2021 Summer Student Fellows

Please join us in congratulating our 2021 Summer Student Fellows and their Faculty Mentors. Results of their work were shared at the 2021 Symposium; see 2021 SRF Brochure.

Student Fellow: Heather Schoenherr, Biochemistry
Faculty Mentor: Dr. Daniel Adsmond, Arts, Sciences and Education, Physical Sciences
Project:  An Investigation of the Role of Conformation and Energetics in the Ability of Sulfa Drugs to form Cocrystals

Cocrystallization occurs when two or more different chemical compounds combine to form a crystal. Interest in cocrystallization continues to grow in drug research: cocrystalization changes the chemical properties of all compounds in the cocrystal. These properties include – but are not limited to – melting point, solubility, and shelf life. The research here centers on sulfisomidine (SID), a drug in the sulfa family of antibiotics that is resistant to cocrystallization. To convert from the vinylogous imidine tautomer seen in the drug crystal to the amidine tautomer observed in cocrystals, SID must undergo a hydrogen shift from one nitrogen to another. Then, to become capable of cocrystallization, the molecule must experience a dihedral angle rotation of approximately 180°. Our research focused on determining the energy barrier relevant this dihedral rotation. Using the molecular modelling software Gaussian09 and its peripheral graphic program GaussView, the molecule was built and subjected to various manipulations and calculations. First, the structure was optimized to a local minimum, and the dihedral angle of interest was recorded (approximately 22°). Next, the optimized structure was subjected to several relaxed potential energy surface (PES) scans in which the dihedral angle was increased by increments of 10° -- and optimizing at each step -- until it rotated an entire 360°. These scans showed a rough estimate of the changes in energy associated with the dihedral rotation. The minima of the scans were extracted and optimized to determine the two energy minima of rotation, which were calculated to be 22° and 149°. The energy barrier could also be roughly estimated at 10.3 kJ/mol. However, this is not an accurate estimate of the energy barrier, as the PES scans do not exactly calculate a lowest energy pathway between minima. Using structures from the PES scans, the true transition structures can be determined with a QST3 calculation, which can then be used in an IRC calculation to determine the minimum energy pathway between the minima on both sides. This would give an accurate estimation of the energy barrier that exists between the two minima and show the molecular geometry changes as the molecule overcomes the barrier.

 

Student Fellow: Kiara Y. Torres Garcia, Pharmacy 
Faculty Mentor: Dr. Qian Ding, Pharmacy, Pharmaceutical Sciences 
Project: The association of Disease-modifying antirheumatic drugs (DMARDs) on Alzheimer’s disease

Although neurological diseases and autoimmune disorders appear to involve similar pathological mechanisms, the relationship between these two disease categories remains unknown. Hence, the study objectives were to assess the incidence of Alzheimer’s disease or dementia (AD/Dementia) among patients with autoimmune disorders and to identify the association of disease-modifying antirheumatic drugs (DMARDs) with the incidence of neurological diseases. A cross-sectional secondary data analysis was performed using Medicare Current Beneficiary Survey (MCBS) 2017 and 2018 data. Patients who were at least 18 years old and had an ICD-10-CM diagnosis code for autoimmune disorder diseases, were identified from the MCBS data. The incidence rate of AD/Dementia was compared between patients with autoimmune disorders and those without autoimmune disorders. The impacts of using DMARDs on reducing the risk of neurological diseases among patients with autoimmune disorders were also evaluated and odds ratios (ORs) were estimated for the incidence rate in the univariate analyses. The Adjusted OR (AOR), 95% Confidence Interval (CI), and p-values were calculated by controlling for confounding factors in logistic regression. The population totaled 18,929 Medicare beneficiaries and according to the statistical analyses, among these, 4405 were diagnosed with autoimmune disorder diseases. The results showed that the following population had a higher incidence of autoimmune disease diagnosis: Adults (18-64), Women, and African Americans. Patients with autoimmune diseases had a significantly higher prevalence of comorbidities. Also, patients diagnosed with autoimmune diseases had a significantly higher incidence of having AD (OR: 3.76% vs. 2.2%, P<0.0001) / Dementia (OR: 5.74% vs. 3.72%, P<0.0001). The logistics regression showed the following population with a higher incidence of AD/Dementia: RA patients (AOR: 1.71, 95% CI: 1.5 -1.95, P <0.001), Advanced age (65+), Hispanic ethnicity, Underweight BMI, and patients with two or more comorbidities. In contrast, results demonstrated an association between the use of DMARDs (AOR: 0.33, 95% CI: 0.15-0.71, P <0.01), being in the overweight, obese, or extreme or high-risk obese population, and a decrease in the likelihood of having AD/Dementia.

 

Student Fellow: Wyatt Varga, Biology
Faculty Mentor: Mr. William Killian, Arts, Sciences and Education, Physical Sciences
Project:  Effects of Hydrogen Bonding on Viscosity in 1-butanol

Calculating the effects Hydrogen bonding can have on a molecule is a difficult and lengthy process that requires many calculations, however viscosity may have a relationship with Hydrogen bonds that can help calculate those effects. Viscosity is a quantity expressing the magnitude of internal forces, measured by force per unit area, and can be calculated in a multitude of ways. We decided to use the Muller-Plathe method of calculating viscosity of 1-Butanol via a simulation. Using LAMMPS to create an environment containing 1-Butanol and applying a multitude of functions under specific conditions and OPLS-AA force field parameterization. The first step in this process was to create a box for the simulation to take place in. The volume of this box was very important to keep in mind because density has a huge effect on the viscosity of a substance. The next step was to thermalize the system by assigning a random velocity to each molecule so that it will reach a random configuration to provide more realistic results. Finally, we applied the Muller-Plathe formula to calculate the average viscosity for the duration of the simulation. The calculations that came from this method are comparable to what can be found in literature, with about 50% error. Given another summer I believe we would be able to attempt other methods to try and improve further on our findings.

 

Student Fellow: Burgess Ingersoll, Pre-Med
Faculty Mentor: Dr. Sonali Kurup, Pharmacy, Pharmaceutical Sciences 
Project: Design and synthesis of novel dual targeted EGFR/AURK inhibitors as anticancer agents 

Mutant epidermal growth factor receptor kinase (mEGFR) inhibitors have been approved in the treatment of mEGFR-positive non-small cell lung cancer (NSCLC). However, resistance to mEGFR inhibitors has developed rapidly and caused treatment failures. Resistance to current anti-EGFR therapies has resulted due to the inability of current therapies to inhibit newer EGFR mutants or has involved continued cancer cell proliferation through non-EGFR dependent pathways. Aurora kinases (AURK) are mitosis-related kinases that play a role in cell division and sustain processes that support tumor progression. Simultaneous inhibition of mEGFR and AURK using a mEGFR inhibitor and an AURK inhibitor in combination have shown synergistic anticancer effects in NSCLC and been effective in overcoming resistance to current anti-EGFR therapies. A single molecule with dual-targeted mEGFR/AURK inhibitory attributes could be expected to demonstrate the enhanced anticancer effects but also improved pharmacokinetics and patient compliance. Compound 1 was previously developed as a dual-targeted mEGFR and AURK inhibitor in the Kurup lab with moderate enzymatic and NSCLC inhibition. Three novel compounds have been synthesized as analogs of 1 in an effort to improve dual mEGFR/AURK inhibitory potencies. Both electron-donating and electron-withdrawing groups have been incorporated to evaluate the effects of a modification in the substitution pattern on mEGFR and AURK inhibition. Compound synthesis has involved a nucleophilic aromatic substitution reaction and a microwave-catalyzed Sonogashira coupling. Reaction progress has been monitored via thin-layer chromatography. Target compounds and intermediates have been purified using flash chromatography. Compounds have been characterized via mass spectrometry and nuclear magnetic resonance. Future studies will focus on the evaluation of the effects of the compounds on mEGFR, AURK, and NSCLC cells.

 

Student Fellow: Maria Gonzalez, Pharmacy/MPH combined program
Faculty Mentor: Dr. Michael Reger, Health Professions, Public Health 
Project: Assessing Cultural Competence Among Student Pharmacists in Michigan

The concept of cultural competency is a point of action for many universities, but this is of particular importance for schools of pharmacy and health professions to improve culturally appropriate patient care for future healthcare professionals. Current research suggests that knowledge may be higher than skills for pharmacy students (Echeverri et al., 2019), indicating a need to convert this knowledge to practice. The primary objective of this study was to add to the existing research by evaluating surveys distributed to pharmacy students at two schools of pharmacy in the state of Michigan as a tool to gauge familiarity with cultural competency domains. An electronic survey was distributed to pharmacy students at the University of Michigan and Ferris State University from May 25 to June 15, 2021, to assess perceptions of the various measures or domains of cultural competency like experience, awareness, and skills. Due to the short time frame of survey availability, the sample size was small, with the survey attempted by 24 students. Of the completed surveys 47.8% were fourth-year students, 78.3% identified as female, and 65.2% as white/Caucasian. Independent sample t-tests were performed using SPSS to determine if significant differences existed between mean responses of pharmacy students at Ferris State University and the University of Michigan. There were no significant differences between responses assessing skills and experience, education, and awareness, however there were significant differences observed in the responses assessing familiarity with resources like The National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care (The National CLAS Standards) and Purnell Model for Cultural Competence, with Ferris State University scoring significantly higher in familiarity with these resources (p = < 0.001). Despite some limitations to the study such as the small sample size and homogenous sample group, this study provides a preliminary assessment of cultural competencies among pharmacy students and indicates the need for further studies with a larger sample size and over a longer period.

 

Student Fellow: Benjamin Vander Ploeg, Applied Mathematics
Faculty Mentor: Dr. Luis Rivera, Arts, Sciences and Education, Physical Sciences
Project: Canonical Approaches to Triatomic Molecules

Previous works calculated energy potential approximations for diatomic molecules to high degrees of accuracy. Extending this methodology to higher dimensions (triatomic molecules in specific) required writing a generalization in two dimensions. Without a generalization for diatomic molecules, the task of approximating triatomic molecules becomes tedious with large room for error. Canonical transformations of the Lennard-Jones reference potential and diatomic molecules have the same “shape.” The importance of this comes up when using the inverse canonical transformation to get an approximation of the target potential. This generalization would allow high accuracy approximations for diatomic molecules while needing to only know a handful of points – there is no longer a need to know the location of the potential well. Extending this to triatomic molecules would become simple, as fixing one variable would generate 2D splices of the 3D curve, thus allowing interpolation across these splices to gain an approximation of the target triatomic molecule.  Furthermore, a program could then be created that provides the user with quick access to approximations for any diatomic or triatomic molecule. 

 

Student Fellow: Cole McGowen, Biology - Environmental 
Faculty Mentor: Dr. Anne Spain, Arts, Sciences and Education, Biological Sciences 
Project: Methane Munching Microbes: Composition and Activity of Methanotrophic Bacteria in a Central Michigan Bog

Sphagnum moss peatland bogs play a crucial ecological role, acting as carbon sinks, storing large amounts of carbon and other greenhouse gasses (e.g., methane), that would otherwise end up in the atmosphere. While bogs are often considered extreme, due to low pH and nutrients, and biodiversity, initial research aiming to characterize the diversity and ecology along three locations (from the land to the kettle hole) of a bog in Central Michigan showed that the site was characterized by a moderately acidic pH (5.2-5.9), and high levels of plant and bacterial diversity (19 species and 68 phyla detected, respectively). Further, methanotrophic (methane-eating) lineages surprisingly accounted for 1-3% of the total bacterial sequences in samples from 2019. Due to these results, it was predicted that the peat in this bog would have the ability to consume methane by a bacterial process called methane oxidation. Thus, the experiments performed this summer aimed to study methane consumption at the three locations in more detail by 1) measuring methane concentrations from each; and 2) measuring methane oxidation rates from the three same locations. Water was collected in 120ml serum bottles and fixed with NaOH on site, to preserve methane, which was later measured by gas chromatography. Live water samples and peat cores (divided up depth wise, into 5cm sections) and were obtained in triplicate, transported to the University of Oklahoma on ice, and used to measure rates of methane oxidation. Both the methane levels and the rates of methane oxidation (calculated by the loss of methane in the headspace of the serum bottles) were highest in peat closest to the land, which contained methanotrophic lineages Methylomonas and Methylobacter. Methane concentration and methane oxidation rates decreased along the transitional gradient (moving from the land to the kettle hole), in which a shift in composition of methanotrophs was also observed. These two experiments and their results give us a better understanding of the who, where, and why of methane consumption in our happening in our Central Michigan bog.