Rachel E. Rau, MD

Dr. Rachel Rau’s research aims to develop novel therapies for the treatment of leukemia in children. By working in the lab to better understand the biology of leukemia, her research findings identify new therapeutic targets that are developed and tested for use in the patient care clinic.

The survival rate for children with leukemia has improved substantially over the last several decades. This improvement in survival rate is largely due to the work of scientists who have refined the chemotherapy regimens used to treat cancer. However, the gains in survival have plateaued over the last few years, which indicates we are reaching the limits of what can be accomplished using standard, non-specific chemotherapy drugs. New treatment strategies are necessary to make further meaningful advances in outcomes.

From the time Dr. Rachel Rau entered medical school, she knew she wanted to be a pediatric cancer doctor. However, she had only considered the patient care aspect of this profession until her residency at Johns Hopkins introduced her to the laboratory of Dr. Patrick Brown, a prominent leukemia researcher. Under Dr. Brown’s guidance, Dr. Rau conducted an investigation to learn more about the incidence and clinical significance of a gene mutation called nucleophosmin (NPM), which occurs in pediatric acute myeloid leukemia (AML). They determined that patients with NPM mutations had a better prognosis than patients without such mutations. Based on this data, subsequent Children’s Oncology Group (COG) AML trials categorize patients that have NPM mutations as ‘low-risk’ — assigning them to a less intense treatment regimen, potentially sparing these patients from unnecessary treatment-related toxicity. The experience demonstrated to Dr. Rau the powerful way in which laboratory-based research could impact patients on a global scale, thus beginning her desire to pursue a research-focused career.

Dr. Rau continued her research training with Dr. Brown during her fellowship in pediatric hematology/oncology at Johns Hopkins University. During that time, she developed an expertise in the molecular biology of blood cancers and mouse modeling techniques. She was among the first to demonstrate cooperation between two of the most commonly occurring mutations in AML — NPM and FLT3/ITD mutations. This work was published in the Journal of Experimental Hematology and presented at the American Society of Hematology (ASH) national conference. In support of this work, she received a St. Baldrick’s Foundation Fellowship Grant.

While her time in the Brown lab provided outstanding training in basic laboratory techniques, she knew that to successfully translate laboratory findings into new therapies, she needed additional training in the conduct of clinical research. An opportunity to pursue that training came in 2012 when she was recruited by Texas Children’s Cancer Center to participate in the K12 Pediatric Oncology Clinical Research Training Grant. This training grant has allowed her to continue her laboratory-based research and to obtain formal training in clinical research through mentorship and didactic coursework.

In the lab, Dr. Rachel Rau is currently working to better understand how abnormalities in the regulators of gene expression (called epigenetics) contribute to the development of leukemia. The ultimate aim is to find ways to therapeutically target these aberrations.

Through one of her lab projects, she has identified a possible therapeutic target for a subset of AML that is difficult to treat. She is collaborating with a biopharmaceutical company that has developed an inhibitor of this specific target. Her results in the lab have shown promising positive results. These data will be presented at the ASH National meeting this year, with plans to publish it as a manuscript in 2015. More importantly, this work should serve as rationale for the development of a clinical trial in the short term that she will develop in collaboration with the biopharmaceutical company.

She is also establishing a clinical research program that is aimed at developing clinical trials to test new therapeutic agents. She serves as the Study Chair for a Children’s Oncology Group (COG) trial that is testing whether a drug called pegcristantaspase can be used in place of a drug called Erwinase® for patients with acute lymphocytic leukemia (ALL). While Erwinase® must be given to patients 6 times on a Monday, Wednesday, Friday schedule by painful intramuscular injection, pegcrisantaspase is given once through an intravenous (IV) line. This drug has the potential to substantially lessen the pain and burden of care for children with leukemia.

Additionally, Dr. Rau serves as Vice Chair of 2 Phase I COG trials that are testing promising new agents for the treatment of childhood cancer. The knowledge and experience she is gaining through these projects will facilitate the translation of her laboratory discoveries into clinical trials.