Physician Investigator (Cl) General Internal Medicine, Mass General Research Institute

Assistant Professor of Medicine Harvard Medical School

Assistant Physician Medicine-General Internal Medicine, Massachusetts General Hospital

MD Albert Einstein College of Medicine 1994

antigens cd38; atopic dermatitis; chemokine ccl1; chemokine ccl8; chemokines cc; dermatitis; dermatitis atopic; epstein-barr virus infections; hla-dr antigens; receptors ccr8; receptors leukotriene b4; receptors purinergic p2; skin immunity; skin inflammation; th2 cells

Immune mechanisms operative at the skin barrier interface promote effective immunity to pathogens, while simultaneously promoting tolerance to innocuous environmental antigens and commensal microorganisms. Chronic inflammatory conditions of the skin arise when homeostatic tolerance mechanisms are subverted to facilitate inappropriate immune activation. 

Atopic dermatitis is the most common chronic inflammatory skin disorder. It has a complex poorly understood pathogenesis characterized by Th2 inflammation, skin eosinophilia, skin-barrier dysfunction, and a chronic relapsing course that causes much morbidity.

A major goal of my lab is to advance our understanding of the immune and inflammatory pathways that sustain chronic atopic dermatitis. We are specifically interested in deciphering how innate leukocytes such as IL-4-spectrum macrophages and Group 2 innate lymphoid cells fuel the chronic inflammation of atopic dermatitis.

Our research builds on our prior work in which we discovered that the human chemokine CCL18 and its functional mouse homolog are novel agonists of the CCR8 chemokine receptor. A key translational impetus for our mechanistic and in vivo studies is that, in multiple clinical trials, CCL18 is a top cutaneous biomarker of atopic dermatitis disease activity.

We are thus intent on defining the cellular, molecular and epigenetic mechanisms by which the innate immune system sustains inflammation and eosinophilia in chronic atopic dermatitis, and are pursuing this with mouse and human model systems.  

Another research focus, though in its early stages, is to elucidate mechanisms by which skin innate cells elicit effective adaptive immunity to Staphylococcus aureus.  This is an exciting research direction for both its scientific and translational impact.