Dan G. Duda, DMD, PhD
Assistant Professor of Radiation Oncology
Harvard Medical School
Associate Biologist in Radiation Oncology
Edwin L. Steele Laboratory for Tumor Biology
The long-term goal of my research is to gain fundamental insight into solid tumor cellular biology and to translate this knowledge into improved therapies. The focus of my current work is the study of role of different populations of bone marrow-derived cells in tumor angiogenesis and cancer progression.
Adult stem cells of bone marrow origin may directly or indirectly participate in the process of new vessel formation in tumors, and their involvement may be critical for tumor growth. However, controversial evidence has been offered for some of the same tumor models in regard to the role of bone marrow-derived cells. I overcame these problems by using genetic tagging with green fluorescent protein, mouse transparent window models, and intravital multiphoton laser scanning microscopy (MPLSM), and demonstrated that the contribution of BMDCs to functional tumor endothelium is marginal, and dependent on tumor type, stage, site, and mouse strain. In tumors relapsing after suboptimal doses of radiotherapy, the major contribution of BMDCs was carried out by myelo-monocytes. In an ongoing clinical trial of bevacizumab in rectal cancer patients, I characterized multiple subpopulations of blood cells expressing endothelial markers. We found that enumerating these cells may be a useful biomarker for anti-angiogenic therapy. Moreover, I recently showed that quantification of these cells in the peripheral blood of recurrent glioblastoma patients is a potentially useful surrogate marker of response.
I am currently evaluating these cells in pediatric tumors, and sarcoma, ovarian and head-and-neck cancer patients in NCI-funded trials. I am also investigating the early events of metastatic progression. I recently discovered that stromal cells survive and contribute to tumor take in tumor tissue transplantation models. I used MPLSM and multiple transgenic mice to reveal the transplantability kinetics of stromal cell types during tumor fragment grafting. Finally, I established an in vivo system in non-malignant tissue to investigate the functional vessel formation during adipogenic transformation of fat cell precursors, and uncovered the reciprocal regulation between adipogenesis and angiogenesis. Next, I demonstrated the transplantability of fat tissues and the role of VEGF using in vivo microscopy and various GFP-transgenic mice. Finally, we investigated comparatively adult and cord blood precursor cells as vascular cell sources for tissue engineering.
A significant portion of my time is devoted to teaching tumor angiogenesis and stem cell biology as well as various experimental techniques through daily co-supervision of research fellows and graduate and undergraduate students. My trainees have already published and received awards from the Japanese Government, AHA, and Whitaker, Ford and Susan Komen Foundations. In the past three years, I have been teaching in the MIT-HMS Health, Science and Technology Program, in ASTRO and RTOG Translational Meeting for residents in Radiation Oncology, and in the yearly Methods in Bioengineering course organized by the Steele Laboratory.