Life-saving predictions from the ICU

Similar to the “precogs” who predict crime in the movie Minority Report, but for sepsis, the deadly response to infection. Read more

Five hot projects at Emory in 2017

Five hot projects at Emory in 2017: CRISPR gene editing for HD, cancer immunotherapy mechanics, memory enhancement, Zika immunology, and antivirals from Read more

Shaking up thermostable proteins

Imagine a shaker table, where kids can assemble a structure out of LEGO bricks and then subject it to a simulated earthquake. Biochemists face a similar task when they are attempting to design thermostable proteins, with heat analogous to shaking. Read more

Cancer

Magnanimous magnolias keep on giving

Honokiol, the versatile compound found by Emory dermatologist Jack Arbiser in the cones of magnolia trees, makes a surprise appearance in a recent paper in Nature Medicine.

Jack Arbiser, MD, PhD, and colleagues originally isolated honokiol from magnolia cones. It can also be found in herbal teas.

The paper, from Sabrina Diano, Tamas Horvath and colleagues at Yale, probes the role of reactive oxygen species (ROS) in the hypothalamus, a part of the brain that regulates appetite. In the paper, Horvath’s laboratory uses honokiol as a super-antioxidant, mopping up ROS that suppress appetite. Arbiser initiated the collaboration with Horvath after finding, while working with Emory free radical expert Sergei Dikalov, how effective honokiol is at neutralizing ROS.

The paper is intriguing partly because it’s an example of a situation where ROS, often thought to be harmful because of their links to aging and several diseases, are actually beneficial. In this case, they provide a signal to stop eating. A recent paper from Andrew Neish’s lab at Emory provides another example, where probiotic bacteria stimulate production of ROS, which promote healing of the intestine.

Arbiser notes that since honokiol can increase appetite, the compound may be helpful in situations where doctors want patients to eat more.

“This might be particularly valuable in patients who are nutritionally deficient due to chemotherapy and provides a rationale for adding honokiol to chemotherapy regimens,” he writes.

Satiety producing neurons in the hypothalamus

A note of caution: in the Nature Medicine paper, honokiol is infused directly into the brain.

Honokiol has been shown to counteract inflammation and slow the growth of blood vessels (important in fighting cancer). Collaborating with Arbiser, Emory endocrinologist Neale Weitzmann has recently found that honokiol stimulates osteoblasts, the cells that build bone, suggesting that it could reduce bone loss in osteoporosis.

Posted on by Quinn Eastman in Cancer Leave a comment

Emory researchers receive grants to further work in pediatric brain tumor research

Dr. Castellino explains his research on medulloblastomas to participants attending the SBTF’s Grant Award Ceremony.

Two Emory researchers are being recognized by the Southeastern Brain Tumor Foundation (SBTF) for their work in pediatric brain tumor research.

Tracey-Ann Read, PhD, assistant professor in the Department of Neurosurgery, Emory University School of Medicine and director of the Pediatric Neuro-Oncology Laboratory at Emory was awarded a $75,000 grant for her work. She is studying the cell of origin that is responsible for the highly malignant pediatric brain tumor known as an Atypical Teratoid Rhabdoid Tumor (AT/RT). She is also developing a mouse model to study this very lethal brain cancer that occurs in early childhood.

Robert Craig Castellino, MD, assistant professor of pediatrics at Emory and pediatric hematologist/oncologist at Children’s Healthcare of Atlanta at Egleston received $50,000 to support his research efforts. He is studying how the childhood brain cancer, known as medulloblastoma, can metastasize from the brain to other sites in the body, specifically the spine. Medulloblastoma is the most common pediatric malignant brain tumor.

SBTF board members and researchers who were awarded grants pose following the April ceremony.

Read and Castellino received the awards at the SBTF’s Grant Awards Ceremony in April at Emory University Hospital Midtown. Two other researchers from Duke University were also presented with grant money for their contributions in brain tumor research in adults.

Emory neurosurgeon Costas Hadjipanayis, MD, PhD, is the president of the Southeastern Brain Tumor Foundation. He says research, from young investigators such as these, is crucial in the race to find a cure for brain tumors. As federal research funding becomes even more difficult to obtain with cuts in funding, private foundation grants, such as from the SBTF, can permit researchers to start important research projects that can provide preliminary data for bigger grant proposals.

The SBTF awards $200,000-300,000 each year to major medical centers throughout the Southeast in support of cutting-edge brain and spinal tumor research.

 

Posted on by Janet Christenbury in Cancer Leave a comment

What cancer researchers can learn from fruit fly genetics

What can scientists studying cancer biology learn from fruit flies?

Quite a lot, it turns out.  At a time when large projects such as the Cancer Genome Atlas seek to define the changes in DNA that drive cancer formation, it is helpful to have the insight gained from other arenas, such as fruit flies, to make sense of the mountains of data.

Drosophila melanogaster has been an important model organism for genetics because the flies are easy to care for, reproduce rapidly, and have an easily manipulated genome. This NCI newsletter article describes how some investigators have used Drosophila to find genes involved in metastasis.

Emory cell biologist Ken Moberg says that he and postdoctoral fellow Melissa Gilbert crafted a Drosophila-based strategy to identify growth-regulating genes that previous researchers may have missed. Their approach allowed them to begin defining the function of a gene that is often mutated in lung cancer. The results are published online in Developmental Cell.

Part of the developing fly larva, stained with an antibody against Myopic. Groups of cells lacking Myopic, which lack green color, tend to divide more rapidly.

Moberg writes:

Many screens have been carried out in flies looking for single gene lesions that drive tissue overgrowth. But a fundamental lesson from years of cancer research is that many, and perhaps most, cancer-causing mutations also drive compensatory apoptosis, and blocking this apoptosis is absolutely required for cancer outgrowth.

We reasoned that this class of ‘conditional’ growth suppressor genes had been missed in prior screens, so we designed an approach to look for them. The basic pathways of apoptosis are fairly well conserved in flies, so it’s fairly straight forward to do this.

Explanatory note: apoptosis is basically a form of cellular suicide, which can arise when signals within the cell clash; one set of proteins says “grow, grow” and another says “brake, brake,” with deadly results.

Gilbert identified the fruit fly gene Myopic as one of these conditional growth regulators. She used a system where mutations in Myopic drive some of the cells in the fly’s developing eye to grow out more – but only when apoptosis is disabled.

Gilbert showed that Myopic is part of a group of genes in flies, making up the Hippo pathway, which regulates how large a developing organ will become. This pathway was largely defined in flies, then tested in humans, Moberg says. The functions of the genes in this pathway have been maintained so faithfully that in some cases, the human versions can substitute for the fly versions.

Myopic’s ortholog (ie different species, similar sequence and function) is the gene His-domain protein tyrosine phosphatase, or HD-PTP for short. This gene is located on part of the human genome that is deleted in more than 90 percent of both small cell and non-small cell lung cancers, and is also deleted in renal cancer cells.

How HD-PTP, when it is intact, controls the growth of cells in the human lung or kidney is not known. Gilbert and Moberg’s findings suggest that HD-PTP may function through a mechanism that is similar to Myopic’s functions in the fly.

Besides clarifying what Myopic does in the fly, their paper essentially creates a map for scientists studying HD-PTP’s involvement in lung cancer, for example, to probe and validate.

Posted on by Quinn Eastman in Cancer 1 Comment

A path to treatment of lymphedema

Lymphedema, or swelling because of the impaired flow of lymph fluid, can occur as a consequence of cancer or cancer treatment. Chemotherapy can damage lymph ducts, and often surgeons remove lymph nodes that may be affected by cancer metastasis. Lymphedema can result in painful swelling, impaired mobility and changes in appearance.

Young-sup Yoon, MD, PhD

Emory scientists, led by cardiologist and stem cell biologist Young-sup Yoon, have shown that they can isolate progenitor cells for the lining of lymph ducts. This finding could lead to doctors being able to regenerate and repair lymph ducts using a patient’s own cells. The results are described in a paper published recently in the journal Circulation.

The authors used the cell surface marker podoplanin as a handle for isolating the progenitor cells from bone marrow. Previous research has demonstrated that podoplanin is essential for the development of the lymphatic system.
In the paper, the authors use several animal models to show that the progenitor cells could contribute to the formation of new lymph ducts, both by becoming part of the lymph ducts and by stimulating the growth of nearby cells.

“This lymphatic vessel–forming capability can be used for the treatment of lymphedema or chronic unhealed wounds,” Yoon says.

Isolated lymphatic endothelial cells (red) incorporate into lymph ducts (green) in a model of wound healing in mice.

The authors also show that mice with tumors show an increase in the number of this type of circulating progenitor cells. This suggests that tumors send out signals that encourage lymph duct growth – a parallel to the well-known ability of tumors to drive growth of blood vessels nearby. Yoon says the presence of these cells could be a marker for tumor growth and metastasis. Because tumors often metastasize along lymph ducts and into lymph nodes, studying this type of cells could lead to new targets for blocking tumor metastasis.

A recent review in the journal Genes & Development summarizes additional functions of the lymphatic system in fat metabolism, obesity, inflammation, and the regulation of salt storage in hypertension.

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When bone marrow goes bad

Plasma cells live in our bone marrow. Their job: to make antibodies that protect us from bacteria and viruses. But if those plasma cells grow unchecked, that unchecked growth leads to multiple myeloma.

Sagar Lonial, MD

Multiple myeloma is a type of cancer that results in lytic bone disease, or holes in the bones. What’s more, the cancerous cells crowd out normal bone marrow resulting in anemia or a low white count, leaving a person vulnerable to infections.

Sagar Lonial, MD, an oncologist at Winship Cancer Institute, Emory University, treats people with multiple myeloma. The prognosis for people with this type of cancer is poor; however, researchers are gaining on the disease. Twenty years ago, the survival rate was two to three years; now, it’s four to five.

Lonial says one of the keys to improving patients’ prognosis is increasing their enrollment in clinical trials and better access to life-extending drugs.

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Posted on by Robin Tricoles in Cancer Leave a comment

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.

Posted on by Quinn Eastman in Cancer Leave a comment

HER2-positive breast cancer treatment options studied

Emory oncologist Ruth O’Regan, MD, is leading a trial testing whether Afinitor can reverse resistance to Herceptin in metastatic HER2-positive breast cancer patients. As part of the trial, some patients been receiving a drug called Afinitor (everolimus) along with chemotherapy and Herceptin (trastuzumab).

Ruth O'Regan, MD

About 25 percent to 30 percent of breast cancers are HER2 -positive, which means they test positive for a protein called human epidermal growth factor receptor-2 (HER2). This protein promotes the growth of cancer cells, making HER2 -positive breast cancers more aggressive than other types.

They also tend to be less responsive to hormone treatment. That’s the bad news. The good news is that this type of cancer responds extremely well to Herceptin.

Herceptin specifically targets HER2 cells, killing them while sparing healthy cells, so side effects are minimal. Its effectiveness has made Herceptin the gold standard of treatment for HER2 -positive breast cancer.

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Posted on by Jennifer Johnson in Cancer Leave a comment

Hold out your finger: Epidemiologist developing test for colon cancer risk

Years from now physicians may be able to determine whether you’re at increased risk for colorectal cancer by drawing blood from the tip of your finger.

Emory University researchers are working to identify biomarkers to detect a person’s chances of developing colon cancer. Much like blood pressure and cholesterol tests can indicate heart disease risk, researchers here hope that some day the makeup of blood and urine will be able to tell who’s at risk for colorectal cancer, why they may be at risk and what they can do to reduce their risk.

Postdoctoral fellows Joy Owen and Veronika Fedirko examine samples in Robin Bostick’s lab at the Winship Cancer Institute of Emory University.

For now, the Emory study team is analyzing the rectal tissue samples of people with colon adenomatous polyps, non-cancerous growths considered precursors to colon cancer, and comparing them to rectal tissue samples from people who don’t have polyps. They’re also looking at whether the differences they detect in rectal tissue can also be found in blood or urine. Currently, no accepted tests exist to determine whether someone may be at risk for colon cancer.

“Most people would rather provide a blood or urine sample than get a rectal biopsy,” says Robin Bostick, MD, MPH, Rollins School of Public Health epidemiology professor and study principal investigator. Bostick is also a clinical faculty member at the Winship Cancer Institute at Emory and a Georgia Cancer Coalition Distinguished Cancer Scholar.

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Posted on by adobbs in Cancer 1 Comment

Looking at simple foods to protect against breast cancer

Researchers at the Winship Cancer Institute of Emory University have found that the hormone adiponectin may reduce the ability of cancer cells to migrate from the breast and invade other tissues. Adiponectin appears to protect against the effects of obesity on metabolism, the heart and blood vessels, the researchers say.

Fat cells make up most of the breast tissue, and some of the hormones produced by fat cells can have tumor-stimulating effects. Previous studies have shown that women with high body mass index (highest fifth) have double the death rate from breast cancer compared to those in the lowest fifth.

Dipali Sharma, PhD

The key to translating this research for patient care lies in finding a way to increase a person’s adiponectin, says Dipali Sharma, PhD, assistant professor of hematology and medical oncology at Winship.

Currently, Winship scientists are testing a molecule found in certain foods that appears to mimic the effects of adiponectin. The molecule is found in grapes, cabbage and green tea.

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Posted on by Vince Dollard in Cancer Leave a comment

Nanotechnology may help surgeons detect cancer

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.

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