Castells Laboratory

Mariana Castells, MD, PhD 

As a clinician, I serve as an attending at Brigham and Women’s Hospital for two to three months a year and attend four half-day clinics per week at the BWPO Allergy Service. I am in charge of the Adverse Drug Reaction and Desensitization Program for inpatients and outpatients at Brigham and Women’s Hospital and perform evaluation of about 200 patients per year with drug adverse reactions, providing diagnostic and treatment options, including high risk desensitization procedures. I am the PI of various clinical trials – IgA deficiency on patients receiving IVIG, leukotriene measurement in patients with mastocytosis, bone loss in patients with mastocytosis, and MATA grass on immunotherapy for grass pollen allergies.

As a teacher, I give formal and informal rounds daily while attending and four times a week while on the outpatient duty. I teach Brigham and Women’s Hospital and Beth Israel Deaconess Medical Center residents, students from Harvard Medical School, and fellows in training from the Allergy and Clinical Immunology training programs at Brigham and Women’s Hospital, Children’s Hospital, and Massachusetts General Hospital. I participate in the PD (Patient Doctor) 2 Preceptor-Student Project and formally precept two students per year in weekly 2-hour sessions. I am a mentor for the Career Development Project at the BWH and direct one mentee for three years. In the last ten years, I have directed an Introductory Course for Allergy Fellows, held at the Brigham and Women’s Hospital. The course provides an immersion in basic and clinical allergy and immunology with 25-30 core curriculum topics. The lectures are given by faculty from Brigham and Women’s Hospital including myself, Beth Israel Deaconess Medical Center, Tufts, Massachusetts General Hospital and The Children’s Hospital. Attendance at the Course has included all the Allergy Fellows in Training for the Partners hospitals and other major hospitals in Boston. Written evaluations provided yearly by participants indicate outstanding reviews.

As a researcher, I have my own research laboratory and work on mast cell inhibitory mechanisms. I cloned the gene for LilRB4, which belongs to a family of inhibitory receptors expressed in mast cells, macrophages and NK cells. I elucidated one ligand for LilRB4, the blood vessel integrin avb3 and demonstrated that the interaction between LilRB4 and avb3 is functional, in that avb3 inhibits the antigen-induced bone marrow-derived mast cell activation and release of mediators. I have now turned my efforts to the study of an inhibitory mast cell-dependent process that leads to temporary cell desensitization and unresponsiveness to antigen. I created a cellular model for mast cell IgE-dependent temporary desensitization and provided the first molecular target of this phenomenon, the signal transduction and activator of transcription factor 6 (STAT6). The model has now provided evidence for inhibition of calcium flux during desensitization and blocking the internalization of the FceR1 receptor.

Bench Research

Project: In-vitro mouse mast cell model of antigen desensitization 

Clinical Research 

Project: IgA 
Project: Leukotrienes in Patients with Mastocytosis 
Project: MATA Grass Study
Project: Bone Loss in Patients with Mastocytosis