Jade McDaniel and L. M. Viranga Tillekeratne Dr.
Each year, millions of people are diagnosed with cancer. In order to fight back, countless drugs are currently being developed as possible treatments for the disease. Histone deacetylase (HDAC) inhibitors are chemical compounds that can be used to reverse repressed transcription of tumor suppressor genes. They are currently used to treat several targeted cancers, but there is much room for improvement to make them work more efficiently without causing unwanted side effects. The aim of our research was to investigate new metal-binding groups to be incorporated into HDAC inhibitors and make them more class or isoform selective. In order to do this, we obtained several compounds predicted to successfully bind with zinc (Zn2+) ions and analyzed their chelating ability using nuclear magnetic resonance and ultraviolet spectroscopy. We also performed several reactions aimed at synthesizing an HDAC inhibitor with the new metal-binding group attached. Our research identified that several groups tested possessed significant ability to bind to Zn2+. Moving forward, once the metal-binding groups are incorporated, the compounds can be tested on cancer cells to determine their ability to inhibit cell growth.
Allison Grim and Fan Dong Dr.
Gfi1 is known as a nuclear transcriptional repressor that positively regulates B and T cell development and is required for the development of granulocytes. Gfi1 supports granulocyte differentiation at the expense of monocyte differentiation by repressing genes encoding Monocyte-Colony Stimulating Factor (M-CSF) and PU.1, which favor monocyte differentiation. However, the molecular mechanisms by which Gfi1 acts in myeloid development remain incompletely understood. For instance, in contrast to a previous publication reporting that Gfi1 increased the activation of Erk1/2, Dr. Dong’s lab has recently found that Gfi1 inhibits Erk1/2 phosphorylation/activation. The exact pathway leading to Gfi1-mediated inhibition of Erk1/2 activation is yet to be elucidated. Since Gfi1 is a nuclear transcription factor, it is possible that Gfi1 may inhibit Erk1/2 activation by regulating the expression of a cytoplasmic regulator of Erk1/2 activation. In preliminary data obtained from Dr. Dong’s lab, Gfi1 was shown to upregulate the expression of mSlap2. Interestingly, mSlap2 is a cytoplasmic protein that has been shown to inhibit the activation of Erk1/2. We hypothesize that mSlap2 may play a key role in Gfi1-mediated inhibition of Erk1/2 activation in response to Granulocyte-Colony Stimulating Factor (G-CSF).
Amber Smith, Aastha Chada, Ryan Homan, and Gabriella Baki Dr.
Caffeine has recently become popular as a component of topical anti-aging cosmetic products due to its wide-ranging biological activity. The aim of this study was to determine the amount of caffeine that permeated through a skin-like synthetic membrane from marketed eye creams. A prestige and a mass anti-aging eye cream for women and an anti-aging eye cream for men were selected to be studied. Physicochemical characteristics, including pH, appearance and droplet size were studied. Permeation of caffeine was tested in vitro using Strat-M®membrane on Franz diffusion cells. Caffeine was analyzed using HPLC. Appearance of the products slightly differed, their pH was similar. All three eye creams were monodisperse, the average droplet size varied between 1-3.5 μm. The mass product for women contained the highest amount of caffeine in 1 g eye cream. In this 24-hour study, the largest caffeine permeation (0.49%) via Strat-M® membrane was observed from the prestige eye cream for women. Eye creams containing caffeine will be formulated using in silico modeling and tested for in vitro release and in vitro permeation. Data from this preliminary study will guide in designing the creams. A. S. acknowledges support from the UT Office of Undergraduate Research (FYSRE).
Eanas Abutaha and Heather Conti Dr.
Cancer patients have many side effects in their immune system as a result of anti-cancer treatments, such as radiation and chemotherapy. However, one of the most consistent and debilitating complications in patients undergoing head-neck radiation is Oral Mucositis. Oral Mucositis is characterized as the painful development of exposed ulceration on the oral mucosal tissue. Although it is well known that oral mucosa cells are significantly damaged during these therapeutic radiations, an effective treatment is yet to be discovered. Preliminary data indicates that the inflammation produced by tissue damage is connected to a particular interleukin known as IL-17. This investigation focuses on answering if IL-23 and IL-17, defensive cytokines located in mucosal tissues, are causing a dysregulation of inflammation in the oral cavity after head-neck radiation. Based on preliminary data, a reasonable hypothesis is as follows: Wild type mice are susceptible to damage associated with head-neck radiation due to an upregulation of IL-17 and IL-23. By determining the protein levels of IL-23 and IL-17 in tongue tissues exposed in radiation, data can be further analyzed, thereby resulting in a more complete understanding of the overall project.
Shirley Yee, Tao Yang, and Guofa Liu Dr.
Studies have shown that the Slit-Robo signaling pathway is important in guiding neural and non-neural cell migration through attraction and repulsion. In addition, Slit and Robo play important roles in tumorigenesis, cancer progression, and metastasis. Specifically, Robo1 binds to a tubulin protein known as TUBB3. The purpose of this research is to investigate the involvement of Slit and Robo signaling in glioblastoma progression. Though the mechanisms have yet to be fully explored, a connection between the presence of the Slit protein and the rate of cancer cell invasion, specifically glioblastoma, may exist, which can lead to a better understanding of the Slit/Robo/TUBB3 pathway and the promising development of new drugs to target specific cancers. Here, the effects of Slit2 was investigated for human embryonic kidney (HEK) and glioblastoma multiforme (T98G) cells. HEK cells showed no difference with the presence of Slit2 medium in the wound healing assays, but interestingly, Slit2 instead promoted migration in T98G cells. On the other hand, Taxol, a drug that stabilizes microtubules, may play a role in inhibiting cell migration. From the Western blot and immunoprecipitation, it suggests that a connection exists between Robo1-TUBB3 and Slit2 regulation of this interaction.
We have studied the structural, energetic, electronic, and magnetic properties of Fe16N2 doped with 3d transition metal elements (Mn, Co, Ti, Cr, V, and Ni). Special quasirandom structures were implemented to simulate doping throughout a range of concentrations (0% – 18.75%). Ab initio methods have been used to compute the optimal structures of pure and doped Fe16N2, for which formation energies were calculated. Our results indicate that all dopants lead to an increase in thermal stability. The HSE06 hybrid functional was applied to compute the electronic and magnetic properties of each material. Our findings predict Fe16N2 to exhibit a magnetic moment of 2.844 μB/Fe, which agrees well with previous works. We find that all dopants reduce the magnetization of Fe16N2, however, the magnitude of this decrease varies substantially depending on the dopant. Therefore, we propose that certain dopants may be beneficial to applications by serving to improve the stability of Fe16N2, while only decreasing the magnetization slightly. We have also studied the end-member compounds (Mn16N2, Co16N2, Ti16N2, Cr16N2, V16N2, and Ni16N2). Theoretical structures of these compounds are computed; all of which are determined to be dynamically stable, with the exception of Ti16N2. Electronic structures and magnetic moments are also reported.
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