Legends of Allergy and Immunology – Dean D. Metcalfe
Cem Akin1, Knut Brockow2, Karin
Hartmann3, Gunnar P. Nilsson4
1. Division of Allergy and Clinical Immunology, Department of Medicine,
University of Michigan, Ann Arbor, Michigan, USA
2. Department of Dermatology and Allergy Biederstein, Technical
University of Munich, Faculty of Medicine, Munich, Germany
3. Division of Allergy, Department of Dermatology, University Hospital
Basel and University of Basel, and Department of Biomedicine, University
Hospital Basel and University of Basel, Basel, Switzerland
4. Division of Allergy and Immunology, Department of Medicine,
Karolinska Institutet and Karolinska University Hospital, Stockholm,
Sweden.
As many other physicians and researchers, we have had the great pleasure
to be fellows in the laboratory of Dean Metcalfe, the Laboratory of
Allergic Diseases, National Institute of Allergic and Infectious
Diseases (NIAID), NIH, Bethesda, USA (Figure 1). The open atmosphere,
research driven by curiosity, hypotheses originating from clinical
observations, and mutual trust and respect are the cornerstones of
Dean’s mentorship. Dean and his laboratory have made major contributions
on mast cell biology, from basic studies on the regulation of mast cell
development and functions, to clinical studies on mast cells in
diseases, such as systemic mastocytosis. After more than 50 years of
exploring human mast cells, Dean’s impact on what we know today about
these cells, their biology and how they affect diseases is outstanding
and unique.
It has been almost half a century since Dean started as a Clinical
Associate in Allergy and Immunology at the NIAID in 1974, a place he has
been loyal to ever since, except for the years 1977-1979 when he was a
fellow in Rheumatology and Immunology at Robert B. Brigham Hospital and
Harvard Medical School, Boston, MA, in the laboratory of the legendary
K. Frank Austen. This time was important for shaping his future career
and interest in the ingenious mast cell. Back at the NIH, he reunited
with Michael Kaliner at the Allergic Diseases Section and continued his
work on mast cells, while initiating the clinical protocols on
mastocytosis. In 1985, Dean was awarded his own section within NIAID
named after his beloved cell – “Mast Cell Biology Section”, a section
that he led until his retirement at the end of 2022. In 1994, he became
the Head of the Allergic Diseases Section, which in 1995, became the
Laboratory of Allergic Diseases, and where he remained Chief until 2017.
One of Dean’s many characteristics is his open mind to novel ideas and
to explore new fields. The 1990s started a new era in mast cell biology
with the identification of stem cell factor (SCF) and its receptor KIT
as being critical for growth and development of the mast cell lineage.
Dean’s lab was instrumental for early discoveries on human mast cell
development from CD34-positive progenitor cells1, and
the effect of SCF on these cells. Besides these seminal discoveries in
basic mast cell biology, Dean and his laboratory also have had a major
impact on our understanding on the role of mast cells in health and
disease including mast cell disorders, particularly mastocytosis. In
1991, Dean published a classification of mastocytosis that served as
major model for later classifications through today2.
He also was one of the key contributors for establishing and later
continuously advising the European Competence Network on Mastocytosis
(ECNM) until this date. Among his many fundamental discoveries in
mastocytosis is the identification of the KIT D816V mutation in
mastocytosis which became a diagnostic criterion and therapeutic target
for mastocytosis (Figure 2)3. These aberrant mast
cells were also demonstrated in a subset of patients with idiopathic
anaphylaxis4. More recent work from his laboratory
includes the description of exosomal transfer of mutated KIT to other
cells 5, and the identification of a new mast
cell-derived condition, i.e., vibratory urticaria 6.
Dean is a true legend in the field of allergy and mast cell biology, a
prolific writer, and an outstanding mentor to many well-established
scientists and clinicians. Most importantly, his dedication and research
has contributed to improving the lives of patients suffering from
mastocytosis and other mast cell-driven diseases.
Conflict of interest: The authors declare no relevant COI for this
article
Contribution: All authors contributed to the writing of the manuscript
and approved its submission.
ORCID:
Cem Akin: https://orcid.org/ 0000-0001-6301-4520
Knut Brockow: https://orcid.org/ 0000-0002-2775-3681
Karin Hartmann https://orcid.org/0000-0002-4595-8226
Gunnar Nilsson https://orcid.org/0000-0001-6795-5512
Correspondence: Gunnar Nilsson e-mail gunnar.p.nilsson@ki.se