After completing his training in Hematology and Oncology, Dr. Castillo stayed on as a faculty member at the Brown University Medical School, providing clinical care and devoted to clinical research and teaching. His research focused on factors associated with increased risk of developing blood cancers. Using meta-analytical methods, he identified smoking as a risk factor for Hodgkin lymphoma, transfusions for chronic lymphocytic leukemia, and an increased risk of blood cancers in individuals with diabetes. He has also used large databases such as SEER and Medicare to study rare lymphomas such as Burkitt, marginal zone, lymphoplasmacytic lymphoma and HIV-associated lymphomas. His work has been published in the Journal of Clinical Oncology, Blood, Cancer, and the American Journal of Hematology.

Since 2013, he has been the clinical leader at the Bing Center for Waldenstrom Macroglobulinemia (WM). WM is a rare disease with approximately 1,000 new cases per year in the US. His epidemiological research showed that patients with WM have longer survival than previously thought with higher risk of developing second cancers, however. The Bing Center is the largest research center in the world focused on WM. Besides providing clinical care for over 1,000 patients per year, Dr. Castillo has secured research grants to study novel non-chemotherapeutic agents for the treatment of WM. At the Bing Center Clinic, he is the principal physician providing care with the help of two nurse practitioners. Based on the center's research, ibrutinib was the first drug ever approved by the FDA for the treatment of WM. Dr. Castillo is currently running groundbreaking clinical trials evaluating novel agents, such as venetoclax, daratumumab, ulocuplumab and BGB-3111. Dr. Castillo the objective of creating a national clinical trials group for WM to facilitate the execution of randomized studies focused on improving the treatment of WM. In addition, Dr. Castillo has been invited to serve as a member of a number of national and international committees such as the National Comprehensive Cancer Network and the International Workshop for WM. As part of these committees, Dr. Castillo has helped formulating diagnosis and therapeutic guidelines for patients with WM. Due to the large patient population, he has studied rare clinical presentations in WM patients, including rituximab intolerance, pleural effusions and meningeal involvement by WM Bing-Neel syndrome), and hyperviscosity. His research has been published in the New England Journal of Medicine, Lancet Oncology, Blood, Leukemia and the British Journal of Haematology.

Teaching is one of Dr. Castillo's favorite activities. Throughout the year, he has a busy schedule of invited lectures within the US and abroad, especially Europe and Latin America. These teaching sessions are not only oriented to physicians, as a substantial proportion of these are directed to patients’ support groups. He works closely with the International WM Foundation and the Lymphoma Research Foundation to provide education to patients via in-person presentations, teleconferences and printed informational material. He also enjoys mentoring colleagues, fellows, residents and medical students at HMS and outside. His mentees have presented their research at national and international meetings and published their findings in high-impact journals. His is proud to see that his mentees continue doing meaningful research, and he is always happy to help with study design, statistical support or constructive criticism of protocols and manuscripts.

Dr. Castillo is ABIM certified in hematology.