Mr. Sergey Boyarskiy
Mentor: Dr. Daniel Kamei
Title: Drug delivery using peptide co-polymer vesicles
Dr. Daniel Kamei and Sergey Boyarskiy
Sergey Boyarskiy is a third year Bioengineering major. Since his first year he has been conducting research in identifying a novel gene that is responsible for apoptotic regulation in Drosophila melanogaster under the guidance of Dr. Frank Laski in the Molecular, Cell, and Developmental Biology department. Currently Sergey is working with Dr. Daniel Kamei in the Bioengineering department on the characterization of self-assembling synthetic polypeptide vesicles.
Previous research in the Kamei lab has shown that under appropriate chemical conditions, a co-block peptide polymer made of 60 lysine and 20 leucine (K60L20) peptides is able to self-assemble into bi-layer vesicles with internal diameters of up to 1um. Since then the group has invested into manipulating these polymers for use as delivery vehicles for cellular targets. For example, changing the lysine residues into homo-arginines created vesicles with similar shape and properties that are less cytotoxic and are able to enter cells at a much higher rate. In particular, Sergey will be working on encapsulating doxorubicin, a cancer drug, into the vesicles and delivering both into cells, where the vesicles will release the drug and be either degraded or recycled. He is also characterizing the vesicles’ activity, toxicity, and cellular kinetics inside the cell. Sergey would also like to thank all the members of the Kamei lab for their valued support as well as the Howard Hughes Undergraduate Research program.
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Mr. Nasser Heyrani
Mentor: Dr. Larry Zipursky
Title: Identification of cell surface molecules involved in synapse formation during neuronal development
(Dr. Larry Zipursky and Nasser Heyrani)
Nasser Heyrani is a third year Psychobiology major/ Biomedical Research minor conducting research under the guidance of Dr. Larry Zipursky and Susan Yee. The Zipursky lab is interested in understanding the molecular mechanisms regulating neuronal connection specificity.
Proper neuronal development and communication are dependent on the intricate combinations of synapses that must occur between neurons. In the fruit fly, Drosophila melanogaster, there are around 250,000 neurons with millions of synaptic connections.
Nasser’s project focuses on identifying cell surface molecules in the Drosophila
genome responsible for proper synapse formation during development. Each ommatidia, ~750 of which form the compound eye of the fly, contain eight photoreceptor (R) cells. The first six (R1-R6) make synapses in the lamina while R7 and R8 grow through the lamina and connects in the medulla. The R7 and R8 axons terminate in
two distinct layers in the medulla. Examining a small subset of known mutants for cell
surface proteins will allow for identification of mutant phenotypes in single R7 or R8 cells. If there is an axon targeting phenotype in R7 or R8 neurons, we will know whether that gene is required for target specificity. The second part of Nasser’s project focuses on where cell surface molecules responsible for proper synapse formation are expressed. Different combinations of similar cell surface molecules in neighboring neurons could be responsible for the specific connections each make or one kind of molecule could be expressed in each type of neuron which would lead to specific targeting to the corresponding layer in the brain. Using genetic techniques, Nasser will examine the expression pattern of many cell surface molecules and look for genes that are expressed in subsets of neurons. These genes can be required for axon target specificity and will be further analyzed.
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Mr. James Hui
Mentor: Dr. Yung-Ya Lin
Title: Avian Influenza Detection and Imaging using Magnetic Resonance Imaging
Dr. Yung-Ya Ling and James Hui
James Hui is a third year Biochemistry major conducting research under the guidance of Prof Yung-Ya Lin in the Department of Chemistry and Biochemistry. James’ research involves imaging the avian influenza virus using Magnetic Resonance Imaging.
Nearly five decades after the discovery of magnetic resonance (MR), we have benefited tremendously as a society from MR’s ability to remotely probe matter and living tissues. However, we have merely been scratching the surface of MR’s potential. One active area of research in the field involves the quest to improve MR’s contrast for tissues or molecules of interest; When individual nanoparticles, which are made of superparamagnetic iron oxide (SPIOs), are coated with antibodies and are released into biological media, they will bind specifically to virus particles and self-assemble into aggregates. These aggregates can change the magnetic properties, mainly the spin-spin relaxation time (T2), of the surrounding water molecules, making these virus-nanoparticle clusters visible using magnetic resonance. He wishes to test this application for detecting H5N2 virus in vitro and, if possible, in vivo.
Such an MR based H5N2 detection method provides many benefits, such as sensitivity and speed, over the traditional method. The method used in this project is readily adaptable: by changing the antibodies on the SPIOs we may target any other virus or molecules for imaging using MR. This prospect has the potential to change medicine and biomedical research in mind blowing ways. For example, we may be able to readily monitor tumor cells’ growth and distribution in vivo using MRI; this will provide a more direct picture of diseases than what the current methods can offer.
To allow him to conduct fruitful research in the interdisciplinary field of molecular imagining, James wishes to obtain a MD/PhD degree after his time at UCLA.
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Ms. Ashley Koegel
Mentor: Dr. Dennis Slamon, Dr. Juliana Oh
Title: Characterization of H37/RBM5 lung cancer tumor suppressor gene
Ashley Koegel and Dr. Juliana Oh
Ashley Koegel is a fourth year biochemistry major. She has been conducting research under the guidance of Drs. Dennis Slamon and Juliana Oh since the start of her second year at UCLA. She is currently working in the Slamon Lab in MRL on a project characterizing the H37/RBM5 tumor suppressor gene in lung and breast cancers. H37 is located at chromosome 3p21.3. Deletion at 3p21.3 is one of the most prevalent (occurs in >80% of lung cancers) and one of the earliest genetic alterations in lung cancer. Therefore uncovering the molecular pathways of this gene holds particular promise for the development of new cancer diagnostics and therapeutics. Compared to adjacent normal tissue, the H37 transcript and/or protein is underexpressed in ~75% of primary non-small cell lung carcinomas. In addition, when transfected into A549 lung cancer cells, H37 significantly inhibits cell growth both in vitro and in vivo. Using A549/H37 cells, Ashley has participated in research to show that the molecular mechanism of H37 tumor suppression involves both G1 cell cycle arrest and apoptosis.
Based on data from earlier yeast-two hybrid screenings, Ashley is currently investigating the H37-MTA1 (Metastasis Associated Protein 1) protein-protein interaction in vivo. MTA1 protein is an Estrogen Receptor (ER) co-regulator which binds to ER and is also known to be involved in the HER2 oncogene pathway in breast cancer. Given that H37 was initially discovered to be differentially expressed in HER2 overexpressing breast cancers, and that the 3p21.3 region is also frequently deleted early in breast cancer, the H37-MTA1 interaction may explain the potential role that H37 has in the HER-2/ Estrogen Receptor (ER) pathway in human breast and lung cancers. In addition, Ashley is using siRNA techniques to knock down the expression of H37 mRNA in immortalized breast and normal lung epithelial cells in order to investigate the role of H37 in preventing tumor initiation. This research could potentially lead to earlier detection of lung (and breast) cancer and the development of novel therapeutics. Upon graduation, Ashley plans to pursue a joint M.D./Ph.D program studying translational oncology research. Ashley would like to thank all of the members of the Slamon Lab for their support and invaluable guidance.
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Ms. Anne Liu
Mentor: Dr. Jeffrey H. Miller
Title: Developing an Antibiotic Sensitivity Profile for Escherichia coli
Dr. Jeffrey H. Miller and Anne Liu
Anne Liu is a third year Microbiology, Immunology and Molecular Genetics major under the mentorship of Dr. Jeffrey H. Miller since her first year, winter quarter at UCLA.
The increasing number of antibiotic resistant bacteria poses a major
health problem. One way to combat this issue is to improve the
efficacy of existing antibiotics with combination therapy. Potential
targets for such drugs would be bacterial proteins that provide
intrinsic antibiotic resistance. We developed a high throughput system
using the complete Escherichia coli knockout collection to identify
genes whose loss increases sensitivity to subinhibitory concentrations
of seven antibiotics: ciprofloxacin, vancomycin, rifampicin,
ampicillin, sulfamethoxazole, gentamicin, and metronidazole. Screening
using several subinhibitory concentrations of each antibiotic revealed
154 knockout strains (the "sensitivity profile") that were highly
sensitive to one or more of the antibiotics. Further sensitivity
analysis of these strains was achieved by determining the minimum
inhibitory concentrations (MIC). The results of these studies may help
identify inhibitor molecules that will target these hypersensitive
genes and, consequently, increase bacterial killing efficiencies of
antibiotics at less toxic levels to humans.
Anne would like to thank the Howard Hughes faculty, scholars, and contributors; the URC/CARE directors and staff; and her lab mentor and colleagues for fueling her research passion. She has a strong appreciation for the amazing survival capabilities and defenses of microorganisms. After all, prokaryotes first existed about 3.5 million years ago.
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Ms. Katherine Ng
Mentor: Dr. Steven Smale
Title: Chromatin Remodeling During an Inflammatory Immune Response
Katharine Ng and Dr. Stephen Smale
Katharine Ng is a fourth year Microbiology, Immunology and Molecular Genetics major conducting research under the guidance of Dr. Stephen Smale. The Smale laboratory is interested in understanding the transcriptional regulation of pro-inflammatory genes.
Previous work done in the Smale lab has grouped bacterial lipopolysaccharide (LPS)-inducible genes into three major regulatory classes based on kinetics of induction, requirement for de novo protein synthesis and requirement for nucleosome remodeling complexes. Efforts to decipher the differential transcriptional regulation of these classes of pro-inflammatory genes have increasingly focused on the regulatory role of chromatin structure and nucleosome remodeling. Assaying for inducible DNase I hypersensitivity can provide information about changes in accessibility of local chromatin structure that take place upon stimulation, and DNAse I hypersensitivity has been found to be associated with regulatory regions of many genes. Katharine's project involves the utilization of DNase I hypersensitivity assays to monitor nucleosome remodeling at the promoters of LPS-inducible genes in each of the three classes and locate novel regulatory elements of these genes. It is hoped that understanding the pattern of DNase I hypersensitivity will aid in a more comprehensive understanding of the complex differential regulation of these genes.
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Ms. Kathy Ngo
Mentor:
Dr. Utpal Banerjee/ Dr. John Olson
Title: Response to Mitochondrial Dysfunction – Retrograde Signaling and mtDNA Maintenance in Mitochondrial Biogenesis
Kathy Ngo and Dr. John Olson
Kathy is a junior working under Dr. Utpal Banerjee and Dr. John Olson since her first year at UCLA. She has been working in several projects in the lab using the Drosophila eye as a model system. This includes a genome-wide screen to identify essential genes involved in eye development and an initial characterization of a novel lineage tracing system to provide excellent control in both temporal and spatial gene expression. Working with a group of undergraduates as part of the Undergraduate Research Consortium in Functional Genomics, they have shown that mutation of sac1, a gene encoding for a Phosphatidylinositol Phosphatase, results in ectopic induction of JNK and Hh signals. She is currently working with Raghavendra Chavourkar, a postdoctoral fellow, to understand how mitochondrial biogenesis is regulated in response to stress stimuli, such as mitochondrial dysfunction and how such retrograde signaling affects cell differentiation:
Mitochondrial biogenesis is dependent upon the coordinated expression of the mitochondrial and nuclear genome. Perturbation of cellular communication between these genomes can result in a wide array of mitochondrial diseases including neurodegenerative diseases, muscular weakness, cardiac failure, diabetes, renal dysfunction, and hepatic diseases. Using D. melanogaster as our animal model, our long-term goal is to understand how communication between the mitochondrion and nucleus is regulated by identifying key components and factors facilitating such crosstalk. We hypothesize that in the fruit fly: mitochondrial dysfunction can lead to dosage-dependent compensatory mechanism, resulting in an increase in both mitochondrial mass and mitochondrial number, mediated by a family of PGC-1 coactivators and a group transcription factors called Nuclear Respiratory Factors (NRFs).
Based on our preliminary findings and rationale, this project aims to elucidate how oxidative phosphorylation (OXPHOS) proteins are regulated to control mitochondrial biogenesis in vivo. The project is two-fold: first, we propose that in response to mitochondrial dysfunction and energy depletion, the Drosophila NRF is upregulated to provide a compensatory mechanism for the necessary energy demand, causing an increase in mitochondrial number and mass. The second goal is to identify novel genes from families of NRF, PGC and its coactivators, and proteins involved in the mtDNA replication machinery that can modulate mitochondrial biogenesis using an ectopic expression system in the Drosophila eye.
She would like to thank the Howard Hughes Medical Institute and National Institute of Health for their generous funding. She would like to express her gratitude toward her mentors: Dr. Utpal Banerjee and Dr. John Olson for providing her such a wonderful and enriching research experience. Finally she would like to thank Raghavendra and everyone in the Banerjee lab for their advices and support throughout the project.
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Ms. Sacha Prashad
Mentor: Dr. Hanna Mikkola
Title:
Sacha Prashad and Dr. Hanna Mikkola
Sacha Prashad is a fourth year Molecular, Cell and Developmental Biology major conducting research under the mentorship of Dr. Hanna Mikkola. Dr. Mikkola has previously shown that in mice, the placenta is one of the first organs to harbor self-renewing, multipotential hematopoietic stem cells (HSCs). Sacha is investigating whether the human placenta possesses a similar ability to support HSC development, and possibly even generate HSCs de novo. Recent work in the Mikkola lab has shown that placental hematopoiesis in the human occurs as early as 4 weeks developmental age, as evidenced by the presence of multilineage progenitors/candidate HSCs in 4 week placental tissue explant cultures. Sacha’s project involves localizing these putative HSCs in their placental niche using candidate stem cell surface markers. In the future, these putative HSCs will be isolated, and their ability to engraft and function in vivo will be examined by using immundeficient animal models. The characterization of the placental niche of the HSC will illustrate how HSCs are generated and protected during fetal development, and ultimately allow for the recreation of this microenvironment ex vivo so that HSCs may be expanded from cord blood, or generated from embryonic stem cells for therapeutic purposes.
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Mr. Kevin Roy
Mentor: Professor Guillaume Chanfreau
Title: The role of double-stranded RNA endonucleases in eukaryotic gene regulation
Kevin Roy and Dr. Guillaume Chanfreau
Kevin, a fourth-year major in Biochemistry, performs research under the direction of Dr. Guillaume Chanfreau in the Department of Chemistry and Biochemistry. The Chanfreau Laboratory investigates the regulation of gene expression primarily at the post-transcriptional level, using the model eukaryote Saccharomyces cerevisiae, commonly known as baker’s yeast. In particular, the laboratory is interested in the regulatory role of class III riboendonucleases, which cleave double-stranded RNA (dsRNA), focusing on the yeast nuclear RNase III homolog Rnt1p. Rnt1p is responsible for the regulation of various mRNAs, some of which control the import of iron, as well as the processing of a number of non-coding RNAs, including precursors to ribosomal RNA and small nuclear and nucleolar RNAs. Kevin is investigating the structure of Rnt1p by mapping its independently folded domains through limited proteolysis. While the structure of the dsRNA binding domain of Rnt1p is well characterized, the role of other domains in assisting substrate recognition and catalyzing cleavage is unknown. Identifying these stable domains may facilitate further structural studies with the goal of understanding the mechanism of RNase III binding and cleavage. Kevin is also investigating the function of two nuclear-encoded proteins found to associate with the large subunit of the mitochondrial ribosome. These two proteins have been found by sequence homology to contain the class III riboendonuclease catalytic domain, but there is no known functional role for either protein. Kevin is analyzing the processing of mitochondrial RNA in yeast strains deficient in each of these proteins. Accumulation of unprocessed mitochondrial RNA may reveal substrates for these putative RNases III and identify a role for dsRNA processing in mitochondrial gene regulation. Greater understanding of the regulation of mitochondrial genes in yeast may elucidate common mechanisms for mitochondrial gene expression in higher eukaryotes. Furthermore, a comparison of the mode of regulation in mitochondria with that in the prokaryotes may reveal evidence for the endosymbiosis theory of the origin of mitochondria. More complete characterization of all yeast RNase III activity will bring insight into the mechanisms by which eukaryotic RNases III recognize their dsRNA substrates and catalyze cleavage while preventing cleavage of non-substrate dsRNA in vivo. Kevin will continue his research while pursuing his Masters degree as a Departmental Scholar from Fall 2007 to Spring 2008. Afterwards, he intends to pursue an M.D./Ph.D. degree to combine his research and clinical aspirations.
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Mr. Tuan Tran
Mentor: Dr. April Pyle
Title: Characterization of Cripto-1 in Human Embryonic Stem Cells
Tuan Tran and Dr. April Pyle
Tuan Tran is a third year Molecular, Cell and Developmental Biology major and a Biomedical Research minor conducting research under the mentorship of Dr. April Pyle. He is investigating the role of Cripto-1 (CR-1) in stem cells, also referred to as teratocarcinoma-derived growth factor-1 (TDGF-1). CR-1 is known to be expressed in early embryo developmental stages and is often upregulated in tumors. CR-1 acts as a coreceptor for Nodal or Vg1/GDF-1 proteins in the transforming growth factor beta (TGF- b) signaling pathway, which is critical for controlling cell fate choices such as cellular differentiation, proliferation, and growth. Signaling strength, duration, and initiation time of CR-1 are all significant factors that determine mouse embryonic stem cell (mESC) commitment to the cardiomyocyte or neuronal lineage. Although CR-1 has been extensively studied in mESC differentiation, Tuan aims to elucidate its role in human embryonic stem cells (hESCs) or cancer initiation. Lentiviral transduction of short-hairpin RNA (shRNA) will be utilized to reduce CR-1 gene expression and establish a stable cell line. This stable cell line will be used as a tool to characterize the role of CR-1 in modulating hESC fate. Additionally, an inducible system will be used to upregulate CR-1 in hESCs and characterize its role in tumor initiation or growth. Upon completing his undergraduate studies, Tuan will pursue a dual MD/PhD degree.
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Ms. Karen Yan
Mentor: Dr. Ren Sun, Dr. Fuqu Yu
Title: Systems Biology Study on the Combinatorial Effect of Multiple Drugs on Multiple Myeloma
from left to right: (Dr. Ren Sun, Karen Yan, Dr. Fuqu Yu)
Karen Yan is a third year Biochemistry major conducting research under the guidance of Dr. Ren Sun and Dr. Fuqu Yu. Earlier research projects conducted in Sun's laboratory by Karen aimed to address questions regarding the mean tumor selectivity of different drugs on A549 non-small lung cancer cells. Karen is currently investigating the synergistic effect of optimized drug combination in MM.1S and MM.1R cell lines. Multiple myeloma (MM) is a plasma cell neoplasm that remains incurable despite recent discovery of chemotherapeutic agents targeting malignant B cells. Clinical manifestations of MM include skeletal destruction, renal failure, anemia, and hypercalcemia.
Using primary T cells as control, Karen will be optimizing the dose response curves for Dex-sensitive MM.1S and Dex-resistant MM.1R human MM cell lines. MM.1R was developed from parental MM cells that acquired resistance to conventional MM therapy, dexamethasone (Dex). Artificial Neural Network (ANN), an information processing paradigm, will be used to generate models to describe cell survival upon drug treatment. ANN is inspired by the highly interconnected neurons in the biological nervous system to receive and generate multiple data inputs and outputs. This research could potentially lead to better understanding of cross talk between multiple signaling pathways in MM cells that have acquired drug resistance and the optimal drug combinations in treating MM cells. In addition, the lab is interested in developing a luciferase reporter to study intermediate signaling pathways in MM cells. Karen would like to thank all the members of the Sun Lab for their support and invaluable guidance.
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Mr. Jesse Zaretsky
Mentor: Dr. Utpal Banerjee
Title: A search for new hematopoietic genes: characterization of an uninvestigated Drosophila lymph gland structure using enhacer-trap reporters
Jesse Zaretsky and Dr. Utpal Banerjee
Jesse Zaretsky is a third year Microbiology, Immunology, and Molecular Genetics major conducting research in the lab of Dr. Utpal Banerjee. After graduation, he plans to pursue an M.D./Ph.D combined degree.
Jesse’s research seeks to better understand the genetic basis for development of the Drosophila lymph gland, a model system for vertebrate hematopoietic development and innate immunity. Previous studies have characterized the Drosophila lymph gland as a regulated site of proliferation and differentiation of blood cell progenitors. This happens in a spatially restricted manner, forming three distinct zones of maturation. The larger, primary lobes of the lymph gland are divided into an outer cortical zone where large scale differentiation of maturing hemocytes occurs, a meduallry zone full of quiescent prohemocytes, and a small posterior signaling center that functions as a niche in maintaining the quiescence of the medullary zone, but likely also has other currently unknown roles.
Jesse’s project uses GFP and GAL4 enhancer trap insertions to map gene expression over the life of the larvae in order to identify novel markers with distinct spatio-temporal patterns of expression. Particular focus is given to the secondary lobes, the relatively uninvestigated structures posterior to the well characterized primary lobes. Several lines have been chosen out of the initial screen for follow up study, including in-situ hybridization for gene identification, functional/phenotypic analysis of mutants, and in one case exploration of the role of a multicopper oxidase and hypoxia in regulation of hemocyte differentiation.
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