Walker Inman [cv]
Master's Graduate Student, MechE

The focus of this project is to design and produce a high throughput bioreactor for liver tissue incubation.  (In static 2D cultures, liver cells rapidly loose the biosynthetic and drug-metabolizing functions found in vivo.  The perfused bioreactor enables incubation of liver tissue for longer periods of time and helps cells maintain their specific functions.)  This bioreactor will be designed with emphasis placed on cell viability, ease of use and high throughput testing, efficiency of cell usage, and the cost effectiveness of manufacturing on medium and large scales.  

Ben Cosgrove [cv]
Ph.D. Student, BE
Collaborators: Prof. Douglas Lauffenburger (BE/ChemE/Biology, MIT)

In this project, the cell signaling pathways that underlie apoptosis and proliferation signaling decisions in primary hepatocytes are analyzed using 2D and 3D culture systems. Initially, the signaling pathways and cell fates will be characterized for adenoviral sensitization of TNF-alpha induced programmed cell death. 3D hepatocyte cultures should provide a more in vivo-like system than epithelial cell lines for deducing the complex signaling interplay between adenovirus-mediated effects and TNF-alpha signaling. Signaling characterizations will be carried out using a variety of techniques including kinase assays to sample multiple cell signaling nodes, two-photon immunofluorescence microscopy, and multi-color flow cytometry.

Ajit Dash [cv]
Ph.D. Student, BE
Collaborators: Prof. Steven R. Tannenbaum (BE, MIT)

Developing a 3-D in-vitro co-culture model for prostate
cancer. Characterizing the system, and developing markers that help evaluate
efficacy and toxicity of anti-tumor therapy.

Shawdee Eshghi
Ph.D. Student, BE
Collaborators: Harvey Lodish (BE/Biology, MIT; Whitehead Institute)

Interactions between hematopoietic stem cells and extracellular matrix molecules are the least well characterized component of the hematopoietic stem cell niche in the bone marrow. We hypothesize that adhesion to matrix proteins is a dynamic property and that as cells progress to more differentiated phenotypes, they will express different cell surface adhesion molecules and adhere to different proteins with different strengths. These differences can be exploited to identify signaling pathways specific to stem cells and to develop substrates that specifically support stem cell adhesion and proliferation.

Albert Hwa [cv]
Ph.D. Student, BE
Collaborators: Prof. Donna Stolz (CBI, Univ. of Pittsburgh) Prof. Peter So (BE/MechE, MIT) Rebecca Fry (CSBi/CEHS, MIT)

Many liver physiological behaviors require cooperation of multiple cell types other than hepatocytes. My project aims to develop a protocol of incorporating non-parenchymal cells into our hepatocyte reactor cultures, and to provide structural and functional characterization of this co-culture system.

Gene delivery to hepatic capillary beds in tissue-engineered liver microreactors,
in comparison to standard cell culture. The objective is to develop an improved
in vitro methodology for studying barriers to in vivo gene delivery, including
extracellular transport and cellular uptake.

J. Ricardo Llamas Vidales [cv]
Ph.D. Student, BE

My thesis project involves the characterization of expression, activity, and
polarization of liver transporter proteins using primary hepatocyte cultured in
the 3-D bioreactor developed here at BPEC. The project will include analysis of
gene expression (with the use of q-RT-PCR), protein expression (using Western
Blots), and imaging of the transporters and their substrates for polarization
and activity assessment. The specific aims of this project will be:
characterization of gene and protein expression of transporter proteins in 3-D
bioreactor hepatocyte cultures; imaging of transporter proteins for
polarization assessment and activity; assessment of transport, metabolism, and
possible toxic effects of still to be determined well-characterized
pharmaceutical compound for comparison with in vivo properties.

Corey Moore [cv]
Ph.D. Student, ChemE
Collaborators: Prof William Deen (BE, ChemE; MIT), Prof. John Essigmann (BE, CEHS; MIT), Prof. Leona Samson (BE, CEHS; MIT)

In vitro toxicology is a field viewed with great potential for mediating the economic burden on the pharmaceutical industry for cheap, high-throughput alternatives to in vivo drug toxicity testing. Growth within this field is currently stifled by the overall lack of correlation between in vivo and in vitro toxicity models. My goal is to utilize the liver chip and some of its improved in vitro-in vivo correlations, e.g. phase I and II drug-metabolizing enzymes, to provide a new tool for in vitro toxicology studies, using the model compound aflatoxin B1.

Joe Shuga
Ph.D. Student, ChemE
Collaborators: Harvey Lodish (BE/Biology, MIT; Prof. Leona Samson (BE, CEHS; MIT)

The aims of my project are (a) to develop an in vitro genotoxicity assay using erythropoietic culture and (b) to use this culture system, and genetic perturbation, to study the dynamics of DNA damage and repair. Currently, my experiments focus on optimizing the culture conditions that will be employed in the later stages of my thesis work.

Nate Tedford [cv]
Ph.D. Student, BE
Collaborators: Prof. Douglas Lauffenburger (BE/ChemE/Biology, MIT)

Non-viral gene delivery studies in primary liver cells and tissue-engineered liver bioreactors. Quantitative studies of vector/plasmid trafficking and expression of gene payload for the development of a mathematical model describing gene delivery in a three-dimensional tissue construct. Further analysis and optimization of model parameters could provide insight for increased non-viral transfection efficiency and development of novel polymer carriers.

Anand Sivaraman
Postdoctoral Associate, ChemE

Recent reports indicate that it takes nearly $800 million dollars and 10-15 years of development time to bring a drug to market. During the drug development process, in vitro systems are used in the pharmaceutical industry to assess drug uptake and metabolism, enzyme induction, drug interactions affecting metabolism and hepatotoxicity. Nearly 90% of the lead candidates identified by current in vitro screens fail to become drugs. Among lead compounds that progress to Phase I clinical trials, more than 50% fail due to unforeseen human liver toxicity and bioavailability issues, resulting in an unmet need for a more predictive in vitro screen for pharmacological applications. This can help fail compounds much earlier in the drug discovery process. In collaboration with Pfizer, we are evaluating a scalable microreactor system that fosters development of 3D-perfused micro-tissue units, as a model for drug metabolism, transport and toxicity, using a broad spectrum of gene expression, protein expression and biochemical activity metrics. Additionally, I am interested in understanding biophysical and biochemical cues that might affect the transcriptional regulation of the differentiated function of hepatocytes.

Karel Domansky [publications] [images]
Research Scientist, BE

Design and fabrication of microfluidic devices for cell self-assembly and 3D tissue formation. Development of perfused microbioreactor arrays in the multi-well microplate format for high-throughput screening using high-performance 3D micro-tissues.

Jim Serdy
Staff Scientist, BE
Collaborators: Prof. Linda Griffith (ME/ChemE/Biology, MIT); Prof. Ely Sachs (ME/Lab for Mfg. & Productivity, MIT)

Syntheses and characterizations of graft copolymers for biomedical applications. Surface modification of biomaterials to regulate protein and cell recognition. Current study: Synthesis of biodegradable comb-like copolymer having PEO side chain and polymethylmethacrylate having polydimethylsiloxane side chain.

Albert Weng
Visiting scientist (from Industrial Technology Research Institute, Taiwan)
Collaborators: Prof. Frank Gertler (Biology, MIT)

Establish a method for either reversing activation or
maintaining quiescent status of hepatic stellate cells

Tommy Wong
Visiting Scientist (US Army Research Laboratory)
Institute for Soldier Nanotechnology

Engineering cellular nano-dynamics in the development of a physiomic LiverChip sensor for infectious viruses. Primary goals of the project are: to improve the in vivo-like characteristics of the liver tissue grown in the LiverChip by refining the metabolic parameters, to develop models of signaling network involved in viral infection of liver cells, and to investigate the use of appropriate nano-tools to help detect cellular response signals.