Laboratory of Nicholas Theodosakis, MD, PhD

Overview

The Theodosakis Lab studies the role of protein misfolding and aggregation in skin aging and disease. Using neurodegenerative disorders such as Parkinson's disease as a model, we study how UV-induced accumulation of damaged melanosomal proteins, including melanocyte-derived alpha-synuclein, leads to long-term dyspigmentation and skin atrophy, as well as the incidence and behavior of melanoma.

Research Projects

Chronic Proteinopathy as a Contributor to Photoaging

Aggregation of amyloid-generating proteins such as tau and alpha-synuclein in the brain contributes to degenerative diseases such as Alzheimer's and Parkinson's disease through a number of cellular and tissue-level mechanisms. Our previous work has identified UV as a potent trigger for aggregation of alpha-synuclein made by cells in the skin. Using previous work in neuroscience as a roadmap, our lab seeks to understand how misfolding and aggregation of synuclein family members and other proteins contributes to skin aging and chronic UV damage.

The Role of Protein Aggregation in Cutaneous Immune Regulation

Microglia, resident phagocytic cells of the innate immune system in the brain, are thought to contribute to progression of neurodegenerative disorders by driving inflammation in response to pathologic protein aggregates. Our lab's previous work has demonstrated that synuclein aggregation in the skin alters skin-resident macrophage dynamics, contributing to a range of pigmentary and age-related skin disorders. We are currently studying the role misfolded protein may play in autoimmune diseases of the skin, as well as tumor surveillance.

Exploring Novel Drivers of Tanning and Pigmentary Dysfunction

Chronic hyperpigmentation (dark spots) caused by diseases such as melasma, exposure to certain drugs, or secondary to inflammatory triggers such as acne or eczema are some of the most common problems in dermatology, affecting up to 50% of adults globally at some point in their lives. Current treatments are frequently ineffective, and require long periods of consistent application to generate results. Moreover, relapse is common, with many forms of hyperpigmentation intermittently recurring throughout patients' lifetimes. In order to better treat and prevent chronic hyperpigmentation, our lab studies how factors such as UV, inflammation, aging, and genetics interact to cause unwanted melanin production by pigment cells in the skin.

Research Team

Nicholas Theodosakis, MD, PhD
Principal Investigator

Nicholas Theodosakis, MD, PhD is an Instructor in Dermatology at Harvard Medical School and a board-certified dermatologist at the Massachusetts General Hospital. Dr. Theodosakis attended the University of Virginia as an Echols Scholar, graduating Phi Beta Kappa with Distinction with degrees in Chemistry and Psychology. He then completed his MD and his PhD degree at the Yale School of Medicine, where he received the Medical Scientist Training Program Alumni Graduation Award, as well as multiple young investigator grants and awards from the Joanna M. Nicolay Melanoma Foundation, the American Skin Association, the Dermatology Foundation, and the NCI, and co-authored over 20 original publications. Dr. Theodosakis completed dermatology residency at the Harvard Combined Dermatology Residency Program and a postdoctoral fellowship at MGH with Dr. David Fisher studying the role of protein misfolding in pigmentary disease and skin aging. Dr. Theodosakis' research and clinical interests focus on disorders of pigmentation, pigment cell biology, and the role of misfolded protein stress in melanoma and anti-melanocyte autoimmune diseases such as vitiligo and alopecia areata.

Remi Joseph
Medical Student

Haoxin Hu
Research Technician

Serena Fazal
Medical Student

Talya Cohen-Neamie
Medical Student

Publications

View publications

Open Positions

We routinely hire undergraduate, post-bac, and medical students for paid research positions. If you are interested in applying for a position, please email Dr. Theodosakis with your CV and a brief (one paragraph) personal statement.

email: ntheodosakis@mgh.harvard.edu