Showing 1-20 of 294 results
James Ch'ng M.D.
Funded: 07-01-2018 through 06-30-2020
Funding Type: St. Baldrick's Fellow
Institution Location: Los Angeles, CA
Institution: University of California, Los Angeles affiliated with Mattel Children's Hospital

Epstein-Barr virus (EBV) is a common viral infection that in the vast majority of people causes only minor or no illness. However, in some situations it can play a role in the development of certain forms of cancer, such as lymphoma. One way that it might contribute to the development of cancer is by affecting the way that cells use energy because viruses and cancers both require increased energy to support rapid growth. By studying how EBV changes the way that cells use energy, Dr. Ch'ng hopes to learn whether changes in cell energy use are a factor in the development of cancers associated with EBV and whether these changes can be targeted to treat these forms of cancer.

Kelly Faulk M.D.
Funded: 07-01-2018 through 06-30-2020
Funding Type: St. Baldrick's Fellow
Institution Location: Denver, CO
Institution: University of Colorado affiliated with Children's Hospital Colorado

Leukemia is a cancer of blood cells that can be caused by a variety of genetic changes. The leukemia cells of some children have a genetic change in which a gene (KMT2A) is broken and combined with other genes that typically do not interact with one another (this is called "rearranged"). This genetic rearrangement then alters how other genes are turned on or off in the cell, turning on genes that drive the development of leukemia. This leukemia can be seen in all ages but is most common in infants. Unfortunately, it is a very aggressive leukemia with a high risk of relapse and poor overall survival. A drug named pinometostat has been developed that directly targets the underlying changes that occur with this genetic rearrangement and specifically kills these leukemia cells. When pinometostat was tested by itself in these leukemia patients, it was proven safe and showed killing of leukemia cells in some patients. Dr. Faulk and colleagues have developed a new clinical trial that combines pinometostat with standard chemotherapy for kids and young adults with relapsed or resistant leukemia with a KMT2A gene rearrangement. This trial is testing the safety of pinometostat when it is given with other chemotherapy medicines, seeing how the drug is broken down by the body, and determining how the drug affects the body. The trial is also determining if pinometostat works better to fight cancer when given with other chemotherapy rather than alone. If proven safe, the drug may then continue in further testing to better understand how effective it is in this type of leukemia. The long-term goal is to improve the cure rate for this group of high-risk leukemia patients and provide these children with more treatment options that they urgently need.

Neekesh Dharia M.D., Ph.D.
Funded: 07-01-2018 through 06-30-2020
Funding Type: St. Baldrick's Fellow
Institution Location: Boston, MA
Institution: Dana-Farber Cancer Institute affiliated with Boston Children's Hospital, Harvard Medical School

Despite progress made in the treatment of pediatric cancers, several childhood cancers, such as high-risk neuroblastoma, Ewing sarcoma and rhabdomyosarcoma, continue to have poor survival rates. It is critical that we identify new therapies for these cancers, especially now that we are learning how cancers are driven by specific changes in proteins that bind DNA and control transcription. Researchers are beginning to identify potential vulnerabilities in cancers by systematically deleting almost every single gene in a cancer cell, and describing in greater detail the mutations and other events that occur in pediatric cancers. Dr. Dharia's team is integrating data from such approaches to discover specific vulnerabilities in high-risk neuroblastoma, Ewing sarcoma and rhabdomyosarcoma. Different types of cancer cells require different instructions or programs to survive, and Dr. Dharia proposes the identification of these programs will lead to new targets to treat these cancers. By identifying, validating and characterizing new targets for treatment of these childhood cancers, Dr. Dharia hopes to discover new therapies for cancer care. This research will take advantage of drugs that are already available and ideally identify completely new ways to treat these cancers.

Daniel Peltier M.D., Ph.D.
Funded: 07-01-2018 through 06-30-2020
Funding Type: St. Baldrick's Fellow
Institution Location: Ann Arbor, MI
Institution: University of Michigan affiliated with C.S. Mott Children’s Hospital

Bone marrow transplantation (BMT) is required to cure many childhood cancers. However, bone marrow transplantation is often complicated by severe and often fatal side effects. Both the beneficial anti-cancer effects and harmful side effects of bone marrow transplantation are due in part to the new immune system that the patient receives. Unfortunately, we do not know how to precisely fine tune this new immune system to make BMT safer for more children. Dr. Peltier's work seeks to further understand how a component of this new immune system is controlled by a recently identified class of genes called non-coding RNAs (ncRNA). These ncRNA genes do not make proteins like classic genes, but instead regulate the production and function of proteins made by classical genes. His early data shows that unique ncRNA genes from multiple classes of ncRNAs are turned on and off following BMT. However, it is not known if or how these unique ncRNA genes influence the new immune system after BMT. Dr. Peltier seeks to further understand the function of these ncRNAs following BMT, which may suggest ways of developing medicines to improve BMT.

Samara Potter M.D., M.B.A.
Funded: 07-01-2018 through 06-30-2020
Funding Type: St. Baldrick's Fellow
Institution Location: Houston, TX
Institution: Baylor College of Medicine affiliated with Texas Children's Hospital, Vannie E. Cook Jr. Children's Cancer and Hematology Clinic

Despite recent advances in technology, very little is known about many types of rare and high risk childhood cancers. Since the numbers of these patients are so small, it has been very difficult to study how best to take care of them. Dr. Potter is using technology to look at the genetic code of these rare tumors, in order to learn more about why and how they occur, as well as how they change over time. This knowledge will help to create tests to diagnose these patients, as well as to develop more effective, less toxic treatments.

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 06-30-2018
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.