The following summarizes our senior fellows' research:

Laura Klesse (3rd year fellow 2007-2008)

Pilocytic astrocytomas are the most common glioma in children.  Optic gliomas, a low grade pilocytic astrocytoma, are extremely common in children with Neurofibromatosis type 1, a genetic disorder associated with an increased risk of malignancy.  Optic gliomas can cause significant problems including growth disturbances, vision loss and progression.  Unfortunately, little is know about the biology of these tumors or how they are best treated.  Optic gliomas most commonly develop in children under the age of six and are treated with chemotherapy or radiation – our current best option.  Since these therapies are given to children with actively developing brains, however, they carry significant risk for long term problems, including developmental delay, growth failure and increased risk of a second cancer.  To better understand the biology of optic gliomas, in order to identify better treatment options, we have created mouse models of Neurofibromatosis that allow us to selectively ablate NF1 in specific cells. We removed NF1, the gene for Neurofibromatosism, from astrocytes of the optic nerve, as astrocytes are the cells from which optic gliomas appear to form.  In mice where NF1 is ablated from astrocytes alone, optic gliomas do not form.  When we delete NF1 from astrocytes and remove one copy of NF1 from the surrounding cells, optic gliomas do form.  These two mouse models provide for a unique opportunity to identify the factors that are critical for driving astrocytes to proliferate aberrantly and form gliomas.  By understanding how these tumors form, and the signaling mechanisms which underlie their development, we hope to identify novel target that we can use to develop better therapies. 

J. Allyson Niece (3rd year Chief fellow 2007-2008)

My research interest is in the histocytic disorders, specifically hemophagocytic lymphohistiocytosis (HLH) and Langerhans cell histiocytosis (LCH).  I am completing a retrospective chart review in the three largest pediatric academic medical centers in Texas for HLH.  I will be compiling data from Texas Children’s Hospital in Houston, Children’s Medical Center of Dallas and Christus Santa Rosa Medical Center at the University of Texas-San Antonio. In addition, I will be conducting a prospective screening study of children in the pediatric intensive care unit (PICU) at Children’s Medical Center Dallas.  I hope to identify early markers of HLH to hasten diagnosis and initiation of therapy.  My research is funded through an Amgen grant for the academic year 2007-2008.

Jason Litten (3rd year fellow 2007-2008)

Hepatoblastoma is a rare embryonal tumor of the liver in children associated with particular cytogenetic aberrations and genetic syndromes.  I am working in Gail Tomlinson’s Laboratory at The Hamon Center for Therapeutic Oncology Research at UT Southwestern with our institutional hepatoblastoma tissue bank.  Our laboratory is describing the putative role of a novel candidate gene in hepatoblastoma.  We believe that this gene is central to the development of hepatoblastoma and may be a target for future therapeutic interventions.  In addition to direct involvement in all components of this project, my particular role is investigating epigenetic phenomena that contribute to this gene’s expression in normal and hepatoblastoma tissue.  I am supported by a grant from The Saint Baldrick’s Foundation – http://www.stbaldricks.org/#.

Recent Graduates

Tamra Slone (2004-2007)

Acute lymphoblastic lymphoma (ALL) is the most common malignancy of childhood and infection is one of the most common causes of morbidity and mortality in these children.  Ten percent of children with ALL develop temporary insulin-dependent hyperglycemia during treatment and are at increased risk of infection.  The prevalence of obesity has more than doubled in the past two decades in the U.S. as has the incidence of diabetes and pre-diabetes.  We hypothesize there is also a subgroup of children with ALL who have pre-diabetes (impaired glucose tolerance and/or impaired fasting glucose) and are also at increased risk of infectious complications.  My clinical research project is a prospective study in which I am evaluating children with ALL during induction chemotherapy for the development of pre-diabetes and infectious complications.  I am also developing a phase II study incorporating Alimta, a multi-targeted antifol, into the treatment protocol for relapsed ALL with the support of the Children's Oncology Group's relapsed ALL committee.

Cindy Neunert (2004-2007)

I am interested in hemostasis and thrombosis and ITP with specific interests outlined below:
1) Elective surgery in patients with hemophilia has increased since the introduction of factor concentrate.  Despite the increase in both major and minor procedures there are no guidelines established for hemostatic coverage during these procedures.  I recently completed a retrospective review on port a cath procedures and plan to look at additional minor procedures. 
2)  Idiopathic Thrombocytopenic Purpura is one of the most common diagnoses bringing children to the attention of pediatric hematologist.  The platelet count is currently considered the best marker for risk of intracranial hemorrhage and is used as outcome measure in research.  We propose that development of a valid and reliable bleeding severity score will assist in improved clinical outcome measures.

Jennifer Wright (2004-2007)

My research is in late cardiac toxicity from anthracyclines.  The two areas I am specifically interested in are the use of cardiac MRI to evaluate cardiac function in survivors and sub-clinical toxicity in survivors who received low doses of anthracycline.  I'm currently analyzing the data from cardiac MRIs done in young adult survivors of ALL as part of an NIH sponsored study on cardiovascular risk factors and fitness.  Additionally, I'm about to open a cardiac toxicity study for survivors of ALL treated on a local protocol that received 60 or 150 mg/m2 of daunorubicin.  These patients, who have been off therapy for up to 17 years, will have an echocardiogram and cardiac MRI performed to find the incidence of sub-clinical toxicity and to compare echo and MRI.  If we find that there are a substantial number of patients with cardiac toxicity, we will also do genetic polymorphism testing for allele mutations known to be associated with heart disease.