Sara Rockwell PhD, FASTRO

Professor of Therapeutic Radiology and of Pharmacology; Associate Dean for Scientific Affairs

Research Interests

Microenvironmental heterogeneity in solid tumors; Experimental cancer therapy; Biological effects of ionizing radiation; Effects of hypoxia and low pH

Research Summary

My research focuses on laboratory studies aimed at improving our understanding of the biology of solid tumors and improving the treatment of cancer. Several different projects related to these broader goals are ongoing in the laboratory. Research in my laboratory examines the micro environmental heterogeneity within solid tumors and explores the effects of these heterogeneous and often unphysiologic environments on the biology of tumor cells and of the stromal elements within solid tumors. From the time they are microscopic, solid tumors contain regions of severe hypoxia, unphysiologically low pH, and nutrient deprivation. The micro environmental inadequacies within solid tumors alter the proliferation patterns of the cells, the metabolic pathways used by the cells, the ability of the cells to tolerate stress, DNA damage, and other injuries, and the response of the cells to radiation and to antineoplastic drugs. We are examining these alterations and studying their implication for the development and progression of solid tumors. We are also working to develop therapeutic strategies which use our knowledge of the metabolic features of these cells improve to cancer therapy.

Extensive Research Description

Research in my laboratory examines the microenvironmental heterogeneity within solid tumors and explores the effects of these heterogeneous and often unphysiologic environments on the biology of tumor cells and of the stromal elements within solid tumors. From the time they are microscopic, solid tumors contain regions of severe hypoxia, unphysiologically low pH, and nutrient deprivation. As these tumors grow, they induce angiogenesis, but the vascular beds that develop within tumors are abnormal in both structure and function. The microenvironmental inadequacies within solid tumors have profound effects on cell physiology, altering the proliferation patterns of the cells, the metabolic pathways used by the cells, the ability of the cells to tolerate stress, DNA damage, and other injuries, and the response of the cells to radiation and to antineoplastic drugs. We are examining these alterations and studying their implication for the development and progression of solid tumors.

We are also working to develop therapeutic strategies which use our knowledge of the metabolic features of these cells improve to cancer therapy. In a collaborative project headed by Dr. Peter Glazer we are examining the effect of the adverse environments within solid tumors on gene expression, mutation rates, and DNA repair. The findings from this project suggest that the environmental stress developing within tumors early in their development may lead to the development of genomic instability and genetic heterogeneity in malignancies. One long-term project examines the metabolism, cytotoxicity, and therapeutic use of bioreductive alkylating agents which are selectively activated to toxic species by cells that are hypoxic.

Another series of studies is examining the role of nutrition and other lifestyle factors in the development, progression, and therapy of cancer. One series of studies examined the implications of subclinical vitamin A deficiency in determining the sensitivity of the lung to radiation injury and in altering the pattern of lung metastases. Another series of ongoing studies has examined the effects of the over-the-counter "alternative medicines" which are widely marketed to and used by many cancer patients. There have been very few rigorous studies examining the effects of these alternative medicines in model tumor systems or examining their interactions with conventional, effective cancer therapeutic agents to assess whether the alternative medicines may potentially be useful, ineffective, or harmful to patients being treated for cancer. Our projects address this problem.

Another project has examined the effects of PHY906, a state-of-the-art formulation of a traditional Chinese herbal medicine, on the intestinal injury induced by radiation, to assess whether PHY906 could be useful in reducing the toxic side effects of pelvic or abdominal radiotherapy.

Ethics of Peer Review: A Guide for Manuscript Reviewers. This web-based course was written for the NIH Office of Research Integrity and is freely available for use in courses on Ethical Issues in Research. The course consists of four elements:

1. Ethics of Peer Review: A Guide for Manuscript Reviewers. (http://medicine.yale.edu/therapeuticradiology/Images/Ethical_Issues_in_Peer_Review_tcm307-34211.pdf) A didactic reading, with references, designed to serve as a handout for participants in the course.

2. A PowerPoint presentation (http://medicine.yale.edu/therapeuticradiology/Images/Ethics_of_Peer_Review-Overview_tcm307-34212.ppt), which can be used by the teacher to cover the material discussed in the handout.

3. A PowerPoint presentation (http://medicine.yale.edu/therapeuticradiology/Images/Ethics_of_Peer_Review-Case_studies_tcm307-34213.ppt), presenting 12 case studies illustrating various ethical issues which might arise during the review of scientific manuscripts.

4. A Guide for the Discussion Leader (http://medicine.yale.edu/therapeuticradiology/Images/Ethics_of_Peer_Review_case_studies-guide_for_discussion_leader_tcm307-34214.pdf), which discusses each case and suggests points for discussion.

Selected Publications