Warren symposium follows legacy of geneticist giant

If we want to understand how the brain creates memories, and how genetic disorders distort the brain’s machinery, then the fragile X gene is an ideal place to start. That’s why the Stephen T. Warren Memorial Symposium, taking place November 28-29 at Emory, will be a significant event for those interested in neuroscience and genetics. Stephen T. Warren, 1953-2021 Warren, the founding chair of Emory’s Department of Human Genetics, led an international team that discovered Read more

Mutations in V-ATPase proton pump implicated in epilepsy syndrome

Why and how disrupting V-ATPase function leads to epilepsy, researchers are just starting to figure Read more

Tracing the start of COVID-19 in GA

At a time when COVID-19 appears to be receding in much of Georgia, it’s worth revisiting the start of the pandemic in early 2020. Emory virologist Anne Piantadosi and colleagues have a paper in Viral Evolution on the earliest SARS-CoV-2 genetic sequences detected in Georgia. Analyzing relationships between those virus sequences and samples from other states and countries can give us an idea about where the first COVID-19 infections in Georgia came from. We can draw Read more
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melanoma

Fighting cancer with combinatorial imagination

In his undergraduate days, Winship Cancer Institute dermatologist and cancer researcher Jack Arbiser was an organic chemist. That may be why he recognized an organic synthesis reagent based on the metal palladium as a potential anti-cancer drug.

We’re talking about Tris-DBA-palladium. Arbiser and colleagues showed in a 2008 Clinical Cancer Research paper that this deep purple stuff (see photo) is active against melanoma, and since then, against other types of cancer such as pancreatic cancer, multiple myeloma, and CLL leukemia.

Tris-DBA-PD has a deep purple color. The palladium atoms can be seen in the diagram as two blue balls at the center. From Wikipedia.

Since it’s used in organic synthesis, you might expect Tris-DBA-palladium not to be very soluble in water. A new paper in Scientific Reports demonstrates that this issue can be addressed by hooking up the reagent to nanoparticles made of hyaluronic acid, which targets tumor cells. They are effective against melanoma in mice, the paper shows.

“We have already demonstrated that Tris DBA palladium by itself has activity against melanoma in mice,” Arbiser writes (in his VA grant summary). “However, we believe that we can make Tris DBA palladium into an even more powerful drug by adding it to nanoparticles that are guided to the tumor.”

In an email to Lab Land, Arbiser says he arrived at Tris-DBA-palladium by using his chemist’s imagination, in a “your chocolate landed in my peanut butter” kind of way.

“I got the idea for looking at this compound because it is a complex of Pd with a curcumin-like structure, and I figured it might have the characteristics of platinum and curcumin together,” he says. Read more

Posted on March 6, 2019 by Quinn Eastman in Cancer Leave a comment

Virus hunting season open

New viruses have been popping up in industrial water-cooling towers, in Antarctica and salty deserts. Erwin van Meir, from Winship Cancer Institute of Emory University, and his collaborators managed to find two inside someone’s metastatic tumor.

Working with Terry Fei Fan Ng and Eric Delwart from UCSF, Van Meir identified two new species of anellovirus, a family of viruses first discovered in the 1990s. The new viruses come from a patient with a melanoma that had metastasized to the brain and was operated on at Emory University Hospital.

The results were recently published in Oncotarget.

“We have no evidence that these two viruses were involved in the tumor’s formation, but the data are proof of principle that the metagenomics method used can discover more unknown viruses in human brain tumors,” Van Meir says.

Erwin Van Meir, PhD

Metagenomics is the study of genetic material obtained directly from the environment. The approach is often used to study bacteria, but it is equally valid for viruses. In this paper, investigators used enzymes to chew up human and bacterial DNA, enriching for viral DNA protected by the viral capsid.

Estimates from the USAID’s PREDICT program point to thousands or even millions of viruses, present in mammals and birds, which remain unknown to humans. According to Annual Review of Virology from this summer, Viruses with Circular Single-Stranded DNA Genomes are Everywhere! – and that includes Anelloviridae, for which there is “still no convincing direct causal relation to any specific disease.”

Anelloviruses are relatively primitive in that they do not encode a viral polymerase (the enzyme that copies DNA) and thus need to rely upon the host cell and replicate inside the nucleus. The new ones were named Torque teno mini virus Emory1 (TTMV Emory1) and Torque teno mini virus Emory2 (TTMV Emory2). The research team gave a nod to Emory by using its colors in the virus genome cartoons accompanying the publication. Read more

Posted on November 14, 2017 by Quinn Eastman in Cancer Leave a comment

Melanoma mutation likes fat for fuel

Cancer cells love glucose, the simple sugar the body uses for energy, so a high-fat, low-carb diet should starve them, right?

Where does this idea come from? Most cancer cells display enhanced glucose uptake, a phenomenon known as the Warburg effect, after 1931 Nobel Prize winner Otto Warburg.

Resurgent interest in exploiting the Warburg effect was described by Sam Apple in NYT Magazine and by Bret Stetka for NPR. High-fat, low-carb “ketogenic” diets are known to be effective against some types of epilepsy, and have also been explored by endurance athletes. Ketogenic diets have been tried as a clinical countermeasure against cancer in a limited way, mainly in brain cancer.

Before everybody gets too excited, let’s think about how particular cancer-driving mutations affect cell metabolism, suggests Winship Cancer Institute researcher Jing Chen. His team’s work in mice suggests that cancers with a common melanoma mutation (BRAF V600E) will grow faster in response to a ketogenic diet. In addition, the Winship researchers found that lipid-lowering agents such as statins curb these cancers’ growth, even in the context of a more normal diet.

The results were published on January 12 in Cell Metabolism.

Caveats: the findings cover just one mutation and need to be tested clinically.

Consumers and cancer patients already get a lot of advice about the right diet to fight cancer, but this research points toward an intriguing concept:  a “precision diet,” tailored to an individual patient’s cancer.  Read more

Posted on January 13, 2017 by Quinn Eastman in Cancer Leave a comment

Melanoma mutation rewires cell metabolism

A mutation found in most melanomas rewires cancer cells’ metabolism, making them dependent on a ketogenesis enzyme, researchers at Winship Cancer Institute of Emory University have discovered.

The V600E mutation in the gene B-raf is present in most melanomas, in some cases of colon and thyroid cancer, and in the hairy cell form of leukemia. Existing drugs such as vemurafenib target the V600E mutation — the finding points to potential alternatives or possible strategies for countering resistance. It may also explain why the V600E mutation in particular is so common in melanomas.

Researchers led by Jing Chen and Sumin Kang have found that by promoting ketogenesis, the V600E mutation stimulates production of a chemical, acetoacetate, which amplifies the mutation’s growth-promoting effects. (A feedback mechanism! Screech!)

The results were published Thursday, July 2 in Molecular Cell.

More on this paper here.

Posted on July 6, 2015 by Quinn Eastman in Cancer 1 Comment

Explainer: oncolytic viruses

A recent publication from Bill Kaiser’s and Ed Mocarski’s labs in Cell Host & Microbe touches on a concept that needs explaining: oncolytic viruses.

Viruses have been subverting the machinery of healthy cells for millions of years, and many viruses tend to infect particular tissues or cell types. So they are a natural starting point for researchers to engineer oncolytic viruses, which preferentially infect and kill cancer cells.

Several oncolytic viruses have progressed to advanced clinical trials. Amgen’s “T-Vec”, a modified herpes simplex virus, could be the first to be approved by the FDA this year based on its efficacy against metastatic melanoma.  Read more

Posted on February 16, 2015 by Quinn Eastman in Cancer Leave a comment

Cancer immunotherapy, meet chimera

697px-Chimera_d'arezzo,_fi,_03

In Greek mythology, the chimera was a monstrous fire-breathing creature composed of the parts of three animals: a lion, a snake and a goat.

Adoptive cell transfer is advancing as a cancer immunotherapy technique. It involves removing some of a patient’s immune cells, culturing them in the laboratory, and then infusing the cells back into the patient. The idea is to enhance the ability of the immune cells to attack the tumors far beyond what the immune system was able of doing on its own.

Two promising examples are the National Cancer Institute’s approach of treating advanced melanoma with IL-2-stimulated immune cells, and several investigators’ approach of genetically engineering T cells to attack leukemias or lymphomas.

Jacques Galipeau and colleagues at Winship Cancer Institute have developed a chimeric molecule for stimulating immune cells, which appears to have unique powers beyond simply the sum of its two parts. The molecule is called GIFT4, a fusion of the immune signaling molecules GM-CSF (often used in cancer treatment) and IL-4.

Read more

Posted on June 20, 2014 by Quinn Eastman in Cancer, Immunology Leave a comment

Cancer’s shield: PD-1

Gina Kolata has a section front story in Tuesday’s New York Times exploring the potential of a relatively new class of anticancer drugs. The drugs break through “shields” built by cancers to ward off the threat posed by the patient’s immune system. Many are based on blocking PD-1, an immune regulatory molecule whose importance in chronic infections was first defined by Emory’s Rafi Ahmed.

Of course, not every cancer research development described as transformative in the New York Times lives up to the hype. But the clinical trial results, reported in the New England Journal of Medicine, are solid enough that the researchers Kolata talks with think they are seeing “a moment in medical history when everything changed.” [Winship Cancer Institute’s John Kauh was a co-author on one of the 2012 NEJM papers.]

Let’s take a moment to examine some of the roots of this story. Rafi Ahmed didn’t set out to study cancer. For the last two decades, he and his colleagues have been studying T cells, parts of the immune system that are critical for responding to infections. Read more

Posted on October 15, 2013 by Quinn Eastman in Cancer, Immunology 2 Comments

Making “death receptor” anticancer drugs live up to their name

Cancer cells have an array of built-in self-destruct buttons called death receptors. A drug that targets death receptors sounds like a promising concept, and death receptor-targeting drugs have been under development by several biotech companies. Unfortunately, so far results in clinical trials have been disappointing, because cancer cells appear to develop resistance pathways.

Death receptor-targeting drugs under development include: drozitumab, mapatumumab, lexatumumab, AMG655, dulanermin.

Winship Cancer Institute researcher Shi-Yong Sun, PhD and colleagues have a paper in Journal of Biological Chemistry that may help pick the tumors that are most likely to be vulnerable to death receptor-targeting drugs. This could help clinical researchers identify potential successes ahead of time and maximize chances of a good response for patients.

Postdoctoral fellow Youtake Oh is the first author. Winship deputy director Fadlo Khuri, MD and Taofeek Owonikoko, MD, PhD, co-chair of Winship’s clinical and translational research committee, are co-authors. Khuri’s 2010 presentation on death receptor drugs and lung cancer is available here (PDF).

Sun’s team shows that mutations in the cancer-driving genes Ras and B-Raf both induce cancer cells to make more of one of the death receptors (death receptor 5). In addition, they show that cancer cells with mutations in Ras or B-Raf tend to be more vulnerable to drugs that target death receptor 5.

Shi-Yong Sun, PhD

These mutations are known to be more common in some types of cancer. For example, roughly half of melanomas have mutations in B-Raf. Vemurafenib, a drug that inhibits mutated B-Raf, was approved in August 2011 for the treatment of melanoma. K-ras mutations are similarly abundant in lung cancer.

The selection and targeting of tumors via their specific mutations is a growing trend. Sun says lung, colon and pancreatic cancer are all cancer types where Ras and Raf mutations are common enough to become useful biomarkers. In lung cancer, Sun’s team’s results could be especially welcome news because, as a 2009 review concluded:

Recent studies indicate that patients with mutant KRAS tumors fail to benefit from adjuvant chemotherapy, and their disease does not respond to EGFR inhibitors. There is a dire need for therapies specifically for patients with KRAS mutant NSCLC.

 

Posted on January 10, 2012 by Quinn Eastman in Cancer Leave a comment

Sunscreen: Looking Beyond the Numbers

Recently, the Food and Drug Administration created new regulations to establish standards for sunscreen manufacturers to follow before they label their products.

Under the new regulations, which will go into effect in 2012, sunscreen products that protect against all types of sun-induced skin damage will be labeled “broad spectrum” and “SPF 15” or higher on the container. Only products that have been tested to ensure they protect against both UVA (ultraviolet radiation A) and UVB (ultraviolet radiation B) radiation will be allowed to use this labeling. Broad-spectrum sunscreens of SPF 15 and higher can also be labeled as protective against skin cancer and premature aging. The maximum SPF value is set at 50-plus because the FDA says anything higher doesn’t provide a significant amount of additional protection.

Manufacturers will have to include warning labels on products that are not broad spectrum. Products that claim to be water resistant must indicate how long the consumer should expect to be protected in the water, and using such language as “waterproof” or “sweat proof” will not be allowed.

“Skin cancer is the most common form of cancer in the United States, and the number of people affected keeps rising. Simply getting into the habit of using a sunscreen every day – with the appropriate levels of protection – can make a significant difference in preventing many skin cancers, as well as premature aging,” says Washington. If you’re looking into anti-aging treatments though, you can go to experts such as Dundee Dermatology or Mint Nutrition.

These new regulations will help consumers understand the difference in degrees of sun protection, and choose carefully. To learn more about dermatology, you can choose to attend conferences such as this Aesthetics Conference.

Washington also suggests staying out of direct sunlight between 10 am and 2 pm, seeking shade when you are outdoors, remembering to reapply sunscreen every two hours and wearing protective clothing.

Posted on August 5, 2011 by admin in Uncategorized Leave a comment

Eye diseases and immune system link studied

Drawing shows areas of the eye

Emory Eye Center researchers are looking at the role of the immune system in the inflammation of the eye and the progression of eye diseases.

Santa Ono, PhD, professor of ophthalmology, Emory School of Medicine and researcher at the Emory Eye Center, and Emory senior vice provost for undergraduate education and academic affairs, and his team at the R. Howard Dobbs Jr. Ocular Immunology Lab, focus on the immune component of age-related macular degeneration (AMD), ocular cancer (melanoma and retinoblastoma) and ocular inflammation.

Santa J. Ono, PhD

Macular degeneration is the leading cause of sight impairment and blindness in older people. The macula, in the center of the retina, is the portion of the eye that allows for the perception of fine detail. AMD gradually destroys a person’s central vision, ultimately preventing reading, driving, and seeing objects clearly

In a recent article of Emory Magazine, Ono, an ocular immunologist, says, “If a person with AMD looks at graph paper, some of the lines will be wavy instead of straight. Certain parts of the image are no longer being transferred to the brain.”

Read more

Posted on February 22, 2010 by admin in Uncategorized Leave a comment