School of Medicine
Leukemia, Lymphoma, and Myeloma Program
Area of interest
My research focus reflects my training as both a geneticist and a clinical oncologist. It is an exciting time for translational research in oncology, as the completion of the human genome sequence and rapidly advancing technologies (genomic arrays, siRNA, targeted molecular therapies, next generation sequencing, etc.) are beginning to be used successfully. I eagerly anticipate applying these techniques to better understand the genetic etiology of lymphoma. This would include both typical genomic surveys of tumors-at the epigenetic, DNA, and RNA level-as well as classical genetic screens, either on cell lines or model organisms, to identify new genes or pathways involved in lymphoma formation or growth. As a subset of this broader topic of cancer biology/genetics, I am particularly interested in treatment strategies that derive from the emerging concept of personalized medicine. The recognition of the variation in the genetic makeup of tumors and the variation in the genetic makeup of the hosts is key to further progress in treating cancer. The future of oncology lies in defining and leveraging this variation to provide more tailored therapies to patients.
The FCGR3A gene, has been shown in retrospective studies to predict responses to rituximab, a monoclonal antibody frequently used in the treatment of B-cell non-Hodgkin lymphoma. We are conducting a retrospective clinical trial eventually seeking to translate these observations into clinically useful treatment algorithms. At the same time, while establishing this clinical pharmacogenetic proof of principle using the known FCGR3A polymorphism, we seek novel polymorphisms that likewise will improve and individualize future lymphoma therapies. To do this, my laboratory is utilizing an unbiased genomic approach, rather than the candidate gene approach used to identify FCGR3A and most other known clinically relevant polymorphisms. In collaboration with Howard McLeod's lab, we are mapping polymorphisms that determine rituximab sensitivity, as well as a variety of other drugs used to treat hematologic malignancies, using an ex vivo genetics strategy with the CEPH pedigree lymphoblastoid cell lines. In addition to rituximab, we are particularly interested in epigenetic modifying drugs, such as hypomethylating agents and histone deacetylase inhibitors. Finding SNPs that mediate drug resistance is a novel strategy to better determine how these drugs work in cancer cells, since this is still relatively poorly understood.
Another project that is ongoing in my lab is the development of pet dogs as a relevant large-animal model of human lymphoma. In collaboration with veterinary researchers and clinicians at NC State, we are characterizing canine lymphomas using gene expression arrays and other genomic strategies. By identifying and exploiting similarities between human and canine lymphomas, we can use pet dogs as a model to understand lymphoma biology. Also, because these dogs need treatment as well, they are valuable as subjects to expedite clinical trials of new therapeutics. We anticipate that this will lead to improved lymphoma treatments in both dogs and humans.
Awards and Honors
1986 National Merit Scholarship
1989 National Science Foundation Summer Research Award
1990 Undergraduate degree honors -- magna cum laude
1991-94 National Science Foundation Graduate Fellowship
1998 Medical Scholars Fellowship, Stanford University
2002 Excellence in Teaching Award, Tufts University Medical School
2004 Outstanding Thoracic Fellow Award, M. D. Anderson
2004, 2007 Janice Davis Singletary Fellowship Award, M. D. Anderson