Josephine Allen
Biomedical Engineering Department/IBiS Program
B.S. 2000 - Biology, California State Northridge 
M.S. 2002 - Biology, California State Northridge
PhD Thesis advisor: Guillermo Ameer

Doctoral Research Project
The characterization or understanding of cellular interactions with a biomaterial surface is important to the development of novel biomaterials and bioengineered tissues. The overall goal of Josy's research is to characterize cellular processes on a biomaterial in a non perturbing, real time, and quantitative manner, thereby enabling the monitoring of cell phenomics within bioengineered tissues. Specifically, we seek to describe the interactions between cells and newly developed biodegradable elastomeric biomaterials using a technique referred to as 4-D elastic light-scattering fingerprinting (4D-ELF). This study explores whether 4D-ELF, which was recently developed for the non-perturbing assessment of the morphology of living cells for cancer diagnosis, can be used as a tool to monitor cell differentiation. The spectral analysis of light scattered by living tissues can potentially provide information about the size scale of internal structures within the cell. We therefore hypothesize that interfacial cell/biomaterial interactions will affect sub-cellular structures in defined ways, giving rise to specific light-scattering “fingerprints” that can be used to describe a corresponding cellular process. 

Jacob Borden
Chemical & Biological Engineering Department
B.S. 1997 - Chemical Engineering,
Rose-Hulman Institute of Technology
M.S. 1999 - Chemical Engineering, Auburn University
M.B.A. 2002 - Business Administration, Springhill College
PhD Thesis Advisor: E. Terry Papoutsakis

Doctoral Research Project
The bacteria Clostridium acetobutylicum is of interest for two main reasons. First, the relevance of increasing oil prices cannot be overstated, with an emphasis on finding alternate means of efficiently generating higher-chained organics. With the ability to produce the solvents ethanol, butanol, and acetone, C. acetobutylicum is of interest in regards to optimization and selectivity in converting raw sugars to desirable end products. Secondly, C. acetobutylicum is a suitable model organism for the study of common pathogens such as C. perfringens , C. tetani , and C. botulinum . Until recently, gene/function analysis has relied on characterization of a single mutational event by a set of quantifiable phenotypes. However, a recent method has been proposed for imposing a phenotype, and extracting out genome-wide information concerning which genes are in fact responsible for bringing about the observed phenotype. Using genomic libraries, selective pressure will screen for relevant phenotypes (solvent tolerance, long fermentation duration, etc), and the selected library hybridized on a full-genome microarray. In this way, hybridization signals from the full-genome array can be traced to the genes conferring a growth advantage against the selective pressure.

Steve Bull
Department of Chemistry
B.S. 2002 - Chemistry, University of North Carolina, Chapel Hill
PhD Thesis advisor: Thomas J. Meade & Samuel I. Stupp

Doctoral Research Project
Steve Bull started his NIH training appointment September 1, 2004. He received his B.S in chemistry (biochemistry tract) with honors from the University of North Carolina at Chapel Hill . Steve has finished his course requirements for his Ph.D. at Northwestern in Inorganic Chemistry. His research contains aspects of chemistry and biology and incorporating them with nanotechnology and Magnetic Resonance Imaging. More specifically his research is aimed at non-invasive imaging of self-assembling biomaterials. Steve's research, under Prof. Samuel I. Stupp and Thomas J. Meade, incorporates both nanotechnology and MRI. Steve is creating biocompatible MR active peptide amphiphile nanofibers for imaging within the body. This work is envisioned to allow for in vivo imaging of the implanted gels to study degradation and morphology. He is also working on length control of the self-assembling peptide amphiphile nanofibers, which will be used in drug delivery.

Sofia Garcia
Chemical & Biological Engineering Department
B.S. 2003 - Chemical Engineering, University of Texas, Austin
PhD Thesis Advisor: William M. Miller

Doctoral Research Project
The ability to expand hematopoietic stem cells (HSCs) in an ex vivo environment would facilitate the development of many therapeutic applications for HSCs. HSCs of the bone marrow differentiate into all of the mature blood cells found in the body. Previous studies have shown that, although HSCs are able to self-replicate extensively in vivo , they tend to differentiate into more mature blood cells when cultured ex vivo . In other studies, HSC numbers have been maintained under conditions of co-culture with a stromal cell layer for up to seven weeks. However, co-culture with stromal cells is not a viable option for human transplantation due to contamination and regulatory issues. We are using a supported lipid monolayer containing bioactive lipopeptides to mimic the co-culture environment, which enables us to investigate key aspects of the bone marrow microenvironment. This well-defined system provides an easy way to isolate and combine various components of extracellular matrix and cell-surface molecules, such as different integrin ligands and immobilized cytokines, thereby allowing for a better understanding of the biological signals that regulate the self-renewal of adult HSCs.

Joanna Gonzalez
Chemical & Biological Engineering Department
B.S. 2002 - Chemical Engineering, M.I.T.
PhD Thesis Advisor: Vassily Hatzimanikatis

Doctoral Research Project
Polyketides are important natural products since a number of them have been found to have important properties that allow them to function as antibiotics.  The synthesis of polyketides includes a number of variables that can be altered to produce different polyketide molecules.  However, due to the large number of variables, it has proven hard to predict at the beginning of an experiment the final structure of the resulting poyketide and consequently, its properties.  I am working on applying computational methods to generate all the possible polyketide structures that can be synthesized from a specific set of monomers. It would then be possible, from the computer-generated list of structures, to determine a target polyketide structure and identify the pathway necessary to produce it.  In other words, we would know which enzymes are necessary for the production of a specific polyketide and that knowledge might prove helpful in manipulating the genes to produce the target structure.

Doctoral Research Project
Ellen is developing novel applications for Dextran-coated iron oxide nanoparticles which will be used as imaging agents to increase contrast in magnetic resonance (MR) images. Dextran-coated iron oxide nanoparticles are biocompatible agents that are used as T2, MR contrast agents to enhance medical imaging. Ellen is working to develop and utilize multimodal imaging agents by adding a fluorescent molecule to the surface of the Dextran-coated iron oxide nanoparticles allowing for the detection of cellular uptake and cell migration by fluorescence microcopy as well as MRI. IOGO (iron oxide green oregon) is a multimodal contrast agent that was synthesized by adding a fluorophore (Oregon green 488) to the surface of dextran coated iron oxide particles. Cell studies, done with several different cell lines, have demonstrated the uptake of IOGO into cells and the ability to image the cells by fluorescence microscopy. This agent could have many medical applications. For example, one application we are considering is the labeling of pancreatic transplant tissue to track tissue viability and rejection. This will help in the study of pancreatic transplantation as a therapy for type 1 Diabetes. Another application that is being worked on is attaching a novel stilbene to the surface of the IOGO particles that has an affinity to the plaques that form in the brains of Alzheimer's patients.  This would allow the plaques to be visualized by magnetic resonance imaging and provide an ante mortem diagnostic tool for Alzheimer's disease.

Stacey Finley
Chemical and Biological Engineering Department
B.S. 2004 - Chemical Engineering, Florida A & M University
PhD Thesis advisor:  Vassily Hatzimanikatis

R. Warren Sands
Biomedical Engineering and Medical Scientist Training Program Candidate
Laboratory of Dr. Phillip Messersmith

Doctoral Research Project
     Type 1 diabetes affects 1.5 million people in the United States alone. Moreover, the disease leads to severe metabolic complications including microvascular and macrovascular disease, leading to increased morbidity and mortality. Despite recent improvements in insulin delivery, maintenance of euglycemia has proven difficult and the prevention of the long-term clinical sequelae is nearly unavoidable.
     Islet transplantation, unlike insulin delivery, maintains tight glycemic control via feedback mechanisms. Yet, current islet isolation and transplantation techniques lead to decreased islet functionality and islet death. The loss of islets and decreased functionality of the surviving islets is problematic in the face of a shortage of organ donations, as only approximately 3,000 cadaveric pancreases become available for transplantation each year and current islet transplantation protocols require two to four pancreas organs for each recipient. Furthermore, islet transplantation requires surgical implantation of the islets into the portal vasculature and following the procedure patients require immunosuppression.
     Using an enzymatically crosslinked hydrogel, the goal of our work is to design a scaffold that can deliver islets to the body noninvasively while increasing islet survival and functionality following islet cell procurement, isolation, and transplantation.
     The hydrogel consists of poly (ethylene glycol) (PEG) modified with glutamine and lysine residues that crosslink to form a network in the presence of transglutaminase and calcium. Importantly, the properties of the hydrogel can be facilely modified to limit molecular permeability, control degradation in vivo, and to locally incorporate growth factors, immunosuppressants, or other pharma.

Keith Alsaker
Chemical & Biological Engineering Department
B.S. 2000 - University of Minnesota-Twin Cities
PhD thesis advisor: E. Terry Papoutsakis

Doctoral Research Project
With a US market of 1.8 billion pounds per year in 2001 and demand increasing, the solvent butanol is an attractive target for developing an environmentally friendly process using renewable resources. Such processes using strains related to the obligate anaerobe Clostridium acetobutylicum were commercially profitable until the mid-1950s. One reason for its demise was the lack of tools and methodologies to modify the catalyst itself, the microorganism.  Keith's research aims to identify targets that may enhance tolerance of C. acetobutylicum to solvents. As cells in culture become stressed by butanol, the phenotype changes: the cellular membrane composition is altered, specialized proteins keep vital proteins properly folded, etc.   Monitoring such stress responses at the transcriptional level using high throughput technologies like DNA microarrays is the first step towards the molecular understanding of solvent toxicity and, hence, towards the generation of improved, solvent-tolerant industrial strains.

Jeffrey Michael Barrett
Department/Program: IBiS
B.S. in Molecular Biology (Microbiology Dept. at BYU)
PhD Thesis advisor: Karen Kaul

Courtney Berkholtz
Chemical & Biological Engineering Department/IBiS Program
B.S. 2001 - Biology, University of Delaware
PhD Thesis advisor: Lonnie D. Shea

Doctoral Research Project
Follicle maturation involves precise communication between the granulosa cells and the oocyte. There are many women who suffer from infertility diseases such as polycystic ovarian syndrome (PCOS), premature ovarian failure (POF), and chemotherapy-induced sterility that are a result of improper signaling and the cause of oocyte meiotic incompetence. An alginate hydrogel can provide the follicle with the three-dimensional stability required for proper development of the granulosa cell-oocyte complex (GOC). Within this matrix, the GOC will be able to grow and the biochemical environment between the granulosa cells and the oocyte can be examined. Determining the paracrine signaling will provide insight into the mechanism of maturation of the follicle and will ultimately lead to the development of a successful in vitro maturation technique.

Kendrick C. Boardman, Jr.
Department of Biomedical Engineering
BS Mechanical Engineering, MIT, 1995
MS Biomedical Engineering, Northwestern University, 1999
PhD Thesis Advisor: Melody A. Swartz

Doctoral Research Project
Rick Boardman is working in the Integrative Cell and Tissue Mechanics Laboratory of Melody Swartz investigating the role of interstitial fluid flow and a variety of other stimuli on lymphatic vessel development (lymphangiogenesis). He has developed a unique in vivo mouse tail model for observing lymphangiogenesis and examining its mechanical and molecular regulation. This will form a foundation for understanding the biological regulation of tissue fluid balance, including lymphedema and tumor spread through the lymphatics.

Jeffrey L. Dalsin
Biomedical Engineering Department
B.S. Life Sciences, University of Illinois
PhD thesis advisor: Phil Messersmith

Doctoral Research Project
Jeff's current project involves the modification of clinically relevant biomaterial surfaces with novel molecules in order to mediate cell adhesion. Because of its well-known anti-fouling properties, poly(ethylene glycol) (PEG) is covalently attached to surfaces of various metals and metal oxides, including gold, titanium oxide, and chromium oxide through a bioinspired approach. NIH 3T3 fibroblasts are then cultured on these modified substrates and cell adhesion and spreading is examined using fluorescent microscopy.

Caralynn Helm
Chemical & Biological Engineering Departmential
B.E. 2000 - Chemical Engineering, Vanderbilt University
M.S. 2002 - Chemical Engineering - Northwestern University
PhD Thesis Advisor:Melody A. Swartz

Doctoral Research Project
The primary objective of Cara’s work is to create a functional, three-dimensional, interconnected capillary network in vitro using lymphatic endothelial cells embedded in a fibrin matrix. This effort utilizes a physiologically relevant matrix in conjunction with both functional drivers (e.g. interstitial flow) and biochemical actuators (e.g. matrix-bound growth factors) for the organization process. The matrix-bound growth factors, necessary for a system constantly undergoing interstitial flow, requires the creation of multi-domain fusion proteins that have an active protein of interest on one end and a substrate sequence on the other end to allow integration into the matrix. Additionally, she will optimize the physical matrix attributes of the fibrin, in effort to produce a synergy between the mechanical and chemical cues fostering the organization process.

Erinn Mee
Department of BMBCB
Biology, Indiana University (B.S., 1997)
PhD thesis advisor: Neil E. Welker

Doctoral Research Project
In the laboratory of Dr. Neil Welker, Ms. Mee is currently studying the effect of temperature on gene expression in Bacillus stearothermophilus, a gram-positive moderate thermophile. Using two-dimensional gel electrophoresis, it was determined that this organism utilizes a different subset of key genes depending on its growth temperature. By comparing the upstream region of several genes utilized only at higher growth temperatures, the lab hopes to find a regulatory sequence(s), and possible corresponding protein(s), used by the organism to "read" its environment. During the last year, Ms. Mee developed a novel subtractive hybridization technique to isolate such genes from B. stearothermophilus. Currently, she is performing Northern Blot Analysis to confirm the differential expression of genes isolated by this technique. She is also pursuing Two-Dimensional Gel Electrophoresis to identify additional temperature responsive genes that were overlooked by subtractive hybridization. Using these temperature responsive isolates, Ms. Mee plans to identify the function of the isolated genes through sequence homology, and elucidate the regulatory elements required for a temperature response.

Christopher Ramsborg
Chemical & Biological Engineering Department
B.S. 1996 - Chemical Engineering, Leland Stanford Junior University
PhD thesis advisor: E. Terry Papoutsakis

Doctoral Research Project
Ex vivo expanded T-lymphocytes based adoptive immunotherapy has the potential to develop into a powerful therapeutic tool. Ex vivo expanded T-lymphocytes can be used to treat iatrogenic infections, viral infections and several types of cancer. Controlling ex vivo culture conditions and understanding the effects of culture parameter perturbations is paramount to maximizing expansion while maintaining function. We use cDNA microarrays to observe the effects of autologous plasma on the temporal gene expression patterns of T-lymphocytes. We also develop cDNA microarray analysis methods, including advanced data normalization and filtering techniques as well as hierarchical clustering and self-organizing maps to: 1) Study the differential gene expression in ex vivo expanded T-lymphocytes cultured with versus without autologous plasma with emphasis on identifying “novel” serum induced genes, finding a gene expression “fingerprint” that correlates with ex vivo T-lymphocyte proliferation and explore the molecular basis of poorly expanding. 2) Investigate the transcriptional program of T-lymphocytes in the early activation period and evaluate the role of plasma in inducing T-lymphocyte activation pathways. 3) Construct new T-lymphocyte regulatory networks based on observed gene expression patterns. Microarray data will be validated using quantitative RT-PCR and flow cytometry. The improved understanding of the cellular mechanisms of ex vivo T-lymphocyte expansion could result in the modification of current protocols to increase expansion, thus improving clinical efficacy and decreasing ex vivo culture time.

Tatiana Segura
Chemical Engineering Department
BS in Bioengineering from University of California Berkeley
PhD Thesis Advisor: Lonnie D. Shea

PhD Thesis Project
Tissue engineering aims to develop functional tissue replacements by providing an environment that directs progenitor cell differentiation into a functional tissue. This environment is created using a scaffold that provides a mechanical support and function as a drug delivery vehicle. Tatiana's research involves developing hydrogel-based scaffolds for controlled gene-therapy vector delivery to tissues.

Melissa Starkey
Department of Civil Engineering/IBiS Program
BS - Biotechnology, Rutgers University
PhD thesis advisor: Mathew R. Parsek

Doctoral Research Project
Melissa Starkey is researching exopolymeric substance (EPS) production in non-mucoid Psedumonas aeruginosa. P. aeruginosa is an important bacterium in both environmental and industrial contexts, but is perhaps most notable for its persistence in cystic fibrosis infections. It is commonly believed that alginate, a polymer of uronic acids, is a major constituent of P. aeruginosa exopolymeric substance (EPS) and that alginate is required for biofilm formation. Ms. Starkey and her collaborators recently demonstrated that alginate is not the major component of non-mucoid P. aeruginosa EPS, but rather, EPS isolated from strain PAO1 contains primarily neutral and amino sugars. Additionally, as compared to wild type strain PAO1, mutants defective in alginate production have similar biofilm phenotypes and antibiotic resistance profiles. These findings indicate that alginate is not necessary for biofilm formation or antibiotic resistance in P. aeruginosa. Ms. Starkey’s current focus is on identifying genes responsible for non-mucoid EPS production and elucidating their roles in biofilm development and morphology.

Chris Tieche
Department of Biomedical Engineering
B.S. 1996 - Gen. Engineering, University of Illinois Urbana-Champaign
M.S.E. - 1999 - Aero and Astro Engineering - Purdue University
PhD Thesis Advisor: Shu Q. Liu

Doctoral Research Project
Elastin, a major ECM protein constituting the elastic laminae and fibers of arterial vasculature, is not known as a ligand of the integrins found in platelets and leukocytes. Therefore, it is possible that integrin-mediated activation of these blood cells is not induced by elastin, thus facilitating the use of elastin as a potentially low thrombogenic blood interface material. Platelets and leukocytes, however, have a non-integrin elastin receptor, enabling attachment to elastin, potentially without the integrin-associated activation.

Wyatt N. Vreeland
Chemical Engineering Department
BS in Chemical Engineering, University of Tulsa, May 1997
PhD Thesis Advisor: Annelise Barron

PhD Thesis Project
Wyatt Vreeland's research focuses on improved technologies for electrophoretic DNA sequencing and genotyping. As DNA mobility during electrophoresis in aqueous buffer is essentially constant for DNA chains of any length, electrophoresis is typically conducting in a polymeric sieving medium. The loading of these viscous media into modern DNA electrophoresis microchannels can be problematic. Thus, Vreeland is developing novel "mobility modifying" molecules that enable highly efficient separations of DNA by capillary and chip electrophoresis in the absence of sieving medium.