NIH Training Program

Stem Cell Engineering represents the convergence of the biological and physical sciences, engineering, and ethics and law. Our interdisciplinary Stem Cell Biological Engineering program funded by the National Institutes of Health was established in 2011 to formally organize new training opportunities in stem cell biological engineering, while dissolving traditional academic barriers to interdisciplinary graduate science education. Fellows are supported for 24 months, in the 2nd and 3rd years of their doctoral studies.

This program provides pre-doctoral training opportunities in the biology of stem cells and its application to the enhancement of human health. Program participants work at the interface of biology and engineering, preparing them to be leaders in academia and industry. A three-month industrial internship experience is a key facet of this program.

Program Leadership

Dr. David Schaffer
Program Director
Professor
Chemical and Biomolecular Engineering, and
Helen Wills Neuroscience Institute
Director, Berkeley Stem Cell Center
  Dr. Kevin Healy
Program Director
Professor
Bioengineering, and
Materials Science and Engineering

 

2018-19 Stem Cell Biological Engineering Fellows


Meagan Esbin

A critical and fundamental step in stem cell viability and differentiation is the ability for genes to be rapidly modulated in response to the expression of transcription factors such as Sox2 or Oct4. The binding of these transcription factors, often many kilobases away from their target promoter, must be reliably communicated to the promoter to activate gene expression. In metazoans, this role is coordinated by two transcriptional co-activators, TFIID and SAGA. However, these factors have rarely been studied inside live cells at endogenous levels and their dynamics and roles during transcriptional activation remain poorly characterized. By implementing a toolkit of cutting-edge imaging techniques, we can finally begin to visualize these protein complexes and characterize their previously elusive transcriptional roles and dynamics in live cells.

Alec Heckert

Transcription is regulated by stochastic binding of transcription factors (TFs) to regulatory DNA sequences. While decades of in vitro biochemistry have afforded a detailed view of the interaction between individual TFs and DNA, our knowledge of other factors influencing binding, including competition between TFs in the crowded nuclear milieu, remains at an early stage. I apply recent advances in microscopies including photoactivated localization microscopy (PALM), single particle tracking, and fluorescence correlation spectroscopy (FCS) to understand the DNA binding dynamics of type II nuclear receptors, a class of ligand-activated TFs that require heterodimerization with a common factor, the retinoid X receptor (RXR), in order to bind DNA. My work addresses how competition for RXR influences type II NR binding dynamics. I am especially interested in how perturbations such as the concentrations of competitors, including fusion proteins that occur in acute promyelocytic leukemia, change the ability of these factors to interact with chromatin and activate transcription in response to their respective ligands.

Juan Hurtado

In order to elucidate the path between stem cells and the diffrerentiation of complex tissues, considerable work has focused on mapping cells' developmental relationships to each other, otherwise known as lineage tracing. State-of-the-art lineage tracing methods use genomically-integrated DNA barcodes that accumulate random mutations over time to bioinformatically construct lineage trees by sequencing populations of cells. Unfavorably, these methods use Cas9 to generate indels within DNA barcodes, eventually destroying Cas9's target site, halting mutagenesis, and limiting the number of generations over which lineages can be mapped. I aim to use a site-directed mutagenesis tool known as EvolvR to exclusively generate substitution mutations rather than indels within DNA barcodes, facilitating long-term lineage tracing in stem cell models of human organogenesis and disease.

Eric Qiao

Stem cells sense and respond to the mechanical properties of their environments. For example, neural stem cells can be influenced to differentiate towards one fate or another solely by altering the stiffness of their culture environment. Studies suggest that stem cells exhibit mechanotransduction of viscoelastic cues as well as stiffness cues. I am using neural stem cells and engineered hydrogels with tunable stress-relaxation properties to study how stem cells integrate viscoelastic cues, with the goal of developing materials capable of controlling stem cell fate in culture.

Caylin VanHook

Stem cell therapies offer strong therapeutic promise for regenerative medicine; however, continuous monitoring of differentiation, migration and proliferation of stem cells in vivo remains difficult. Magnetic Particle Imaging (MPI), a new imaging modality, is especially suited for long-term in vivo cell tracking: its iron-oxide tracers have an ~80-day half-life, it is both linear and quantitative, and it has a current sensitivity of 200 cells per voxel. We have previously demonstrated that MPI can be used for long-term tracking of the biodistribution of stem cells. My project is to develop MPI techniques for sensing the viability of stem cells; this is essential for classifying successfully differentiated stem cells from those phagocytosed by macrophages.

Andrew Widjaja

Neurodegenerative diseases become more prevalent with age and are affected by mitochondrial dysfunction resulting from mitochondrial DNA mutations and oxidative stress. Studies suggest that the accumulation of reactive oxygen species produced by mitochondria of mature cell populations results in cognitive decline that accompanies aging. I am using neural stem cells to investigate how certain stress response mechanisms may worsen with age, and whether such declines may be reversed.

 

Program Information