Degree Programs and Certificate
Cell Receptor and Signal Transduction Dynamics in Cell and Tissue Engineering
Jennifer Linderman
Deptment of Chemical Engineering
Deptment of Biomedical Engineering
Program in Bioinformatics
The University of Michigan
Ann Arbor, MI 48109
The binding of extracellular ligands (e.g. hormones, growth factors, adhesion molecules, drugs of abuse) to cell surface receptors and the ensuing signal transduction events drive cell behavior. Understanding the relationships between receptor-level events and cellular responses offers new insights in fields as diverse as immunology, pharmacology and tissue engineering. Current projects involve: (1) developing mathematical/computational models of G-protein coupled receptor dynamics to understand and predict drug activity, (2) measurement and modeling of tumor necrosis factor roles in tuberculosis granulomas, (3) developing approaches for multi-scale modeling in immunology, (4) bone tissue engineering, particularly the roles that oxygen concentration and nanoscale patterning of adhesion ligand play, and (4) analysis of image data to obtain parameters for signal transduction networks.
Cheminformatics for Analyzing Large Volumes of Heterogenous Pharmaceutical Data
David Wild
School of Informatics (Cheminformatics)
Indiana University
Bloomington, IN 47408
Drug Discovery, in common with all other scientific disciplines, has experienced a "data deluge" in the last decade, with huge volumes of chemical, biological and genomic information being generated both internally in pharmaceutical companies, and also in the public domain. We are developing a variety of techniques for aquiring, aggregating, organizing and data mining this information, including the application of Cheminformatics, Cyberinfrastucture, Semantic Web and Web 2.0 techniques. We have created an extensive cheminformatics cyberinfrastructure consisting of databases and computational services, and are now building data mining and knowledge discovery tools to exploit this informaiton. In the longer term, we hope to develop a new generation of searching and data mining applications which take into account a vast variety and volume of scientific information.
Development of "Smart" Polymers for Diagnostic and Therapeutic Applications
Mohamed E.H. El-Sayed
Department of Biomedical Engineering
The University of Michigan
Ann Arbor, MI 48109-2110
Recent advances in drug design and combinatorial synthetic chemistry have led to the development of several classes of novel therapeutic molecules including peptides, proteins, monoclonal antibodies, immunotoxins, lysozymes, plasmid DNA, antisense oligodeoxynucleotides, and short interfering RNA. Despite the established potential of these macromolecules, their development into stable and clinically-active drugs with defined dosage regimens remains a significant challenge. The primary motivation of our research is to transform these promising drug candidates into actual therapeutic and diagnostic agents. Our laboratory focuses on the rational design and synthesis of novel polymeric carriers that can effectively "communicate" with different epithelial and endothelial barriers encountered within the body to selectively deliver their therapeutic cargo to the diseased tissues with cellular and sub-cellular accuracy. These optimized drug delivery systems will enhance the therapeutic activity of the incorporated drug while eliminating or minimizing its potential side effects. Our research has a multidisciplinary nature and utilizes a wide range of sophisticated techniques including polymer and bioconjugate chemistry, radiochemistry, cellular and molecular biology, microscopy, in vitro cell culture, and in vivo evaluation using animal models.
Micro/Nanotechnology for Cell & Tissue Engineering
Shuichi Takayama
Department of Biomedical Engineering
Macromolecular Science & Engineering
The University of Michigan
Ann Arbor, MI 48109-2099
Many biological studies, drug screening methods, and cellular therapies require culture and manipulation of living cells outside of their natural environment in the body. The gap between the cellular microenvironment in vivo and in vitro, however, poses challenges for obtaining physiologically relevant responses from cells used in basic biological studies or drug screens and for drawing out the maximum functional potential from cells used therapeutically. One of the reasons for this gap is because the fluidic environment of mammalian cells in vivo is microscale and dynamic whereas typical in vitro cultures are macroscopic and static. To overcome this challenge for cell-based drug testing as well as development of cell-based therapies, our laboratory develops a variety of micro- and nanotechnological devices and materials. For example, we develop programmable microfluidic systems that enable spatio-temporal control of both the chemical and fluid mechanical environment of cells. Microengineered cell culture substrates and scaffolds are fabricated to guide tissue formation and enhance function. The technologies and methods close the physiology gap to provide biological information otherwise unobtainable and to enhance cellular performance in therapeutic applications. Specific biomedical topics of interest include subcellular signaling in normal and cancer cells, in vitro fertilization on a chip, studies of the effect of physiological and pathological fluid mechanical stresses on airway epithelial cells, and microfluidic stem cell engineering. In the nanoscale regime, reconfigurable nanopatterned protein surfaces are developed for on-demand cell spreading and retraction. Tunable nanochannels that can manipulate single DNA molecules are also utilized with the aim of single molecule DNA analysis.
Pharmaceutical Material Science
Gregory E. Amidon
Department of Pharmaceutical Science
College of Pharmacy
The University of Michigan
Ann Arbor, MI 48109
The most effective contributors to pharmaceutical sciences in the 21st century, particularly in an industrial setting, will benefit from a fundamental understanding of the properties of pharmaceutical materials. Pharmaceutical Materials Science focuses on connecting phenomena that occur at a molecular and microscopic scale to macroscopic performance. This facilitates the characterization and design of pharmaceutical materials and drug delivery systems with the necessary physical, chemical, mechanical, and performance properties needed to meet drug delivery and manufacturing requirements. In our work, we focus on characterizing the particle, powder, and the compact properties of pharmaceutical materials with the objective of connecting molecular and particulate properties to macroscopic/bulk properties and performance and developing predictive tools that can improve our understanding and efficiency. The current regulatory environment and economic pressures require a comprehensive understanding of materials and their impact on product performance and manufacturing to improve efficiency. An additional component is the development of "small scale" testing strategies that require small quantities of material. The ultimate goal is the efficient and scientific design of pharmaceutical materials and processes to meet unique drug delivery system needs.
Pharmacometrics for Personalized and Community Medicine
Rose Feng
Department of Pharmaceutical Science
College of Pharmacy
The University of Michigan
Ann Arbor, MI 48109
Pharmacometrics is the science of interpreting and describing pharmacology in a quantitative fashion. This involves pharmacokinetics (PK), pharmacodynamics (PD) and disease progression modeling with a focus on populations and variability. In this area, models based on biology, physiology, pharmacology, and pathophysiology or disease are used to quantitatively describe the interaction between a drug and a patient, and the resultant desired response or adverse drug event. This knowledge would substantially improve the rational, safe and effective use of drugs, and lead to better outcomes for the individual patient. Currently, our research concentrated on (1) Development of PK and mechanism-based PK/PD models using a population approach to optimize the dose and dose-regimen in clinical trials and the development of drug delivery system; (2) Development of physiologically based pharmacokinetic (PBPK) models to link the preclinical and clinical data and assist the prediction of the exposure of adults and pediatrics (neonates, infants and children) to xenobiotics; (3) Estimation of optimal blood sampling time windows for the estimation of PK parameters by a population approach.
Reconfigurable Clinical Manufacturing of Personalized and Complex Health Care Products
Henry Y. Wang
Department of Chemical Engineering
Department of Biomedical Engineering
The University of Michigan
Ann Arbor, MI 48109
The evolving health care product industry encompasses a wide array of new and emerging biomedical products that are complex and combination in nature and will be faced with a variety of unique, inter-related challenges requiring diverse technical and engineering solutions. They are shifting from the traditional pharmaceutical business model of a limited number of "blockbuster" drug products to a large number of "personalized" combination products that must be economically developed, manufactured, and provided to the consumer. Corresponding to the diverse array of products, there is also greater variety in capacity demand and scaling needs, indicating a greater diversity in production scale and dictating a need for various multi-product facility schemes. Furthermore, the regulatory requirements of this industry coupled with long lead-time typically require that large capital investment decisions for new capacity be made before final product approval. The risk is compounded by difficulties in market forecasting, which will only worsen as the array of these complex medical products increases. Overlaying all these issues are the socio-economic factors of increased societal pressure to reduce costs and of the need for industry responsiveness to address epidemics and for other security threats.
The need is clear for the research and development of engineering practices that can increase development and manufacturing flexibility, reduce the time and cost involved in providing shifting patient demand as well as potentially reducing the lead time while utilizing existing capacity. Our research addresses the pertinent engineering practices in the design, development and clinical manufacturing of various complex medical products and suggests a futuristic clinical manufacturing strategy utilizing various reconfigurable but modularized processing units and illustrates their integrated use. Engineering applications of process intensification and different reconfigurable specialty and compouding pharmacy designs are explored, as are technical approaches specific to the industry such as disposable processing components and the recent FDA's Quality Be Design (QbD) initiative. Integration of all these within the concept of a distributed product development and clinical manufacturing network stressing agility and flexibility is advocated. The related issues of risk based process and cleaning validation, scheduling, and supply chain management are also being addressed in this context.
Systems Biology in Drug Discovery and Development
Peter J. Woolf
Department of Chemical Engineering
Department of Biomedical Engineering
The University of Michigan
Ann Arbor, MI 48109
The molecular pathways that determine how a drug functions are complex and incompletely understood. However, to develop new drugs we need a systems level understanding of how this molecular system works in order to select appropriate drug targets and to choose which patients will likely respond to the drug.
In our group, we develop systems level models of molecular pathways for drug development. These models are created using state of the art machine learning technologies including Bayesian networks and information theoretic experimental designs. Using these tools we generate predictive models of disease progression and drug response. Our group has a particular focus on modeling diabetes complications and tumor metastasis in an effort to identify potential drug targets to halt these processes. We are also developing clinical tools for patient tailored models that allow a doctor to predict the impact of various clinical treatments on the patient's health. By coupling advanced computational tools with biological and clinical modeling, we are developing a new approach to managing and treating disease.