Seminar: Christopher Madl, Ph.D. Stanford University

Speaker: Christopher M. Madl
Affiliation: Stanford University

CBE Seminar Series: Winter 2020

Engineering the Cellular Microenvironment to Study Development and Disease

Dynamic maintenance of the extracellular matrix (ECM) is crucial to proper tissue homeostasis. When the healthy wound healing response goes awry, aberrant ECM deposition leads to fibrosis, causing reduced tissue functionality and, in some cases, organ failure. Despite the critical role of ECM remodeling in regeneration and disease, present in vitro models are unable to adequately capture the dynamic and complex changes in ECM mechanics and biochemistry that occur in vivo. In my talk, I will describe a multifaceted strategy to elucidate unappreciated mechanisms behind cell-ECM interactions impacting homeostasis and disease, drawing on protein engineering, bioorthogonal chemistries, and stem cell biology. I will focus on work completed during my Ph.D., using engineered materials to identify critical ECM properties that are required for neural stem cell expansion. My work leveraged the well-defined properties of recombinant elastin-like proteins to selectively tune matrix stiffness and degradability independent of hydrogel microstructure, swelling, nutrient transport, and cell-adhesive ligand concentration. This led to the unexpected observation that matrix degradation and remodeling are required for neural stem cells to maintain their stem cell phenotype and to subsequently differentiate into mature, functional neurons. I will conclude with a brief overview of my postdoctoral research, characterizing the interplay between extrinsic mechanical changes in the tissue microenvironment and intrinsic cellular defects in aging and disease. As part of this project, I developed a novel hydrogel system that enables real-time tracking of individual cells as matrix stiffness is altered by user-selected, minimally invasive stimuli.  Together, these research projects highlight the power of engineered platforms in elucidating novel biological mechanisms implicated in development, disease, and aging.

Biography

Christopher Madl is a Life Sciences Research Foundation (LSRF) Postdoctoral Fellow in the laboratory of Prof. Helen Blau at Stanford University, studying how changes in the aging tissue microenvironment impair muscle stem cell function.  He completed his B.A. in Engineering Sciences and Chemistry and his M.S. in Engineering Sciences at Harvard University, working with Prof. David Mooney.  Christopher completed his Ph.D. in Bioengineering at Stanford University, working with Prof. Sarah Heilshorn to design novel materials for neural stem cell expansion and to incorporate bioorthogonal chemical functionalities into engineered protein biomaterials in a site-selective manner.  His research employs materials chemistry, protein engineering, and stem cell biology approaches to develop improved in vitro models of development and disease that capture the dynamic complexity of native cell-extracellular matrix interactions.

 

Date/Time:
Date(s) - Jan 17, 2020
10:00 am - 11:00 am

Location:
Boelter Hall 3400
420 Westwood Plaza Los Angeles CA 90095