Fall 2012 group photo.

Bramie Lenhoff

Primary Investigator. Contact: lenhoff@udel.edu

Bramie is the Allan P. Colburn Professor in the Department of Chemical Engineering at the University of Delaware (UD). In addition to the research described on this and other pages, he is involved in several other activities at UD, including being Director of the COBRE on Membrane Protein Production and Characterization, Associate Director of the Chemistry-Biology Interface Training Program, a faculty member in the Center for Molecular and Engineering Thermodynamics and a member of the management team of the Delaware INBRE Further information is available in his CV He has taught a wide variety of courses in the undergraduate and graduate programs in chemical engineering.

Amit Vaish

Postdoctoral Researcher. Contact: anv@udel.edu

Amit's research is focused on developing a mechanistic understanding of the membrane-associated proteins crystallization process. We have been using scattering and NMR techniques to investigate this phenomenon over molecular and nanoscopic length scales.

Rahul Bhambure

Postdoctoral Researcher. Contact: rahulb@udel.edu

Rahul studies the role of change in ligand density on protein transport and adsorption in polymer-modified ion-exchange media.

Ion-exchange chromatographic separation “a workhorse” for the downstream processing plays a key role in removal of various product related and unrelated impurities associated with biotherapeutic proteins. Ligand type and ligand density had a pronounced effect on the performance of polymer-modified ion exchange resins. This project seeks to provide a better understanding of the role of ligand density changes on the resin performance through characterization of the interplay between protein transport and adsorption using various experimental techniques such as inverse size exclusion chromatography, batch uptake, isocratic retention and confocal microscopy.

Anvar Samadzoda

Graduate Student. Contact: anvars@udel.edu

Co-advisor: Anne Robinson

Anvar's research focuses on the development of a mechanistic understanding of crystallization of membrane proteins. In his work, he has used two model proteins - reaction center from R. sphaeroides and OmpX expressed in E. coli - with their respective crystallization conditions and utilized a variety of biophysical and colloid science techniques in order to extensively characterize crystal-yielding solutions.

Anvar graduated from the Middle East Technical University, Anvara, Turkey with a BS in Chemical Engineering in 2007. He worked in consumer goods industry as a Formulations and Processing R&D Engineer for about 2 years before joining the lab.

Kristin Valente

Graduate Student. Contact: kvalente@udel.edu

Co-advisor: Kelvin Lee

Kristin’s research centers on characterizing secreted host cell proteins from Chinese hamster ovary (CHO) cells, which are the dominant expression system for monoclonal antibodies and other recombinant proteins. Using a variety of proteomic techniques, proteins are identified from harvested cell supernatant and tracked across downstream chromatography steps in order to correlate chromatographic retention to protein sequence.

Jim Angelo

Graduate Student. Contact: jmangelo@udel.edu

Jim studies protein sorption and transport behavior within polymer-modified stationary phases for ion-exchange chromatography, specifically within materials composed of cross-linked saccharidic polymers.

Polymer-modified derivations allow for increased protein capacity and uptake rates which have a significant impact on the optimization of downstream processes. The goal of Jim's project is to identify the limitations of these materials by characterizing the mechanisms of adsorption, desorption, and transport of proteins by utilizing advanced microscopy techniques to observe and analyze the stages of protein sorption on a microscopic level. Coupling these results with macroscopic studies performed in column and batch systems allows for the determination of transport parameters and mechanisms essential in the modeling of uptake and elution behavior, which is crucial for the design and improvement of preparative-scale separations.

Dan Greene

Graduate Student. Contact: dggreene@udel.edu

Co-advisor: Norman Wagner

The phase behavior of native protein solutions underlies many physiological phenomena and is important in industrial processes such as crystallization and precipitation. It has been shown that in the presence of sufficient salt, such that long-ranged electrostatic interactions between protein molecules are screened, protein solutions exhibit a liquid-liquid phase separation that is metastable to a solid-fluid equilibrium. Additionally, kinetically trapped phases such as gels and arrested glasses can form within the liquid-liquid coexistence region. Currently, short-ranged isotropic colloidal models are used to qualitatively describe protein solution phase behavior. The reference state diagram for the adhesive hard sphere dispersion is now known precisely. However, models using centro-symmetric interaction forces do not account for the known anisotropy of the protein molecule and its interactions with other proteins, and thus fail to accurately describe the behavior. To address this, recent theoretical work on patchy particles attempts to understand how the anisotropy in the potential may affect phase behavior. For example, patchy models have been used to describe the phase behavior of the model protein, lysozyme. A key to testing these predictions is a complete characterization of the phase behavior of model proteins, including the composition and microstructure of the dense phases that form upon phase separation. Some of these phases are kinetically arrested and as such are metastable and may depend on the preparation history. Here we explore a model protein system, ovalbumin, using xray, neutron and light scatteirng techniques as well as electron microscopy to better understand how anisotropy affects protein phase behavior; in particular, we are interested in the effect on the microstructure of protein dense phases.

Stijn Koshari

Graduate Student. Contact: kosharis@udel.edu

Co-advisor: Norman Wagner

Biopharmaceuticals, in particular monoclonal antibodies (mAbs), have seen a major growth in development and market value over the last few decades. Their importance in a wide variety of clinical settings and treatments has led to extensive research of their storage, transportation, and clinical delivery. Biopharmaceutical powders allow to enhance the stability during storage and can be applied directly in dry powder inhalation and sustained drug delivery methods. Spray and freeze drying are popular methods to produce these powders. In general, these methods are limited by the sensitive character of mAbs to the process conditions, with the risk of triggering denaturation or aggregation. Hence, fundamental research into the effect of the drying conditions on the final powder properties is essential. In addition, the release characteristics during drug delivery are influenced by the distribution of the protein in the dried powders. The goal of this research collaboration is to study the structural characteristics of spray and freeze dried mAb formulations with the help of advanced scattering techniques to understand the link between process conditions and final properties.