Research

The Bunick Lab applies biochemistry, structural biology (X-ray crystallography, Cryo-EM), and cell biology techniques to investigate biological processes of human skin. As a board-certified and practicing dermatologist, Dr. Bunick tackles scientific questions that can improve clinical care of patients. We have ongoing, cutting-edge translational research in the following areas:

Molecular mechanisms of intermediate filament (IF) assembly

IFs, which include keratins, are fundamental filamentous assemblies that comprise the cellular cytoskeleton, regulate cellular signaling, and form an essential component of the human skin barrier. The Bunick Lab discovered a novel assembly mechanism shared among IFs, and we continue to investigate its function regulating IFs, including in dermatologic and oncology diseases.

Molecular mechanisms of human skin barrier integrity

Keratin IFs regulate the human skin barrier through two key processes: filaggrin aggregation of keratins to form an impermeable proteinaceous barrier in the stratum corneum, and keratins binding desmoplakin at desmosomes to enhance cell-cell adhesion in the epidermis. The Bunick Lab has determined the only filaggrin structure and 75% of all keratin structures to date, and investigates the mechanisms of keratin assemblies in skin barrier function.

Two recent proteins studied are human profilaggrin and the keratin 1/10 complex because of their importance to skin barrier integrity and association with clinically relevant skin diseases. NIH/NIAMS estimates that up to 90 million Americans suffer from some form of atopic dermatitis. Atopic dermatitis and other forms of severely dry skin, such as ichthyosis vulgaris, are associated with defects or mutations in profilaggrin and its processed fragment, filaggrin. Similarly, mutations mapped to keratins 1 or 10 are linked to several clinical disorders of keratinization (keratinopathies). Work on these proteins led to a 2.2 Å resolution crystal structure of the profilaggrin S100 calcium-binding domain and several 2.0 Å to 3.3 Å resolution crystal structures of complexes between the 1B and 2B helices of K1 and K10.

Acne vulgaris pathogenesis, antibiotic resistance, and the microbiome

Building from our structure of the acne drug sarecycline bound to the 70S ribosome, we investigate how acne drugs function in their pathogenic target, Cutibacterium acnes, and how that impacts clinical efficacy and antibiotic resistance. One goal is to discover science that can alleviate antibiotic resistance and promote antibiotic stewardship in the clinic. We also investigate how C. acnes regulates the microbiome niche of the pilosebaceous unit.

Molecular mechanisms of skin therapeutics in patient care

The Bunick Lab works to understand the biochemical mechanisms of dermatologic drugs. Recent work on the structural mechanism of the acne vulgaris drug sarecycline was published in PNAS and Nucleic Acids Research, and there are ongoing drug development projects in the lab in acne vulgaris, psoriasis, atopic dermatitis, cancer, and more.