2015 Early Career Investigator Grant Recipient — Cesar Castro, MD

Project Summary

Studies depict ovarian cancers as highly heterogeneous and dynamic entities where uniform treatment strategies do not always apply. Not surprisingly, use of patient specimens obtained at the time of initial surgery does not always predict response to targeted therapies administered later during cancer recurrence. In response, clinical trials are increasingly analyzing pre- and post-treatment initiation biopsies. Conventional methods of analyses limit the depth and breadth of information attained from these often scant biopsies, especially at the protein level. An even broader analysis involving all three fundamental parameters – DNA, RNA, and protein – and scant amounts of specimen collected at key time periods could reveal key biological interrelationships and treatment response.

This work seeks to advance and leverage novel nanotechnologies, with its minimal sample amount needs, to generate broader insights into ovarian cancer treatment effects. We developed a technology that can simultaneously analyze >100 proteins within small needle biopsies (down to a single cell). By circumventing the risks of more invasive biopsies, serial testing becomes feasible. The new method exploits DNA barcodes for antibody (i.e. protein) sensing. Here, each antibody of interest is linked to a unique strand of DNA, 70 letters (A,C,G, or T) long. Each unique strand, in essence, represents a barcode; the types of barcode visualized reflects the protein diversity seen within a biopsy and the amount reflects their quantity. Compared to conventional methods, the new DNA-barcoding technology: i) detects hundreds of markers simultaneously, ii) works well in single cells or small numbers of cells, iii) does not destroy valuable samples, iv) is fast and cost-effective and v) can be combined with other genetic (DNA and RNA) analysis techniques to offer true integrated analyses.

Bio

Dr. Castro is Director of the Cancer Program at the Massachusetts General Hospital (MGH) Center for Systems Biology, Instructor in Medicine at Harvard Medical School, and Attending Physician at the MGH Cancer Center. As a Regent’s Scholar, Dr. Castro attended the University of California – Berkeley leading to receipt of both bachelor’s and master’s degrees. He attained his medical degree from the University of California – San Francisco where he also pursued Internal Medicine residency training. Dr. Castro completed a combined medical oncology fellowship between the MGH and the Dana-Farber Cancer Institute in Boston. During this period, he also received a master’s in medical sciences from Harvard Medical School. Dr. Castro is a translational gynecologic oncologist with experience developing and harnessing nanotechnology and molecular imaging platforms for ovarian cancer tumor detection and serial analyses. He currently focuses on advancing novel profiling technologies to generate true integrated readouts of DNA, RNA, and protein within scant ovarian cancer specimens down to the single cell level. He has served as Chair of the In Vitro Diagnostics Working Group within the NCI Alliance for Nanotechnology in Cancer. Dr. Castro’s research has included funding by the National Institutes of Health, Department of Defense, and the MGH Executive Committee on Research.