Peer-reviewed	$5.4M	36
NCI	$3.6M	15
NIH	$1.4M	16
NSF	$0.2M	1
Other P-R	$0.2M	4
Non peer-reviewed	$1.0M	22
Total	$6.4M	58

1. To develop an integrated basic-translational research group to study the cellular and molecular aspects of ionizing radiation damage in human tumors, with a specific emphasis on overcoming radiation resistance. Studies focus on identifying and characterizing specific molecular targets, modulation of which produces an enhancement of the anti-tumor radiation effect.

The translational component of this research is to develop an interactive laboratory-clinical group to investigate the use of molecularly targeted agents with ionizing radiation using pre-clinical experimental human tumor models with the ultimate goal of performing clinical Phase I, II and III clinical trials.

2. To pursue research in technological innovations in radiation therapy delivery to improve cancer detection and treatment. We are currently pursuing P01-funded research and development with the world’s first tomotherapy unit (a technology that permits adaptive, helical, intensity-modulated RT).

3. To develop and implement new and improved imaging technologies and cell-specific contrast agents. We are pursuing a variety of functional MRI methods, as well as innovative PET-CT agents to study proliferation, hypoxia, and other end points. The primary purpose here is to move toward “theragnostic” radiation therapy, where the radiation management of a given tumor can be individualized by incorporating all possible knowledge, including tumor and nodal anatomic definition, the impact of motion and respiration, molecular features which identify tumors that would be “selectively” boosted, and responses during treatment to tailor radiation boost doses in accordance with the most resistant portion of the tumor, a concept referred to as “dose-painting by number”.

We are also developing imaging innovations, including advanced mammographic techniques. An active research program in angiogenesis and vascular imaging serves as an interdisciplinary bridge for various anti-angiogenesis clinical trials. Other molecular imaging focus areas are the development of cell-specific imaging contrast agents and the development of contrast agents and techniques for ultrasound imaging.

4. Through the NIH Disparities Program, to actively serve the Native American Lakota Sioux population through our interaction with our extension cancer program centered in Rapid City, South Dakota.

• Development and application of tomotherapy. (Technology in Cancer Research and Treatment 1:311-6, 2002)
• Demonstration that EGFR inhibition modulates radiation response in cancer of the head and neck with resultant improvement in survival and local control (NEJM 354:567-78, 2006)
• Development and clinical testing of NM404 cancer specific imaging agents (patents and patents pending).
• Evaluation of PSA recurrence-free survival versus p53 status (Int J Radiat Oncol Biol Phys 53:574-89, 2002)
• Development of dose intensification by schedule shortening to overcome the effects of accelerated repopulation (JCO 23:3760-3767, 2005)
• First neurocognitive assessment in brain metastases patients thru an international, multicenter phase III trial (JCO 21:2529-36, 2003)