Showing 1-20 of 289 results
Kellie Haworth M.D.
Funded: 11-01-2017 through 10-31-2020
Funding Type: St. Baldrick's Scholar
Institution Location: Memphis, TN
Institution: St. Jude Children's Research Hospital

Do you ever get a cold sore on your lip, or know someone who does? That sore is caused by a virus that destroys the cells in your lip. As the virus spreads, the sore gets bigger. Viruses are great at killing cells and spreading. But, the sore eventually goes away because the immune system attacks the infected cells, killing them and stopping the viral infection, allowing your lip to heal. Imagine if we could get both the virus and the immune system to kill cancer cells instead of lip cells! Previously Dr. Haworth's team used a safe version of the cold sore virus to infect a common type of hard-to-treat childhood cancer cells. The virus directly killed cancer cells and caused the immune system to attack the cancer cells that the virus missed. Dr. Haworth's team is testing ways to make the virus and immune system work better together. Dr. Haworth is infecting model tumors with the virus, and giving immune cells designed to attack the tumor, hypothesizing that giving both virus and immune cells will cure the tumor. Awarded at The Research Institute at Nationwide and transferred to St. Jude Children's Research Hospital.

Corey Falcon M.D.
Funded: 07-01-2017 through 06-30-2019
Funding Type: St. Baldrick's Fellow
Institution Location: Birmingham, AL
Institution: University of Alabama at Birmingham affiliated with Children's of Alabama

ALL is the most common blood cancer occurring in children. Great strides have been made in the treatment of this disease, but new less toxic therapies for high risk ALL are needed. A new effective therapy is chimeric antigen receptor T-cells (CAR-T) which involves altering a patient’s own cancer fighting cells (T-cells) to express a protein able to recognize a protein on ALL cells (CD19), thus promoting killing of ALL cells. This form of therapy is much less toxic than traditional chemotherapy, but it is still associated with unwanted side effects. Dr. Falcon is working on ways to eliminate anti-CD19 CAR-T if severe side effects occur. This will greatly enhance the safety of this promising treatment. A portion of this grant is generously supported by the Not All Who Wander Are Lost Fund which was named after Kiersten Dickson’s favorite quote from J.R.R. Tolkien and honors the memory of a free spirited, courageous young woman who battled a rare, incurable cancer. This fund hopes to advance cutting edge immunotherapy treatments for pediatric cancers.

Justina McEvoy Ph.D.
Funded: 07-01-2017 through 06-30-2020
Funding Type: St. Baldrick's Scholar
Institution Location: Tucson, AZ
Institution: University of Arizona Medical Center

Rhabdomyosarcoma is a pediatric cancer of the developing skeletal muscle. The mechanisms that drive this tumor are poorly understood. From Dr. McEvoy's preliminary analysis, one possible mechanism is epigenetic deregulation of a group of long noncoding RNAs (lncRNA). This is exciting because lncRNAs play a role in tumorigenesis in other cancer types, including a subset of pediatric tumors. This presents a unique opportunity to develop novel therapeutic approaches for children with rhabdomyosarcoma. Dr. McEvoy's team hypothesizes that lncRNA deregulation is essential for rhabdomyosarcoma development. This study is working to understand the underlying mechanisms that drive this disease and identify potential new therapies. These results will have tremendous impact on patients, especially those with metastatic disease since only 20-40% will survive using current treatments.

David Mulama Ph.D.
Funded: 07-01-2017 through 06-30-2020
Funding Type: International Scholar
Institution Location: Duarte, CA
Institution: Beckman Research Institute of the City of Hope

Kaposi sarcoma-associated herpesvirus is a virus that causes cancer known as Kaposi sarcoma, which is very common in HIV+ children, especially in Africa and sometimes in individuals who get an organ transplant. Dr. Mulama is designing and testing a vaccine that prevents and treats the viral infection, as well as antibodies to detect infection in people. He will also test the vaccine so that one day it can be used as a treatment to prevent Kaposi sarcoma-associated herpesvirus infection and Kaposi sarcoma in more than 40,000 patients worldwide each year.

Reducing Ethnic Disparities in Acute Leukemia (REDIAL) Consortium Member
Funded: 07-01-2017 through 06-30-2018
Funding Type: Consortium Research Grant
Institution Location: Orange, CA
Institution: Children's Hospital of Orange County

This institution is a member of a research consortium which is being funded by St. Baldrick's: Reducing Ethnic Disparities in Acute Leukemia (REDIAL) Consortium. For a description of this project, see the consortium grant made to the lead institution: Baylor College of Medicine, Houston, TX.

Kevin Shannon M.D.
Funded: 07-01-2017 through 06-30-2018
Funding Type: Research Grant
Institution Location: San Francisco, CA
Institution: University of California, San Francisco affiliated with UCSF Benioff Children's Hospital

Glucocorticoids, which are sometimes called "steroids", are a type of drug used to treat all children, adolescents, and adults with acute lymphoblastic leukemia (ALL). In fact, there is substantial evidence that glucocorticoids are the single most effective drugs used to treat ALL, and that relapse is frequently due to the fact that they stop working. Although glucocorticoids have been used for over 50 years, we still do not fully understand how they kill ALL cells and why some ALL cells become resistant and cause relapse. Dr. Shannon has developed a novel approach for generating, transplanting, and treating ALL in models that now provides an unprecedented opportunity to uncover mechanisms of drug response and resistance. The purpose of this research project is to study ALL cells that have become resistant to glucocorticoids during treatment in order to identify the underlying reasons and to use this knowledge to develop better ways of treating them.

William Weiss M.D., Ph.D. 
Funded: 07-01-2017 through 06-30-2018
Funding Type: Research Grant
Institution Location: San Francisco, CA
Institution: University of California, San Francisco affiliated with UCSF Benioff Children's Hospital

Half of neuroblastomas are high-risk neuroblastoma, with poor survival. Understanding abnormalities that drive high-risk neuroblastoma (drivers) enables development of therapies against specific drivers. Until 2015, we had identified drivers for half of high-risk neuroblastomas. Recently, most remaining high-risk neuroblastomas were shown to have high levels of TERT, a protein that helps chromosomes replicate. It is still not clear how a protein that helps chromosomes replicate could drive cancer. Perhaps TERT is needed for neuroblastoma tumors to grow, but is not driving the tumor. To distinguish these possibilities, Dr. Weiss is testing whether TERT can drive neuroblastoma in human stem-cell models. In Dr. Weiss' system, stem cells generated from normal human blood or skin cells, are differentiated to form a cell type called neural crest, from which neuroblastoma is derived. He is introducing known drivers into these cells to generate a model for neuroblastoma. Some known drivers (MYCN) lead to neuroblastoma, while others (ALK) do not. Dr. Weiss is using this model to test whether TERT is a driver, or is required for neuroblastoma in the context of other drivers (ALK). Successful completion will generate a model to evaluate whether therapy directed against TERT could help children with neuroblastoma. This grant is generously supported by the Amanda Rozman Pediatric Cancer Research Fund created in memory of Amanda Rozman and honors her courageous battle with neuroblastoma by funding promising new to improve the efficacy and number of treatments available for relapsed and refractory neuroblastoma.

Adam Green M.D.
Funded: 07-01-2017 through 06-30-2020
Funding Type: St. Baldrick's Scholar
Institution Location: Denver, CO
Institution: University of Colorado affiliated with Children's Hospital Colorado

High-grade gliomas (HGG) are aggressive brain cancers that affect both adults and children. Current treatment options are very limited, and the vast majority of patients die of their tumors within five years of diagnosis. One subtype of high-grade glioma that almost exclusively occurs in children, diffuse intrinsic pontine glioma (DIPG), is the last incurable childhood cancer, with zero percent long-term survivors. To address these tumors, Dr. Green and team have focused on a new field of cancer treatment called epigenetics, which literally means “above genetics” and refers to all changes to DNA that do not involve changes to the DNA sequence itself, but instead affect which genes are made into protein. Through prior work, Dr. Green's team has found a gene, BPTF, which controls the expression of many other genes and appears to drive HGG and DIPG growth. Dr. Green aims to determine how exactly BPTF drives growth by interacting with other genes, to measure how BPTF inhibition works with drugs called HDAC inhibitors and whether this strategy could work with current standard treatments, and to measure the effect of a new chemical that inhibits BPTF that could serve as a precursor to medicines targeting BPTF.

Amanda Winters M.D., Ph.D.
Funded: 07-01-2017 through 06-30-2019
Funding Type: St. Baldrick's Fellow
Institution Location: Denver, CO
Institution: University of Colorado affiliated with Children's Hospital Colorado

Dr. Winters' research involves developing more effective and more targeted therapies for children with acute myeloid leukemia (AML), a type of leukemia that continues to have poor outcomes. The therapy for pediatric AML has not changed much in 20-30 years, and many children who receive this therapy relapse. There is a protein on many AML cells called CD123, which marks the earliest leukemia cells. In adults there are drugs that target this protein which are being studied in clinical trials. However, no one has studied whether CD123 is a useful target in pediatric AML. Dr. Winters is looking at CD123 protein expression in AML samples from pediatric patients, as well as investigating whether expression of CD123 marks the primitive leukemia cells in these patients - that is, those that give rise to the leukemia and cause relapse. She is also testing some of the same drugs that are being used in adult clinical trials on these pediatric samples in a laboratory setting, to see if they may be useful in pediatric patients. These studies are expected to generate new therapy options for children with difficult-to-treat AML.

Paul Jedlicka M.D., Ph.D.
Funded: 07-01-2017 through 06-30-2018
Funding Type: Research Grant
Institution Location: Denver, CO
Institution: University of Colorado affiliated with Children's Hospital Colorado

Ewing Sarcoma is an aggressive disease affecting children and young adults. Patients are treated with intensive chemotherapy. This helps some, but not all, with early disease, works poorly in those with advanced disease, and can have serious side effects. Searching for new and better therapies, Dr. Jedlicka's lab has found a new protein that works abnormally in Ewing Sarcoma and that could be a new target for treatment. Dr. Jedlicka is working to understand more about how this protein works and how best to block it, to see if it could be a useful new treatment.

E. Anders Kolb M.D.
Funded: 07-01-2017 through 06-30-2018
Funding Type: Research Grant
Institution Location: Wilmington, DE
Institution: Alfred I. Dupont Hospital for Children of the Nemours Foundation

Recently the Meshinchi lab discovered that mesothelin, a cancer-specific antigen, is highly expressed in a subset of childhood AML cases, a result that both highlights the distinct genetic differences between adult and pediatric cancers and opens the door for the development of more targeted therapies. Dr. Kolb is developing novel combinations of bispecific T-cell engaging antibodies, called SMITEs (Simultaneous Multiple Interaction T-cell Engagers) that will co-target mesothelin and the AML marker CD33. These T-cell engaging protein pairs physically link cancer cells to cytotoxic T-cells resulting in more potent and selective killing than single agents alone.

David Mulama Ph.D.
Funded: 07-01-2017 through 06-30-2020
Funding Type: International Scholar
Institution Location: Kakamega, Eldoret
Institution: Masinde Muliro University of Science and Technology

Kaposi sarcoma-associated herpesvirus is a virus that causes cancer known as Kaposi sarcoma, which is very common in HIV+ children, especially in Africa and sometimes in individuals who get an organ transplant. Dr. Mulama is designing and testing a vaccine that prevents and treats the viral infection, as well as antibodies to detect infection in people. He will also test the vaccine so that one day it can be used as a treatment to prevent Kaposi sarcoma-associated herpesvirus infection and Kaposi sarcoma in more than 40,000 patients worldwide each year.

Jessica Blackburn Ph.D.
Funded: 07-01-2017 through 06-30-2018
Funding Type: Research Grant
Institution Location: Lexington, KY
Institution: University of Kentucky Research Foundation affiliated with Kentucky Children's Hospital

Many cancer treatments kill both normal and cancer cells. Drugs used in standard cancer treatments have long term effects in children, such as causing developmental delays or second cancers later in life. Dr. Blackburn's team is working to find new drugs that kill cancer cells, but do not affect normal cells. By discovering characteristics that are unique to cancer and finding a drug that recognizes that specific characteristic, they will be able to selectively kill cancer cells. Their research goal is to improve cancer treatments so that children can live long, normal lives after their cancer is cured.

Loren Walensky M.D., Ph.D.
Funded: 07-01-2017 through 06-30-2018
Funding Type: Research Grant
Institution Location: Boston, MA
Institution: Boston Children's Hospital affiliated with Dana-Farber Cancer Institute, Harvard Medical School

High grade gliomas (HGG) are a vicious subtype of pediatric brain tumors that remain the leading cause of death among children with cancer. New therapeutic strategies are urgently needed to combat this scourge. By mining genomic datasets from HGGs, Dr. Walensky's team has identified a unique susceptibility profile based on retention of wild-type p53 status and dual expression of the negative regulators HDM2 and HDMX. Whereas p53 can be mutated or deleted to avoid cell cycle arrest or apoptosis, a frequent alternative mode of p53 suppression relies on overexpression of HDM2 and HDMX. Small molecules have been developed to target HDM2 specifically, but co-expression of HDMX causes resistance. Only a stapled peptide modeled after the critical p53 transactivation helix is capable of blocking both HDM2 and HDMX, a feature that has prompted its advancement to Phase I/II clinical trials in adult cancers. As the recipient of the St. Baldrick’s Research Grant with generous support from the Team Campbell Foundation, Dr. Walensky is testing a novel therapeutic strategy for pediatric HGG based on a dual-targeting stapled peptide inhibitor of HDM2/HDMX. He believes that the proof-of-concept data to emerge could provide a compelling rationale for conducting a clinical trial in these otherwise rapidly fatal pediatric brain cancers. The Team Campbell Foundation was created in memory of Campbell Hoyt who passed away from Anaplastic Ependymoma. Their mission is to improve the lives of families facing a childhood cancer diagnosis through raising awareness, funding research and providing psycho-social enrichment opportunities.

Brian Ladle M.D., Ph.D. 
Funded: 07-01-2017 through 06-30-2020
Funding Type: St. Baldrick's Scholar
Institution Location: Baltimore, MD
Institution: Johns Hopkins University School of Medicine affiliated with Johns Hopkins Children's Center

Dr. Ladle is using the body’s own immune system to destroy cancer - specifically a class of cancer in children originating from connective tissues called sarcomas. Using fire as an analogy, Dr. Ladle seeks to build an intense flame of a powerful immune response which will specifically kill the cancer cells. To create this fire, one must follow specific steps. The kindling, which must be easily burned, is protein targets on the cancer cells (termed tumor antigens) recognized by the immune system. Next, the spark to ignite the kindling is initial inflammation in the tumor against these tumor antigens. Finally, to feed the fire, fuel or lighter fluid can be added in the form of recently approved immune modulator drugs which, when infused into patients, bind to immune cells residing in the tumor and activates them to kill the tumor cells. Each ordered step is essential in building an effective fire. This project addresses each of these key aspects for generating a successful immune response to treat sarcomas – creating new tumor antigens, adding inflammation to jump start the immune response against these antigens, and combining with new immune modulators allowing the immune cells to be active in destroying sarcomas.

Michael Koldobskiy M.D., Ph.D.
Funded: 07-01-2017 through 06-30-2019
Funding Type: St. Baldrick's Fellow
Institution Location: Baltimore, MD
Institution: Johns Hopkins University School of Medicine affiliated with Johns Hopkins Children's Center

Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Despite dramatic improvements in treatment outcome in recent decades, relapsed and resistant disease remains a leading cause of childhood death from cancer. Dr. Koldobskiy studies the ways in which leukemia cells rely on "epigenetic" modifications, or chemical marks that modify the expression of genes without a change in the genetic sequence itself. Variability of epigenetic marks allows leukemia cells flexibility in turning genes on and off, and may account for resistance to treatment. By dissecting the mechanisms of epigenetic modification in childhood ALL, he aims to identify new targets for treatment.

Sriram Venneti M.D., Ph.D.
Funded: 07-01-2017 through 06-30-2018
Funding Type: Research Grant
Institution Location: Ann Arbor, MI
Institution: University of Michigan affiliated with C.S. Mott Children’s Hospital

Diffuse intrinsic pontine gliomas (DIPG) are lethal pediatric brain tumors with no treatments. In order to develop cures we need to understand their biology. Cancers survive on fuel to generate energy to support their uncontrolled proliferation. One of the fundamental nutrients that drive the energy production is the amino acid glutamine. How glutamine is taken up and metabolized by DIPG tumor cells is not know. Further it is not known if inhibiting cancer cells from taking up and metabolizing this fuel is therapeutic. To address this significant gap in our knowledge, Dr. Venneti is studying glutamine metabolism in DIPG cancer cells and evaluating inhibition of glutamine metabolism as a potential therapeutic strategy. This grant is made with generous support from the McKenna Claire Foundation established by the Wetzel family in memory of their daughter, McKenna. Their mission is to cure pediatric brain cancer by raising awareness, increasing community involvement and funding research.

Patrick Grohar M.D., Ph.D.
Funded: 07-01-2017 through 06-30-2018
Funding Type: Research Grant
Institution Location: Grand Rapids, MI
Institution: Van Andel Research Institute affiliated with Helen Devos Children's Hospital, Spectrum Health Hospitals

The goal of this study is to develop new therapies for Ewing sarcoma by targeting a protein called EWS-FLI1. Many people believe that the key to improving outcomes for Ewing sarcoma patients is to develop new drugs that block EWS-FLI1. In order for this to be successful, there is a need to understand exactly what happens to the Ewing sarcoma cell when EWS-FLI1 is turned off. Dr. Grohar is using the latest technology to both characterize the consequence of EWS-FLI1 silencing and identify novel compounds that turn EWS-FLI1 off.

David Kirsch M.D., Ph.D.
Funded: 07-01-2017 through 06-30-2018
Funding Type: Research Grant
Institution Location: Durham, NC
Institution: Duke University Medical Center affiliated with Duke Children's Hospital & Health Center

Diffuse intrinsic pontine glioma, also referred to as brainstem glioma, is a pediatric cancer that accounts for the majority of deaths from brain tumors in children. Although radiation therapy is the standard of care for brainstem gliomas, the median survival of children with this tumor type is less than one year from diagnosis. In order to improve the treatment of these patients, Dr. Kirsch's team is using a model of brainstem glioma that can be used to evaluate the effectiveness of new therapies. Using this model, they are testing whether removing a protein called ATM, which is the target of drugs now entering clinical trials, will enhance radiation sensitivity in brainstem gliomas. They hypothesize that deleting this target, when given in combination with radiation therapy, will increase the number of tumor cells killed by radiation and will therefore improve survival in brainstem gliomas when they have a specific gene mutation commonly found in this childhood brain tumor. If successful, these studies will inform the design of future clinical trials testing this strategy in children with brainstem gliomas. This grant is named for Hannah’s Heroes, a St. Baldrick’s Hero Fund created in honor of Hannah Meeson and pays tribute to her fight by raising awareness and funding for all childhood cancers because kids like Hannah “are worth fighting for.”

Katherine Hyde Ph.D.
Funded: 07-01-2017 through 06-30-2018
Funding Type: Research Grant
Institution Location: Omaha, NE
Institution: University of Nebraska affiliated with Children's Hospital & Medical Center, Nebraska

Acute myeloid leukemia (AML) is a cancer of the immature cells in the bone marrow. One common chromosomal abnormality found in pediatric AML is the inversion of chromosome 16 (inv(16)). Current treatments for inv(16) AML are associated with significant toxicity, as well as serious long-term chronic effects. Therefore, there is a pressing need to develop new, more targeted treatments for children with inv(16) AML. Inv(16) generates a fusion gene called CBFB-MYH11. CBFB-MYH11 causes changes in gene expression, which are the first step in the development of leukemia. Because Cbfb-MYH11 is expressed in all inv(16) leukemia cells, it makes an attractive drug target. Currently, there are no CBFB-MYH11 inhibitors suitable for use in humans. However, it is possible that other proteins cooperate with CBFB-MYH11, some of which may be better drug targets. One potential co-factor is HDAC1. Dr. Hyde's team found that HDAC1 binds CBFB-MYH11 and is required for its activity. They also found that an HDAC1 inhibitor significantly blocks the growth leukemia cells in culture. In this project, Dr. Hyde is testing whether HDAC1 is an important co-factor of CBFB-MYH11 and if HDAC inhibitors effectively target Cbfb-MYH11+ leukemia cells in vivo. These results will have direct clinical implications for children with inv(16) AML.