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Southeastern Brain Tumor Foundation

A twist on epigenetic therapy vs cancer

Epigenetic therapies against cancer have attracted considerable attention in recent years. But many of the drugs currently being studied as epigenetic anticancer therapies may have indiscriminate effects. A recent paper in Cancer Research from brain cancer researcher Erwin Van Meir’s laboratory highlights a different type of target within cancer cells that may be more selective. Postdoctoral fellow Dan Zhu is the first author of the paper.

Erwin Van Meir, PhD

The basic idea for epigenetic therapy is to focus on how cancer cells’ DNA is wrapped instead of the mutations in the DNA. Cancer cells often have aberrant patterns of methylation or chromatin modifications. Methylation is a punctuation-like modification of DNA that usually shuts genes off, and chromatin is the term describing DNA when it is clothed by proteins such as histones, a form of packaging that determines whether a gene is on or off.

In contrast to mutations that are hard-wired in the DNA, changes in cancer cells’ methylation or chromatin may be reversible with certain drug treatments. But a puzzle remains: if a drug wipes away methylation indiscriminately, that might turn on an oncogene just as much as it might restore a tumor suppressor gene.

The ability of an inhibitor of methylation to treat cancer may depend on cell type and context, explains chromatin/methylation expert and co-author Paula Vertino. She points out that one well-known methylation inhibitor, azacytidine (Vidaza), is a standard treatment for myelodysplastic syndrome, but the strategy of blanket-inhibition of methylation can’t be expected to work for all cancers. A similar challenge exists for agents that target histone acetylation in a global fashion.

Epigenetic therapies seek to modify how DNA is packaged in the cell.

Van Meir’s laboratory has been studying a tumor suppressor protein called BAI1 (brain angiogenesis inhibitor 1), which prevents tumor and blood vessel growth. BAI1 is produced by brain cells naturally, but is often silenced epigenetically in glioblastoma cells. His team found that azacytidine de-represses the BAI1 gene.

Methylation won’t turn a gene off without the help of a set of proteins that bind preferentially to methylated DNA. These proteins are what recognize the methylation state of a given gene and recruit repressive chromatin. Zhu and colleagues in Van Meir’s group found that one particular methyl-binding protein, MBD2, is overproduced in glioblastoma and is enriched on the BAI1 gene.

“Taken together, our results suggest that MBD2 overexpression during gliomagenesis may drive tumor growth by suppressing the anti-angiogenic activity of a key tumor suppressor. These findings have therapeutic implications since inhibiting MBD2 could offer a strategy to reactivate BAI1 and suppress glioma pathobiology,” the authors write.

By itself, MBD2 appears to be dispensable, since mice seem to be able to develop and survive without it. Not having it even seems to push back against tumor formation in the intestine, for example. Targeting MBD2 may represent an alternative way to steer away from cancer cells’ altered state.

Van Meir cautions: “We need to have a better understanding of all the genes that are turned on or off by silencing MBD2 in a given cancer before we can envision to use this approach for therapy.”

Vertino and Steven Hunter, both at Emory, are co-authors on the paper. The work was supported by grants from the NIH and the Southeastern Brain Tumor Foundation and the Emory University Research Council.

Posted on by Quinn Eastman in Cancer 1 Comment

Brain tumor patient gives back and moves forward

Jennifer Giliberto

Don’t sweat the small stuff.

That’s the motto 36-year-old Jennifer Giliberto now lives by after recently welcoming a third child into the world. Late night feedings, diaper changes, mounds of dirty laundry and caring for two older boys (ages six and eight) would certainly be a challenge for most moms. But this mom is different.

Four years ago, Giliberto was diagnosed with a brain tumor – a slow growing Grade II astrocytoma located in her posterior right temporal lobe. The shocking diagnosis left Giliberto and her family with many choices and decisions to make.

Giliberto’s inspiring story was profiled on CNN on Aug. 16, 2011 in a special “Human Factor” segment, which takes a look at people accomplishing something significant after overcoming the odds.

The Long Road Ahead

After her second child was born in 2005, Giliberto began noticing a pattern of problems with her fine motor skills. Neurological testing revealed little, but an MRI (magnetic resonance imaging) revealed a lesion and possible tumor in the brain. Follow-up MRIs over the next year showed no new growth, but in June 2007, a definite brain tumor was detected by MRI.

While taking the watch and wait approach to determine if the tumor would grow, she became involved with the Southeastern Brain Tumor Foundation (SBTF) as a volunteer. She focused her efforts on raising money to support critical brain and spinal tumor research. She also met Emory neurosurgeon Costas Hadjipanayis, MD, PhD.

Hadjipanayis, an assistant professor in Emory’s Department of Neurosurgery, would soon become Giliberto’s physician. He confirmed her diagnosis and recommended surgical removal of the tumor.

Costas Hadjipanayis, MD, PhD and patient Jennifer Giliberto

On August 18, 2008, at Emory University Hospital Midtown, Hadjipanayis removed Giliberto’s brain tumor. “Jennifer underwent a craniotomy and had a gross total resection of the tumor, with no complications,” explains Hadjipanayis, who is chief of neurosurgery at the hospital. “She spent one night in the neurosurgical ICU and her recovery afterwards went well.”

Then he encouraged her to embrace life and live it to the fullest. Giliberto has taken her doctor’s orders to heart, and lives life with a new purpose than before.

Giving Back

To support and encourage other brain tumor patients, Giliberto serves as a patient and family advisor at Emory University Hospital Midtown. She visits with hospitalized patients and their families who are in similar situations as the young mother of three.

“This has been a very fulfilling experience and an outlet to give back,” says Giliberto. “Being a patient is lonely, even when you know you have support. Working to assist other patients and families and improve a system goes a long way to ease that lonely journey of the patient experience.”

Patient and family advisors also work to improve hospital processes and procedures from a patient perspective.

She also serves as vice president of the Southeastern Brain Tumor Foundation, continuing the mission to raise funds for research. The SBTF consistently funds innovative brain tumor research at Emory’s Winship Cancer Institute.

And she is a devoted wife and mother.

Moving Forward

Last year, when Giliberto and her husband decided they would like to expand their family of four, she consulted with Hadjipanayis. He, once again, encouraged her to live life and move forward. They did, and their youngest child was born in July 2011.

While Giliberto has remained stable since her surgery in 2008, she continues to have MRI’s every six to nine months to check for any tumor recurrence. Astrocytomas, even once removed, can recur and can also become cancerous.

But for now, it’s on with life as she knows it – stable, moving ahead and enjoying every day with a new sense of hope.

And as for the small stuff – Giliberto’s learned there’s just no reason to sweat it at all.

Posted on by Janet Christenbury in Uncategorized 2 Comments

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

Brain Tumor Foundations Join Together to Raise Awareness and Funds for Research

“Two Voices, One Vision: Sharing Hope Across Generations” is the vision and message this year as two well-known brain tumor foundations join together to raise awareness and money for brain and spinal tumor research and support.

The Southeastern Brain Tumor Foundation (SBTF) is joining forces with the Brain Tumor Foundation for Children (BTFC) for the 2011 Race for Research, to be held on July 23 at Atlantic Station in Midtown Atlanta. The joint run and walk will highlight the shared mission of both groups in the fight against brain tumors.

Costas G. Hadjipanayis, MD, PhD

Costas G. Hadjipanayis, MD, PhD

Emory neurosurgeon Costas Hadjipanayis, MD, PhD, is the president of the Southeastern Brain Tumor Foundation. He says the annual race is the major fundraising event for the SBTF, raising money to support critical, cutting-edge brain and spinal tumor research at major medical centers in the Southeast, including Emory. Over the past decade, the SBTF has raised more than $1.2 million for research.

Since 1983, the BTFC has been serving the pediatric brain tumor population, providing $1.5 million in emergency financial assistance for families over the past 10 years, in addition to providing resources for numerous patient programs and research.

According to Hadjipanayis, the Race for Research has drawn, in recent years, over 2,000 participants annually from throughout the Southeast and across the U.S. By joining forces with the BTFC, attendance is expected to grow, as is the fundraising goal of $300,000 this year for the two not for profit organizations.

Hadjipanayis, who is also chief of the neurosurgery service at Emory University Hospital Midtown, hopes this event will help in gaining greater exposure for brain tumor awareness in both children and adults, while raising funds for important research.

To find out more about the 2011 Race for Research 5K run and 2K walk, visit upport.sbtf.org/2011Race.

Information about the SBTF can be found by visiting www.sbtf.org. For more information about the BTFC, see www.braintumorkids.org.

Posted on by Wendy Darling in Uncategorized Leave a comment