TRAINEES

CBI trainees come to Illinois from highly regarded undergraduate programs, nationwide. Regardless of their undergraduate majors, they have in common the potential to perform cutting-edge discipline-spanning work at the interface of chemistry and biology.

 

Alec Murray

Enzymes are responsible for the majority of life’s processes. Greater understanding of the active site, the catalytic mechanism, and allosteric pathways could grant insight into methods to improve or control catalytic activity. Throughout my experience as a CBI trainee, I hope to better understand these complex systems and apply this knowledge to the fields of medicine or protein engineering.

CBI Cohort 2021

Chemistry

Jesse Horne

Inspiration for future drug leads often comes from the world around us— the natural world. Both plants and microorganisms provide an untapped potential for novel pharmaceutical compounds— including for the treatment of cancer, Alzheimer’s disease, and many others. My previous research experience while at The University of Alabama included a nanoparticle-based drug discovery platform for sodium-ion channel subtype-selective drug leads to inhibit cancer metastasis with Dr. Yuping Bao. The platform was also evaluated for determining tropomyosin receptor kinase B binders towards future Alzheimer’s disease treatments. I have also worked with Dr. Ryan Summers to determine caffeine’s effect on the common reporter gene lacZ in Escherichia coli. Broadly, my interests include synthetic biology, microbial engineering, bioprocessing, and cell culture. I look forward to continuing the applied engineering of biological systems

CBI Cohort 2021

Chemical and Biomolecular Engineering

Dylan T. Blaha

T cells are critical for the destruction of virus-infected cells and cancer cells. The key cell-surface molecule involved in recognition of the virus or cancer antigens is called the T cell receptor (TCR). The TCR binds to an antigen peptide delivered to the cell surface and presented by our own proteins, encoded by the major histocompatibility complex (MHC), known as human leukocyte antigen (HLA) in humans. Graft vs leukemia (GVL) results from the treatment of patients with an HLA-mismatched (allogeneic) bone marrow transplantation. Researchers attribute the clinical benefit of GVL to allogeneic MHC that induce strong T cell responses. In a previous collaboration, we showed it was possible to use a single mutation in a murine MHC molecule to generate ‘allo-like’ reactions that could overcome tolerance and induce anti-cancer cytotoxic T cells. I hypothesize that it is possible to experimentally identify the most therapeutically effective MHC mutants using deep mutational scans of MHC molecules, screening for both MHC protein stability and TCR affinity. Candidate MHC mutants will possess the ability to present cancer antigens that overcome tolerance. To test this, I will use a mouse MHC protein, and three syngeneic mouse models with the glioblastomas GL261, SMA-560, and CT2A. The results will also provide a deeper understanding of the molecular details of interactions among peptides, class I MHC proteins, and TCRs.

CBI Cohort 2020

Biochemistry, Kranz lab

Hashni Epa Vidana Gamage

Breast cancer is the most common malignancy amongst women worldwide. Immune-oncology interventions for the treatment of breast cancer have thus far been underwhelming, providing strong rationale for the development of drugs to increase their efficacy. Although undoubtedly multifactorial, one major obstacle to immune-therapy is the highly immune-suppressive microenvironment of breast tumors – a phenomenon that is strongly maintained by myeloid immune cells. Our work focuses on developing small molecule modulators of the nuclear receptor Small Heterodimer Partner and Farnesoid X Receptor, and specific probiotic approaches to ‘re-educate’ myeloid cells away from being pro-tumorigenic to eliminate the immune-suppressive microenvironment of breast tumors. Reactivation of the immune system is expected to enhance the efficacy of immunotherapy and provide durable or curative care for metastatic breast cancer patients.

CBI Cohort 2020

Molecular and Integrative Physiology, Nelson lab

Megan Ringling

An overall focus in the Blanke lab is to understand the mechanisms secreted bacterial protein toxins use to modulate host cells, and how that modulation contributes to a pathogen-produced disease state in humans. The goal of my research is to characterize the molecular basis and mechanism that leads to the known risk for development of gastric cancer, an increased risk that is solely due to infection with human gastric pathogen Helicobacter pylori (Hp). Specifically, I am characterizing a prominent secreted virulence factor, vacuolating cytotoxin A (VacA), and how the variation within the gene encoding VacA contributes to the known risk for gastric cancer development. Since VacA is secreted into the extracellular environment, it is a useful target for drug development, my work can be a foundation for strategies that could be developed to neutralize toxins before they enter host cells.

CBI Cohort 2020

Microbiology, Blanke Lab

Joenisse M. Rosado-Rosa

Since the development of antibacterial drugs, the emergence of drug-resistant bacteria have posed a huge challenge for treating bacterial infection, especially in case of multidrug-resistant bacteria. There has been a significant efforts from the scientific community to develop novel antibiotics that can counteract these. Complementary to these efforts, the National Vaccines Advisory Committee has called for developing vaccines against drug resistant bacteria. During my graduate studies, I aim to develop platforms to develop live attenuated vaccine candidates. I envision doing this by engineering a biorthogonal system to utilize an unnatural analog of essential cofactor found in central metabolism pathways such as glycolysis, TCA cycle, among others, in virulent bacterial strains. As a result of this, the virulent bacteria will only be able to survive in the presence of a defined unnatural cofactor; consequently, this will control the bacterial growth in vivo which will leading to virulence attenuation after a defined period of time, creating a live attenuate vaccine candidate. Particularly, I am targeting essential Nicotinamide adenine dinucleotide (NAD) dependent enzymes. I have designed synthetic strategies to substitute the adenine moiety with noncanonical hydrophobic bases that disrupt hydrogen bonding interactions in the enzyme’s active site and create a biorthogonal enzyme that utilizes defined unnatural cofactor analog. This will impede scavenging, thus causing the bacterial strain to have deterred growth in the absence of the noncanonical cofactor, leading to in vivo attenuation.

CBI Cohort 2020

Chemistry, Mehta lab

Kai Gui

Alzheimer’s disease is a complex neurodegenerative condition with limited therapeutic options. Recent developments for new treatments have focused on targeting amyloid beta peptide aggregation, but this strategy has shown little success in clinical trials. New potential therapeutic targets are emerging, including hyperphosphorylated tau protein, metal dyshomeostasis, oxidative stress, neuroinflammation and mitochondrial dysfunction. My research involves the design and synthesis of novel multi-functional compounds, chemical agents that target multiple hallmarks of Alzheimer’s disease for therapeutic and diagnostic purposes. Molecules that modulate mitochondria health, an understudied therapeutic target, are of special interest to my research

CBI Cohort 2020

Chemistry, Mirica lab

Jonnathan Marin

Cystic Fibrosis (CF) is a hereditary disease caused by loss of function mutations in the CFTR anion channel, which is responsible for HCO3- and Cl- secretion in airway epithelia. As is also the case for other channelopathies, current treatment options do not address functional deficiency for all mutations. The field of molecular prosthetics offers a unique and broad treatment option for this class of diseases. Our group has previously shown that a molecular prosthetic candidate, Amphotericin B (AmB), a polyene macrolide natural product, can restore HCO3- secretion in cultured CF airway epithelial due to its capability of self-assembling into a multimeric ion channel. Preliminary data from our group, in addition to biological inspiration, suggest that the ion-selectivity of AmB could be tuned through synthetic modifications. I aim to synthesize targeted derivatives of AmB, modified on the pore-lining region of the channel, and study the ion selectivity and other electrophysiological parameters. These studies will enable a better understanding of the underlining small molecule base ion channel function and corresponding therapeutic potential for various channelopathies.

CBI Cohort 2020

Chemistry, Burke lab

Melanie Brunet Torres

Influenza is an infectious virus that causes a potentially life-threatening respiratory tract
infection known as the flu. Towards the end of its replication cycle, the influenza viral components
assemble in the host cell’s plasma membrane and they are surrounded by a lipid-containing
envelope as the progeny virus buds from the host cell. The influenza A viral envelope is enriched
with cholesterol and sphingolipids, and drugs that deplete their levels in the host cell are correlated
with lower influenza virus production. Based on numerous indirect studies, the influenza virus is
hypothesized to assemble and bud from plasma membrane domains that are enriched with
cholesterol and sphingolipids. This hypothetical cholesterol and sphingolipid enrichment at the
site of influenza A virus assembly and budding has not been definitively established. This is
because cholesterol and sphingolipids cannot be imaged at the site of influenza virus budding
unless fluorophores that may alter the intracellular lipid distribution are used. My research aims to
overcome this obstacle by using the high-resolution NanoSIMS method developed in my advisor’s
lab for imaging rare isotope-labeled lipids with as high as 90-nm-lateral resolution. The ability to
visualize the majority of the cholesterol, sphingolipid, and influenza hemagglutinin proteins at the
site of influenza budding will be a definitive test of the hypothesis that the influenza virus buds
from cholesterol and sphingolipid-enriched plasma membrane domains.

CBI Cohort 2020

Chemical and Biomolecular Engineering, Kraft lab

Mandira Banik

The blood-brain barrier is a highly selective layer of endothelial cells that impedes passage of 98% of all known small molecules, inorganic complexes, and DNA-based probes into the brain. Furthermore, the central nervous system’s complex vasculature often results in inconsistent probe uptake by target neural and glial cells. Due to these major challenges, many powerful probes for small molecules and metal ions implicated in brain illnesses have limited use as in vivo detection agents. My research focuses on the development of biocompatible, noninvasive, and highly specific endogenous and artificial nanocarriers to deliver sensors for transient and essential small molecules and metal ions across the blood-brain barrier. This will further our knowledge of neurodegenerative disorders and brain cancers.

CBI Cohort 2020

Chemistry, Lu lab

Susanna Barrett

Natural products and their derivatives make up a large portion of the antibiotic structural space. However, the list of new antibiotic scaffolds has barely grown in the past 50 years which has led to rampant antibiotic resistance with very few avenues to combat it. With advancements in bioinformatics, ribosomally synthesized and post translationally modified peptides (RiPPs) have become easier to identify than ever before and many of these peptides have the potential to become powerful therapeutics. One class of RiPP, the lasso peptides, holds great clinical promise due to their excellent proteolytic and thermal stability. Additionally, their relatively promiscuous modifying enzymes enable the creation of large libraries which I plan to harness to engineer a lasso peptide with improved antibiotic activity. Furthermore, I aim to create a suite of lasso peptide analogs that work together to wipe out common resistance mutations, creating a therapeutic platform that not only kills the bacteria, but also combats its predictable evolutionary countermoves.

CBI Cohort 2020

Chemistry, Mitchell lab

Alex Battiste

The recent explosion in genomic data, accompanied by advances in bioinformatic tools, has generated a treasure trove of information about bacterial natural products.  Since most drugs, including antibiotics, are based off natural products, this information offers a novel route for the discovery of new antibiotics.  However, our ability to rapidly purify novel natural products has remained limited because many of them are not expressed under standard laboratory conditions.  My research aims are to use bioinformatic tools to identify novel natural products, including natural products of previously uncharacterized classes, and to develop improved ways of isolating these identified natural products, primarily utilizing heterologous expression in easily manipulatable hosts such as E. coli.  These novel natural products will then be tested for antimicrobial activity in the hopes of developing promising antibiotic lead compounds. 

CBI Cohort 2020

Chemistry, Mitchell lab

Katherine Greskovich

Neurodegenerative amyloid diseases, including Alzheimer’s Disease and Parkinson’s Disease, are an increasing health burden in the United States. These diseases are characterized by the intracellular or extracellular agglomeration of peptide β-sheets (amyloid fibrils) associated with neuronal cells. As of now, no cure nor early diagnostic test exists for these diseases. My research involves the synthesis of gold nanoparticle agents that absorb in the near-IR region and are functionalized with small molecule agents that target amyloid fibrils, allowing for early-stage detection and possible interception of amyloid fibrils in vivo.

CBI Cohort 2020

Chemistry, Mirica lab

Sydney McKee

Natural products encompass a broad spectrum of the pharmaceutical industry, including prolific anticancer therapeutics such as vinblastine and Taxol. My research focuses on the selection of natural products with synthetically tractable scaffolds that have previously shown promising anticancer activity but have not yet been further pursued. I will synthesize these compounds and variants thereof, with the aim of potentiating desirable activity, and will perform target identification analyses to elucidate novel or underrepresented pathways. Additionally, I intend on continuing to probe the mechanistic pathways and efficacy of a novel analog for the treatment of glioblastoma multiforme (GBM), a malignant brain tumor in which therapeutic options are scarce. Current chemotherapy relies on temozolomide, a DNA alkylating agent that is inefficacious for those harboring MMR deficiencies and/or those expressing MGMT. The generation of a therapeutic that circumvents these mechanisms of resistance could benefit a larger population afflicted with GBM.

CBI Cohort 2020

Chemistry, Hergenrother lab

Michael Mulligan

The advent of large chemical libraries and high throughput screening has enabled the rapid identification of drug candidates for cancer allowing for more drug personalization than previously possible. The specificity granted by this approach is often necessary to selectively differentiate cancer cells from healthy cells. My research is focused on identifying small molecules with anticancer activity, and performing subsequent SAR studies which simultaneously inform protein target identification campaigns as well as identify analogs with promising therapeutic potential. This approach seeks to pair translational relevance with the exploration of fundamental chemical biology through the elucidation of novel protein targets/pathways.

CBI Cohort 2020

Chemistry, Hergenrother lab

Andrew Rice

Thiopeptides are a class of ribosomally-synthesized and post-translationally modified peptides (RiPPs) that are heavily modified, incorporating thiazol(in)es, dehydroalanines and dehydrobutyrines, and a formal aza-Diels-Alder reaction to form a nitrogenous heterocycle. Recently, bioinformatic efforts have highlighted the incredible structural diversity that remains to be explored within this class. My research will involve the bioinformatics-guided discovery of novel thiopeptides, as well as interrogating the mechanism of the formal aza-Diels-Alder reaction.

CBI Cohort 2020

Chemistry, Mitchell lab

Jazmin Aguilar-Romero

Polymeric nanoparticle drug delivery systems have tremendous potential for controlled release of therapeutic agents (e.g., small molecules, siRNA) to targeted cells under physiological conditions. However, degradation of commonly used polyester-based delivery systems relies on bulk erosion hydrolysis and is thus very slow and unresponsive to the range of physiological conditions found within cells and tissues. The goal of my research is to synthesize an acid-degradable, acid-amplifying nanoparticle that is sensitive to the lower pH values observed in endosomes and among certain tissues. My initial challenge has been to develop a system that is stable to physiological pH (7.4), but quickly degrades at endosomal pH (6.0-6.5). These features would promote endosomal release as well as enable targeting of acidic cancer tissues. Thus, two potential applications on which I am focused are (1) improved delivery into cells via endocytosis and (2) amplifying the slightly acidic pH in tumor tissue for targeting of cancer cells. 

CBI Cohort 2019

Chemistry, Zimmerman lab

Sara Eslami

As antibiotic resistance becomes increasingly prevalent, discovery of new antibiotics and investigation of novel mechanisms to treat bacterial infections has become a burgeoning area of research. Lanthipeptides, a class of natural products, are ribosomally synthesized and post-translationally modified peptides i.e. RiPPs, characterized by post-translationally crosslinked lanthionine residues. The van der Donk group has been particularly instrumental in discovering and elucidating the mechanisms behind this class of RiPPs. My research involves utilizing bioinformatics to discover previously unidentified lanthipeptides as well as novel biosynthetic enzymes and their corresponding natural products.

CBI Cohort 2019

Chemistry, van der Donk lab

Rachel Martini

Research Description: Cytochrome P450s (CYP) are proteins present in all domains of life that catalyze diverse monooxygenation reactions which are important for many biological functions and biopharmaceutical applications. One of their important features is their self-protection mechanism that directs the oxidizing power of the enzyme towards the substrate instead of allowing it to damage the enzyme itself. This gives CYPs the high turnover rates that make it a good candidate for use in biocatalysis. In order to better understand this mechanism and allow for its adaptation in other enzymes, my work will focus on installing a similar self-protection mechanism into an artificial enzyme that mimics CYP with high activity.

CBI Cohort 2019

Biochemistry, Lu lab

Catharine Brady

Reactive oxygen species (ROS) are short lived and chemically reactive species containing oxygen such as singlet oxygen, superoxide, and peroxynitrite. At endogenous concentrations, these species have been shown to be important in cellular signaling and redox homeostasis. Alternatively, increased levels are associated with oxidative stress, are damaging to cells, and can result in apoptosis and necrosis. My research is focused on developing small molecule near-infrared light-controllable donors of ROS to allow for spaciotemporal control and monitoring of dosage to help study the roles and pathways of ROS, as well as applying these donors to photodynamic therapy of cancer.

CBI Cohort 2019

Chemistry, Jefferson Chan lab

Gabriela Ibarra

Ultrasound imaging is one of the more cost-effective and wide-spread imaging modalities in the clinic. Soundwaves have deeper penetration capabilities than light, which makes ultrasound one of the premier modalities for deep tissue imaging and allows for the noninvasive diagnosis of diseased states. To improve the image quality and contrast of ultrasound images, gas-filled microbubbles can be administered to serve as ultrasound contrast agents. However, due to their size, current ultrasound contrast agents limit the use of ultrasound imaging to only studying circulation related conditions. My project involves the development of stimuli responsive nanobubbles as ultrasound contrast agents to expand and improve the use of ultrasound to study inflammation, cardiovascular disease, and cancer.

CBI Cohort 2019

Chemistry, Jefferson Chan lab

Aliki Kolliopoulos

Advances in the field of tissue engineering are increasingly reliant on biomaterials that instruct, rather than simply permit, a desired cellular response. Craniofacial bone defects are common in the context of congenital, traumatic, and post-oncologic conditions. Such bone defects are often large in size and heal poorly, motivating regenerative medicine efforts. A particular barrier to regenerative healing is the significant immune and inflammatory response post injury which can inhibit cell recruitment, vascular remodeling, and new tissue biosynthesis. My laboratory is developing a class of mineralized collagen biomaterial capable of meeting a wide range of design requirements for successful deployment into CMF bone defects, notably the ability to conformally fit complex defect geometries and support stem cell osteogenesis. My research aims to understand the effect of scaffold biophysical properties (microstructure, stiffness, alignment, mineral morphology) on the recruitment and subsequent activation status of macrophages. My ultimate goal is to demonstrate biomaterials capable of modulating the kinetics of the macrophage response post injury as a means to accelerate implant integration and subsequent bone regeneration.  

CBI Cohort 2019

Chemical and Biomolecular Engineering, Brendan Harley lab

Sophie McClain

Under normal physiological conditions, alpha-synuclein is an intrinsically disordered neuronal protein primarily localized in the presynaptic terminals of nerve cells.  However, abnormal alpha-synuclein accumulation in the brain is a prominent pathogenic feature in a number of neurodegenerative diseases including multiple system atrophy, dementia with Lewy bodies, Alzheimer’s disease and, most prevalently, Parkinson’s disease. It is widely accepted that these aggregates are in large part composed of oligomeric alpha-synuclein fibrils rich in beta-sheet character; however, the initial driving force behind aggregation and the aggregation pathway of alpha-synuclein are not well understood. My research aims to improve our understanding of alpha-synuclein conformation and aggregation as it relates to the chemistries the protein encounters in its local environment. Gold nanoparticles provide a readily modifiable platform with which to model interactions between alpha-synuclein and nanoscale biological entities such as lipid vesicles through variations including nanoparticle size, shape and surface chemistry. Uncovering new information regarding the fundamental properties and behaviors of alpha-synuclein will improve our understanding of its native function as well as the role it plays in the development of Parkinson’s and other neurodegenerative diseases.

CBI Cohort 2019

Chemistry, Cathy Murphy lab

Andrew Blake

Many human diseases are tied to lack of protein function. These diseases present challenging targets for modern therapeutics, as traditional drugs do not impart missing functionality into a system.  Use of a small molecule replacement, or molecular prosthetic, could serve to directly replace missing function, thereby treating the fundamental cause underlying these diseases. Our lab has recently demonstrated the ability of one such small molecule, hinokitiol, to serve as a molecular prosthetic iron transporter via mobilizing iron across cell membranes. My project primarily aims to expand the breadth of transporter deficiencies treated by hinokitiol. I also seek to understand the fundamental biophysical factors governing transmembrane transport by small molecules, with the goal of engineering this functionality into otherwise bioactive molecules.

CBI Cohort 2018

Biochemistry, Martin Burke lab

Zac Dewald

RNA-dominant diseases are a class of degenerative diseases affecting neurological, muscular and cardiovascular function and include notorious disorders such as myotonic dystrophy, fragile X syndrome and spinocerebellar ataxia. Currently, there are no cures for RNA-dominant diseases, due in part to a lack of understanding of the mechanisms that drive these diseases as well as gaps in the therapeutic development pipeline. My research focuses on developing unique, conditionally active animal models which I can then use to study the mechanisms driving the RNA-dominant diseases in a highly controlled manner and help accelerate the drug development process. My work currently focuses on the disease Myotonic Dystrophy type one, but these models can be adapted to aid research in a wide range of diseases.

CBI Cohort 2018

Biochemistry, Auinash Kalsotra lab

Jiming Chen

Ligand selectivity is an important consideration in drug design since it is often desirable to target a specific protein with minimal effect on other similar proteins. The origins of ligand selectivity are not always apparent from protein structures because different proteins with highly conserved sequence, structure, and binding pocket residues can have significantly different affinities to the same ligand. An example is strigolactone receptors in the parasitic weed Striga hermonthica, which have a ~10000-fold higher affinity to the ligand than strigolactone receptors in host plants. My project aims to use ancestral gene reconstruction in conjunction with molecular simulation to resolve the mechanistic origin of this high ligand affinity difference between the parasite and host plant receptors

CBI Cohort 2018

Chemical and Biomolecular Engineering, Diwakar Shukla lab

Tim Precord

Natural products and their derivatives constitute a significant portion of clinical therapeutics. In an era of rapidly expanding antibiotic resistance among clinically problematic bacteria, the importance of novel natural compound discovery is paramount. Modern advancements in genomics has facilitated the discovery of ribosomally-encoded peptidic natural products and can be leveraged for the exploration of uncharacterized natural compound chemical space. Among these, the radical S-adenosyl methionine enzyme-tailored ribosomal peptides represent a significantly diverse and underexplored subclass of natural products. My bioinformatics-guided investigation of this group of peptides has the potential to uncover a broad range of new chemical structures that may be tested for activity as lead compound scaffolds as well as reveal fundamental natural product chemistry.

  

CBI Cohort 2018

Chemistry, Douglas Mitchell lab

Kristen Muñoz

Gram-negative bacteria have emerged that are resistant to most antibiotics, a troubling trend since a new class of antibiotics for Gram-negative pathogens has not been introduced in the clinic in 50 years. Central to the issue with discovering novel antibiotics for Gram-negative bacteria is the limited understanding of the physicochemical features that affect cell-membrane permeability and accumulation within these pathogens. As a result, we are interested in elucidating the physicochemical parameters necessary for small molecules to accumulate in Escherichia coli, a problematic Gram-negative pathogen.

CBI Cohort 2018

Chemistry, Paul Hergenrother lab

Roy J Rodriguez Carrero

Methane has an important role in the global carbon cycle and it has significant economic and environmental consequences. Biological methane is produced solely by an unusual group of archaeal organisms known as methanogens. The metabolic pathway for methane production involves a set of unusual enzymes and cofactors rarely seen outside of methanogenic archaea and anaerobic methane-oxidizing organisms. Among these, one of the most interesting enzymes is methyl-coenzyme M reductase (MCR), which catalyzes the last step in methanogenesis and the first step in anaerobic methane oxidation. MCR contains several unusual modified amino acids, the role of which is mostly unknown. My research project aims to understand why these modifications are found in MCR. The difficult nature of MCR has made it a challenge to elucidate the many mysteries that surround this enzyme. However, using a mix of bioinformatic, genetic and biochemical approaches it is possible to formulate a plan to answer some pertinent questions about this enzyme.

CBI Cohort 2018

Microbiology, Bill Metcalf lab

Lindsay Chatkewitz

Personalized cancer therapies are quickly becoming the preferred method of treatment for many cancer patients. Identification of the cause of carcinogenesis is the first step in determining which personalized therapies can be utilized. While understanding and identifying each person's cancer-specific mutations can be difficult, finding therapies to target them can be even more challenging. My project aims to combat this by utilizing the overexpression of enzymes in cancerous cells as a target for novel chemotherapies. Identifying and optimizing new therapeutic molecules will help us diversify our arsenal of anti-cancer drugs. 

CBI Cohort 2018

Chemistry, Paul Hergenrother lab

Justin Miller

Cytochrome P450 enzymes are best known for their oxidation chemistries that metabolize drugs in the human body. Less well known are those in other organisms (e.g., plants) that employ P450s to modify any number of natural products used as defense compounds against insect predation and/or microbial infection. Many of these natural products are the source of pharmaceutical skeletons that allow humans to benefit from some very exotic plant P450 chemistry. Key among these are derivatives of the terpene indole alkaloid (TIA) pathway whose early products (leading to strictosidine) are synthesized in at least 80 medicinal plants and whose later products (leading to species-specific products) are utilized in cancer and viral treatments. Working in this pathway that includes at least five P450s, I am designing enzymes that transfer their particular regio- and stereo-selectivities to a wider array of substrates with the goal of developing novel natural product-like compounds.

CBI Cohort 2018

Chemistry, Mary Schuler lab

Matthew Boudreau

Research Description: Increasingly, personalized cancer therapies are becoming the gold-standard for cancer treatment. While cancer is a product of a multiplicity of aspects, every patient’s disease is driven by a specific set of genetic mutations that induce a cancerous phenotype. The advent of modern genome sequencing has allowed for the identification of specific mutations in oncogenes that are considered highly causative of developing cancer. Our aim is to leverage these known driver mutations in the discovery of novel inhibitors for specific oncogenes. These specific inhibitors will provide a high-impact endeavor for therapeutics as well as provide chemical probes for the perturbation of complex cancer biology. 

CBI Cohort 2017

Martin Garcia Chavez

Research Description: Drug-resistant Gram-negative bacteria have emerged as one of the major problems in public health. This resistance arises from the fact that Gram-negative bacteria have an outer membrane that inhibits the penetration of small molecules and drugs. Therefore, elucidating the chemical properties that allow for the penetration of small molecules into Gram-negative bacteria would provide the information needed to construct antibiotics that are active against Gram-negative bacteria. 

CBI Cohort 2017

Page Daniels

Research Description: Peptide derived antibiotics can be biosynthesized in two distinct ways: non-ribosomal synthesis or ribosomal synthesis followed by post-translational modifications. RiPPs, otherwise known as ribosomally synthesized and post-translationally modified peptides, are interesting discovery targets due to their vast distribution and diversity. A RiPP modifying class of enzymes, class I lanthipeptide dehydratases (LanB) transfer glutamate from a charged tRNA onto a peptide Ser/Thr side chain to form an ester bond. The enzyme then catalyzes elimination of glutamate to yield Dha/Dhb. A class of unclassified truncated LanB-like enzymes (sLanB) that completely lack the conventional elimination domain potentially present a new type of functional enzymatic chemistry. I aim to investigate the roles of a subset of sLanBs in a biosynthetic gene cluster in Bacillus halodurans.

CBI Cohort 2017

Nicholas Pino

Research Description: From regenerative medicine to emerging models of cancer development, stem cell research has been amongst the most important areas in modern science. We aim to further our understanding of stem cells by developing chemical biology tools that employ the natural biochemical environment of these cells to identify and characterize them. In this interest, we strive to design probes that can be used not only by our lab, but by other labs with similar interests in applications ranging from research in basic stem cell biology to research in stem cell-related medicine. 

CBI Cohort 2017

Imran Rahman

Research Description: Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a major class of natural products. RiPP precursor peptides are typically composed of a N-terminal leader sequence, and a C-terminal core sequence. The leader sequence is recognized by post-translational modification enzymes which install modifications on the core peptide. These post-translational enzymes tolerate changes in the core peptide, which allows for synthesis of peptide libraries which may have therapeutic use. I aim to investigate the leader peptide recognition mechanism in class II lanthipeptide synthetases, called LanMs. LanMs install dehydroamino acids and lanthionine linkages in the core peptide. Understanding the mechanism of substrate recognition in LanMs will allow for their use in combinatorial biosynthetic systems for the discovery of new therapeutics.

CBI Cohort 2017

Valeria Sanabria Guillen

Research Description: The estrogen receptor (ER), a hormone-activated transcription factor, plays a critical role in the development and prognosis of breast cancer. Despite the emergence and widespread use of drugs that target ER, a profound need remains for next-generation estrogen receptor ligands that show improved therapeutic outcome and reduced side effects while fending off resistance. Our work focuses on the development of estrogen receptor modulators and degraders as potential therapeutics for breast cancer, with a focus on improving potency, oral bioavailability, and effectiveness in mutant and treatment-resistant in vitro and in vivo models.  As part of this process, we seek to elucidate differential molecular mechanisms that are mediated by the structure-activity relationship of different ligands with ER, assessing their impacts on hormone-dependent gene transcription, signal transduction pathways, regulation of cell proliferation, and epigenetic regulation of ER-dependent genes.

CBI Cohort 2017

Kyle Shelton

Research Description: IThiopeptides are a class of ribosomally-synthesized natural products that are heavily post-translationally modified and often display antibiotic activity. Modifications that are common amongst thiopeptides include conversion of cysteines, serines, and threonines to thiazoles and (methyl)oxazoles, dehydration of alanines and threonines, and a ubiquitous 6-membered nitrogenous heterocycle. Several known thiopeptide congeners are adorned with additional—even exotic—modifications and the responsible enzyme(s) and bioactivity ramifications remain unknown. My project aims to characterize these structural decorations through in vitro biosynthetic reconstitution and structure-activity relationship studies.

CBI Cohort 2017

Andrew Buechler

Research Description: Aminoacyl-tRNA synthetases (aaRSs) and tRNA play fundamental roles in protein synthesis. The aaRSs covalently link specific amino acids to their cognate tRNAs, and these aminoacylated tRNAs subsequently interpret the genetic code that is embedded in mRNA to translate proteins. In addition to their canonical roles in protein synthesis, both aaRSs and tRNA are involved in a wide variety of other vital functions. My research focuses on novel roles of both leucyl-tRNA synthetase (LeuRS) and tRNA as chemical signals. In particular, LeuRS in E. colimigrates to the periplasmic space and fragments in response to certain stresses. E. coli also secretes LeuRS and tRNA at its stationary phase of growth. In addition, exogenous tRNA modulates human cell migration and assembly in tissue culture from a monolayer to tightly packed clusters of cells. I am investigating the role of dynamic LeuRS localization and its fragmentation during the E. coli stress response. Additionally, I am studying how tRNA influences human cells in the context of the microbiome, where I hypothesize that RNA factors serve as signals between host and microbe cells.

CBI Cohort 2016

Martin McLaughlin

Research Description: Identifying, characterizing, and engineering natural products expands both our pool of potential new drugs and our knowledge of natureís biochemical repertoire. Ribosomally translated and post-translationally modified peptides (RiPPs), a class of natural products, are particularly amenable to discovery and structure-function studies because their peptide scaffolds are genetically encoded. After translation of these peptides, tailoring enzymes perform exotic modifications that are critical for bioactivity of the mature natural products. Many RiPPs and their modifications are too complex for industrial-scale organic synthesis, but some of the tailoring enzymes appear to exhibit relaxed substrate specificity, potentially allowing for the use of recombinant protein expression and enzymatic synthesis to produce libraries of engineered RiPPs. My work focuses on discovery of RiPPs with novel or challenging chemical modifications and mechanistic characterization of the tailoring enzymes involved in their biosynthesis.

CBI Cohort 2016

Sarah Perlmutter

Research Description: The majority of small molecule drugs approved over the past two decades have originated from high throughput screening (HTS) libraries. However, most current synthetic libraries are generally comprised of relatively planar molecules that lack stereochemical complexity, limiting the potential number of drug targets. My research focuses on using the Complexity-to-Diversity (CtD) strategy developed by the Hergenrother lab to help improve complexity of molecules in HTS libraries. The CtD strategy utilizes chemoselective reactions to dramatically change the core ring structures of natural products to create distinct new scaffolds which maintain or increase structural complexity as measured by fraction sp3 and number of stereogenic centers.

Sarah was also awarded a NSF Graduate Research Fellowship.

CBI Cohort 2015

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The production of this website was supported by Grant No. T32 GM070421 from the Ruth L. Kirschstein Institutional National Research Service Award. Its contents are solely the responsibility of the Chemistry-Biology Interface Training Program at UIUC and do not necessarily represent the official views of the NIH Research Training and Career Development.