Doctoral Defense - Jacob Reynolds

About the Event

The Department of Biomedical Engineering

Michigan State University

Ph.D. Dissertation Defense

July 8, 2025 at 10:00AM EST

1404 Interdisciplinary Science and Technology Building and Zoom

Contact Department or Advisor for Zoom Information

ABSTRACT

ADVANCING MICROPHYSIOLOGICAL SYSTEMS: DEVELOPMENT OF A SCALABLE PLATFORM FOR MODELING DEVELOPMENTAL AND REPRODUCTIVE TOXICITY

By: Jacob Reynolds

Advisor: Brian Johnson

Human birth defects including cleft lip and cleft palate (collectively orofacial clefts, OFCs) arise from complex, multifactorial causes, including poorly understood environmental exposures that can disrupt critical developmental pathways. As the number of chemicals in the environment continues to grow, there is an urgent need for innovative approaches to identify hazardous exposures and improve our understanding of the etiology of human birth defects. This dissertation presents multiple new approach methodologies (NAMs) designed to advance the study of OFCs. To contextualize current knowledge, identify regulatory data gaps, and align with an established regulatory framework, a network of adverse outcome pathways is developed, linking disruption of the Sonic Hedgehog (SHH) signaling pathway to OFC formation. In parallel, digital manufacturing techniques—such as computer numerical control (CNC) machining and laser welding—are explored and applied to fabricate custom microplate-based microphysiological models. These contributions to digital manufacturing aim to support the broader adoption of NAMs in developmental toxicity testing by providing a cost-effective, tractable method well suited to create custom throughput compatible models. These technologies are further leveraged to refine an in vitro model of orofacial development, enabling the study of SHH signaling in a format compatible with high-throughput screening. Additionally, a retrospective in silico analysis of existing in vivo and in vitro data is conducted to evaluate the feasibility of repurposing current assays and existing data for predicting developmental toxicity associated with OFCs. Collectively, this work introduces and integrates multiple NAMs to enhance the mechanistic understanding and predictive assessment of environmental contributors to OFC etiology.

Persons with disabilities have the right to request and receive reasonable accommodation. Please call the Department of Biomedical Engineering at 884-6976 at least one day prior to the seminar; requests received after this date will be met when possible.