Center for Clinical and Translational Science

Dr. Michelle Lowes, a graduate of the Clinical Scholars Program and an Assistant Professor of Clinical Investigation in the Laboratory for Investigative Dermatology, recently received a 3 year independent investigator RO1 grant from the NIAMS branch of the National Institutes of Health entitled ‘Origin and Function of Inflammatory Dendritic Cells in Psoriasis.’ Dr. Lowes is currently a member of the Rockefeller Early Phase Physician Scientists (REPPS) (http://repps.rockefeller.edu/) and an alumnus of the Clinical Scholars Program.

Dr. Lowes’s broad research area is skin immunology, with a “dendritic cell-centric” focus. The classic functions of dendritic cells (DCs) are to sense “danger”, migrate to local lymph nodes, and present antigen for T cell activation and adaptive immunity. The skin disease psoriasis is an ideal model to study DCs because they accumulate in psoriatic inflammatory lesions, and they are readily accessible in skin samples of involved areas making it possible to study the impact of novel agents that modulate disease activity.  Dr. Lowes has developed and refined techniques to phenotype, localize, isolate, and study both DC and T cells from healthy and diseased human skin. The lab first described a population of “inflammatory” myeloid DCs, which are as abundant as T cells in psoriasis skin lesions. These inflammatory DCs were reduced with every treatment for psoriasis examined, but not decreased if the treatment did not improve the psoriasis.

The central hypothesis of Dr. Lowes’s is that circulating CD16+ monocytes are recruited into the skin and become activated by the local environment to develop into inflammatory DCs. These monocytes migrate into the skin due to the chemotactic gradient of fractalkine. There are many examples of monocytes becoming inflammatory DCs and macrophages in murine models, including colitis, infections, atherosclerosis, and myocarditis.

Although much less in known in humans, circulating CD16+ monocytes are elevated in psoriasis and other conditions, including sepsis, rheumatoid arthritis, HIV infection, and coronary artery disease. The experiments in this project will directly enhance our knowledge of monocyte populations and the DCs and macrophages they give rise to, and support the development of new treatment protocols to target these cells in psoriasis and other autoimmune diseases.

Dr. Lowes obtained her medical degree from the University of New South Wales, Australia, and her PhD from the University of Sydney, Australia. She is a board-certified Dermatologist in Australia. Dr. Lowes came to Rockefeller University in 2001 when she joined the Clinical Scholars Program. She has been an NIH-funded investigator since 2006 and has also received funding from The Doris Duke Foundation, The Dana Foundation, and the Rockefeller University Clinical and Translational Science Award (CTSA).