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 Select Current Research Projects

Alexander Lekan
Salicylic Acid as a Cardioprotective Agent Against Epirubicin-Induced Cardiotoxicity

Over 1 million people receive chemotherapy treatments each year in the United States. Anthracycline are some of the most effective and common chemotherapeutics in use today, with epirubicin being one of the most prescribed anthracyclines. However, its long-term clinical usefulness is limited by its severe cardiotoxicity. Although the exact mechanisms of anthracycline-induced cardiotoxicity are not yet fully understood, the most prominent hypothesis is the generation of reactive oxygen species (ROS) induced by epirubicin is one central mediator of direct and indirect cardiac side effects. Given the potent anti-tumor activity of anthracyclines, recent research has focused on possible cardioprotective agents that can diminish the cardiotoxicty of these valuable chemotherapeutics. Antioxidants are the most studied novel cardioprotective agents to counteract the generation of ROS, particularly members of the flavonoid family, such as Kaempferol. There has been little investigation, though, into the phenolic acid family of antioxidants. This study will investigate the cardioprotective effects of salicylic acid (a phenolic acids antioxidant) against epirubicin-induced cardiotoxicity. First, cardiomyocyte cells will be isolated from chicken embryos and maintained at 37 C, 5% CO2, with media being replaced when necessary. Cells will first be treated with varying amounts of epirubicin (0.1-10 M, in RPMI 1640 media) and an MTS cell viability assay will be used to determine which concentration causes significant cell death, or cardiotoxicity. Cells will then be pre-treated with varying concentrations of sodium salicylate (5.0-50 M, in RPMI 1640 media) for two hours prior to epirubicin treatment with the previously determined concentration for 24 hours. An MTS cell viability essay will then be used to measure the viability of the cells after pre-treatment with sodium salicylate and later exposure to epirubicin. A crystal violet assay will also be used to quantitatively determine the relative density of cells. Results of this study are pending.


 

Lauren Beglin
Snake Venom as a Suppressor of Inflammation in Rheumatoid Arthritis

Nearly 1.3 million people in the United States suffer from rheumatoid arthritis (RA). It has been suggested that snake venom can be used to relieve inflammation associated with RA. The goal of this study is to develop an alternate treatment for RA that would be as effective and have fewer side effects than those currently available. This study seeks to further understanding of Thailand Cobra venom (TCV) and Cobroxin (CBX), a commercial product containing TCV, as suppressors of inflammation. It was hypothesized that treating inflamed cells with TCV and CBX would decrease MMP-9 production, demonstrating a decrease in inflammation. RA will be modeled in vitro using lipopolysaccharide (LPS) to induce inflammation as shown by MMP-9 production in human foreskin fibroblasts (HFFs), cells similar to those found in joints. In this study, HFFs were treated with 1, 5, 10, 15 or 20 ug/mL LPS for two hours (immediate) and twenty-four hours (prolonged) to determine its effects on cell viability. Results from an MTS cell viability assay showed statistically significant cell death for the immediate 15 and 20 ug/mL treatments and the prolonged 1, 5, 10 and 15 ug/mL treatments. As a result, both 15 and 20 ug/mL immediate and prolonged treatments were eliminated as options for further experimentation. An ELISA was run to analyze the cell supernatant for the presence of MMP-9 after LPS treatment. Results showed a statistically significant increase in MMP-9 production for the prolonged 5 and 10 $mu$g/mL treatments. It was determined that the 5 $mu$g/mL LPS treatment was most suitable for modeling RA in vitro. HFFs were treated with TCV or CBX (0.014, 0.14, 1.4, 2.1 or 2.8 ug/mL) to determine effect on cell viability. Results from an MTS cell viability assay showed statistically significant cell death for TCV 2.8 ug/mL and CBX 0.014 and 2.8 ug/mL. As a result, both TCV and CBX 2.8 ug/mL were eliminated as options for further experimentation. Finally, RA will be modeled in vitro; LPS-induced, inflamed HFFs will be treated with either TCV or CBX and the MTS cell viability assay and the MMP-9 ELISA will be repeated to determine effects on cell viability and changes in MMP-9 production.


 

Justin Linetski
Caffeine-Induced Apoptosis in Neuroblastoma Cells: An In Vitro Study

Neuroblastoma is one the most common and dangerous nervous system cancers. The disease has twice the incident rate of leukemia for children within their first year, and a survival rate of only 30%. As of now, there are limited options for treating neuroblastoma. Current options, such as surgery, have limited efficacy, due to the tendency of neuroblastoma to metastasize to locations such as the spinal cord or bone marrow. However, recent studies have suggested that caffeine may have anti-cancer properties, as it induces apoptosis in some types of cancerous cells. This study will determine both the effectiveness and mechanism of caffeine as a treatment option for neuroblastoma. Human neuroblastoma cells (SH-SY5Y) and control (non-cancerous) human foreskin fibroblast (HFF) will be maintained at 37 C, 5% CO2 and sub-cultured, with media replenished as needed. Cells will then be treated with various concentrations of caffeine (0.01-10 mM) for 48 hours. An MTS cell viability assay will be used to measure the viability of SH-SY5Y and HFF cells after treatment. Additionally, a Caspase 3/7 assay will be used to measure the Caspase activity in both the SH-SY5Y and HFF cells to determine whether apoptosis or necrosis has occurred. It is hypothesized that caffeine treatment will decrease SH-SY5Y viability via apoptosis, rather than necrosis, in the SH-SY5Y cells. The treatment is not expected to significantly decrease HFF viability. Results are pending.


 

Vanita Mangru
Improved Efficacy of Chemotherapeutic Tamoxifen with Addition of Vitamin D3

Finding an efficient treatment for cancer is a top priority in the medical field. Many research studies have discovered useful cancer treatments like Tamoxifen, an anti-tumorigenic agent used by patients who are suffering from estrogen-positive forms of breast cancer. The drawbacks of this treatment, however, are the severe side effects associated with this drug, including cataracts, uterine cancer, and stroke. Recently, cholecalciferol vitamin D3 (VD3) has been studied in association with the reduced risk and incidence of cancer. 22-oxacalcitriol (OCT) is a VD3 analogue that was specifically designed to study and understand the effects of VD3 on cancerous cells in vitro. OCT is chemically similar to VD3, but does not induce hypercalcemia, which is a side effect of VD3 treatment. The goal of this study is to determine the effect of combination treatments of Tamoxifen and OCT, and Tamoxifen and VD3, as compared to Tamoxifen alone on both estrogen-positive breast cancer cells and non-cancerous cells. It is hypothesized that the combination of Tamoxifen and OCT/VD3 will be effective in inducing apoptosis of estrogen-positive breast cancer cells, such that the concentration of Tamoxifen can be decreased while maintaining similar efficacy to Tamoxifen alone at higher concentrations. Reducing the necessary dose of Tamoxifen would reduce both the harmful side effects and the cost of treatment, and overall, improve breast cancer treatment. In this study estrogen receptor negative breast cancer cells (MCF-7) and non-cancerous control human foreskin fibroblasts (HFF) were maintained at 37 C, 5% CO2 and sub-cultured and media replenished as needed. Cells were treated with varying concentrations of VD3 (2.58 M, 2.58 nM, 2.58 pM and 2.58 fM), OCT (2.39 M, 2.39 nM, 2.39 pM and 2.39 fM) and Tamoxifen (2.5 M, 5 M, 10 M, 15 M and 20 M) individually in triplicate, for 24 hours to determine baseline cell viability after treatment. An MTS cell viability assay was used to measure the viability of MCF-7 and HFF cells after treatment. Results are pending.


 

Anna Molotkova
Improving Leukemia Treatment Using Gold Nanoparticles for Drug Delivery

There are approximately 287,963 people living with leukemia in the United States and 20,000 of them have Chronic Myeloid Leukemia (CML). CML is a slow progressing blood and bone marrow disease, where the bone marrow over-produces white blood cells. Currently, tyrosine kinase inhibitors are used to treat CML. Tyrosine kinase inhibitors (TKIs) inhibit cancer growth by preventing the oncogenic function of the BCR-ABL gene. Bosutinib, a TKI, is effective for most patients with CML, but shows significant overall toxicity. Developing a more targeted drug delivery system using gold nanoparticles may decrease the negative side effects of Bosutinib on the body. It is hypothesized that if CML cells are treated with Bosutinib-coated gold nanoparticles (AuNP), then the toxicity of Bosutinib will decrease, while efficiency of the drug will increase. The goal of this study was to use gold nanoparticles to deliver Bosutinib in order to develop an improved treatment for CML. CML and human foreskin fibroblasts, HFFs, (non-cancerous) will be treated with Bosutinib, with and without AuNPs, and cell viability will be measured. CML cells (K-562) and HFFs were maintained at 37 C, 5% CO2 and sub-cultured and media replenished as needed. Cells were first treated with varying concentrations of Bosutinib (0.1, 0.25, 0.50, 1, and 2 μM in 0.01% DMSO) in triplicate, for 48 hours. An MTS cell viability assay was used to measure the viability of CML and HFF cells after treatment, and the concentration that produced the optimal level of viability will be used for the final treatment of the Bosutinib-coated gold nanoparticles and the Bosutinib drug alone. Scanning electron microscopy was used to analyze the morphology of the cells. Results are pending.


 

Katherine Guo
Using Dihydroartemisin to Improve Treatment of Pancreatic Cancer In Vitro

Pancreatic cancer is the leading cause of cancer-related deaths, and the majority of patients die within 6 months of diagnosis. Although gemcitabine is a first-line chemotherapeutic drug for pancreatic adenocarcinoma, acquired drug resistance is the major cause of failed treatment. Once chemoresistance is established, gemcitabine begins to promote cancer cell proliferation, angiogenesis, and suppression of apoptosis, which is activated by gemcitabine-induced up-regulation of Nuclear Factor kappa-Beta (NF-kB). Dihydroartemisinin (DHA), a known NF-Kb inhibitor, prevents cell proliferation by downregulating Bax and Bcl-2, proteins that are important to metastasis. With limited options to prevent gemcitabine resistance, novel treatment options should be investigated. In this study, treatments will be targeted toward reverting pancreatic adenocarcinoma cells (PANC-1) to a gemcitabine-susceptible state. First, PANC-1 cells must be made gemcitabine resistant. Cells will be maintained at 37 C, 5% CO2 and sub-cultured and media replenished as needed.Cells will then be treated with varying concentrations of gemcitabine (0.1-0.5 M in distilled water) for 48 hours. An MTS cell viability assay will be used to measure the viability of PANC-1 cells after treatment, and the concentration producing the optimal level of viability will be used to produce gemcitabine-resistant cells. This concentration will be added to the growth media of the cells and prolonged exposure will produce resistant cells. The cell viability assay will be repeated after treating gemcitabine-resistant PANC-1 cells with varying concentrations of DHA (5-50 M in ethanol) in media. This will give baseline viability for DHA treatment, and the concentration that gives optimal viability will be used for further experimentation. Furthermore, the fungal metabolite, gliotoxin, has also been shown to inhibit NF-Kb and induce apoptosis. In combination with gemcitabine, gliotoxin is anticipated to significantly reduce the production of gemcitabine-induced NF-Kb and the resulting suppression of apoptosis. Results are pending.


 

Drew Missey
Purification of Dye-Contaiminated Water Using Treated Fique Leaf Fibers

Blue jeans are an extremely common fashion choice for people of all ages. Their production involves the use of indigo dye, some of which goes into wastewater and is purified before being dumped into a nearby waterway. However, this dye is extremely difficult to remove using traditional filtration methods, and as a result stays in the water in relatively large concentrations. Once disposed of into existing waterways, it clouds the water, which prevents sunlight from getting through the surface. This limits the growth of algae, which leads to a chain reaction disrupting the entire ecosystem. However, a recent study by a team of scientists in Columbia has found that a natural fiber from the fique plant (Furcraea andina) can be used to remove the dye from wastewater. The fibers are submerged in a solution made from sodium permanganate, and then treated using an ultrasonic procedure. This method takes advantage of nano-sized cavities found in the cellulose in the fibers, and uses these cavities to grow manganese oxide molecules inside them, which then react with the dye and break it down.The biggest advantage to this method is that it only requires a basic chemistry lab and equipment, lowering the barrier for entry greatly. The original study showed this method to have 97-99% effectiveness. In this study, the effects of varying concentrations of sodium permanganate on the effectiveness of removing the dye will be tested. Algae will be grown in an environmental growth chamber, and then subcultured into 5 separate cultures. The results can be used to determine the most effective use of this method to purify the water. This concentration can be used for further experimentation concerning the use of other fibers, and the effects on the growth of algae after purification. Results are pending.


 

Rebecca Rosenthal
Memantine Treatment for Prevention of Apoptosis in Traumatic Brain Injury

Traumatic brain injury (TBI), defined as a force to the head that disrupts normal brain function, is the cause of one third of injury related deaths in the United States. Due to the complexity of the brain and cascade of events that constitute TBI, very few effective treatments exist for the prevention of long-term brain damage resulting from TBI. One consequence of TBI is neuronal cell death by excitotoxicity caused by an influx of ions into the cell. In the presence of excess neurotransmitters, particularly glutamate, released upon TBI, N-methyl D-aspartate (NMDA) receptors open ion channels and allow high concentration of Ca2+ ions to enter neurons. Memantine hydrochloride, a drug currently used for the treatment of Alzheimer s disease, blocks NMDA receptors so that excess Ca2+ ions cannot enter the cells and may be an effective treatment for excitotoxicity. In this study, memantine will be studied as a pharmaceutical treatment for TBI. Human neuroblastoma cells (SH-SY5Y) will be maintained at 37 C, 5% CO2 and sub-cultured, with media replenished as needed. Cells will then be treated with various concentrations of memantine (1.0 uM, 10 uM, 25 uM or 50 uM). The optimal concentration of memantine for treatment will be determined via MTS cell viability assay. Untreated and memantine treated cells will be seeded into a chamber slide. The cells will then be injured using a scratch assay to simulate TBI. Cell migration and changes in morphology will be qualitatively compared between the treated and untreated cells using light microscopy. Results are pending.


 

Daria Beatini
Remyelination of Neuronal Axons Using Maurotoxin Therapy in Multiple Sclerosis

Multiple sclerosis (MS) is an autoimmune disease characterized by the inflammation and demyelination of neuronal axons in the central nervous system, caused by T-cells of the immune system crossing the blood brain barrier and attacking healthy myelin. There are two types of myelinating cells in the body, oligodendrocytes, which myelinate axons of the central nervous system (CNS) and Schwann cells, which myelinate axons of the peripheral nervous system (PNS). The inflammation associated with MS, damage to the myelin sheath, as well as damage to myelinating oligodendrocytes inhibits action potential signals from traveling between neurons, causing a variety of debilitating symptoms, such as severe loss of vision and paralysis. Current therapies for MS include the use of immunosuppressant drugs, which often have serious negative side effects, such as increased risk of infection. Scorpion venom (Maurotoxin) has been shown to block the potassium channels in CNS cells, thereby reducing inflammation and allowing propagation of action potential signals, thus offering a potential treatment for many autoimmune diseases, including MS. In this study, myelinating Schwann cells will be used as a model for a MS because of their similarity to oligodendrocytes and relative ease to study in vitro. Cells will be treated with varying concentrations of maurotoxin at 10, 1, 0.1, and 0.01 nM, diluted in Dulbecco's Modified Eagle's Medium (DMEM). An MTS cell viability assay will be used to determine the optimal concentration of maurotoxin to use in future studies. Fluorescence microscopy will be used to determine the levels of maurotoxin-induced myelin production, using the FluoroMyelin Red Fluorescent Myelin stain. It is hypothesized that maurotoxin will increase myelin production, and will become a useful therapeutic option for reducing the symptoms of MS. Results are pending.


 

Patricia Perfect
The Effect of Methionine Starvation on Chemotaxis in Enterobacter Species

In the public health field, the gradual rise of antibiotic resistance among species of bacteria is a prime concern. Because certain classes of antibiotics cannot be used to treat infections caused by resistant bacteria, applied treatments are less successful, and formerly curable infections become fatal. As a result, the transmission of such infections must be prevented. Studies have determined that antibiotic resistance is primarily acquired through horizontal transfer mechanisms, especially conjugation. Transmission of resistance genes is therefore dependent on bacterial migration, or chemotaxis, which is characterized by continuous modification of swimming patterns to approach chemically favorable conditions. The goal of this study is to suppress tumbling, the reversal of the flagellar rotation, thereby inhibiting conjugation and restricting the spread of resistance genes. Methionine starvation is induced in Enterobacter aerogenes and Enterobacter cloacae through two methods to effectuate smooth swimming: (1) introduction of varying concentrations of methionine analog norleucine to cultures of E. aerogenes and E. cloacae, and (2) transformation with replication initiation factor of a methionine auxotroph. A modified capillary assay is performed to indirectly measure the accumulation of bacteria in repellent imipenem. SEM imaging is also be used to analyze changes in morphologies of the bacterial strains. Results are pending.