Quantitative Systems Pharmacology Certificate

Abhyudai Singh, Ph.D.

Professor
Office: 302-831-8447

Bio: Prof. Singh’s research interests are in the area of Systems and Control with applications to systems biology and medicine. Employing mathematical techniques used for studying engineering control systems we model and analyze the dynamical nature of gene-protein networks inside living cells. These mathematical models help us uncover and understand the complex feedback circuitry encoded by these networks, and how deregulation in feedback control can lead to diseased states.

Recent research efforts have focused on developing computational tools for studying the stochastic dynamics of gene-protein networks at a single cell resolution. We are also building methodologies that will combine these computational techniques with high-throughput experimental data for reverse engineering gene-protein networks and mapping novel regulatory mechanisms within them. Using such joint computational-experimental approaches we are characterizing the gene regulatory network within Human Immunodeficiency Virus and designing strategies to manipulate this networks for therapeutic benefit.

Ryan Zurakowski, Ph.D.

Department Chair
Professor

Bio: Dr. Zurakowski’s group develops mathematical models of diseases. By understanding the way that viruses and cells interact, we can learn about the behavior of things we cannot measure from the behavior of things we can. Using models and methods we developed, we have been able to prove that patterns of dead-end HIV DNA circles seen after a particular drug is given to HIV patients prove that HIV continues to replicate in hidden regions of the human body even when HIV medicines have stopped all directly measurable replication. The methods we developed to study HIV can also be applied to traditional engineering applications.

The models we develop allow us to suggest novel experiments that reveal otherwise unmeasurable disease behaviors.  We validate our models against clinical and in vitro data using Bayesian inference techniques. The measurements used in our applications are subject to measurement uncertainties of a type not seen in traditional engineering applications. The data is also routinely subject to censoring. In order to accurately use the information present in this kind of data, we also develop novel models of uncertainty.

We have used the methods described above to make a number of significant contributions to the understanding of HIV disease. Using treatment interruption data collected by our collaborators at the IRSI-Caixa AIDS research foundation in Barcelona, Spain, we published the first direct estimates of HIV drug efficacy and residual viremia. Using data from an integrase inhibitor intensification study, also by our collaborations in Barcelona, we were able to demonstrate the presence of persistent, efficient, cryptic viremia in a subset of treated HIV patients with no measurable virus. This finding was validated by a subsequent experiment by our collaborators at the University of California, San Francisco. We have also applied our novel Bayesian inference methods to data from our collaborators at the Ragon Institute of Harvard, MIT, and Massachusetts General Hospital, allowing them to demonstrate that a novel subset of T Cells exhibits order of magnitude higher infection rates than any other known subtype. The findings discussed here are already influencing the direction of HIV treatment and cure research.

Many of the system identification techniques we have developed for our disease system studies also have application in guidance and tracking problems. Inspired by the biomedical applications, we have developed the first formulation of the Kalman filter for censored data systems. We are currently applying this novel estimation technique to a number of tracking and surveillance problems of interest to the Army Research Laboratories.

Students and postdocs interested in working with Dr. Zurakowski can expect to develop and apply advanced mathematical and statistical techniques for data analysis and experiment design, and to apply these to novel experimental data from human disease trials. For information about joining the lab, please email Dr. Zurakowski outlining your specific interests and attach a copy of your CV.

Aminul Islam, Ph.D.

Assistant Professor 

Bio: Dr. Islam’s research focuses on multiscale modeling to investigate the disease dynamics and quantitative systems pharmacology modeling to predict the effects of treatments in complex biological systems. His work spans applications in pulmonary fibrosis, ocular drug delivery, osteoimmunology, oncology, and women’s health, with disease contexts including COVID-19, macular degeneration, osteoporosis, and cancer.

In the classroom, Dr. Islam emphasizes the connection between theory and real-world application. His teaching philosophy is grounded in creating an engaging and inclusive environment both in person and online by incorporating case studies from current research, interactive computational modules, and industry-relevant examples. He is particularly passionate about integrating modeling frameworks into biomedical engineering curricula to enhance critical thinking and problem-solving skills.

Yixiang Deng, Ph.D.

Assistant Professor

Bio: Yixiang Deng is an Assistant Professor in the Department of Computer and Information Sciences at the University of Delaware. She serves as the Principal Investigator of the Computational Intelligence for Dynamical Systems Laboratory, where her research explores the intersection of machine learning and complex physical or biological systems.

Prior to joining UD, Dr. Deng was a Postdoctoral Fellow at the Ragon Institute of MGH, MIT, and Harvard (2022–2024), working with Prof. Daniel Lingwood. During her fellowship, she also collaborated with Prof. Douglas A. Lauffenburger at MIT and was co-advised by Prof. Galit Alter.

Dr. Deng earned her Ph.D. from Brown University in 2021 under the advisement of Prof. George Em Karniadakis. She holds a B.Eng. degree from Shanghai Jiao Tong University, completed in 2015.

Emily Day, Ph.D.

Professor

Bio: Dr. Day engineers nanoparticles with unique physicochemical properties and implements these tools to enable high precision treatment of diseases including aggressive cancers, hematologic disorders, and gynecologic/reproductive health conditions. Additionally, her team studies nanoparticle interactions with biological systems from the subcellular to whole organism level to elucidate structure/function relationships in nanomedicine. Her expertise includes: the development of nanoparticles for targeted drug, nucleic acid, and/or antibody delivery; (ii) the use of photoresponsive nanoparticles for light-activated therapy; and (iii) the coating of nanoparticles with specific molecules (e.g., passivating agents, targeting ligands, or cell-derived membranes) to achieve desired biointerfacing capabilities. Ultimately, Dr. Day aims to transition the technologies developed in her lab from concept to clinical application. Students and postdocs who work with Dr. Day perform basic and translational research at the interface of medicine, biology, chemistry, materials science, and nanotechnology. 

Cathy Fromen, Ph.D.

Centennial Associate Professor For Excellence in Research and Education
Graduate Admissions Co-Director

Bio: Respiratory diseases remain a challenging therapeutic problem, resulting in high morbidity and mortality. These conditions range from infectious diseases of influenza, tuberculosis and pneumonia, to known genetic and immunological disorders of cystic fibrosis (CF), allergy, and lung cancers, and finally to acquired conditions dominated by airway obstructions and lung remodeling in COPD, asthma, and pulmonary fibrosis. With each of these diseases, physiological/pathological changes occur on many length scales, with dysfunction on the molecular level causing changes in cellular interactions, dynamics of the microenvironment, and resulting whole organ function. We are interested in applying engineering fundamentals and innovative tools with the latest understanding in immunology to better predict how these changes manifest at each length scale. Importantly, we seek to understand how these changes impact the efficacy of inhaled therapeutics and to develop translational aerosol designs in new therapeutic areas.

Three main areas of interest include:

1. Leveraging 3D printing to advance in vitro tools for pulmonary drug delivery testing

2. Using engineered particles to probe lung biology and immune function

3. Engineering novel therapeutics for controlled immune stimulation in the lung

Jason Gleghorn, Ph.D.

Associate Professor

Areas of Special Interest: The Gleghorn Lab is an interdisciplinary research group that is focused on understanding how cells assemble into functional tissues.  We develop and use microfluidic and microfabrication technologies to determine how cells behave and communicate within multicellular populations to form complex 3D tissues and organs.  In particular, we use developing organs, microfabricated 3D organotypic culture models, quantitative analysis, and computational methods to investigate the biophysical forces and chemical signals that drive tissue growth, homeostasis, and disease.  Our work integrates fundamental engineering, molecular, cell, and developmental biology, and materials science to delineate cellular behaviors and interactions at the cellular, tissue, and organ length scales.  The long-term goals of this research are to develop techniques to engineer physiologically relevant 3D culture systems with well-defined structure, flows, and cell-cell interactions to study tissue-scale biology and disease. These techniques in combination with what we learn in our studies of the native cellular behaviors and interactions in the embryo will be used to define new therapeutic approaches for regenerative medicine.

Brian Kwee, Ph.D.

Assistant Professor

Areas of Special Interest: The Kwee Laboratory develops innovative approaches to enhance the efficacy of skeletal muscle tissue engineering therapies. These therapies include methods for combining muscle cells, supporting cells (i.e. endothelial cells that form blood vessels), and/or cytokines with biomaterials to treat muscle injuries and diseases. We are specifically interested in applying concepts of immunoengineering and cell manufacturing to enhance these therapies:

IMMUNOENGINEERING

It is becoming increasingly appreciated that the immune system plays a critical role in tissue regeneration. However, impaired or prolonged inflammation can lead to adverse tissue responses, such as fibrosis and necrosis. We design cell and drug delivery biomaterials that can recruit host immune cells and modulate them to promote muscle regeneration. Our designed biomaterials control the number and type of innate and adaptive immune cells (i.e. macrophages and T-cells) at sites of injury and disease to induce pro-regenerative inflammatory microenvironments.

CELL MANUFACTURING

The clinical success of cell therapies is limited by cellular functional heterogeneity, where cells from different donors or subpopulations within a donor exhibit varying potency. Our work focuses on reducing this heterogeneity with fluorescence-activated cell sorting (FACS) to identify cell subpopulations of varying therapeutic potency in biomaterials.  We focus on sorting these cells by integrin/cadherin expression and evaluating how these cell subpopulations function and/or form tissues in biomaterial scaffolds. We are applying this cell manufacturing approach to endothelial cells and muscle cells combined with biomaterials to engineer vascularized muscle tissues.

Smitty Oakes, Ph.D.

Assistant Professor

Areas of Special Interest: The Oakes Research Laboratory leverages nanoscale biomolecular self-assembly and microfabrication to engineer immunotherapies and drug delivery systems that target innate immunity to regulate autoimmunity and cancer metastasis. See our lab website (oakesimmuno.com) for regular updates and news on our team, open positions, research initiatives, publications, community and STEM outreach, and resources for collaboration.

The innate immune system provides a rapid, initial response to immunological challenges, such as infection, vaccination, and biomedical device implantation. Vaccines are one of the most important innovations in human history, allowing us to eradicate some infectious diseases by utilizing innate cells to initiate highly specific adaptive immune responses. Likewise, biomaterial-based devices such as artificial hips and coronary stents, are implanted every hour of the day to provide lifesaving and quality-of-life improvements – innate immune cells cleanup the damaged tissue from surgical insertion. A challenge for both vaccines and implants is their limited control over these innate immune responses. Recent advances in nanotechnology and material science provide a path to achieve such precision. Our team charts a unique path focused on innate immunity by combining novel engineering platforms, advanced transcriptomics techniques, and targeting of intracellular gene expression networks. We apply this central focus on innate immunity to i) create therapeutics that counter autoimmunity, ii) engineer approaches to fight cancer, and iii) decode tissue-specific innate immune cells surrounding implants.

Dr. Robert “Smitty” Oakes, PhD is an Assistant Professor in the Department of Biomedical Engineering at the University of Delaware. Jointly, he holds an appointment with the Department of Veterans Affairs (VA) as a Career Development Awardee (CDA-2). Dr. Oakes completed the final stage of his postdoctoral training at the University of Maryland in the laboratory of Christopher M. Jewell where he is focused on therapeutics for autoimmunity. Dr. Oakes completed the first stage of his postdoctoral training in the Laboratories of Lonnie Shea and Jacqueline Jeruss at the University of Michigan where he focused on implantable diagnostics for monitoring cancer progression. He completed his doctoral work on neuroimmune responses to brain-machine interfaces in the Laboratory of Patrick Tresco at The University of Utah. He received a B.S. in Physics and a B.A. in Theology from Lenoir-Rhyne University. In 2023, he was awarded the BioInterfaces Rising Star Award from the Burroughs Wellcome Fund and the Society for Biomaterials for his research contributions in immunoengineering. Collectively, he has authored 26 publications in leading journals (e.g., ACS Nano, Nature Communications, Cancer Research), received funding support from an NIH T32 Postdoctoral Fellowship in cancer biology, and his VA research is supported by a CDA-2 on immunotherapy design.

John Slater, Ph.D.

Associate Professor

Areas of Special Interest: It is well established that microenvironmental cues influence cell fate but the molecular mechanisms that drive this phenomenon remain elusive and the ability to precisely control a cell’s local environment remains difficult. The Slater Lab focuses on the development and implementation of new fabrication methodologies to create biomimetic patterned surfaces and 3D multicellular constructs that allow for precise control over the presentation of both biophysical and biochemical cues that can be tuned to elicit desired cellular traits. The lab is applying these highly structured biomaterials to a number of topics including the recapitulation of desired cellular phenotypes, reduction of cellular heterogeneity in culture, lineage-specific stem cell differentiation, and development of high-throughput drug screening models.

Millie Sullivan, Ph.D.

Alvin B. and Julie O. Stiles Professor of Chemical & Biomolecular Engineering
Professor of Biomedical Engineering

Areas of Special Interest: “A wealth of potential therapeutic opportunities remains untapped within cells. For example, DNA delivered to the nucleus can interact with the native nuclear machinery to stimulate cellular production of essentially any protein of interest, whereas short interfering RNA (siRNA) delivered to the cytosol can initiate gene silencing (and the corresponding lack of protein production). Because of the exquisite specificity of these processes and the fundamental role for proteins in biology, nucleic acid medicines have unparalleled potential to modulate tissue regeneration and cure a wide range of devastating diseases, including cancers, cardiovascular diseases, and infectious diseases, yet no nucleic acid products are currently marketed. Meanwhile, various intracellular organelles are also the therapeutic targets for numerous small molecule medicines such as chemotherapies, but poorly controlled delivery regimens often cause severe side effects, multi-drug resistance phenotypes, and in some cases, a total lack of efficacy.

Our group addresses challenges in therapeutic delivery by coupling “traditional” chemical engineering strengths in molecular design, molecular self-assembly, and chemical reaction kinetics with cross-disciplinary strengths in cell and extracellular matrix (ECM) biology and the cell-material interface. We develop and use nanoscale materials to understand and probe cellular “unit ops,” with long-term applications including targeted drug delivery for prostate and breast cancer, and gene therapy for wound and tissue repair.”

Donna Woulfe, Ph.D.

Associate Professor

Areas of Special Interest: Dr. Woulfe's research interests focus primarily on the intracellular signaling mechanisms of platelet activation and how signaling in platelets contributes to thrombosis in vivo. Agonists that extend formation of the platelet plug generally bind to G protein-coupled receptors on the platelet surface. Dr. Woulfe's previous studies have focused on how platelets become activated by agonists that bind to G protein-coupled receptors and how platelet signaling stabilizes platelet aggregates as they grow. A key finding from these studies was that platelets from mice lacking certain isoforms of the serine/threonine kinase Akt (particularly Akt2) have defects in platelet secretion, fibrinogen binding, and stable aggregate formation. Akt2-/- mice are also resistant to thrombosis in an arterial injury model. In contrast, the Akt substrate, Glycogen synthase kinase (GSK)3beta, is a negative regulator of platelet signaling and thrombosis. Platelets from mice lacking one allele of GSK3beta are hyperresponsive to agonists and the mice are more susceptible to thrombosis than their wildtype counterparts. We have more recently shown that arrestin-2 regulates the function of PI3K and Akt signaling and function in platelets and have new collaborative projects centered on understanding the influence of hyperglycemia/diabetes on platelet function in vitro and in vivo.

Our newest work focuses on understanding novel interactions of platelet surface molecules and how they contribute to platelet signaling and thrombosis.  In this regard, we are focusing on the agonist-dependent interaction of the thrombin receptor PAR4 with the ADP receptor P2Y12.  We are also working to understand the stoichiometry and function of P2Y12 in resting and activated platelets and how two mutations in P2Y12 identified in patients with bleeding disorders may alter the interactions of P2Y12 with itself, G protein, or other receptors.  Finally, we are exploring the role of a novel Ca++-dependent Ca++ channel, termed TMEM16f or anoctamin 6, in the shedding of small platelet fragments called microparticles.  Preliminary data suggest that these platelet-derived microparticles may contribute to thrombosis and understanding the mechanism by which pro-coagulant microparticles are generated may suggest novel ways to inhibit their generation, function and ultimately, reduce cardiovascular risk.