A photo of William Zacharias.

William J. Zacharias, MD, PhD


  • Assistant Professor, UC Department of Pediatrics
  • UC Department of Internal Medicine

About

Biography

I study how the lung is built during development and how it regenerates after injuries like flu and pneumonia. We use a mix of techniques in the lab to study lung regeneration, lung development, epigenetics and stem cell biology.

In particular, I am enthusiastic about the potential to find better treatment for patients who have experienced an acute lung injury from an infection like flu or COVID. Currently, we have no therapies for people who end up on a ventilator with severe lung injury. Our only option is to try to prevent further damage by restricting the negative impacts of a ventilator. Our major goal is to understand lung regeneration well enough to develop drugs that could help patients on the ventilator get better faster and more often. In my research, I am working to understand the mechanisms that underlie regeneration in the lung, so my colleagues and I can find treatments that will promote proper regeneration during the recovery after severe lung injury.

In my clinical practice, I specialize in pulmonology and critical care medicine for adult patients. I provide my clinical services at UC Health, but I chose to work at the Cincinnati Children’s Hospital Medical Center due to the research environment at Cincinnati Children’s and because my research is focused on understanding mechanisms that impact both children’s and adults’ health. Cincinnati Children’s is a unique environment where I can serve both the adult and pediatric populations at the same time, understand the connection between children’s health and adult health and work to improve the care of children with lung diseases when they become adults. I became an intensive care unit (ICU) doctor because I truly appreciate the chance to assist the sickest patient, and I hope that both children and adults with severe lung injury will benefit from our work.

I have more than five years of experience in intensive care medicine, and more than ten years of experience as a research scientist. My research has been published in a multitude of respected journals, including Nature, Cell, Science Translation Medicine, American Journal of Respiratory Cell and Molecular Biology and Immunity.

MD: University of Michigan, Ann Arbor, MI, 2011.

PhD: University of Michigan, Ann Arbor, MI, 2011.

Residency: Hospital of the University of Pennsylvania, Philadelphia, PA.

Fellowship: Hospital of the University of Pennsylvania, Philadelphia, PA.

Certifications: Internal Medicine; Pulmonary Medicine; Critical Care Medicine.

Research Areas

Pulmonary Biology

Publications

Selected

PI3K signaling specifies proximal-distal fate by driving a developmental gene regulatory network in SOX9+ mouse lung progenitors. Khattar, D; Fernandes, S; Snowball, J; Guo, M; Gillen, MC; Jain, SS; Sinner, D; Zacharias, W; Swarr, DT. eLife. 2022; 11:e67954.

Selected

The balance between protective and pathogenic immune responses to pneumonia in the neonatal lung is enforced by gut microbiota. Stevens, J; Steinmeyer, S; Bonfield, M; Peterson, L; Wang, T; Gray, J; Lewkowich, I; Xu, Y; Du, Y; Guo, M; et al. Science Translational Medicine. 2022; 14:eabl3981.

Selected

A potent myeloid response is rapidly activated in the lungs of premature Rhesus macaques exposed to intra-uterine inflammation. Jackson, CM; Demmert, M; Mukherjee, S; Isaacs, T; Thompson, R; Chastain, C; Gray, J; Senthamaraikannan, P; Presicce, P; Chetal, K; et al. Mucosal Immunology. 2022; 15:730-744.

Selected

Inflammatory blockade prevents injury to the developing pulmonary gas exchange surface in preterm primates. Toth, A; Steinmeyer, S; Kannan, P; Gray, J; Jackson, CM; Mukherjee, S; Demmert, M; Sheak, JR; Benson, D; Kitzmiller, J; et al. Science Translational Medicine. 2022; 14:eabl8574.

Selected

The Cellular and Physiological Basis for Lung Repair and Regeneration: Past, Present, and Future. Basil, MC; Katzen, J; Engler, AE; Guo, M; Herriges, MJ; Kathiriya, JJ; Windmueller, R; Ysasi, AB; Zacharias, WJ; Chapman, HA; et al. Cell Stem Cell. 2020; 26:482-502.

Selected

In utero gene editing for monogenic lung disease. Alapati, D; Zacharias, WJ; Hartman, HA; Rossidis, AC; Stratigis, JD; Ahn, NJ; Coons, B; Zhou, S; Li, H; Singh, K; et al. Science Translational Medicine. 2019; 11:eaav8375.

Selected

Regeneration of the lung alveolus by an evolutionarily conserved epithelial progenitor. Zacharias, WJ; Frank, DB; Zepp, JA; Morley, MP; Alkhaleel, FA; Kong, J; Zhou, S; Cantu, E; Morrisey, EE. Nature. 2018; 555:251-255.

Selected

Hedgehog is an anti-inflammatory epithelial signal for the intestinal lamina propria. Zacharias, WJ; Li, X; Madison, BB; Kretovich, K; Kao, JY; Merchant, JL; Gumucio, DL. Gastroenterology. 2010; 138:2368-2377.e4.

Alveolar epithelial progenitor cells require Nkx2-1 to maintain progenitor-specific epigenomic state during lung homeostasis and regeneration. Toth, A; Kannan, P; Snowball, J; Kofron, M; Wayman, JA; Bridges, JP; Miraldi, ER; Swarr, D; Zacharias, WJ. Nature Communications. 2023; 14:8452.

Obesity amplifies influenza virus-driven disease severity in male and female mice. Alarcon, PC; Damen, MS M A; Ulanowicz, CJ; Sawada, K; Oates, JR; Toth, A; Wayland, JL; Chung, H; Stankiewicz, TE; Moreno-Fernandez, ME; et al. Mucosal Immunology. 2023; 16:843-858.

From the Blog

Anti-Inflammatories Show Promise for Treating a Late-Pregnancy Complication
Perinatal

Anti-Inflammatories Show Promise for Treating a Late-Pregnancy Complication

William J. Zacharias, MD, PhD3/30/2022

Fresh Perspective on Lung Repair Mechanisms
Heart and Lung

Fresh Perspective on Lung Repair Mechanisms

William J. Zacharias, MD, PhD1/7/2021