Download Current Fellow Research

Pediatric Hematology/Oncology-Fellows’ Research
On this page we describe current and recent fellow research projects to highlight the variety of research
opportunities (clinical, laboratory, quality improvement) in oncology, hematology and stem cell
transplant/immunology.
The table presents a summary of research mentors and areas of research our fellows have participated in
during the last nine years.
Applicants to our fellowship program are encouraged to explore individual UT Southwestern Faculty
pages for each of these faculty mentors for further information regarding their research activities and
interests.
Summary of Current Fellows’ Research
Erin Lampson, M.D., Chief Fellow (2013- 2016)
The main goal of my research is to better understand why some children who
survive acute lymphoblastic leukemia (ALL) have life-long problems with
learning and other cognitive functions, while other ALL survivors do not.
ALL is the most common cancer of childhood, with approximately 3,000 new
cases diagnosed annually in the United States. Over the past several decades,
significant advancements in treatment protocols have resulted in about 90% of
pediatric ALL patients surviving at least 5 years after diagnosis. This improved
rate of cure has, in turn, created a growing population of survivors. In 2005, approximately 50,000
survivors of childhood ALL were living in the United States. Long-term complications of therapy for the
treatment of leukemia are an emerging health concern for the survivorship population.
Many survivors of childhood ALL experience difficulty with attention, memory, speed of information
processing, and/or executive functioning (i.e., higher-order processes such as cognitive flexibility and
problem-solving) following their treatment. Such difficulties can negatively affect school performance,
occupational outcomes, social functioning, and quality of life. Despite generally uniform treatment
protocols, individual neurocognitive outcomes of pediatric ALL are not predictable, and little is known
about genetic profiles that might help identify children at risk for cognitive deficits. The main goal of my
study is to evaluate the relationship between specific genetic polymorphisms and cognitive outcomes
following treatment for childhood leukemia. The results of this study will have the potential to enable the
identification of survivors who are at increased risk for cognitive difficulties following treatment for
childhood leukemia. I hope that this knowledge ultimately will lead to new, individualized therapeutic
strategies that can enhance quality of life, educational, and occupational outcomes in the growing
population of pediatric ALL survivors.
Erika Lopez Bertiery, M.D. (2013- 2016)
Racial and ethnic disparities in childhood cancer outcomes have been identified
in the US. Diagnostic procedures and treatment protocols for pediatric cancer
are standardized in developed countries therefore cancer outcomes should be
fairly equal between different social groups. Unfortunately, this is not the case
and multiple studies have identified racial and ethnic disparities in outcomes
among children with cancer.
My research is exploring the association of Hispanic ethnicity and different outcomes in children with
cancer in Texas. In our state, the size and rapid increase of the Hispanic population provide us with a very
unique opportunity to better understand the scope of these disparities. My research study will provide
critical data to inform future intervention and policy to decrease disparities among children with cancer.
Gauri Sunkersett, D.O. (2013-2016)
Hematopoietic stem cell transplantation (HSCT) is a curative therapy used for a
variety of high-risk and relapsed cancers. Unfortunately, Graft versus host
disease (GVHD), a complication where the new immune system attacks the
host, occurs in 20-50% of HSCT patients and accounts for 15-30% of deaths
following allogeneic HSCT. Interestingly, changes in the composition of the
bacteria residing in the gut (gut microbiota) affect the health of cancer patients
in numerous ways: determining response to cancer chemotherapy, modulating
the incidence of life-threatening bacterial bloodstream infections, and
increasing the risk of developing intestinal GVHD.
I will be examining the relationship between changes in the gut microbiota of these high risk patients and
determine whether cancer therapies, such as chemotherapy and antibiotics, deplete beneficial gut
microbes thereby resulting in expansion of inflammatory bacteria and development of intestinal GVHD. I
will be utilizing a murine model to conduct these series of experiments and employing techniques such as
16S rRNA sequencing, metagenomic shotgun sequencing, gut microbiome bioinformatics analysis,
bacterial group qPCR, flow cytometry, and ELISA. As a secondary aim, I will be investigating the use of
anti-inflammatory Clostridia (AIC) and/or AIC-derived small-chain fatty acids in the prevention or as
curative therapy for intestinal GVHD. Focusing on the gut microbiota as a causative agent for iGVHD is
a paradigm shift that could significantly alter the management of cancer patients undergoing HSCT. I
have successfully obtained funding through the Children’s Cancer Fund to support my research efforts.
Kathryn Dickerson, M.D. (2014-2017)
Although much progress has been made in the treatment of pediatric leukemia,
acute myeloid leukemia (AML) remains difficult to cure. Epigentics, or nonDNA based regulation of gene expression, has emerged as a promising
therapeutic target for many human cancers. Our lab is interested in a specific
type of epigentic machinery called Polycomb Repressive Complex 2 (PRC2).
PRC2 has two nearly identical catalytic domains, EZH1 and EZH2, that
combine with PRC2’s other components EED and SUZ12 to form noncanonical (working as less than 3 components together) and canonical (working
as all 3 components together) PRC2 complexes respectively. EZH2 is known to
have both a gain-of-function or oncogenic and a loss-of-function or tumor suppressor role in a cellspecific manner in many blood cancers. The role of EZH1, however remains poorly understood. PRC2 is
also involved in normal blood development in a highly cell specific manner. We hypothesize that
canonical and non-canonical PRC2 complexes interact with different partner proteins and/or RNAs, and
distinct chromatin regions depending on the cellular context. We hope that our laboratory work will not
only identify important features of the cell-type-specific regulation mediated by this key epigenetic
pathway, but provide critical insights in developing strategies for therapeutic targeting of PRC2 activity in
blood cancers.
Samuel John, M.D. (2014-2017)
Nearly 90% of children with Pre- B acute lymphoblastic leukemia (ALL) will
have their cancer go into remission, however patients with high risk disease still
have a 20% risk of their leukemia returning. Understanding how leukemia is
able to survive after being treated with chemotherapy is important in order to
develop more effective ways to treat this disease. One way leukemia cells may
be able to do this is by activating a type of receptor on the cell surface called an
immunoreceptor tyrosine- based inhibitory motif (ITIM) receptor. When these
receptors are activated, they decrease the immune system’s ability to identify and kill pathogens such as
bacteria or tumor cells. Other studies have shown ITIM receptors may directly allow for leukemia cells to
develop and survive in the body. In this study, we will investigate whether exposure to steroids, which is
used to treat leukemia, leads to increased levels of ITIM receptors on the surface of leukemia cells and
how increased expression of these receptors may protect leukemia from the effects of chemotherapy and
the body’s immune system. We will use established leukemia cell lines and primary leukemia samples in
our experiments. This study may explain and solve the problem of how small amounts of leukemia
continue to survive and grow in the body after treatment with chemotherapy and cause this disease to
relapse. This may lead to the development of new strategies in treating persistent or residual disease in
ALL.
Julia Meade, M.D. (2014-2017)
My main goals are a) to develop a new treatment for an aggressive form of
brain cancer and b) to develop a novel way to see if such treatment is working.
Brain tumor is the second most common cancer in children. One type, called
Atypical Teratoid/ Rhabdoid Tumor (ATRT), is an aggressive cancer that
exclusively affects young children and has a very poor outcome. Even with the
best treatment, which includes intense chemotherapy and radiation, most
children with ATRT do not survive. Those who do, often suffer long-term side
effects such as learning disabilities, behavior problems and the risk of a second
brain cancer developing from radiation therapy. These late effects can be devastating to the child and
family.
Dr. David Boothman and members of his laboratory at UT Southwestern Medical Center recently found
that a medication used to treat adults with cancer called ARQ761 is also very effective at killing ATRT
cells in the laboratory. I have chosen to work with Dr. Boothman with the goal of translating his
discovery from “bench to bedside” to substantially improve our treatment for children with ATRT, by
exploiting the fact that ARQ761 kills cancer cells specifically if they express a protein called NQO1.
Importantly, NQO1 expression is very low in normal tissue of the body, particularly in the brain.
ARQ761 is metabolized by NQO1 to create high levels of hydrogen peroxide (H2O2) that turns on the
DNA repair protein called PARP1. This kills the cell by draining all the energy from it. We discovered
that when ARQ761 is combined with radiation therapy in cells lines and mouse models, the drug can be
used at 1/5 the dose and kills by the same unique cell death mechanism. The first part of my project is to
combine radiation therapy and ARQ761 in ATRT cell lines. Defining the best combination therapy will
allow us to decrease the amount of chemotherapy and radiation needed to cure children with ATRT, and
may lessen side effects that can be so devastating to the child.
The second part of my project is to explore a new way to monitor brain cancer response to ARQ761
treatment. Currently, response to chemotherapy is typically judged by whether the tumor gets smaller on
CT or MRI scan. This means that some children are exposed to treatment for months even though it may
not helping their particular tumor. We have recently developed a novel technique to measure how much
energy a child’s tumor is using while receiving chemotherapy and radiation. In the second part of my
project, I will explore the metabolic changes that occur during combination therapy with the theory that
PARP1 drives NAD+ loss, which inhibits DNA repair and suppresses both glycolysis and the TCA cycle,
and whether this can be monitored in real time, rather than weeks later. Genetically matched ATRT cells,
expressing or lacking NQO1 will be used in vitro and then in vivo in NOD/SCID animal models to
investigate this hypothesis and metabolic changes will be correlated with cell death induction responses.
These data will allow real-time imaging of pyruvate and glucose utilization, as well as lactate and pH
changes as unique biomarkers for response to ARQ761 in future clinical trials. If successful, this will
allow us to know which tumors are responding to therapy and which are not, allowing us to personalize
the care of each patient.
Pediatric Hematology/Oncology- Fellows’ Research
Research Opportunities
Fellow (graduation year)
Jacquelyn Powers-2015
Natalie Pounds-2015
Kathleen Wiertel-2015
Research mentor
General Area of Research
George Buchanan
Ralph Potts
Rolf Brekken
Shannon Cohn-2015
Priya Mahajan-2014
James Brugarolas and
Naomi Winick
Patrick Leavey
Iron deficiency anemia
Mage proteins /oncogenesis
Axl as a target for cancer
therapy
mTOR inhibitors
Sara Helmig-2014
Ajla Wasti-2014
Kenneth Chen-2013
Wilson File-2013
Kasey Leger-2013
Rachel Thienprayoon-2013
Raven Cooksey-2012
Stephen Skapek
Ralph Debreardinis
James Amatruda
Patrick Leavey
Naomi Winick
Naomi Winick
Daniel Bowers
Scott Furlan-2012
Chandrashekhar Pasare
Carrie Laborde-2012
Ellen Plummer-2012
Nicholas Fustino-2011
Amy Fowler-2011
Carrye Cost-2011
Puja Gupta-2010
Amanda Blair-2010
Hanumantha Pokala-2010
Janna Journeycake and
Naomi Winick
George Buchanan
James Amatruda
Naomi Winick
Patrick Leavey
Rolf Brekken
Janna Journeycake
Naomi Winick
Mark Hatley-2009
Cristina Tarango-2009
Martha Stegner-2009
Tim McCavit-2009
Eric Olson
Phil Shaul
Elizabeth Maher
Charles Quinn
PAX genes in childhood
cancers
Rhabdmyosarcoma
Ewing sarcoma
Germ cell tumors
Oncology
Anthracycline chemotherapy
Pediatric palliative care
Metabolic syndrome in brain
tumor survivors
IgG1 and enhancement of
anti-tumor immunity
Leukemia and CNS adverse
events
Iron deficiency anemia
Germ Cell Tumors
TPMT and ALL
Febrile Neutropenia
VEGF signaling
Iron Overload
Fungal infections in
neutropenic patients
Vasculogenesis
Endothelial Cells
Neuro-Oncology
Sickle Cell Disease
Allyson Niece-2008
Jason Litten-2008
Maite de la Morena
Gail Tomlinson
Laura Klesse-2008
Tamra Slone-2007
Jennifer Wright-2007
Cindy Neunert-2007
Louis Parada
Naomi Winick
Naomi Winick
George Buchanan
(Pediatrics)
Gail Tomlinson
Janna Journeycake
Jon Wickiser-2006
Shelley Crary-2006
Histiocytosis
Epidemiology, Cancer
genetics
Neurofibromatosis
ALL
Late effects – cardiac toxicity
Clinical hematology
Cancer genetics
Thrombosis