Elliott Ballino

Mentor: Alex Schuppe
Home Institution: University of Scranton

"Investigations into NHC-difluoroborane Precursors for Novel Transformations with π-Systems"

Boron centered radicals are useful in numerous synthetic applications including reduction and polymerization reactions. Generally, boryl radicals are nucleophilic in nature; however, a recent discovery by Subervie describes the generation of the first electrophilic boryl radical from a N-heterocyclic carbene (NHC) difluoroborane precursor. Initially we sought to harness this radical for novel transformations with electron-rich π-systems. Preliminary results demonstrated that this electrophilic radical can functionalize a silyl enol ether. We believe alternative NHC- and amine difluoroborane radicals could facilitate these transformations with improved efficiency. Therefore, we seek to develop a library of these difluoroborane precursors. We hypothesize that these radicals react regioselectively with radical acceptors like indoles, which will form the foundation for future research.

Bio. Elliott Ballino is a rising senior with a chemistry major and mathematics minor at the University of Scranton. He is the recipient of multiple scholarships and awards at the University of Scranton. He has been a peer tutor in chemistry and mathematics for the past two years and will serve as a General Chemistry Graduate Assistant in the fall.

Audrey Birdwell

Mentor: Allison Walker
Home Institution: Lipscomb University

"The Elicitor-Regulator Relationship between Chloramphenicol and JadR2 for Secondary Metabolite Discovery and Novel Therapeutics"

Bacteria communicate by secreting secondary metabolites in their environment. In a laboratory setting, these secondary metabolites can be analyzed for their bioactive properties such as antibiotics. This research is essential due to the rise in antimicrobial resistance (AMR). AMR remains one of the top threats to global health resulting in millions of infections and thousands of deaths annually. A particularly challenging aspect of novel drug discovery is that secondary metabolite production in bacteria is highly regulated. For example, JadR2 is a DNA binding protein that regulates antibiotic production in Streptomyces venezuelae through binding of its promoter region. Interestingly, in the presence of the drug chloramphenicol (CAM), JadR2 releases from DNA and allowing transcription to occur. We are particularly interested in elicitors (CAM) and regulators (JadR2) of secondary metabolism. To establish CAM and JadR2 as an elicitor regulator pair, we heterologously expressed a Streptomyces promoter with GFP and JadR2 in E. coli. In hopes of discovering novel therapeutics from bacterial secondary metabolites, my project is interested in establishing a method for identifying elictor-regulator pairs through the known relationship between chloramphenicol (CAM) and JadR2 in Streptomyces venezuelae.

Bio. Audrey Birdwell is an upcoming senior at Lipscomb University in Nashville, TN. She is majoring in molecular biology and Spanish with a minor in chemistry. She actively participates in Lipscomb's student life by serving as student ambassador president of Lipscomb Admissions, president of TriBeta Biological Honors Society, vice president of Alpha Chi National Honors Society, and student representative on the Honors College student council. Aside from student life, Audrey has also worked in Dr. Joshua Owen's research lab for three years as an undergraduate researcher. Dr. Owen's research lab investigates a gut-derived metabolite o-valerobetaine and its inhibitory properties on mitochondrial fatty acid oxidation in cancer cells. Currently, she is leading her own research project partially funded by the TriBeta Research Grant awarded to her in the fall of 2023. She has presented her research at Lipscomb University's Student Scholars Symposium in 2023 and 2024. This summer, Audrey was chosen to participate in the Chemical Biology NSF REU at Vanderbilt University. Here, she works as an undergraduate researcher in Dr. Allison Walker’s natural product discovery lab.

Cait Bradley

Mentor: Jeffrey Johnston
Home Institution: Oglethorpe University

"Synthesis of Diastereo- and Enantioselective Catalysts for Aza-Henry Reactions"

The focus of this research is to synthesize diastereo- and enantioselective catalysts for aza-Henry reactions to expand the scope of substituents that can be further used in peptide synthesis. The products of the aza-Henry reactions can then be used to conduct Umpolung amide synthesis (UmAS), developed by the Johnston Lab. Two catalysts, H,4PyrrolidineQuin-BAM (PBAM) and Adamant-AmA (AmA), were produced via a 3-step and 5-step synthesis, respectively, involving a Buchwald-Hartwig amination and microwave radiation. Air and moisture sensitive reagents are required, facilitating the need for degassing and drying methodology. (R,R)-AmA and (R,R)-PBAM were successfully synthesized and further used in enantioselective aza-Henry reactions to create alpha-bromo nitroalkanes via reduction of the nitroalkene. The product of these reactions will then be used towards UmAS, reacting with the aid of electrophilic iodine and stoichiometric base to form an amide.and biologically-relevant carbohydrate-ligand recognition events.

Bio. Cait is originally from Mobile, AL and is currently completing her undergraduate studies at Oglethorpe University in Atlanta, GA. She is majoring in chemistry, with a special interest in organic synthesis. During the summer of 2023, she conducted research at UF Scripps where she synthesized a small bioactive ligand that had the potential to reverse the phenotypes of certain neurological disorders. She is the Co-President of Sigma Zeta Honor Society, Secretary of Chemistry Club, Treasurer of Data Club, a memeber of The National Society of Leadership and Success, along with being a chemistry lab assistant and being a member of the Gabriel lab at her university. Her plan after she graduates this fall is to get accepted into a graduate program and start earning an organic chemistry PhD. She hopes to eventually go into the pharmaceutical industry and work in drug discovery, specializing in medicinal chemistry. 

Grace Heilmann

Mentor: Lars Plate
Home Institution: University of North Carolina at Greensboro

"Determining Protein-Protein Interactions of SARS-CoV-2 Mac1 Domain"

SARS-CoV-2 has been responsible for the death of over 7 million individuals. All coronavirus strains contain a highly conserved macro domain (Mac1) within nonstructural protein 3 (nsp3) that can bind and remove ADP-ribose modifications. The Mac1 domain is responsible for removing ribosylation performed by poly-adenosine diphosphate-ribose polymerases (PARPs) which activate the interferon response (IFN), a cell signaling pathway that mounts an antiviral response. By altering a single amino acid within the Mac1 domain that is responsible for hydrogen bonding and critical for function, we hypothesize that the protein-protein interactions will differ between the wildtype (WT) and the mutant Mac1 as the interactions may be substrates for Mac1 deriboyslation activity. Site directed mutagenesis was used to change arginine at position 40 to alanine, which has been shown to reduce deribosylation efficacy of Mac1. Mass spectrometry was used to determine the protein-protein interactions of the WT Mac1 domain and the mutated Mac1 domain (N40A). Over 50 interactors of Mac 1 were identified after performing mass spectrometry, 2 of which were previously identified interactors of nsp3. These interactors are associated with other post-translational modifications as well as cell stress pathways and may infer future drug targets for coronaviruses. r questions about the identity of catalytic active species.

Bio. Grace Heilmann is a senior majoring in Biology at the University of North Carolina Greensboro. Grace’s academic excellence has been recognized by being on the chancellor’s list since 2022 and receiving biology specific scholarships such as Burrell Biology scholarship and Ms. McIver scholarship. These scholarships are awarded to individuals in the top 5% of their major. She started undergraduate research her sophomore year working on resensitizing glioblastoma cells to cancer therapies. Grace’s future career goals are to pursue a PhD in cancer biology. When Grace is not working in the lab, she is mentoring students in UNCG’s Academic Achievement Center. Grace spends her time coaching students on how to study and transition to a university setting. Grace was awarded student employee of the year in April of 2024 because of her dedication to student success. Grace is currently participating in Vanderbilt’s Chemical Biology REU under Dr. Lars Plate working on proteomics of SARS-CoV-2. 

Erica Hengartner

Mentor: Lauren Buchanan
Home Institution: University of Florida

"Determining Insulin Aggregation Kinetics and Dipeptide Terminal Capping Effects Using 2D IR Spectroscopy and Amide I Transition Dipole Strength"

Vibrational spectroscopy uses infrared, near-infrared and Raman scattering to measure vibrational frequencies between bonded atoms. Two-dimensional infrared spectroscopy (2D IR) is one of these spectroscopic tools with increased structural sensitivity over linear IR methods and unique cross peaks that indicate coupled modes. 2D IR is also used to calculate transition dipole strength (TDS), which quantifies vibrational coupling and delocalization of vibrational modes. TDS values are particularly useful for distinguishing spectrally similar molecules, such as polymorphs of the same peptide. 2D IR and TDS calculations are broadly applicable to peptide structure and dynamics studies in both small peptides, and complex protein systems with β-sheets, α-helices, and disordered proteins. In this study, 2D IR was used to investigate how sequence variations in insulin II, a mouse homologue of the human insulin gene, can affect its aggregation kinetics. The transgenic insulin (B:9-23) variants demonstrated complete aggregation into fibrils (LYLAEV mutant), partial aggregation (E21A mutant), and no aggregation (short 6.9HIP mutant) after two and a half hours. In addition, the stabilization and reduced-charge effects of post-translational protein modifications such as N-terminal acetylation and C-terminal amidation was investigated using alanine dipeptides. These precise studies of molecular interactions demonstrate the advantages of 2D IR in peptide-based studies over other linear methodologies. 

Bio. Erica Hengartner is a rising senior in the University of Florida Honors Program majoring in Chemistry with a concentration in Biochemistry. She is a Florida Bright Futures Scholar (2021-2025) and has received a Jorge Mas Canosa Freedom Foundation Scholarship (2021-2025). At UF, the University Scholars Program Cancer Center funds her mechanobiology research in neuron electrophysiology and long-distance cancer cell signaling. She is also a TA for organic chemistry and is an executive board member of the student chapter of the American Chemical Society. She has completed an NSF-funded Biochemistry REU at AgroParisTech in France (2023) and is currently completing a Chemical Biology REU at Vanderbilt University. Following graduation in May of 2025, Erica aspires to pursue a PhD in Chemistry.

Aria Mingo

Mentor: Steven Townsend
Home Institution: Cornell University

Increasing rates of morbidity and mortality within hospitals are caused by pathogenic bacteria colonizing indwelling medical devices. This abiotic surface adherence is caused by the ability of bacteria to form biofilms. Bacterial biofilms are three-dimensional communities of microorganisms surrounded by a self-produced extracellular polymeric matrix. Bacterial biofilms confer increased resistance to antibiotics, resulting in invasive infections among immunocompromised patients. Human milk oligosaccharides (HMOs), the carbohydrate component of human breast milk, are known to promote growth of commensal bacteria while inhibiting the growth of pathogenic bacteria in the infant gut. Recent studies have shown that outside the neonate, HMOs have both antibacterial and biofilm-inhibiting properties. With this in mind, we employed HMOs as anti-adhesive coatings against various pathogens to assess abiotic bacterial adherence to various materials. HMOs were used to reduce bacterial adhesion on surfaces imitating those most commonly populated by nosocomial pathogens, including catheters, prostheses and pacemakers, among others. The ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species) exhibit high antibiotic resistance and are responsible for 15.5% of hospital-acquired infections. Plastic surfaces (24-well plate base) and glass surfaces (glass coverslip) were exposed to HMOs for 12 hours. After the solution evaporated, bacterial cells were added to the surfaces and incubated. The next day, bacterial density (OD₆₀₀) and biofilm formation (OD₅₆₀) were spectrophotometrically determined. While HMO treatment did not elicit any changes in bacterial density, significant decreases in bacterial adherence were observed across strains assessed in this study. The results indicate that the addition of HMOs reduces the adherence of both gram-negative and gram-positive bacteria on both plastic and glass surfaces. This research highlights the potential for HMOs as protective coatings on indwelling medical devices to mitigate the spread of hospital-acquired infections.

Bio. Aria Mingo is a senior at Cornell University, majoring in Chemistry and minoring in Earth and Atmospheric Sciences. Under the mentorship of the Ober Group, she has conducted research focusing on polymeric additions to various transition metals and studying polymer-grafted nanoparticles (PGNs). In addition to her academic pursuits, Aria has worked as a Scribe at a medical center, gaining practical experience in healthcare documentation. She also served as a student intern at Argonne National Laboratory through Washington State University, where she contributed to the design of a copper precision target for laser analysis. Currently, Aria is interning at Vanderbilt University within the Townsend Lab, investigating the antimicrobial and antibiofilm properties of human milk oligosaccharides (HMOs).

Elvis Perez Galarza

Mentor: Zhongyue J. Yang
Home Institution: Western Carolina University

"Investigating the Impact of Mutations on Substrate Positioning in Fluoroacetate Dehalogenase (FAcD)"

The strong and stable carbon-fluorine (C-F) bonds in per- and polyfluoroalkyl substances (PFAS), used in many industries and consumer products, has caused environmental concerns due to their resistance to degradation. A potential non-toxic and efficient method of PFAS degradation is to use enzymes. An enzyme known as fluoroacetate dehalogenase (FAcD), isolated from bacterium Rhodopseudomonas palustris, hydrolyzes the C-F bond present in a natural toxin, fluoroacetate (FAc). In this work, we used our Python software, Enzy-HTP, to explore how mutations affect substrate positioning and key residue interactions in the active site, focusing on the catalysis of trifluoroacetate (TFA) as a model system for polyfluorinated compounds. A wildtype FAcD-TFA complex was created and subjected ten randomized single-point mutations, resulting in the creation of ten FAcD-TFA variants. Classical molecular dynamics (MD) simulations of 200 nanoseconds were performed and repeated three times for the wildtype structure and each variant structure. By measuring distances between key residues and TFA in the active site, key interactions for the reaction can be analyzed. These interactions are responsible for the positioning and successful cleavage of the C-F bond. Differences in distances observed in the mutated structures compared to the wildtype structure might indicate either enhanced or reduced catalytic activity.

Bio. Elvis Daniel Perez Galarza is an undergraduate from Western Carolina University. He is majoring in Chemistry and minoring in Biology and German. He has participated in undergraduate research at Western Carolina University since his sophomore year with Dr. Channa De Silva. He has recently received an award from the American Chemical Society for his research in inorganic chemistry. He will be the secretary for the Chemistry Club next year and is very involved in the Brinson Honors College at Western Carolina University as well. Elvis has participated in another REU at UNC-Chapel Hill. He is currently working in Dr. Zhongyue (John) Yang’s lab here at Vanderbilt.

Allison Portaro  

Mentor: David Cliffel
Home Institution: University of Louisville

"Photopolymerization of Pyrrole Thin Films"

The photosystem I (PSI) protein complex has near 100% internal quantum efficiency. Biohybrid solar devices now use PSI to harvest light energy. Previous work showed that PSI has the ability to photopolymerize monomers such as pyrrole, forming a conductive polymer to effectively wire the protein. Our investigation into this photopolymerization focuses on thin film growth and specifically the effect of photopolymerization time on the resulting polymer film. To further develop this wiring methodology, photopolymerization was carried out by submerging PSI films in monomer solution and illuminating for a specified time. Photochronoamperometry (PCA) was performed to analyze the photoactivity of the resulting films, and profilometry was utilized to characterize the thickness. Other characterization methods such as SEM, TEM, STEM EDX, and IR were also carried out to further investigate the polymer films. The PCAs showed that peak current density did not significantly increase or decrease over photopolymerization illumination time from 4 to 48 hours, but film thickness did increase over time. SEM imaged the surface morphology of the films, showing network changes from columns to spheres over time. PSI and pyrrole were confirmed to be in the films by their signatures in IR and STEM EDX. The isolated composite spheres have potential for furthering PSI/nanoparticle applications leading to biohybrid energy conversion. 

Bio. Allison Portaro is a rising senior in the University of Louisville Honors Program majoring in Chemistry with a track in Biochemistry. She is a Henry Vogt Scholar (2021-2025) who has received the Tilford and Vicki Riehl Scholarship (2023) and the Freshman Honors Scholarship (2022) from the Department of Chemistry. She is also a member of the Kentucky Academy of Science, the Society of Undergraduate Chemistry Students, and tutors General Chemistry courses. At UofL she conducts biochemical research on the anticancer properties of Salvia (sage) and its effects against breast cancers. Allison is currently completing an NSF-funded REU in Chemical Biology at Vanderbilt University. She graduates in May 2025 and plans to pursue a PhD in Chemistry. 

"Alternative Ligand Metalation Strategies for Alkane Borylation"

Our lab has focused on some of the most challenging substrates for linear hydrocarbon transformations. These substrates are simple alkanes (e.x. n-octane) and are a major chemical feedstock which results from the refinement of petroleum. Hydrocarbons are abundant, cheap, but inherently unreactive, as they lack functionality and only contain carbon-carbon bonds and carbon-hydrogen bonds. It is interesting that catalysts have been developed to react with these molecules; they also show very high selectivity for the terminal -CH3 groups over internal methylenes (-CH2). We have previously identified 2,2’-dipyridylarylmethanes as a highly performing ligand class for undirected alkane borylation (a transition metal catalyst replaces a C-H bond with a C-B bond). Using our novel ligand class, our lab has successfully isolated cyclometalated species of iridium. We plan to expand this chemistry to other transition metals. To do so, we aim to discover new precatalyst candidates across different transition metals by developing a versatile cyclometalation strategy. The newly synthesized aryl bromide ligand precursor (L28/L31) will enable us to access cyclometalated species via transmetalation. After further research, we have successfully isolated, characterized, and crystallized a cyclometalated aryl zinc (Ar-ZnBr). Through transmetalation, we hope to use this Ar-ZnBr to access new potential transition metal precatalysts for alkane borylation and beyond. Early evidence provides potential success of our preliminary transmetalation with ruthenium and rhenium. We are in the process of developing new ligands and stabilized organozinc species for metal-catalyzed reactions. Next steps include optimizing transmetalation conditions and the evaluation of potential applications for isolated metal complexes.

Bio. Montana Price is a rising junior at Tennessee Tech University. She recently graduated with an associate degree in chemistry from Volunteer State Community College near her hometown of Hendersonville, TN. She is currently interning in the Schley Research Lab working on developing a cyclometalation strategy that will enable the exploration of other transition metals to identify and isolate precatalyst candidates. She plans to venture out into forensic pharmacology and conduct research that helps advocate for women’s health. 

Angelica Velasquez

Mentor: Michael Stone
Home Institution: University of Connecticut

"Structural Analysis of Mitoxantrone Binding to AP Sites in DNA: Regarding its Chemotherapeutic Effect"

Apurinic sites (AP sites) are generated in cellular DNA by a variety of alkylating agents. Once formed, AP sites equilibrate in the deoxyribose via a transient aldehyde intermediate. Mitoxantrone (MTX), a chemotherapeutic agent capable of treating various cancers such as lymphomas, breast cancers, and leukemias. The secondary amines present in MTX may react with the aldehyde intermediate at AP sties to form reversible AP-site conjugates (Schiff bases). The chemistry and biology of these AP site conjugates is not well understood. Our study aims to provide insights about the effects of MTX conjugation at AP sites in DNA and how it may alter the DNA duplex. We achieve this by synthesizing site-specific MTX-AP site conjugates. We purify them by HPLC chromatography and characterize it using mass spectrometry. We compare the conjugate to a corresponding unmodified DNA sequence using both thermodynamic and NMR studies. Our data reveals a 4º lower melting temperature (Tm) in the DNA containing an MTX-AP site conjugate. NMR suggests that MTX conjugation at AP sites causes localized structural disturbance to DNA. These structural changes may be responsible for the thermal destabilization of the DNA. Structural analysis serves to unveil the effects of MTX conjugation to DNA at AP sites.

Bio. Angelica is a rising third-year chemistry student from the University of Connecticut. She is gaining experience in an analytical laboratory at her home institution which focuses on the identification of organic pollutants and bioactive compounds. In the previous spring semester, she presented her poster, “Detecting the Presence of PFAS ‘Forever Chemicals’ in Commonly Used Infant Care Products” at UConn’s Randolph T. Major Symposium, where she was awarded 3rd place in Undergraduate Poster Presentations. She has a keen interest in drug development, specifically pertaining to cancer research. In the future, she hopes to further her education in chemistry with regards to cancer therapeutics so that she can make meaningful contributions to the field.

Allison Wightman

Mentor: Daria Kim
Home Institution: Grinnell College

"Understanding Regioselectivity Trends in Ca2+-Mediated Functionalization of Monosaccharides"

Glycans are involved in vital signaling functions and cell-cell recognition. However, the mechanisms the molecular mechanisms that underpin these crucial cellular processes are still poorly understood. Our research aims to develop new methods for the precise structural perturbation of glycans through monomer-selective and regioselective transformations of monosaccharides and glycans.  Conventional approaches to regioselective carbohydrate modification involve lengthy protection, activation, deprotection sequences that are impractical in application to biological glycan modification. However, single-step site-selective transformations may be possible by leveraging the metal-chelating and/or hydrogen-bonding abilities of sugar residues. Our lab has developed a C2-selective acetylation of methyl-mannopyranoside in the presence of CaCl2, which occurs in 10 minutes at a quantitative yield.  This reaction is not only entirely regioselective at the C2 position, but also exhibits substrate-dependent reaction rates that strongly favor mannopyranosides. Our ongoing work aims to clarify the factors which influence the selectivity profile of this reaction. Mechanistic understanding of this process may expand the substrate scope to other monosaccharides and achieve more complex transformations, such as glycosylation to generate complex polysaccharides.

Bio. Allison Wightman grew up in Philadelphia before moving to Grinnell, Iowa to pursue her B.A. degree in Chemistry at Grinnell College. At her undergraduate institution, Allison is involved in investigating the microwave synthesis of α-substituted chalcones under neat reaction conditions under the mentorship of Prof. Stephen Sieck. She is currently participating in the REU program in chemical biology at Vanderbilt University working with Prof. Daria Kim. She expects to graduate from Grinnell College in May of 2025 with a B.A. in Chemistry and then continue her education in graduate school for organic chemistry.