Research

Dr. Panigrahy and his team are developing medicines to block a naturally occurring medical phenomenon called a "cytokine storm." A cytokine storm is an excessive immune response common to infections and autoimmune disorders that can cause dangerous levels of inflammation in the body. In studies done in collaboration with Professors Charles Serhan of Brigham & Women’s Hospital and Bruce Hammock of University of California-Davis, the team in the Panigrahy lab have shown that cell debris from surgery, chemotherapy, toxin exposure and other causes can lead to production of high levels of these pro-inflammatory mediators called cytokines. Their novel approach to inflammation resolution in studies of cancer and other illnesses has been shown to prevent cytokine storm. COVID-19 patients can experience lethal levels of inflammation of lung and other organ tissues also caused by a cytokine storm. These researchers believe that their treatments may work in COVID-19 patients and in children suffering from the multi-system inflammatory syndrome that appears to be associated with COVID-19 just as the drugs developed by this team, now in clinical trials, have worked to treat patients with other illnesses. These scientists hope to begin clinical trials for new COVID-19 treatments within the coming months and are currently pursuing partnerships and funding opportunities.

*CU Kids at Heart founded the CJ Buckley Memorial Fund for Pediatric Brain Cancer Research at Beth Israel Deaconess Medical Center to support the work of the Panigrahy Lab. CU Kids at Heart raises money for this fund through corporate and private donations, not through its Boston Marathon fundraising activities. This new 2020 COVID-19 research is a direct result of studies conducted by this Lab and supported by CU Kids at Heart; see “Study of Simulation of Resolution of Inflammation in Cancer” for more information.

Surgeon-scientist Dr. Stone, with his team at Boston Children’s Hospital, has spearheaded a surgical technique called “Stereoelectroencephalography,” or “SEEG”, for epilepsy and seizure disorders which allows for extremely precise, targeted analysis of brain activity. In a less-invasive surgical procedure than many typical brain surgeries, these electrodes and sensors are placed in a child’s brain for a period of time to document seizure activity and pinpoint its source. Only then is additional surgery performed to remove the seizure-causing tissue. Dr. Stone seeks to improve and advance these minimally invasive techniques to minimize recurrences of seizures and encourage functional regeneration and repair of the brain. His research plans include the further clinical testing of custom micro-wires that record seizure activity from even an individual neuron, or brain cell.

*This research at Boston Children’s Hospital is supported by the CU Kids at Heart Boston Marathon fundraising.

Moyamoya disease is a rare, neurovascular condition in which the walls of the vessels that supply blood to the brain become thickened and narrowed resulting in a reduction of blood flow. This blockage puts patients at risk of transient ischemic attacks (TIAs) and strokes. Dr. Smith and his team—international leaders in understanding and treating this disease—seek to develop novel, noninvasive methods to better evaluate the blood flow in the brain of Moyamoya patients. The underlying goal of this research is to better determine which patients may be candidates for surgery and to improve the team's ability to assess the success of surgical revascularization after treatment. This work is being done by a multidisciplinary team of surgeons, radiologists, and interventionalists.

*This research at Boston Children’s Hospital is supported by the CU Kids at Heart Boston Marathon fundraising.

Increasingly, medical investigators are recognizing that Moyamoya is not just one disease or disorder, but is actually a group of many different conditions that seem to share a common end-pathway with vessel narrowing and stroke. Discovering the genes and mutations that may be associated with Moyamoya is critically important both to determine a prognosis in newly diagnosed patients and to help inform potential future treatments. In this multi-center study, Dr. Smith and his team aim to discover unique genetic causes of Moyamoya that can improve clinical diagnosis, prognosis, and therapy.

*This research at Boston Children’s Hospital is supported by the CU Kids at Heart Boston Marathon fundraising.

A longstanding method to evaluate how well a pediatric patient's Moyamoya surgery worked is to perform a catheter angiogram. While these tests provided a great amount of detail and are necessary before surgery (as learned, in part, from research previously funded by Credit Unions Kids at Heart and now incorporated into national guidelines), improvements in other imaging modalities have now called into question whether the use of catheter angiograms can be reduced in postoperative patients. This study seeks to determine which subset of patients still benefits from catheter angiograms post-surgery, with the goal of reducing the number of post-surgery catheter angiograms overall.

*This research at Boston Children’s Hospital is supported by the CU Kids at Heart Boston Marathon fundraising

One of the primary problems in cerebral palsy and other conditions that relate to brain injury from previous stroke is the inability of the brain to recruit a new blood supply to help with healing an old injury or maximizing recovery of brain near the injury in tissue that remains alive but is unable to work at full capacity due to limited blood supply at the penumbra (stroke edge). This problem is particularly relevant to children with cerebral palsy, as they have had some form of brain injury early in life, but, unlike adults, have a growing brain that may require increasing recruitment of blood supply over time. In this study, Dr. Smith and his team are investigating the molecule netrin-1 as a driver of brain endothelial cell migration, invasion and tube formation specifically in the setting of low oxygen (hypoxia), to mimic the environment of the brain in patients with cerebral palsy. They aim to discover how to better engineer new blood supply to the brain in the hope of maximizing recovery and improving therapeutic response in patients with cerebral palsy.

*This research at Boston Children’s Hospital is supported by the CU Kids at Heart Boston Marathon fundraising.

Recent research shows that radiation and chemotherapy, both standard treatments for most cancers, leave behind dying cancer cells, or "cellular debris." Over the past year, Dr. Panigrahy and his team have demonstrated that during the course of these treatments, the cellular debris can actually trigger tumor-promoting inflammation and the growth of microscopic cancer cells. Their studies show that these traditional cancer treatments are a "double-edged sword"—the very treatment used to cure the cancer is, in fact, also helping it survive. Dr. Panigrahy and his team believe that this cancer growth could be prevented by stimulating the body's naturally-occurring molecules to intervene and "resolve" the inflammation. Their methods to enhance the resolvin pathways are currently in clinical trials for inflammatory diseases, and in the 2019-2020 year, will turn their focus their research on the use of this type of approach for pediatric brain tumors and other cancers. Additionally, this year this team will study pro-resolution lipids called protectins as a way to prevent and treat medulloblastoma, glioblastoma, and other brain cancers via stimulation of resolution of inflammation as well as the combination of resolvins and immunotherapy to synergistically inhibit cancer. This coming year, the Panigrahy laboratory will investigate new pro-resolution lipids called maresins to prevent experimental cancer by clearing tumor debris. “Debris” from non-tumorigenic cells, such as blood vessels and immune cells, generated by steroids, cyclosporine, statins, tamoxifen, or chemotherapy can paradoxically stimulate tumor growth that can be blocked by maresins. These findings also provide new information on why these drugs can increase a patient’s risk of cancer.

*CU Kids at Heart founded the CJ Buckley Memorial Fund for Pediatric Brain Cancer Research at Beth Israel Deaconess Medical Center to support the work of the Panigrahy Lab. CU Kids at Heart raises money for this fund through corporate and private donations, not through its Boston Marathon fundraising activities.

For the second year, Credit Unions Kids at Heart is teaming up with the Team Jack Foundation, a non-profit foundation chaired by New England Patriots running back Rex Burkhead, in the fight against pediatric brain cancer. Credit Unions Kids at Heart will donate $40,000 this year toward the completion of two clinical trials currently sponsored by the Team Jack Foundation. These clinical trials will test the efficacy of two promising targeted agents, MEK162 and TAK580, to stop the progression of pediatric brain cancers. MEK162 is a multi-center national clinical trial that is evaluating the ability of an MEK inhibitor to turn off the Ras/Raf/MAP pathway (which causes uncontrolled cell growth) and shrink or stop the growth of brain tumors. This jointly funded clinical trial is led by research investigators at Dana-Farber Cancer Institute in Boston, Massachusetts. TAK580 belongs to a group of drugs called type II BRAF inhibitors that block the signal that tells tumor cells to divide. This trial is led by the team at Children’s Hospital Los Angeles with participation at the children’s hospitals in the U.S., including Boston Children's Hospital.

*This research is supported by CU Kids at Heart fundraising efforts separate from the Team’s Boston Marathon activities.