Quinn Eastman

Summer undergrad research at Emory booming

This year’s Emory’s Summer Undergraduate Research Experience program is the largest it has ever been. Thursday’s poster session at the Dobbs University Center was split into two shifts so that all 99 participants could have a chance to explain their research. Graduate students in Emory’s Division of Biological and Biomedical Sciences circulated through the crowd, taking notes in order to judge the posters. The majority of participating students worked in biomedical research labs in the Woodruff Health Sciences Center.

Oxford College chemistry major Ashley Hodges explains her work on new potential anti-cancer agents to radiologist Hui Mao

SURE, organized by Emory’s Center for Science Education, is a ten-week program, attracting undergraduates not only from Emory but from other Atlanta-area universities and around the world.

Participants receive a stipend and on-campus housing, and have weekly meetings on ethics, research careers and lab life. About a third of former participants complete a graduate degree, according to follow-up surveys recently published in the journal Life Sciences Education. The main funding comes from Howard Hughes Medical Institute, with additional support from the National Science Foundation, National Institutes of Health and a variety of non-profit foundations.

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Respiratory infection may lead to weaker immunological memory

How you vaccinate helps determine how you protect. This idea lies behind many researchers’ interest in mucosal vaccines. How a vaccine is administered (orally/nasally vs intramuscular, for example) could make a difference later, when the immune system faces the bad guys the vaccine is supposed to strengthen defenses against.

How does the route of immunization affect the quality of immunity later on? For example, is a nasal spray best when trying to prevent respiratory infections?

A recent paper from Emory Vaccine Center director Rafi Ahmed’s laboratory challenges this idea. The paper was published in the Journal of Immunology. Scott Mueller, now an Australian Research Council research fellow at the University of Melbourne, is first author.

Memory T cells are a key part of a response to a vaccine, because they stick around after an infection, enabling the immune system to fight an invading virus more quickly and strongly the second time around. In the paper, the Emory team compared memory T cells that form in mice after they are infected in the respiratory system by a flu virus or throughout their bodies by a virus that causes meningitis (lymphocytic choriomeningitis virus or LCMV).

The authors engineered a flu virus to carry a tiny bit of LCMV (an epitope, in immunological terms) so that they could compare apples to apples by measuring the same kind of T cells. They found that memory T cells generated after a flu infection are weaker, in that they proliferate and stimulate other immune cells less, than after a LCMV infection. This goes against the idea that after a respiratory infection, the immune system will be better able to face a challenge in the respiratory system.

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Staring (cell) death in the face: imaging agents for necrotic cells

DNA usually occupies a privileged place inside the cell. Although cells in our body die all the time, an orderly process of disassembly (programmed cell death or apoptosis) generally keeps cellular DNA from leaking all over the place. DNA’s presence outside the cell means something is wrong: tissue injury has occurred and cells are undergoing necrosis.

Researchers from the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University have devised a way to exploit the properties of extracellular DNA to create an imaging agent for injured tissue. Niren Murthy and Mike Davis recently published a paper in Organic Letters describing the creation of “Hoechst-IR.” This imaging agent essentially consists of the DNA-binding compound Hoechst 33258 (often used to stain cells before microscopy), attached to a dye that is visible in the near-infrared range. A water-loving polymer chain between the two keeps the new molecule from crossing cell membranes and binding DNA inside the cell.

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Targeting antioxidants to mitochondria

Why aren’t antioxidants magic cure-alls?

It’s not a silly question, when one sees how oxidative stress and reactive oxygen species have been implicated in so many diseases, ranging from hypertension and atherosclerosis to neurodegenerative disorders. Yet large-scale clinical trials supplementing participants’ diets with antioxidants have showed little benefit.

Emory University School of Medicine scientists have arrived at an essential insight: the cell isn’t a tiny bucket with all the constituent chemicals sloshing around. To modulate reactive oxygen species effectively, an antioxidant needs to be targeted to the right place in the cell.

Sergei Dikalov and colleagues in the Division of Cardiology have a paper in the July 9 issue of Circulation Research, describing how targeting antioxidant molecules to mitochondria dramatically increases their effectiveness in tamping down hypertension.

Mitochondria are usually described as miniature power plants, but in the cells that line blood vessels, they have the potential to act as amplifiers. The authors describe a “vicious cycle” of feedback between the cellular enzyme NADPH oxidase, which produces the reactive form of oxygen called superoxide, and the mitochondria, which can also make superoxide as a byproduct of their energy-producing function.

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New opportunities in modulating microRNA

Emory geneticist Peng Jin and his colleagues have a review in the June 25, 2010 issue of Chemistry and Biology exploring whether microRNAs offer new possibilities for pharmacology.

MicroRNAs directly regulate other genes

The microRNA pathway represents both a way for scientists to “knock down” the activity of just one gene in the laboratory, and a major way for cells to regulate their genes during development.

MicroRNAs add a big wallop of complexity on top of the standard model of molecular biology, where the information in DNA is made into RNA, and RNAs make proteins. MicroRNAs don’t get turned into protein, but directly regulate other genes.

Andrew Fire and Craig Mello received the 2006 Nobel Prize in Medicine for their discovery that short pieces of RNA, when introduced into cells, can silence genes. This “RNA interference” tactic hijacks the natural machinery inside the cell that microRNAs use.

In 2008, Jin and coworkers published in Nature Biotechnology their discovery that certain antibiotics called fluoroquinolones (ciprofloxacin is one) can make the RNA interference process work more efficiently — in general. In the review, Jin notes that scientists are starting to look for drugs that act more selectively, disrupting or enhancing a particular microRNA rather than many at once:

Since miRNAs play major roles in nearly every cellular process, the identification and characterization of small-molecule modulators of the RNAi/miRNA pathway will yield fresh insights into fundamental mechanisms behind human disease… Moreover, these RNAi modulators, particularly RNAi enhancers, could potentially facilitate the development of RNA interference as a tool for biomedical research and therapeutic interventions.

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2009 H1N1 flu strain could give clues to universal flu vaccine?

Last year, when the H1N1 flu epidemic was a major public health concern, a relatively low proportion of individuals getting sick were elderly, compared to previous flu epidemics. To explain this, scientists hypothesized that flu strains that circulated decades ago were similar enough to the novel swine-origin H1N1 strain to provide some immune protection.

A universal flu vaccine would eliminate the guesswork associated with the yearly flu shot

Now, researchers at Emory’s Influenza Pathogenesis & Immunology Research Center have directly tested that hypothesis in mice, and it holds up. Exposure of mice to flu strains that circulated in 1947 or 1934 induced “robust cross-protective immune responses” and can protect them against a lethal challenge with 2009 H1N1 virus, they report in Journal of Immunology.

Ioanna Skountzou and Dimitrios Koutsananos are co-first authors of the paper.

The Emory team, led by Joshy Jacob, also reports that antibodies produced in response to the 2009 H1N1 flu strain exhibit broad cross-reactivity — they react with other H1N1 strains as well as against H3N2 flu strains. They write:

The fact that the 2009 H1N1 virus can induce such cross-reactive Abs raises the intriguing possibility that viruses such as A/California/04/2009 can be used for vaccines to induce broadly cross-reactive humoral immune responses against influenza viruses. Identifying the mechanism behind this broad reactivity may enable us to design broadly cross-reactive universal influenza vaccines.

National Institute of Allergy and Infectious Diseases director Tony Fauci, when he was at Emory for the H1N1 flu conference in April, discussed the idea of a universal flu vaccine:

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How to build a distinguished career studying vascular biology

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 the “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

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Resurgence of interest in cancer cell metabolism

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.

At 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.

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Regulatory B cells: old dogs reveal their new tricks

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. 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 in Nature Medicine from August 2009 says succinctly: “We propose that autologous GIFT15 B regulatory cells may serve as a new treatment for autoimmune ailments.” 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

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Med into grad program bridges gap between basic and clinical research

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.

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