Category: Science

Baby Poop Study to Link Infant Microbiome and Obesity

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Originally published in Bench to Bedside, the CHOP Research monthly publication

I composed this original article based on an interview with the investigator.

Excerpt:

New parents who find themselves surprisingly attentive to their babies’ poop are in good company. Researchers at The Children’s Hospital of Philadelphia and the University of Pennsylvania are beginning the second phase of a study that is exploring whether baby poop is an important data source to learn how the risk of obesity develops early in life.

The research team is focused on the miniscule but mighty passengers in baby poop: the gut microbiome. The collection of bacteria and other microorganisms that live within the digestive tract and contribute to processing food could reveal a lot about early excess weight gain.

Speeding Up Success with Precision Medicine Cancer Trial

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Originally published in Bench to Bedside, the CHOP Research monthly publication

I composed this original article based on an interview with the investigator, following up on a CHOP press release.

Excerpt:

An innovative new clinical trial launching this year at The Children’s Hospital of Philadelphia may not only help patients who have no further proven treatment options for neuroblastoma, a high-risk cancer, but may also be a model for how precision medicine clinical trials can spur better and faster cancer therapy discoveries in the future.

The trial uses a dynamic design, which allows researchers to quickly translate findings from the lab based on the evolving individual characteristics of each patient’s tumor. It is the first time such a strategy is being applied to a prospective clinical trial in children with cancer. Known as the NExt-generation Personalized NEuroblastoma THErapy (NEPENTHE) trial, it is moving forward with a new $1.5 million grant from Alex’s Lemonade Stand Foundation (ALSF), announced in December.

“The novelty of this trial could be viewed on numerous levels,” said principal investigator Yael Mossé, MD, a CHOP pediatric oncologist and assistant professor at the Perelman School of Medicine at the University of Pennsylvania. “It’s based on rigorous preclinical data, understanding the molecular drivers that are important in this disease. It’s combining multiple novel drugs, not just one at a time. And it’s bringing that to the clinic and assigning patients to therapy based on what their tumor genetics are teaching us at the time that they meet us with relapsed or refractory cancer.”

Possible ‘Central Hub’ Proteins Found in Cancer Cell Growth

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Originally published on Cornerstone, the CHOP Research Blog.

I composed this original article based on an interview with the investigator.

Excerpt:

A study from researchers at The Children’s Hospital of Philadelphia may add new lines to the textbook description of how cancer cells divide uncontrollably and develop into tumors. Their study, published in Nature Communications, identifies and describes an epigenetic mechanism in cancer cells that amplifies the expression of many genes and could be a central hub in cancer cell growth. Unlike most molecular cancer discoveries that advance knowledge of the disease by dividing it into narrower subtypes, this finding could directly apply to multiple cancer types.

“We know the signaling pathway known as the Rb pathway is altered in pretty much every single tumor that you can find in clinical settings,” said Patrick Viatour, PharmD, PhD, the study’s senior author, an investigator at CHOP and assistant professor of Pathology and Laboratory Medicine at the Perelman School of Medicine at the University of Pennsylvania.

Dr. Viatour’s research focuses on a family of proteins in the Rb pathway, called E2f transcription factors, that are an important part of the process of cell division — the cell cycle of reproduction that is carefully controlled in healthy cells but proceeds out of control when cancer cells proliferate. Transcription factors, including the E2f family of proteins, bind to specific target regions of DNA and help to either activate or deactivate expression of certain genes.

As a result of Rb pathway alteration, E2f factors are steadily turned on in cancer. In the study primarily using a mouse model of liver cancer, Dr. Viatour and his team found that E2f1 progressively accumulates as cancer progresses.

Medicine’s Version of Santa’s Workshop: A Laboratory Medicine Q&A

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Originally published on Cornerstone, the CHOP Research Blog.

I conducted, transcribed, and edited this interview, and wrote the introduction.

Excerpt:

Laboratory medicine specialists in pediatrics have a lot in common with Santa’s elves. They are less visible and receive far less of children’s attention than the ones who directly deliver gifts or bedside care, but their behind-the-scenes contributions are essential for the whole enterprise to function correctly. Just think how often you and your family members of any age need to have blood drawn and wait for lab test results to receive the doctor’s diagnosis or a treatment decision.

Michael J. Bennett, PhD, FRCPath, FACB, chief of laboratory medicine at The Children’s Hospital of Philadelphia, is at the forefront of the professional group representing these essential experts in analyzing blood, tissue, chemicals, and cells. Dr. Bennett will serve on the board of the American Association for Clinical Chemistry (AACC) beginning in January 2016 as president-elect, then in 2017 as AACC president.

On the occasion of this new leadership role, Cornerstone sat down with Dr. Bennett, who is director of the Michael J. Palmieri Metabolic Laboratory at CHOP and a professor of Pathology and Laboratory Medicine at the Perelman School of Medicine at the University of Pennsylvania to discuss his insights from 40 years of experience in clinical chemistry in pediatrics.

Latest Findings Add Insight Into Targeted Cancer Immunotherapy

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Originally published on Cornerstone, the CHOP Research Blog.

I composed this original article based on the presentation abstracts for the highlighted scientific presentation, followed by email contact with the investigators.

Excerpt:

Researchers at The Children’s Hospital of Philadelphia reported their latest results from their studies of an investigational personalized cell therapy for a highly aggressive form of acute lymphoblastic leukemia (ALL). Developed by researchers at the University of Pennsylvania and CHOP, the therapy is made from patients’ own immune T cells, which are extracted and bioengineered into CTL019 cells that potentially seek and destroy leukemia cells.

Among the findings, the team reported that 93 percent of pediatric patients reached remission after receiving the therapy for relapsed/refractory ALL. ALL is the most common childhood cancer, with limited effective treatment options for the approximately 10 to15 percent of patients who relapse after standard therapies.

The research team presented these results and more at the American Society of Hematology (ASH) annual meeting in Orlando. They reflect the CHOP-Penn team’s continued process of discovery about the investigational therapy, which is now part of clinical trials active at 15 sites globally, including CHOP.

Drugs May Be What’s the Matter With White Matter in HIV

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Originally published in Bench to Bedside, the CHOP Research monthly publication

I composed this original article based on an interview with the investigators.

Excerpt:

Some of the neurological and psychiatric complications associated with HIV may be side effects of the medications that control the virus, and not caused by the virus itself, according to a new study from researchers at The Children’s Hospital of Philadelphia and the University of Pennsylvania. Their pre-clinical findings were published in the Journal of Neuropathology and Experimental Neurology.

Certain antiretroviral drugs were associated with problems in developing myelin proteins in cell models and animal models, and the drugs were associated with reductions in white matter in autopsy brain samples from a cohort of individuals with HIV, reported the research team led by co-senior authors Judith Grinspan, PhD, research professor of Neurology at CHOP, and Kelly Jordan-Sciutto, PhD, chair and professor of Pathology at Penn’s School of Dental Medicine.

Both senior researchers emphasized that individuals with HIV should continue taking lifesaving antiretroviral drugs as prescribed. They hope their current and future findings can help researchers refine drug designs to reduce side effects, and help clinicians pursue prescribing practices that are risk-informed and tailored to the patient’s age and stage of brain development. These future changes could be particularly important for children with HIV whose brains are still developing.

Studying the Brain’s Fundamental Drum Beat to Understand Autism

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Originally published in Bench to Bedside, the CHOP Research monthly publication

I composed this original article based on an interview with the investigator.

Excerpt:

A drum beat coordinating brain activity and thus organizing the music of life emerges from deep inside the human brain. This electromagnetic neural pulse —eight to 12 beats per second — is known as the resting-state alpha rhythm.

“Alpha rhythms may be the most fundamental brain rhythm, involved in coordinating brain processes from those as simple as hearing tones and those as complex as consciousness,” said  J. Christopher Edgar, PhD, a clinical neuropsychologist and brain imaging researcher in the Department of Radiology at The Children’s Hospital of Philadelphia.

Researchers have known for some time that electromagnetic (neural) brain activity is different in individuals on the autism spectrum. In a series of recent studies, Dr. Edgar and colleagues have shown that the resting-state alpha rhythm is stronger among individuals on the autism spectrum, and that stronger alpha rhythms are associated with more severe clinical symptoms.

With a new grant from the National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health (NIH), Dr. Edgar will use state-of-the-art noninvasive brain imaging called magnetoencephalography (MEG) scanning to measure brain activities, including alpha rhythms, and magnetic resonance imaging to obtain structural brain measures in adolescents with and without autism spectrum disorder (ASD). He aims to find out why that metaphorical drum beat, setting the pace for the activities of other players or different parts of the brain, sounds different in children on the autism spectrum.

On the Trail of a Cancer Predisposition Syndrome

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Originally published in Bench to Bedside, the CHOP Research monthly publication

I composed this original article and complementary blog post based on interviews with the investigator and two parents of children with this syndrome.

Excerpt:

Inside the cells of a developing human embryo is a little piece of “Alice in Wonderland.” While most of our bodies’ genes are expressed from both our mothers’ and fathers’ chromosomes, there is a particular growth-regulating region of chromosome 11 where Dad’s genes make you grow bigger, and Mom’s genes make you small. As in Alice’s adventure, there is potential for some difficult situations to occur when that growth process is not handled with exacting care.

With new grants awarded by the St. Baldrick’s Foundation and the National Cancer Institute, attending physician and geneticist Jennifer M. Kalish, MD, PhD, at The Children’s Hospital of Philadelphia, is going down the rabbit hole to try to set things right. She aims to answer key questions about cancer while helping children with Beckwith-Wiedemann Syndrome (BWS), an overgrowth disorder that can result when epigenetic regulation of growth-regulating regions of chromosome 11 goes awry.

Five Fascinating Facets of Beckwith-Wiedemann Syndrome

Originally published on Cornerstone, the CHOP Research Blog

I composed this blog post as a complement to the above article about the new investigation into BWS.

Excerpt:

1. BWS is a mosaic condition. Some cells and organs or limbs grow unusually large in children with BWS, and some do not. Patterns of this overgrowth vary from child to child. This mosaicism happens because the changes in gene expression that cause BWS arise early when the developing human embryo has relatively few cells — and the changes occur in only some of them. Cells and organs descended from those dysregulated cells have unusual growth patterns, while cells and organs descended from normally developing cells continue to grow at normal rates. This results in a widely varying presentation of the syndrome in different children.

The mosaic nature of the condition makes it challenging to manage the elevated cancer risk that goes along with BWS. As Dr. Kalish noted, “I can see if a child’s arms are bigger. I cannot see what is going on in the liver or kidney.” Each child’s areas of overgrowth are variable, so all young children with BWS must undergo regular cancer screenings.

Cornering a Cancer-Connected Autoimmune Disease

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Originally published in Bench to Bedside, the CHOP Research monthly publication

I composed this original article and related behind-the-science human interest blog post based on interviews with the investigators.

Excerpt:

It is certainly not good news for children to get a double whammy of both cancer and autoimmune disease. Unfortunately, for a small subset of children with neuroblastoma, a common childhood cancer of the peripheral nervous system, an extremely rare autoimmune disorder called OpsoclonusMyoclonus Ataxia Syndrome (OMAS) comes along for the ride. The overactive immune response is believed to be triggered by the cancer.

But there is a twist.

“Patients with neuroblastoma who have OMAS have better outcomes, in terms of their tumor, than patients with neuroblastoma who don’t have OMAS,” said Jessica Panzer, MD, PhD, a pediatric neurologist and attending physician at The Children’s Hospital of Philadelphia who is studying this disease.

That pattern leads Dr. Panzer and other researchers to wonder: Is it possible that OMAS is a case of the body’s immune system finding a successful defense against cancer (but taking it a little too far against healthy cells)? And could we learn safe ways to harness its ability to help more children with neuroblastoma, or even other cancers?

These are among many long-term questions on the distant horizon for researchers who study this little-understood autoimmune disease. First, they need to understand the basics.

Dancing Eyes Brought a Research Team Together

Originally published on Cornerstone, the CHOP Research Blog

I composed this story as a complement to the above article highlighting the science of this team’s collaboration.

Excerpt:

It started at the end of a long day. Jessica Panzer, MD, PhD, then just a few weeks into her pediatric neurology residency at The Children’s Hospital of Philadelphia, was about to go home. Instead, she was called to the emergency room to consult on a 3-year-old girl who could barely walk. What happened then opened up new questions in her budding research career.

Not long after that, Miriam Rosenberg, PhD, started on a convergent path when her own 19-month-old daughter got sick. The toddler first developed problems with excessive drooling and stumbling while she walked. Within a few months, she had a sudden onset of more severe symptoms — unable to walk, severe tremor, unable to feed herself. Dr. Rosenberg and her husband brought their child to the nearest hospital.

Young Investigator Seeks a Target for Targeted Neuroblastoma Therapy

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Originally published on Cornerstone, the CHOP Research Blog

I composed this original blog post based on an interview with the investigator and took the accompanying photo.

Excerpt:

It is scary to learn your child has neuroblastoma, a tumor of the peripheral nervous system that is the most common cancer in infants. It is scarier still when you get test results that show your child is in the half of neuroblastoma patients whose cancer is very aggressive and high-risk. Doctors routinely test neuroblastoma tumor genes to see if there are multiple extra copies of the gene MYCN. Positive results come with that high-risk prognosis. Amplified MYCN occurs in about half of all high-risk neuroblastoma cases.

Currently, there is not a good answer for parents facing this scenario. Doctors have known about the association between amplified MYCN and poor neuroblastoma outcomes for more than 30 years, but that knowledge has not yet translated into improved, targeted treatments.

One researcher who is now trying to make the start of that translation is Robyn Sussman, PhD, a postdoctoral fellow at The Children’s Hospital of Philadelphia. Dr. Sussman has just received a two-year Young Investigator grant from the Alex’s Lemonade Stand Foundation (ALSF) to pursue this line of research. This week, she is joining 50 researchers from across the country at the third ALSF Young Investigator Summit to learn from and engage with leading researchers in pediatric oncology.