Nancy DeMore, M.D.
Dr. DeMore's laboratory focuses on the role of secreted frizzled related protein 2 (SFRP2) in osteosarcoma and the tumor immune microenvironment. Her lab developed a humanized monoclonal antibody to SFRP2 (hSFRP2 mAb) that is effective as monotherapy in pre-clinical models of metastatic osteosarcoma and is synergistic with immunotherapy. Based on these findings, the FDA granted rare pediatric and orphan disease designation for the hSFRP2 mAb.

Nathan Dollof, Ph.D.
Dr. Dolloff's laboratory is developing a cancer vaccine strategy for the treatment of pediatric Acute Myeloid Leukemia (AML). The approach uses an innovative protein platform to target AML-associated antigens to MHC class II molecules on antigen presenting cells, which triggers an anti-AML host immune response. Overall, this work aims to identify new ways to treat AML and develop immunotherapy drug candidates that will one day have a positive impact on the lives of pediatric cancer patients.

Denis Guttridge, Ph.D.
Dr. Guttridge's laboratory is interested in understanding how rhabdomyosarcoma (RMS) tumors develop and in strategizing new therapies that can increase the current 5-year survival, which for high-risk patients hasn’t changed in the last 40 years. RMS is a soft-tissue sarcoma which histologically and molecularly resembles skeletal muscle. However, unlike normal skeletal muscle, terminal differentiation is impaired in RMS, leading to uncontrolled growth and survival. The Guttridge lab showed that the NF-kB pathway contributes to this block in differentiation and new data indicate that myogenic transcription factors contribute to the survival of these tumors. Current efforts are focused on performing pre-clinical studies to target downstream effectors of NF-kB and myogenic factors to limit tumorigenesi s in mouse models of RMS, with the goal to translate these therapies into phase I/II clinical trials.

Jacqueline Kraveka, D.O.
Dr. Kraveka's laboratory is focused on sphingolipid and retinoid mediated therapies in neuroblastoma and pediatric sarcomas, and the function and regulation of the enzyme dihydroceramide desaturase (DEGS-1) in pediatric cancer. She is also actively involved in clinical pediatric research and serves as t he Institutional Principal Investigator (PI) for the Children’s Oncology Group (COG) and Beat Childhood Cancer Research Consortium (BCC). As PI, she is responsible for the conduct of over 50 Phase I, II and III clinical trials for pediatric oncology patients at MUSC.

Casey Landgon, Ph.D.
Dr. Langdon's laboratory's mission is to elucidate the intricacies and mechanisms underlying how different oncogenic events shape cancer cell fate decisions in pediatric sarcomas. Ultimately, the laboratory desires to uncover better and more tailored pharmacological interventions for these devastating childhood cancers. We are focused on Ewing sarcoma, a devastating pediatric bone cancer. Ewing sarcoma patients face a dismal prognosis with few therapeutic advancements in decades. Ewing sarcoma is driven by a fusion oncoprotein, typically EWSR1::FLI1, that creates a new epigenetic and transcriptional landscape in transformed Ewing sarcoma cells. We use a combination of molecular biology and multi-“omic” techniques and pharmacological intervention strategies to assess the cooperativity between the driving fusion and other genetic and non-genetic alterations seen in Ewing sarcomas. We are particularly interested on two main endeavors in the laboratory. First, we seek to determine how disrupted tumor suppressor subcellular localization contributes to Ewing sarcoma development. Second, we are investigating how other transcription factors cooperate with EWSR1::FLI1 and if those factors are future therapeutic targets. Please contact Dr. Langdon for specific details about projects available in his laboratory.

John O'Bryan, Ph.D.
Dr. O'Bryan's laboratory is interested in defining the importance of the RAS family of GTPases in human tumor biology. Although NRAS was initially discovered to be mutated in neuroblastoma, the overall frequency of RAS mutations in neuroblastoma is <2%. However, several lines of evidence suggest that RAS activity, in the absence of mutational activation, may be an important driver of neuroblastoma tumorigenesis. The O’Bryan lab has developed a new approach to inhibit RAS using engineered protein binders called monobodies. His group has developed a number of RAS-inhibitory monobodies that allow for the specific inhibition of RAS within the cell. Using these unique reagents, his group is studying the importance of RAS in neuroblastoma tumorgenesis. Dr. O’Bryan’s lab has found that a subset of neuroblastomas require RAS activity even in the absence of mutational activation. Future, work will use these reagents to probe role of RAS in additional pediatric tumors.

Jezabel Rodriguez-Blanco, Ph.D.
Dr. Rodriguez-Blanco's laboratory focuses in finding better treatments for medulloblastoma, the most common pediatric brain tumor and the cause of 10% of cancer related deaths in children. Survival for this subset of patients improved around 30 years ago when chemotherapy was added to the standard of care regimen. Unfortunately, since them no improvement in the survival of these children has been observed. Tumors in 30% of the cases will recur and we have no treatment currently available for relapsed medulloblastoma. Dr. Rodriguez-Blanco’s lab has identified populations of cancer stem cells that evade therapies and allow medulloblastoma to grow back. Her lab has also uncovered the drivers of these highly aggressive cells and proved that clinically available drugs can deplete these cells from tumors and prevent tumor recurrence. On the other hand, and by using tumor models that recapitulate the mutational landscape of the relapsed disease, Dr. Rodriguez-Blanco’s lab also looks for therapies aimed at specifically targeting relapsed medulloblastoma, and that could be utilized in future clinical trials for these underserved patients.