits for prostate cancer patients in the area of long-term cancer control, a recent New York Times article reports.
At Emory and Georgia Tech’s joint department for biomedical engineering, Shuming Nie and his colleagues are developing tools that could help surgeons define tumor margins in human patients.