2017 Summer Student Fellows

Student Fellow: Brandon Mihelich, Chemistry
Faculty Mentor: Dr. Daniel Adsmond, Arts & Sciences, Physical Sciences 
An Investigation of Ditopic Donor Monotopic Acceptor Pairs in the Design of Ternary Co-Crystals

The goal of the research was to design and synthesize a notoriously difficult type of crystal to grow, a ternary cocrystal. Ternary cocrystals are non-salt crystals that contains three types of molecules in its repeating structure. Cocrystallization can alter the physical properties of the components (solubility, shelf-life, etc.), without altering their chemical properties (medicinal properties, etc.), and has potential applications such as improving pharmaceuticals. The research began by studying the work of previous SRF researchers and Dr. Adsmond, along with any relevant research that had been published. After studying the previous work done, x-ray quality crystals of the two ternary cocrystals previously discovered by SRF researchers were able to be grown so their structure's could be determined, which were previously unknown. Over the course of the summer, 87 experiments were completed, in addition to another 13 experiments which are still in progress. A total of 20 different chemicals were investigated, half of which had never been investigated at Ferris for ternary cocrystallization. To date, the work has resulted in 14 new binary cocrystals, 3 possible ternary cocrystals, and 2 new ternary cocrystal structures.

Student Fellow: Ian Steinke, Chemistry
Faculty Mentor: Dr. Daniel Adsmond, Arts & Sciences, Physical Sciences
An Investigation of the Hydrogen Bond Connectivity between Sulfa Drugs and Nitrogen-Containing Coformers in Co-Crystals

When a crystal is of a high enough quality, the analytical technique of x-ray crystallography can be used to see specific molecular interactions in the crystal. The goal of the research project was to obtain quality cocrystals of sulfa drugs and nitrogen containing compounds (coformers) to observe specific interactions taking place between the two. A variety of sulfa drugs and coformers were dissolved separately in appropriate solvents. Solutions were then allowed to evaporate at a slow, controlled rate and crystals were grown from the solutions. After crystals were obtained, they were analyzed by nuclear magnetic resonance and infrared spectroscopy to determine the ratios of the compounds contained, and any significant changes in hydrogen bonding to indicate if cocrystallization had occurred. Out of eighty-four experiments, eight high-quality cocrystals were obtained; six of the crystals had their crystal structure solved by a team of crystallographers at Eastern Illinois University, Michigan State University, and Grand Valley State University. Crystallographic results show that five of the six structures packed more efficiently than in their original crystal structure, contributing to a more stable crystal structure. In the one structure that didn’t pack more efficiently, the number of hydrogen bonds was significantly greater than it was in the pure compounds.

Student Fellow: Kylee Jones, Biotechnology
Faculty Mentor: Dr. Felix Amissah, Pharmacy, Pharmaceutical Sciences
Effect of Cyclooxygenase Inhibition on the Polyunsaturated Fatty Acid Induced Apoptosis in Lung Cancer Cells

Docosahexaenoic acid (DHA) is a natural compound found in fish oils known to possess anticancer effect.  Aspirin has also been shown to exhibit anticancer effects on various cancers by reducing inflammation associated with cancer.  This enormous health benefit of aspirin is limited by the potential adverse effects including gastrointestinal irritation and excessive bleeding.  A combination of the two compounds may allow for a decrease in the amounts of each compound used for chemoprevention, which may likely decrease the risk of adverse effects. We treated A549 lung cancer cells with either aspirin, DHA or both and performed several experiments including proliferation assay, viability assay, apoptosis assay, clonogenic assay, western blot, and immunofluorescence. Our results indicate that the combination of aspirin and DHA were more effective in preventing cancer cell proliferation and survival.

Student Fellow: Abbey Magolan, Pharmacy
Faculty Mentor: Dr. Felix Amissah, Pharmacy, Pharmaceutical Sciences
Effect of Cyclooxygenase Inhibition on the Polyunsaturated Fatty Acid Mediated Regression of Lung Cancer Cell Migration and Invasion 

Lung cancer metastasis involves several processes including cell migration and invasion into adjacent tissues. Compounds that inhibit cancer cell migration and invasion could be useful in preventing metastasis. Although fish oils such as docosahexaenoic acid (DHA) and cyclooxygenase (COX) inhibitors such as aspirin have been reported to be chemopreventive, the potential benefit that could be obtained by combining them has not been explored.  In this study, we consider inhibiting the cyclooxygenase pathway with the use of aspirin while supplementing the treatment with DHA in the prevention of migration and invasion using the wound-healing and matrigel invasion methods. For migration, lung cancer A549 cells were seeded in ibidi cell culture inserts, allowed to grow to confluence, serum-starved for 24 h, treated and the wound closure was monitored by capturing images 0, 9, and 24 h. The cells for invasion were plated, treated, and imaged at 24 h. Both compounds inhibited lung cancer cell migration and invasion, but the combined treatment shows better inhibition than DHA or aspirin alone.

Student Fellow: Joseph Kohane, Pharmacy
Faculty Mentor: Dr. Tracey Boncher, Pharmacy, Pharmaceutical Sciences 
The Up-Scale Synthesis of Novel PPAR Gamma/Delta Analogs for Alzheimer's Disease

This summer Dr. Boncher and I have been working on synthesizing molecules that have activity at PPAR receptors. These receptors play a crucial role in Alzheimer's disease and these molecules have the potential to not only stop the progression of the disease but to actually have some reversal effect on the disease. The molecules are created via organic chemistry solution phase synthesis. This involves a series of reactions that use building block molecules to create the desired product. We have had solution problems with using what is known as FMOC to form a secondary amine but we recently switched to BOC which is having much better success. Our yields continue to improve as we work toward building the final product. Once the final product molecule is constructed and purified, it will be given to a collaborating college for testing. This summer has been a lot of trial and error but at the end we will have a drug molecule that will be ready for testing and hopefully could make it to clinical trials and even to the market someday.

Student Fellow: Anthony Picard, Public Health
Faculty Mentor: Dr. Emmanuel Jadhav, Health Professions, Public Health
Leading from the Front: Variation between Rural and Urban Accredited Agencies

Over 190 local health departments (LHDs), serving about 19.7 million residents have met the rigorous standards of the Public Health Accreditation Board.  Several studies have identified predictors and barriers to seeking and completing accreditation. Many of the barriers are a hallmark of the burden experienced by rural LHDs, however it appears rural LHDs have been at the forefront of the accreditation movement. The objectives of the current study are to 1) identify variations in leader socio-demographics and organizational characteristics between urban and rural accredited LHDs and 2) examine their variation in health outcomes. Data from the 2016 National Association of City and County Health Officials Profile study was analyze. The accreditation status, was identified using PHAB data. The sample consisted of 151 accredited agencies, of which 90 were classified as rural and 61 as urban. Statistically significant differences were observed at the leadership and organizational levels. At the leadership level, significant differences were observed for age, race/ethnicity, work experience, and education status of the top executive as well as if there was a full-time medical officer assigned to the department. At the organizational level, the most significant differences were between the occupations employed by LHD. Health outcomes between agencies were also found to be statistically significant. 

Student Fellow: Anzhane' Lance, Acturial Science 
Faculty Mentor: Dr. David M. McClendon, Arts & Sciences, Mathematics
Complex Dynamics of a Family of Quadratic Rational Maps

We study the dynamics (i.e. behavior under repeated composition) of the family of quadratic rational maps, where l is a complex number. Dynamical systems are applied in population biology, economics, physics and other areas, so understanding the behavior of simpler mathematical models (such as our family) is relevant to these applications.  Our goal, therefore, is to describe and explain all possible dynamical behavior in the family. To do this, we write computer programs to create images of the parameter space of this family, and use those pictures to divide the set of parameters l into regions, where the dynamical behavior depends only on the region containing l and not on the exact value of l.  For l  in each of these regions, we then study the dynamics using computer computations and math theory. We studied results regarding the dynamics for parameters of an attracting fixed point and/or attracting period 2 cycle.

Student Fellow: Danielle Rustem, Pharmacy 
Faculty Mentor: Dr. Claire Saadeh, Pharmacy, Pharmacy Practice 
Medical Marijuana Use in a Community Cancer Center

Marijuana is currently the most popular illicit drug in the United States. It is commonly used for both medicinal and recreational purposes. Patients with cancer may use marijuana to help manage their cancer symptoms, while others state that they use it to treat their cancer. With an increasing number of patients using marijuana, it is becoming more apparent how little is known about the use of this drug in a clinical setting. We created a survey and recruited patients from the Herbert-Herman Cancer Center to collect information about whether or not patients use marijuana and any symptoms they are experiencing. Our primary goal was to compare the incidence of marijuana use in patients with early versus advanced stage cancer. In addition, we also looked at any differences in drug-drug or drug-disease interactions. We found that overall 18.3% of patients in the Cancer Center use marijuana; however, there was not a significant difference in the incidence of marijuana use between patients with early versus advanced stage cancer (19.6% and 17.6%, respectively; p=.75).

Student Fellow: Catherine Mirto, Biotechnology
Faculty Mentor: Dr. Anne Spain, Arts & Sciences, Biological Sciences
Prevalence of Antibiotic Resistance in Bacteria Exposed to Perfluorinated Compounds versus Bacteria from Pristine Environments

Perfluorinated compounds (PFCs) are persistent and recalcitrant chemicals which bioaccumulate in higher organisms in the food chain; however, their effects on microbial populations have not been well documented. These experiments investigated whether the presence of PFCs in aquatic environments select for antibiotic resistance genes in bacteria isolated from three locations in Oscoda, MI. Aquatic and sediment samples were collected from Clark’s Marsh, a highly contaminated site, with PFC concentrations exceeding 5,000 parts per trillion (ppt). Samples were also collected from a moderately contaminated site along the Au Sable River (0-40 ppt), and from a pristine site at Foote Dam Pond Overlook (0 ppt). Sixty bacterial isolates (20 from each location) were collected and tested in triplicate for resistance to seven antibiotics: aztreonam, ciprofloxacin, sulfamethoxazole/trimethoprim, ceftriaxone, tetracycline, ampicillin, and polymyxin B. No difference in the rates of antibiotic resistance between PFC-contaminated and pristine environments was observed. However, 81.6% of all isolates tested displayed resistance to at least one antibiotic, indicating aquatic environments may serve as reservoirs for antibiotic resistance genes, regardless of PFC contamination.

Student Fellow: Austin Vanwyk, Biology/Pre-Medicine
Faculty Mentor: Dr. Anne Spain, Arts & Sciences, Biological Sciences 
Horizontal Gene Transfer in the Presence of Antiseptics

Antibiotic resistance among bacteria is arguably one of the more troublesome topics in medicine today. Genes for resistance can be transferred between bacteria, and it has been found that environmental stressors such as antibiotics can increase the rate at which transfer occurs. However, little research has been done to see what effect antiseptics may have on transfer of resistances. Chlorhexidine was selected as the antiseptic to be used in this research because of its wide spread use in hospitals. Door handles and other regularly touched surfaces from clinical and non-clinical sources were swabbed and then plated, using a type of agar for gram-positive bacteria and another for gram-negative. Ten gram-negative and 20 gram-positive isolates were obtained and assays were done to determine their resistance to six different antibiotics. Four-gram positive isolates had resistance to the antibiotic ceftriaxone. To assess gene transfer, multiple combinations of ceftriaxone resistant gram-positive bacteria and susceptible gram-negative bacteria were grown together with varying levels of chlorhexidine, the hospital antiseptic. The cultures were incubated for 24 hours then plated on agar containing ceftriaxone. The gram-positive isolates were able to grow on the ceftriaxone plates; however, no gram-negative isolates were grown. This indicates that no resistance transfer occurred, though, more trials could yield different results, preliminary data supports that chlorhexidine does not induce transfer of antibiotic resistance genes.

Student Fellow: Jordan Lee, Biotechnology
Faculty Mentor: Dr. Mark Thomson, Arts & Sciences, Physical Sciences
Geometry Optimization and Energy Calculations for Hydrogen Bonded 1:1 Co-Crystals of Carboxylic Acids with Sulfisomidine and Sulfamethazine

A co-crystal is defined as two or more compounds forming a unique crystal with unique properties. Co-crystallization is currently being explored as a method to change drug storage, delivery, and action by co-crystallizing drugs with other compounds. This project focuses on the co-crystallization of sulfamethazine and sulfisomidine, two antibacterial drugs, with various carboxylic acids. These drugs only differ chemically in the position of a single nitrogen atom, but sulfamethazine forms co-crystals in the lab with relative ease while it is far more difficult to form a co-crystal using sulfisomidine. This project attempts to explain this phenomenon using Gaussian 09W software to complete DFT energy calculations and geometry optimizations. An energy calculation was performed on the original co-crystal, followed by an optimization calculation, and finally a second energy calculation. This sequence of calculations determined that sulfisomidine must change its conformation from the ideal optimized structure more than sulfamethazine does, and therefore must overcome a greater energy barrier. The eventual goal is to apply these findings to practical pharmacological scenarios to improve the effectiveness of these sulfa drugs in the body.

Student Fellows: Benjamin Doyle, Applied Mathematics & Alex Eastwood, Applied Mathematics, Computer Science
Faculty Mentor, Dr. Anil Venkatesh, Arts & Sciences, Mathematics
The Luckiest Abelian Group: Examining the Error Term of Cohen-Lenstra Heuristics

This project explores the class number problem, a conjecture of Gauss that relates to the property of unique factorization. Every integer can be factored uniquely into primes (up to order and sign), and this property extends to some larger number systems as well. For example, the Gaussian integers (complex numbers with integer components) also have the unique factorization property.  The extent to which a number system fails to have unique factorization is measured by an abelian group called the ideal class group; the larger the group, the farther the number system is from having unique factorization. In rough terms, Gauss conjectured that the size of these groups tends to infinity as we take more and more “complicated” number systems (specifically, this refers to imaginary quadratic extensions). One of the main tools for studying class numbers is the Cohen-Lenstra heuristics, which give an asymptotic prediction of how frequently each abelian group will arise as a class group. In this talk, we provide a brief overview of the history of the class number problem. We give concrete examples of the relationship between class group and factorization. Finally, we outline our algorithm and reveal the “luckiest” and “unluckiest” abelian groups relative to the Cohen-Lenstra prediction.

Student Fellow: Jeffery Dickerson, Plastics & Polymer Engineering Technology; Rubber Engineering Technology
Faculty Mentor: Mr. Matthew Yang, Engineering & Technology, School of Design & Manufacturing 
Impregnating Textiles with Shear Thickening Fluids

Non-newtonian dilatant (shear thickening) fluids are materials that increase in viscosity as the applied shear rate increases. Such materials offer a wide variety of applications over an array of industries. This project explored how a textile material could be impregnated to increase protection from impact and penetration. The shear thickening fluid (STF) was created using two ingredients; ethylene glycol (EG) or polyethylene glycol (PEG) as the continuous phase, and silica nanoparticles as the dispersant. Once a proper dispersion has been created, it is then diluted in excess amounts of an organic solvent such as methanol in order to allow the fabric being impregnated to absorb the STF. The fabric is soaked for a predetermined amount of time, hang dried to allow for further absorption into fabric intricacies while allowing methanol to begin evaporating, and finally, the fabric is oven dried in order to evaporate excess methanol leaving a dried material that shows substantial improvement of impact and penetration resistance. Of all the materials used, ethylene glycol and fumed silica showed the best dilatant properties and ease of impregnation into textiles.

Student Fellow: Hunter Pope, Biology/Pre-Medicine
Faculty Mentor: Dr. M. Beth Zimmer, Arts & Sciences, Biological Sciences
Effect of Upper Cervical Spinal Cord Injury on the Hippocampus: Structure and Function

It has been observed through previous studies that spinal cord injury (SCI) causes acute memory and learning deficits in Long-Evans rats. This is thought to be due to neuronal loss or neural plasticity in hippocampal tissue (above the site of injury) as a result of injury-induced changes and microglial activation. It is hypothesized that through this neuronal response to injury, there is a significant loss of the protein brain-derived-neurotrophic-factor (BDNF) and the neurotransmitter serotonin. Because BDNF and serotonin are involved in the mechanism for long-term potentiation, it was hypothesized that loss of said proteins should be observed as correlative to the memory and learning deficits seen in previous studies. The objective of this research project was to measure and analyze the levels of BDNF and serotonin in rat hippocampal tissue through Western Blot analysis and immunohistochemistry. We optimized data collection, analysis, and imaging techniques for these procedures. Results showed no significant differences in the levels of serotonin between sham rats and SCI rats. Further optimization is needed to better analyze the relationship between SCI and BDNF and future experiments will be conducted.