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 fourth 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.
Back to top
Ms. Iris Claire Ha
Mentor: Dr. William Lowry
Modeling embryogenesis in vitro using human embryonic stem cells and human induced pluripotent stem cells
Iris Ha and Dr. William Lowry
Human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells provide great promise for the future development of regenerative therapies as well as a means for modeling human disease in vitro. However, a major challenge in both ES and iPS technology remains to isolate and characterize functionally distinct populations from the large, heterogenous pool of cells formed in culture. To address this issue, our lab is working to generate and enrich for purified cell populations derived from each germ layer—epidermal keratinocytes and neurons from the ectoderm, fibroblasts from the mesoderm, and hepatocytes from the endoderm—and compare these ES and iPS derivatives to their natural counterparts from human primary cultures in terms of morphology, gene expression, and functionality. In doing so, we hope to identify subsets of candidate genes unregulated as ES and iPS cells progress down these three specific lineages and ultimately elucidate the molecular events required for germ layer specification during gastrulation.
Iris would like to thank Bill Lowry, everyone at the Lowry Lab, and the Howard Hughes Undergraduate Research Program for making this project possible.
Back to top
Ms. Vivian Hecht
Mentor: Dr. Robin Garrel
Application of Trypsin Coated Superparamagnetic Nanoparticles on Droplet-Based Microfluidic Devices for Proteomics
Vivian Hecht and Dr. Robin Garrel
Vivian is a third year bioengineering student, and has been conducting research in the lab of Dr. Robin Garrell since her second year.
Vivian’s research involves the development of a more efficient method for performing proteomics research through employing superparamagnetic nanoparticles on a droplet-based microfluidic device.
Droplet-based microfluidic platforms have the ability to simultaneously manipulate multiple small droplets (uL to nL) for a variety of applications. Recent studies have demonstrated the potential of microfluidic devices to significantly improve the speed and efficiency of techniques in proteomics research. The large surface-to-volume ratio of micro and nano-scale droplets enhances the reation rates of enzymatic digestions. Moreover, droplet microfluidic platforms require smaller sample volumes and waste less reagent when compared to conventional methods.
Immobilization of enzymes on superparamagnetic nanoparticles significantly facilitates their separation from a protein solution. Because superparamagnetic substances are not magnetic in the absence of a magnetic field, they can be easily isolated from a solution using a hand-held rare earth magnet and then completely, and uniformly, redispersed. The ease of enzyme separation allows for enzyme recycling, thereby reducing waste and reagent quantities.
Preliminary studies have demonstrated successful digestion of insulin chain-B by trypsin immobilized on superparamagnetic nanoparticles at 37 ºC. Vivian aims to quantify the amount of enzyme attached to her superparamagentic magnetite nanoaprticles and then use the particles to perform enzymatic digestions on a droplet-based microfluidic device.
After completing her undergraduate education, Vivian hopes to pursue a Ph.D.
Back to top
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 fourth 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.
Back to top
Mr. Sattar Khoshkhoo
Mentor: Dr. Carlos Portera-Cailliau
Role of BDNF in the rapid desynchronization of network activity in developing neocortex
Dr. Carlos Portera-Cailliau and Sattar Khoshkhoo
Sattar is a third-year bioengineering major conducting research under the mentorship of Dr. Carlos Portera-Cailliau in the department of Neurology. Over the past two years, Sattar has been investigating a fundamental unanswered question in Neuroscience: How does neuronal activity organize itself in developing cortical networks to allow mature information processing and neural coding?
Early in brain development, neurons in the neocortex have highly synchronized firing patterns during spontaneous activity. In contrast, in the adult neocortex spontaneous activity is sparse and largely decorrelated. Portera-Cailliau laboratory has previously shown that this transition occurs precisely at around postnatal day (P) 12, but how this important transition occurs is not known. One candidate molecule underlying this developmental decorrelation is brain-derived neurotrophin factor (BDNF), which plays an important role as a mediator of structural and functional circuit maturation and plasticity. To Study the Role of BDNF, Sattar overexpresses BDNF in layer 2/3 of mice neocortex using in utero electroporation. Then he records the spontaneous activity of subsets of layer 2/3 neurons in barrel cortex of awake mice. It is conceivable that some neuropsychiatric disorders such as epilepsy, autism, and schizophrenia could be caused by problems in this transition, and could be treated by altering levels of BDNF in the brain.
Sattar intends to pursue a career in the biomedical sciences through an M.D/Ph.D degree.
Back to top
Mr. Tae Hun Kim
Mentor: Dr. James Bowie
Developing a method to study membrane protein folding energetics using a steric wedge
Tae Hun Kim and Dr. James Bowie
Tae Hun Kim is a third year Molecular, Cell Developmental Biology major conducting research under the guidance of Dr. James Bowie. He is originally from Guam, an island in the Pacific Ocean. He is investigating to develop a method to study membrane protein folding energetics using a steric wedge. Compared to the wealth of information known about soluble protein folding, there is very little information about the folding processes for membrane proteins. Similarly, there is a huge discrepancy between the fact that membrane proteins are the target of half of all pharmaceuticals but only comprise less than 1% of all known protein structures in the Protein Data Bank. In order to learn more about the mechanism of protein folding for membrane proteins, he plans to develop a technique using (strept)avidin as a steric wedge to capture the unfolded state of a dually biotinylated target protein membrane. This is based on the assumption that two (strept)avidin molecules can only be simultaneously bound to both biotin sites on the protein of interest when the target protein is in an unfolded state due to steric hinderance. The binding affinity of (strept)avidin for the second biotin site on the target protein will then be correlated to the unfolding energy of the target protein since binding can only occur when the protein samples an unfolded state.
Currently, membrane proteins are studied after treatment of detergents to separate the membrane protein from the lipid bilayer. By developing a method that studies the membrane protein in its natural environment, the lipid bilayer, the principles behind membrane protein folding can be implemented for the advancement of many fields which include but not limited to predicting membrane protein structures and drug designing for better, efficient treatments.
Upon graduation, Tae plans to pursue a joint M.D./Ph.D program. He would like to thank Jim Bowie, Tracy Mitchell, and the rest of the Bowie Lab for their constant support and invaluable guidance.
Back to top
Ms. Jenny Koo
Mentor:Dr. Owen Witte
Title: Polymerase II promoter EF1-alpha drives expression of lentiviral vector with miRNA mimic insert
Adam Singer, Jenny Koo, Jami McLaughin, and Dr. Owen Witte
Jenny Koo is a third year Molecular Cell Developmental Biology major conducting research under the guidance of Dr. Owen Witte and Jami McLaughin Witte. The Witte Lab studies the growth regulation of hematopoietic and epithelial cancers and the immune response.
The role of Bcr-abl gene in leukemia was established in 1960, and recent work in this lab demonstrated that this kinase is critical for the leukemic phenotype of CML and related types of leukemia. Although small molecule inhibitors are effective at eliminating tumorigenesis in some patients, mutations in the Bcr-Abl gene renders insensitivity to the drug. Hence, miRNA mimics have been studied as an option for cancer therapy via RNA interference and mRNA degradation. Jenny’s project focuses on optimizing lentiviral vectors for maximal miRNA delivery. The vector currently used for miRNA delivery is driven by a polymerase II promoter, CMV; however, some studies have shown that the CMV promoter decreases in expressivity over time and in differentiated hematopoietic cells. To overcome this, Jenny will replace the CMV promoter with various and compared the new construct with the original vector. Tests will be conducted to analyze ability of the new constructs to knockdown the Bcr-Abl gene.
Back to top
Mentor: Dr. Hanna Mikkola
Mr. Andrew Lechner
PDGF-B signaling as a regulator of balanced hematopoiesis during fetal development
Andrew Lechner and Dr. Hanna Mikkola
Andrew is a 3 rd year Molecular, Cell and Developmental Biology Major. Andrew works in the laboratory of Dr. Hanna Mikkola, investigating fetal hematopoietic stem cell (HSC) development in mice. While fetal hematopoiesis occurs in many different sites, the Mikkola Lab has identified the placenta as a site of de novo HSC generation and proliferation. Andrew will investigate the placental vascular labyrinth as a potential niche that promotes HSC development and expansion. These studies will help us to understand the mechanisms required in establishing the HSC pool during embryogenesis.
A PDGF-B (platelet derived growth factor) knock out compromises placental labyrinth development in mice. Interestingly, the Mikkola Lab has found that PDGF-B -/- embryos exhibit a decrease in HSC frequency, an increase in committed progenitors, and an accumulation of over-proliferating blast-like cells. Significant numbers of fetal HSCs and multipotential progenitors (MPP) express the PDGF-Rβ (receptor) whereas adult HSCs do not. These results suggest that PDGF-B signaling is utilized specifically in fetal microenvironments to protect developing HSCs.
Andrew will determine whether PDGF-Rβ expression on HSCs/MPPs correlates with their multipotential state by isolating the two populations using a PDGF-Rβ reporter and measuring their differences in function and differentiation potential in vitro and in vivo. Andrew aims to define the mechanisms by which PDGF-B signaling regulates HSC development and whether PDGF-B acts directly on HSCs or indirectly through the microenvironment. These studies will elucidate the molecular cues required for generating HSCs from pluripotent stem cells for use in therapeutic treatments.
Andrew hopes to pursue an M.D./Ph.D. degree in the future and would like to thank Dr. Mikkola for her support and guidance.
Back to top
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 fourth 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.
Back to top
Ms. Kathy Ngo
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 fourth year 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.
Back to top
Ms. Isabella Niu
Mentor: Dr. Andrew C. Diener
Title: Understanding the progression of infection by Fusarium oxysporum within Arabidposis thaliana as it relates to jasmonate-insensitivity
Isabella Niu and Dr. Andrew Diener
Isabella is a third year physiological science major and biomedical research minor. She has been conducting research under the mentorship of Dr. Andrew Diener in the Department of Molecular Cell and Developmental Biology since Winter of 2007, working with Fusarium oxysporum and Arabidopsis thaliana.
Infectious plant diseases are a continual threat to the cultivated crops of our sustainable food supply. In particular, Fusarium wilt disease, which is caused by Fusarium oxysporum, targets many common cultivated plants such as tomato and banana, and specifically cotton and date palms in California. As population levels rise, it is even more important to understand the pathogenesis behind such diseases and develop treatments for these crops in regards to food and biofuel. The molecular interactions between fungal pathogens and their hosts are still poorly understood even after a century of pathology study on soil-born plant diseases. Thus, Isabella’s project focuses on the progression of Fusarium oxysporum within Arabidopsis thaliana. Previously, Isabella grafted various phenotypes of Arabidopsis in order to study long-distant communication in plants, and looked at responses to the plant hormone jasmonate, which is also a toxin produced by Fusarium. Her goal was to discover whether the toxin jasmonate promotes disease symptoms in the shoot or infection of the roots. The results, however, were inconclusive and require further study. In order to more accurately explain the effects of jasmonate on the plant, Isabella is currently working on a staining technique with B-glucoronidase (GUS) to track the progression of Fusarium within Arabidopsis. Being able to visualize the progression of Fusarium within the plant will allow her to address how Fusarium behaves in the vasculature of a resistant versus a susceptible host, and whether or not the fungal pathogen or toxin travels from root to shoot. Isabella aims to understand more about the nature of plant resistance due to jasmonate-insensitivity, and discover whether or not jasmonate promotes fungal infection, disease symptoms or both. Hopefully, her research will contribute to a wider understanding of plant host-pathogen interactions
Isabella would like to thank Dr. Diener, Stephanie and Yumping for all their support and guidance, and Dr. Ira Clark for helping her get started in research and counseling her within the biomedical research minor. In addition, Isabella would like to thank the Howard Hughes Medical Institute for providing such a great instructive program. After undergraduate studies at UCLA, Isabella plans on pursuing a career in medicine. Her background in research will help her critically analyze the problems she meets throughout her medical career, and aid in the development of effective solutions.
Back to top
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 fourth 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.
Back to top
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 fourth 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.
Back to top
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 fourth 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.
Back to top