BBS Faculty Member - Karl Koehler

Karl Koehler

Assistant Professor of Otolaryngology Head and Neck Surgery

Boston Children's Hospital
Center for Life Sciences Building
3 Blackfan Circle
Boston, MA 02115
Tel: 617-919-6030
Email: karl.koehler@childrens.harvard.edu
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 first-of-its-kind cell culture models of the human inner ear and skin using 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 (Liu et al. 2016). This approach holds considerable promise as a drug discovery tool and preclinical testing model for hearing loss and balance disorder therapies. We have ongoing collaborative projects with laboratories in the US and abroad to use this model to study inner ear disease processes and regeneration.

We recently discovered our organoid method could be modified to generate skin tissue. In 2018, we published a manuscript demonstrating how to generate skin organoids containing epidermis, dermis, and hair follicles from mouse stem cells (Lee et al. 2018). This was the first documentation that hair-bearing skin could be derived entirely from stem cells. In follow-up work, we have shown that human hair-bearing skin organoids can be derived from pluripotent stem cells (Lee et al. Nature, in press). 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. These efforts could provide novel insight into human cranial development and lead to drugs or cell therapies for tissue reconstruction and wound healing.



Last Update: 8/5/2020



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 B, Pflum Z, Kim A, Heller S, Liu Y, Shipchandler TZ, Koehler KR†*. Hair-bearing human skin generated entirely from pluripotent stem cells. Nature, 2020, 582(7812), 399-404.

*Corresponding author(s)
†Senior author(s)



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