PC School of Pharmacy faculty have extensive experience in basic science research and clinical research.

Explore the wide variety of research topics in which you can work. For PCSP students applying for the iPRSI, visit the University of Alcala’s Faculty.

Basic Science Research – 2016 PRSI Faculty

Dr. Serge Afeli

Affeli

Title:

MRP5 transporters in urothelial bladder cancer cells survival

Describe your project. No more than 250 words: background, hypothesis, techniques / methods to be used, role of student.

In the U.S., there are nearly 76,000 new cases of bladder cancer, 17,000 related deaths, and $4 billion associated costs annually. The combination therapy cisplatin-gemcitabine is currently the gold standard for bladder cancer treatment. Unfortunately, in patients with unresectable bladder cancer, cisplatin-gemcitabine response rate is only 49% with approximately 38% of patients surviving for up to 18 months. ATP-binding cassette (ABC) transporters are proteins physiologically expressed in cellular and intracellular membranes. They can pump drugs out of cancer cells before they reach their optimum concentration and cause treatment failure. ABCC5 (MRP5) transporter is a key member of the ABC transporter family and has been associated with chemoresistance in pancreatic, non-small cell lung, kidney cancers. However, information about MRP5 transporters in bladder cancer remains scarce. This proposal logically builds on our previous findings and seeks to further elucidate MRP5 transporters gene expression level in bladder cancer cells before and after chemotherapy as well as outline the genetic markers affected by cisplatin and gemcitabine treatment. We will utilize molecular biology techniques including qPCR, western blot, and immunocytochemistry with confocal imaging as well as microarray analysis on urothelial bladder cancer cells. We hypothesize that MRP5 transporters are key regulators of urothelial bladder cancer cells survival, and therefore a better understanding of their physiological role may provide additional options to better manage treatment failure in bladder cancer patients.  Student will be involved in all aspect of the experimental process and be trained to perform all mentioned laboratory techniques.

Timeline:

This project will be ongoing during the spring semester and the preliminary western blot, qPCR, immunocytochemistry experiments will be performed. During the 8 week period of the PRSI, the student will be responsible for confirming the preliminary findings and maintain the cell cultures.

Dr. Giuseppe Gumina

Gumina

Title:

Analogs of puromycin devoid of nephrotoxic adverse effect

Describe your project. No more than 250 words: background, hypothesis, techniques/methods to be used, role of student.

Puromycin is a natural molecule endowed with antitumor and antibiotic properties but not usable in therapy due to its marked nephrotoxicity. We are developing analogs of puromycin that retain the favorable activity spectrum without the nephrotoxic adverse effect. Students will be involved in the multi-step chemical synthesis of novel molecules and the antimicrobial evaluation in collaboration with Dr. Messersmith. The target products are nucleoside analogs, therefore the synthetic strategy involves modification of carbohydrates and coupling with heterocyclic bases. When the target compounds are obtained, students will be involved with the biological evaluation, consisting in antimicrobial studies on strains.

Timeline:

Thanks to PRSI funding from the current cycle we have been able to develop a fluorination method to generate a suitable intermediate to synthesize a target compound to be tested for antimicrobial activity. We are currently scaling up the fluorinated intermediate, which will be converted to the desired product through a 3-step sequence. Most of the work will be dedicated to the synthesis of the target molecule. NMR characterization of new molecules will be done using NMR spectrometers located in the PC department of chemistry and at the University of South Carolina Upstate, accessible thanks to a collaboration with Dr. Ruppel in their Chemistry department. Depending on the state of development, the student will likely be involved with the antimicrobial evaluation of one or more novel compounds, to be performed in our labs with the collaboration of Dr. Messersmith.

Dr. Chris Farrell

Farrell

Title:

Transporter substrate drugs and drug-resistance to the chemotherapy agents.

Describe your project. No more than 250 words: background, hypothesis, techniques/methods to be used, role of student.

Multi-drug resistance (MDR) is a serious issue for late stage cancer patients that are treated with chemotherapy (cytotoxic) drugs and tyrosine kinase inhibitors. Drug resistance occurs through multiple mechanisms within a cancer cell. A well-documented mechanism of drug resistance has been identified through the transporter proteins where the chemotherapy agents and inhibitors are not able to effectively kill the tumor cells. Recently, in vitro studies with colorectal cell lines have successfully identified drugs that cancer drugs are substrates/inhibitors for the transporter proteins. When these drugs that are substrates for the transporters are administered to the colorectal cancer cells, the cells become resistant to the chemotherapy. We hypothesize that when colorectal cancer cells are exposed to transporter substrate drugs, the cancer cells will become drug-resistance to the chemotherapy agents. In the experiments that we will be performing, the colorectal cancer cells will subsequently be treated with a chemotherapy agent that is a transporter substrate to determine drug resistance. The cells will be measured with cytotoxicity assay for drug resistance. The student will treat with the cells with a chemotherapy agent called SN-38 to determine cytotoxicity of the cancer agent and an immunostaining will be performed. The student will perform a staining to establish the protein expression.

 

Timeline:

In the first 4 weeks, the student will be treating the cells with the chemotherapy agent and the measuring with the chemotherapy agent. In the following 4 weeks the student will be verifying the protein expression of the transporter.

Clinical Research – 2016 PRSI Faculty

Dr. Clements

 JClements-240

Title:

Pharmacist-led management of obesity

Describe your project. No more than 250 words: background, hypothesis, techniques/methods to be used, and role of student.

Pharmacists have a pivotal role in chronic disease state management to improve disease-related endpoints, reduce frequency of hospitalizations, lower total health expenditures, and improve adherence. The impact of a pharmacist-led management services, using a collaborative practice agreement, has not been fully explored for obesity management. It is hypothesized that pharmacist-led management of obesity would improve endpoints associated with weight loss over a 6-month period. The first aim is to assess weight loss between baseline and 6 months as absolute change in weight (kilograms and percentage), absolute percentage change in body mass index, and absolute change in waist circumference (inches) with  pharmacist-led management. Adults (over the age of 18 years) with a BMI equal to or greater than 30 kg/m 2 would be recruited to participate in the study and receive pharmacist-led management on obesity. For a patient who signed an informed consent to participate in the study, the pharmacist would conduct an interview assessing medical and medication history; complete assessment; assess patient strategies and motivation to lose weight; develop weight-loss goals with the patient; provide tools; reassess at each monthly follow-up by reviewing history, objective endpoints, and previous goals; and create new goals at each monthly follow-up. Based on patient appointments at two locations of the practice site, approximately 40 patients per week would be asked to participate in the study. A student would assist with recruitment, obtainment of informed consent and completion of the initial interview.

Timeline:

Following IRB submission and approval through Greenville Health System, patients would be recruited to participate in the study and receive pharmacist-led management on obesity. Based on a 40-hour workweek, the principal investigator will be able to dedicate 50% of time to this project. A student pharmacist would help to optimize the use of time by assisting with the recruitment, obtainment of informed consent and completion of the initial interview. With this assistance, the project could quickly evolve for the first aim, which will take 16 months to complete.

Dr. Foushee

Foushee-240

Title:

Study of compatibility for co-infusing intravenous medications

Describe your project. No more than 250 words: background, hypothesis, techniques/methods to be used, role of student.

Septic patients commonly receive multiple intravenous (IV) medications. Practice guidelines require a minimum of physical compatibility before two IV solutions are administered together through a y-site connector. Patients with sepsis require fluid resuscitation as a mainstay of treatment to restore adequate hemodynamics. New data suggests balanced fluids (including lactated ringers, Plasmalyte, and Normosol) may provide beneficial outcomes compared to the fluid historically used for volume resuscitation in septic patients, normal saline (Raghunathan et al. Crit Care Med. 2014;42:1585-91). Compatibility data for many intravenous medications patients may require through Y-site administration with these balanced fluids is lacking and this study would provide information to safely co-infuse these solutions.

Admixtures of IV medications mixed with balanced fluids would be mixed in test tubes to simulate y-site compatibility and compared with solution controls (Allen et al Am J Hosp Pharm 1977; 34:939-43), as performed by most compatibility studies (Trissel Am J Hosp Pharm 1983; 40:1159-60; Trissel Handbook on injectable drugs. Bethesda, MD: American Society of Health-System Pharmacists). Students will complete assessments in triplicate every 15 minutes over a 1 hour time block, and will assess the admixtures for visual incompatibilities against light and dark backgrounds, as well as use a laboratory turbidimeter to determine nonvisible changes in physical compatibility. A PRSI student would be instrumental in all phases of the study, as outlined in the timeline below. The PRSI funding would allow for purchase of the study drugs and no IRB approval is required for this study so students could begin immediately.

Timeline:

  • Weeks 1-3: Drug literature search to determine gaps in current compatibility data for proposed drugs; Creation of drug order list; determination of concentrations to be studied; locating where to order and placing order for drugs; laboratory training; creation of study notebook; drafting introduction and methods for manuscript
  •  Weeks 4-6: Compatibility studies to occur in laboratory
  •  Weeks7-8: Data analysis; results and conclusions drafted for manuscript; creation of poster
  •  Student will complete all steps outline above under supervision of two primary investigators

University of Alcala iPRSI Faculty

Dr. Francisco Javier de Lucio Cazaña

Title:

Cellular microparticles in diabetic nephropathy.

Describe your project. No more than 250 words: background, hypothesis, techniques/methods to be used, role of student.

Background: After cellular stimulation in the broad sense of the term, the cell releases submicrometric membrane fragments, termed microparticles (MP), to the extracellular environment. MP serve as vectors of cell-to- cell communication through the transfer of proteins, bioactive lipids and RNA to target cells. The role of MP in diabetic nephropathy (DN, a high prevalence condidition and the most common cause of end-stage renal disease requiring dialysis) is currently unknown.

Hypothesis: Since proximal tubular cells contribute largely to the development of DN, we hypothesize that when these cells are exposed to hypoxia and high-glucose concentration (these conditions resembling the actual diabetic milieu to which cells are exposed) they release MP that impair the normal cell response to hypoxia

Techniques to be used: Cell culture, Western blot, immunocytochemistry, work in hypoxia cabin, flow cytometry, cell transfection, RT-PCR

Role of the student and timeline: The role of the student is highly dependent on their laboratory experience. Therefore, we will adapt the project to the student’s experience and will develop a tailored training process for 4-5 weeks. Then, the student will perform at least one experiment and will analyze the data obtained.

Dr. Jesús Molpeceres García del Pozo

Title:

COX-2 inhibitors and nanoparticles for the treatment of cancer.

Describe your project. No more than 250 words: background, hypothesis, techniques/methods to be used, role of student.

Background: Nanoparticles are promising drug carriers in the biomedical field since they have shown ability to stabilize unstable drugs, to increase the bioavailability of poorly soluble and low permeability compounds, to control drug release and to target encapsulated drug to certain organs thus reducing adverse effects. Their in vivo behavior depends on several factors such as morphology, particle size, surface charge or the presence of specific ligands on their surface.

Hypothesis: Since COX-2 inhibitors have shown some anticancer potential in several epithelial cancers, we hypothesize that when these drugs are incorporated into polymeric nanoparticles, a more specific pharmacological effect can be obtained after intratumoral administration of these formulations in tumours accesible from the skin surface such as breast or prostate cancer.

Techniques to be used: Electron microscopy, particle size analysis, FTIR, Differential scanning calorimetry, Drug release and permeability studies, Cell culture.

Role of the student and timeline: The role of the student will be to prepare and characterize NP formulations to be further tested for efficacy in cell culture systems.

University del Valle, Guatemala iPRSI Faculty

Dr. Brooke Ramay/ Diego Archila

Title:

Prevalence of antibiotic resistance in healthy subjects in Quetzaltenango, Guatemala

Describe your project. No more than 250 words: background, hypothesis, techniques/methods to be used, role of student.

Antibiotic resistance is of global concern. Antibiotic use, and environmental contamination (microbiological and antibiotic residuals) due to poor sanitation are hypothesized to affect antibiotic resistance, but the contribution of these variables has not been investigated in Guatemala. We are conducting a research project investigating the prevalence of antibiotic resistance in healthy subjects in four communities in the department of Quetzaltenango Guatemala. We will use two cross sectional surveys and laboratory analyses of samples gathered from household participants to identify factors related to antibiotic resistance. Students may participate in gathering data in the field (using cross sectional questionnaire) or laboratory analysis of samples in the Central Campus at UVG. They may additionally participate in analysis and presentation of results.

Timeline:

In the months pertaining to “summer” we will be gathering our second round of data in the field and analyzing samples in the laboratory(June 2017). The potential student will have the opportunity to join the team in the field or in the laboratory. Field work consists of administering surveys in households interacting with participants in Spanish, and with Indigenous language translators. Participants will be asked about previous and current antibiotic use. Laboratory work consists of identifying antibiotic resistant bacteria together with local microbiologists at the UVG campus. In July through August we will be organizing, analyzing and presenting data at the UVG campus which the student may participate in by collaborating with researchers in analysis.