Lindsay Karfeld
Chemical and Biological Engineering Department
B.S. 2001 - Chemical Engineering, Princeton University  
Ph.D. Thesis Advisor: Annelise E. Barron and Thomas J. Meade

Doctoral Research Project

One significant barrier to the development of new generations of biocompatible materials, particularly tissue engineering hydrogels, is an inability to non-invasively evaluate the properties and performance of the biomaterial over time. Magnetic Resonance Imaging (MRI) is capable of whole animal or human imaging at high spatial and temporal resolution, and is an ideal modality for evaluating tissue engineering scaffolds in vivo. Exogenous contrast agents (CAs) increase the relaxation rate of water protons and therefore improve image contrast in MRI. The majority of clinically used CAs for magnetic resonance imaging have low relaxivities and thus require high concentrations for signal enhancement. Recent research has turned toward macromolecules to increase retention time and image contrast. I am creating a novel class of protein polymer-based MRI CAs with improved relaxivity as well as the ability to be incorporated into tissue engineering hydrogels based on the same biomaterial. Protein polymers are created by E. coli's natural biosynthetic machinery, such that they are entirely monodisperse and we can control the exact sequence and length. Thus, we can specify reactive sites that are available for conjugating on bioactive moieties, including gadolinium chelators to create a macromolecular CA. In my work, I am exploring the effect of protein polymer sequence on relaxivity, toxicity and degradation profiles of the CAs, and performance in vivo alone and incorporated into tissue engineering hydrogels.

Swapna Panuganti
Chemical & Biological Engineering Department
B.S. 2005 - Chemical Engineering and Biology
Masachusetts Institute of Technology
PhD Thesis Advisor: William M. Miller

Doctoral Research Project
Hematopoietic stem cells have the ability to give rise to all the different types of blood cells in the body. This research in particular focuses on the mechanisms of hematopoietic stem cell differentiation into megakaryocytes, the precursors to platelets. Platelets are essential for clotting, wound healing, and hemostasis. Other hematopoietic lineages of interest also include granulocytes, which comprise the majority of human white blood cells, and erythrocytes. Due to limited availability of normal human blood donors, there's an increasing stress on current blood bank supplies to harvest blood cells necessary for transfusion. To obtain just one unit of platelets for transfusion, 6-8 units of donated blood must be pooled from several different donors, which can lead to an increased risk of an immune response from the recipient. An attractive alternative is to augment peripheral blood stocks by transplanting megakaryocyte progenitors or fully differentiated platelets derived from ex vivo expanded hematopoietic stem cells. This research involves evaluating various growth factors and additives as well as manipulating the growth environment of hematopoietic stem cells in culture to enhance their expansion and maturation into megakaryocytes. Nicotinamide, a novel additive to hematopoietic stem cell culture that is safely tolerated at high doses in human patients, has been shown to greatly enhance the platelet-producing potential of megakaryocytes in culture. Elucidating the mechanisms through which nicotinamide functions in primary human hematopoietic stem cells has the possibility of leading to its evaluation in a mouse model and perhaps a clinical trial so patients waiting for a platelet transfusion have the possibility of producing their own platelets autologously.

Samuel Seaver
Department of Chemistry
B.Sc. 2000 - Molecular Biology and Biochemistry, Durham University, UK
M.Sc. 2001 - Molecular Modelling and Bioinformatics, Birkbeck College, University of London, UK
PhD Thesis advisor: Luis N. Amaral

Doctoral Research Project

The growing volume of experimental data that confirm the location and sequence of transcription factor binding sites (TFBS) now means that computational models of TFBS can be tested with greater accuracy and reliability. In particular, the size of the TFBS dataset at RegulonDB allows us to study the TFBS distribution and degeneracy in upstream regions of Escherichia coli. The focus of my work is to find trends in the dataset that can be explained using simple mathematical and computational models inspired by biological processes. The result of this work will boost our understanding of bacterial gene regulation in general, gene regulation involving specific transcription factors, and the evolutionary processes involved.

Emily Testa
Chemistry Department
B.S. 2005 - Chemistry, University of Chicago
PhD Thesis Advisor: Thomas Meade

Doctoral Research Project
Emily Testa’s research, conducted in the laboratory of Professor Thomas Meade, centers on the synthesis and characterization of monodisperse polymeric MR contrast agents to be optimized with regards to tR and tm. The generated high relaxivity agent will have biological applications that include fate mapping and drug delivery tracking. To this end her work encompasses the use of peptoids as scaffolds for MR contrast agents, modification of nanoparticles with multiple functionalities, and comparison of different MR contrast agents. She also investigates the coordination chemistry of MR contrast agents as is relevant to these projects.

Bryan Tracy
Chemical & Biological Engineering Department
B.S. 2004 - Chemical Engineering, North Carolina State University
PhD Thesis Advisor: E. Terry Papoutsakis

Doctoral Research Project

The development of microbes for specialty chemical conversion, biofuel generation, and pharmaceutical production remains an immediate scientific and industrial goal. Particularly for bacteria, the pursuit of converting low value biomass and/or industry byproducts into transportation fuels (ethanol and butanol) is motivating a tremendous amount of bacterial strain development. Of considerable interest are bacterial species from the genus Clostridium because of their natural ability to degrade and ferment cellulosic material into ethanol and butanol. Unfortunately though, there are limited genetic tools applicable to Clostridium that may be employed for accelerating strain development. Thus the primary goal of Bryan’s research is to expand the genetic “toolbox” for all Clostridium species, and to concurrently apply these new approaches to the development of superior butanol producing strains. Specifically, he is developing new gene knockout techniques applicable to both solvent forming and pathogenic Clostridium species, such as C. acetobutylicum, thermocellum, botulinum, difficile and perfringens. Additionally, he is adapting reverse genetics approaches, such as plasmid libraries and high throughput flow-cytometry, to the generation and screening of mutant Clostridium libraries. By generating hundreds of thousands of random mutants, and coupling with sensitive multi-parametric screening techniques, their lab has proven the ability to generate higher butanol producing and more solvent tolerant strains in far less time than directed genetic approaches. Bryan continues to advance these techniques and to generate even more desirable phenotypes, which he hopes shall contribute to the world’s eminent need for alternative, sustainable and greener transportation fuels.

Doctoral Research Project
The mammary microenvironment plays important and complex roles during tissue development and can contribute to the progression of breast cancer. I am designing synthetic hydrogels to controllably present microenvironmental cues, both mechanical and biochemical, to mammary epithelial cells and characterizing the resulting phenotype. These hydrogels allow known external cues to be presented separately and are appropriate for exploring the synergy of different factors. As differences in signaling pathways lead to diverse cellular structures, I use non-viral gene delivery to report on transcription factor activity important to specific pathways. A transfected cell array quantifies this activity non-invasively and in a high-throughput fashion, leading to profiles of cellular states at the level of signaling pathways. The effects of different microenvironments can thus be detected at the molecular level and can provide insight into how they affect disease progression.