PiN Faculty Member - Karl Koehler, PhD

Karl Koehler, PhD

Assistant Professor

3 Blackfan Circle
CLS 03002
Boston, MA 02115
Tel: 617-919-6030
Email: karl.koehler@childrens.harvard.edu
Lab Members: Modeling sensory organ development and regeneration
Visit my lab page here.



The Koehler Lab focuses on understanding the development and regeneration of sensory organs. Our primary goal is to elucidate how cells from various layers of the developing embryo converge to form a functioning sense organ. We believe such basic developmental knowledge can provide mechanistic insights needed to design drug, gene, or cell therapies to restore sensory function in patients. We have two major projects focused on the inner ear and skin. As the foundation of these projects, we have pioneered several 3D culture models using pluripotent stem cells.

In previous work, we defined methods for generating mouse and human inner ear sensory tissue, including hair cells and neurons, using step-wise differentiation of stem cells in an organoid culture (Koehler et al. 2013 and 2017). We were the first to show hair cells could be derived from stem cells in 3D culture that look and function similarly to hair cells in the body. This approach holds considerable promise as a drug discovery tool and pre-clinical testing model for hearing loss and balance disorder therapies. In ongoing projects, we use a variety of techniques to investigate inner ear disease processes and regeneration, including gene editing, single-cell genomics, and functional imaging.

In recent work, we have shown how our inner ear organoid model can be modified to produce another sensory tissue: the skin. We can now produce skin organoids containing epidermis, dermis, and hair follicles from mouse and human stem cells (Lee et al. 2018 and 2020). These were the first demonstrations that hair-bearing skin could be derived entirely from stem cells. Notably, we have found that human skin organoids arise with sensory neurons, similar to neurons in the developing head and neck, and can reconstitute planar skin when implanted in a mouse model. A major goal of our future research will be to understand the mechanisms controlling the composition and regional identity of developing skin organoids. A special emphasis will be to build functional somatosensory neural networks in skin organoids. These efforts could provide insight into human development and lead to drugs or cell therapies for a wide range of skin-related diseases and peripheral neuropathies.



Last Update: 9/16/2020



Publications

For a complete listing of publications click here.

 


 

1. Koehler KR, Mikosz AM, Molosh AI, Patel D, Hashino E. Generation of inner ear sensory epithelia in a defined 3D culture. Nature, 2013, June; 500(7461):217-221.
2. Koehler KR, Nie J, Longworth-Mills E, Liu XP, Lee J, Holt JR, Hashino E, Generation of inner ear organoids with functional hair cells from human pluripotent stem cells. Nature Biotechnology, 2017, September; 480:547.
3. Lee J, Boescke R, Tang PC, Hartman BH, Heller S, Koehler KR. Hair follicle development in mouse pluripotent stem cell-derived skin organoids. Cell Reports, 2018, January; 22(1), 242-254.
4. Lee J, Rabbani C, Gao H, Steinhart M, Woodruff BW, Pflum Z, Kim A, Heller S, Liu Y, Shipchandler TZ, Koehler KR. Hair-bearing human skin generated entirely from pluripotent stem cells. Nature, 2020, (in press).



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