BIOTECHNOLOGY TRAINING PROGRAM
Antonio Barberio – Hammond Laboratory
Research Project: My research focuses on tailoring our well developed layer-by-layer nanoparticle system for use in immunotherapies of ovarian cancer. Immunotherapies show great promise in cancer treatment because of their use of the bodies natural defense against disease and their universality. Cancer can be very tricky to treat because of the differences between different types of cancers. Even cancers of the same tissue of origin can express very different bio markers and genetic footprints based on the mutations that led to disease. My goal is to avoid trying to focus on specific aspects of the tumor tissue to treat disease and instead, using layer-by-layer nanoparticles, deliver potent immune activators to the tumor environment, activating the patient’s immune system to fight the tumor. This approach is designed to deliver cytokines that were previously too toxic for systemic delivery by masking the agents from the body using layer-by-layer until they are delivered to the tumor micro environment alone. This approach lends itself to using many activators including many cytokines previously abandoned for their toxicity. It also opens the door to many combination therapies which have proven to be very useful in immunotherapy through the use of embedding different agents in the different particle layers.
Chet Berman – Shoulders Laboratory
Research Project: Successful design of biomolecules of interest has been accomplished primarily using the principles of directed evolution. Through repeated rounds of mutagenesis and selection, scient¬¬¬ists have created countless new biomolecules with entirely novel functions. While it is a powerful technique, directed evolution is limited by a number of factors. Most current selection processes are cumbersome and require the researcher to screen variants for the desired activity. Furthermore, methods such as phage display, PACE, and yeast surface display are ill suited to evolve biomolecules that can function in metazoan cells. This is because the selection process takes place in an environment that differs greatly from that in which the biomolecule is intended to function. I am therefore developing new methodologies for evolving biomolecules in human cells.
Bernardo Cervantes – Prather Laboratory
Research Project: The gut microbiome field is primed for the study of the underlying mechanisms that decide whether a newly arrived microbe succeeds or fails at colonizing. Considerable effort has been invested to improve our understanding of the composition of the human gut microbiome as well as to increase our ability to culture individual members of the microbiome. Up to 77% of the identified prokaryotes in the human microbiome can now be cultured. In addition, the impact of negative microbe-microbe interactions and dynamics of resource degradation/consumption have been shown to be fundamental to the rules of microbial community assembly ex-vivo. My work aims to use this fundamental knowledge and take advantage of high-throughput screening and metabolic engineering to produce negative microbe-microbe interactions that can be leveraged to competitively exclude pathogens from colonizing the human microbiome.
Steve Cohen – Drennan Laboratory
Research Project: Acetogenic organisms use the greenhouse gas carbon dioxide as their sole carbon and energy source using the Wood-Ljungdahl pathway of carbon fixation. This pathway plays a major role in the global carbon cycle, but we have an incomplete understanding of the proteins responsible for the underlying chemistry. My research focuses on using biophysical tools, including crystallography, electron microscopy, and computational simulations, to study how the structures and dynamics of these proteins facilitate their unique and challenging chemistry.
Nick Davis – Dedon Laboratory
Research Project: My research aims to decipher how modifications to non-coding RNA dictates cellular phenotype by regulation of translation.
Stephanie Doong – Prather Laboratory
Research Project: Directed evolution to improve enzyme activities is an attractive method to increase titers in microbial chemical synthesis. However, conventional analytical methods such as chromatography are slow and low-throughput, rendering these projects impractical. Biosensors are one means of providing an efficient, high-throughput screen for products or pathway intermediates. By connecting a reporter, such as a fluorescent protein, to the genetic sensing device, cells can produce an easily-measurable, quantitative output in response to the detected molecule. Biosensors can also be used for dynamic pathway regulation, improving enzyme activity and pathway efficiency by expressing enzymes only when the substrate is present. I am devleoping a biosensor for myo-inositol, an intermediate in the D-glucaric acid pathway.
Rebecca Du – Bathe Laboratory
Research Project: Small interfering RNAs (siRNAs) operate within the RNA interference pathway (RNAi) to degrade target mRNA transcripts and control gene expression in a range of essential biological processes. Given the high sequence specificity and catalytic activity of siRNAs, as well as the fact that they function through an endogenous pathway, siRNAs have remarkable potential for targeted gene silencing. Unfortunately, their potential has not yet been realized, in part because siRNA formulations currently in clinical trials typically use a single siRNA to downregulate a single target transcript, whereas in reality many diseases are caused by dysregulation of multiple genes. In order to overcome this major limitation of current siRNA strategies, my research will investigate the use of structured siRNA/DNA nanoparticles for multiplexed gene silencing. This approach offers the unique ability to deliver precisely controlled amounts of multiple distinct siRNAs through rational design of the nanoparticle scaffold and staple sequences, which can be used to induce maximal gene silencing while minimizing off-target effects. My project will offer mechanistic insight into siRNA-mediated gene knockdown, as well as major potential for therapeutic siRNA applications.
Lisa Guay – Prather Laboratory
Research Project: Biomanufacturing is a sustainable alternative for the production of fuels and chemicals. However, extensive genetic engineering is typically required for economic viability. Directed evolution is a powerful protein engineering method that has been used to increase industrial product yields and selectivity. Nonetheless, directed evolution is often time-consuming and context-dependent. My research is focused on improving the efficiency of protein engineering for whole pathways of enzymes. To this end, I am exploring how the conditions under which directed evolution are applied influence practical outcomes. In particular, I am investigating how much the thermostability of the starting enzymes matters and how systems respond to simultaneous versus sequential evolution of enzymes.
Emi Lutz – Wittrup Laboratory
Research Project: The STING pathway is part of the innate immune system. Activation of STING spontaneously or via exogenous agents can elicit strong antitumor immunity. This project aims to develop novel therapeutics that activate STING in the tumor microenvironment for improved control of tumors and metastases.
Manu Kumar – Lauffenburger Laboratory
Research Project: My research project is Multi-scale modeling of the immune system. Originally from New York, he completed his B.S. in Bioengineering from the University of Illinois at Urbana-Champaign with a focus on computational and systems biology. Manu developed his appreciations for effective writing and communication as a participant in the 2013 Amgen Scholar Program, which emphasized the importance of strong communication skills for scientists. Both at Illinois and MIT, Manu has enjoyed participating in student government, and he is currently serving as the first year representative on the BE graduate student board. When he isn’t in lab, which is always since he does computational work, Manu enjoys getting lost on runs, lost in books, or lost in thought.
Research Project: Despite their profound legacy in combatting infectious disease, vaccine contribution to cancer therapeutics has been modest at best. To strengthen T cell-stimulating subunit vaccines, we have previously developed lipid-formulated vaccine components that interact with serum albumin upon injection, promoting efficient uptake in lymphoid organs and a dramatic increase in potency. To facilitate clinical translation and to potentially improve upon this strategy, we working on elucidating the mechanism behind this strategy. In particular, we are investigating the role of protein carriers in engineering more potent subunit vaccines.
Lauren Milling – Irvine Laboratory
Research Project: Stimulation of the innate immune system has become an attractive strategy for overcoming the immunosuppressive tumor microenvironment. Agonists of the stimulator of interferon genes (STING) pathway, which trigger innate immune activation, can induce durable antitumor responses. However, this drug class generates widespread inflammation – a serious safety concern for patients. My research explores the use of nanoparticles to restrain STING agonists within tumors, target uptake to innate immune cells, and direct subcellular localization. We have tested these nanoparticle delivery strategies in a surgical resection model of recurrent breast cancer in mice and continue to characterize the fine balance between immune activation and safety of cancer immunotherapies.
Noor Momin – Wittrup Laboratory
Research Project: An improved understanding of immune mechanisms in cancer has informed productive interventions using combination therapies. However, with multiple agents, toxicities become increasingly prevalent and severe thereby hindering these treatments from reaching their full curative potential. Particularly now during an era of combination immunotherapy, there is a pressing need to develop a safe and efficacious delivery platform for immunotherapies. Improving the therapeutic index amounts to better localizing the effects of immunomodulatory agents to the tumor. To this end, we intend to develop a platform for intratumoral localization of immunomodulatory payloads via fusion to extracellular matrix-binding modules.
Maxwell Nagarajan – Doyle Laboratory
Research Project: Our research focuses on fundamental and applied topics in soft matter. Much of our research is in the realms of micro/nanofluidic technologies, DNA biophysics, biosensing and rheology. A burgeoning interest is the use of microfludics to synthesize microparticles for both fundamental colloidal studies and applications, such as multiplexed sensing, biomimetic systems and catalysis. We utilize both experimental and computational approaches in our research in order to understand fundamental issues in a wide variety of applications ranging from lab-on-chip separations to polymer rheology to reservoir engineering.
Elizabeth Pearce – Birnbaum Laboratory
Research Project: Her research interests include examining non-immunodominant immune responses to aid in creating better cancer therapies.
Anthony Quartararo – Pentelute Laboratory
Research Project: Protein-protein interactions play critical roles in governing normal cell physiology, but remain challenging drug targets due to their large surface areas of interaction. While antibodies represent the state-of-the-art in this regard, they have limited amenability to chemical tailoring, and cannot cross the cell membrane to reach intracellular targets. In the Pentelute lab, we are interested in the discovery of synthetic, protein-like polymers, termed “xenoproteins,” to address this problem. Specifically, my research is focused on the development of a one-bead-one-compound-based platform for synthesizing and screening large libraries of xenoproteins, and identifying binders to targets of interest. Importantly, the scaffolds to be screened, based on a cystine knottin microprotein, are engineered to be protease-resistant, containing all D-amino acids, and can fold even with extensive randomization and modification. Based on literature precedent for other cystine knottin family members, these scaffolds will also be engineered for cell penetration, with the goal of expanding the scope of the platform to targets within the cytosol.
Adrienne Rothschilds – Wittrup Lab
Research Project: The field of cancer antibody therapeutics has long been dominated by IgG isotype antibodies, with successful IgG treatments such as Trastuzumab and Rituximab against breast cancer and leukemia, respectively. Although IgE isotype antibodies have traditionally been characterized as agents in allergic immune responses, the potential for new cancer immunotherapies using IgE rather than IgG is promising for several reasons. The relatively low concentration of IgE in blood serum (0.02% of circulating immunoglobulins compared to 85% IgG) results in reduced competition of therapeutic IgE for its receptor on effector cells. Additionally, IgE has the high affinity of 1010 M-1 for its FcεRI receptor on its effector cells. My project is exploring the mechanism of IgE as a cancer immunotherapeutic in combination treatments with IgG or other immune system modulators.
Alison W. Tisdale – Wittrup Laboratory
Research Project: A variety of cancers are marked by the overexpression and over-activity of the EGF receptor (EGFR), rendering this protein an attractive therapeutic target. While much research effort has been devoted to development of antibody-based therapeutics against EGFR, including the FDA-approved drugs panitumumab and cetuximab, clinical success has been limited. In particular, mutations in the downstream effector proteins ras and raf are a major cause of low efficacy.
My project focuses on the design of novel antibody-based therapeutics for superior inhibition of EGFR signaling. Building on previous work from the Wittrup lab I will aim to engineer molecules which combine desirable characteristics such as enhanced ligand competition and rapid downregulation of cell-surface receptors as well as favorable biophysical properties.
Alex Wang – Griffith Laboratory
Research Project: My main project is on the design of biomaterials for liver culture. The complex architecture and function of the liver presents a unique challenge in designing physiologically relevant in vitro models. Combining a variety of biology and engineering principles, these models can be more relevant in applications such as drug metabolism and cancer metastases than traditional animal studies. I am using tissue engineering design principles, as well as unique biochemical technologies, to build scaffolds that are both conducive to hepatocyte culture and readily characterized. The application of universal design principles allows these matrices to be adapted for a variety of culture applications that allow us to better study cell signaling and tissue formation in an environment that mimics the native cell state.
Stephanie Wang – Lauffenburger Laboratory
Research Project: Prior work in the lab has demonstrated that resistance to certain targeted cancer therapies, such as kinase inhibitors that impact the MAPK pathway, may arise via reduced proteolytic shedding of receptor tyrosine kinases (RTKs). Increased accumulation of these cell-surface RTKs can lead to bypass signaling and cellular responses that the original therapy intended to inhibit. My research project focuses on characterizing this mechanism in the context of ovarian cancer, since there is a relative lack of effective targeted therapeutics for this disease and a sizeable portion of disease cases are associated with dysregulated MAPK signaling. In addition, I am also interested in investigating how cross-talk between tumor and immune cells may contribute to chemoresistance.
Elizabeth Ward – Imperiali Laboratory
Research Project: Protein glycosylation is present in all domains of life. Prokaryotes are decorated with complex sugar assemblies that facilitate numerous cellular behaviors. The diversity of bacterial glycans has lead to challenges in their study, as the field is lacking in protein-based reagents for their identification. My project is focused on the development of glycan binding proteins through directed evolution that can be functionalized for many uses including cell selection, imaging, and affinity purification.
Kelsey Wheeler – Ribbeck Laboratory
Research Project: The goal of my research is to understand how the mucus environment influences microbial physiology and community dynamics. In particular, I am interested in how mucins modulate virulence and ultimately affect interactions among commensal and pathogenic microorganisms.