Home » Pediatric Pilot Grants awarded to Dr. Karen Rabin and Dr. Alex George
Dr. Susan Blaney, vice chair of Research in the Department of Pediatrics, recently announced the winners of the 2013 Pediatric Pilot Awards Research Grant Program. Ten research applications were chosen by review committee members to receive grant funding in the amount of $50,000 for their projects.
The purpose of the Pediatric Pilot Awards Research Grant Program is to provide initial start-up “seed funding” for research projects. This grant program provides opportunities for new or less established researchers as well as experienced researchers who desire to expand their area of research. The grant projects are awarded based upon their scientific merit and the potential to generate the initial data necessary for a successful grant application submission to the NIH or other external, peer-reviewed funding mechanisms.
The pilot award program is a collaborative effort between Texas Children’s Hospital and its academic partner, Baylor College of Medicine.
Congratulations to the following 2013 pilot grant awardees from the Baylor College of Medicine, Department of Pediatrics, Section of Hematology-Oncology, Dr. Karen Rabin and Dr. Alex George.
Karen Rabin, M.D., Ph.D.
Assistant Professor – Pediatric Hematology/Oncology
JAK inhibition for targeted therapy in acute lymphoblastic leukemia
My research is on acute lymphoblastic leukemia (ALL), which is the most common childhood cancer. In general, we’ve made a lot of improvements in treatment and survival for children with this disease, but there are still some high risk subgroups who do very poorly even with the current treatment that we have. We’re trying to improve treatment for these challenging subgroups.
My laboratory is investigating a new class of treatment called JAK inhibitors. JAK inhibitors block the effect of genes in a pathway called the JAK pathway. In one high-risk subgroup of ALL, with poor survival, the leukemia cells seem to be driven by the JAK pathway, and we believe that JAK inhibitor therapy will shut down the cancer cells, but that other healthy cells in the body won’t be damaged by the treatment.
With this pilot award, we will further investigate JAK inhibitor therapy by treating leukemia cells in test tubes and treating mice with ALL. We want to understand how the JAK inhibitor is killing the leukemia cells, what drug combinations to use and how to translate these findings to improve outcomes for children with ALL. My hope is that these experiments will lead to a clinical trial of JAK inhibitor treatment for children with ALL.
Alex George, M.D., Ph.D.
Assistant Professor – Hematology/Oncology
A randomized controlled trial of a dose-prediction equation to determine maximum tolerated dose of hydroxyurea in sickle cell disease
My research focuses on sickle cell disease, which is a genetic disease of red blood cells. It affects predominantly African Americans but can affect people of all ethnicities. Typically, children under the age of 6 months don’t show any symptoms, but after 6 months we begin to see anemia and signs of blood cell breakdown. We start seeing fairly significant complications in many patients with the disease by the time they reach age one to two.
The problem in all patients with this disease is that the red blood cells are fragile and tend to be sticky, so they can break down and cause problems with normal blood flow. The most common problem we see in patients is a pain crisis. They may experience severe pain in their bones and other tissues because of the interruption of blood flow. Even in the absence of pain crises, though, patients accumulate chronic damage to their blood vessels and critical organs like the lungs, heart, brain and kidneys.
We currently have a medication called hydroxyurea for this condition. It’s a drug that basically induces a different, normal variant of hemoglobin, the defective protein in sickle red cells, thus reducing the fragility and stickiness of these cells. Hydroxyurea is very effective, but it works best when the dose is adjusted to an individual patient’s tolerance of the medication. We currently start every patient at a standard low dose and advance gradually to the maximum dose the patient can tolerate. So, although it eventually works, it takes a lot of time and a lot of clinical resources before we can get patients to an effective dose on the medication.
We’d like to see if there’s a better way. We’d like to be able to determine up front – based on patient characteristics (weight, height, lab tests, etc.) – what their optimal dose will be. This will not only help us prevent the pain crises and other acute problems that come up while a patient is waiting for the medication to become effective, but will hopefully stave off long term damage to the organs as well.
Dr. Russell Ware, my partner on this project, has come up with a possible predictive equation for the optimal dose, based on a previous group of patients on this medication. We are going to clinically test this equation by randomizing our patients into two groups – one that gradually advances on the medication and one that starts out at the dose predicted by this equation. We will be carefully comparing the two methods for safety and effectiveness. For this pilot phase, we’re looking to enroll about 25 patients, but ultimately we’d like to enroll 70 patients in the trial.
By Eden McCleskey
Texas Children’s Hospital