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The Undergraduate Research Scholars Program

2006-2007

Ms. Rina Kakimi
Mr. Jason Kang
Ms. Jennifer Kaplan
Mr. William Kim
Mr. Omid Kohannim
Ms. Janet Lee
Mr. Kenny Lin
Ms. Anne Liu
Ms. Revana Lukman
Ms. Aleksandra Sasha Lukyanets
Mr. David Luong
Ms. Megan Matal
Ms. Melinda McBride
Mr. Leeron Morad
Mr. Lin Naing
Mr. Christopher Ng
Ms. Kathy Ngo
Ms. Angela Nguyen
Ms. Lauren O’Laughlin
Mr. Ariel Ourian
Ms. Tina Keun Park
Mr. Michael Rome
Ms. Audrey Ross




Ms. Rina Kakimi
Mentor: Dr. Hong-Wen Jiang
Funding: Litton Scholar
Title: Spin Torque and Magnetization Dynamics in a Dual Spin Valve

Rina is currently a fourth year physics major. She has been conducting research in the field of spintronics under the guidance of Professor Hong-Wen Jiang in the condensed matter physics department. Her current research focuses on a dual spin valve. A spin valve is a spintronic device used in magnetic sensors and hard disk read heads, in which aligning electron spins with a variable external magnetic field alters the resistance of the material. A dual spin valve consists of two thin spin-polarized ferromagnetic layers. When one layer is rotated relative to the other, the magnetic field of the rotated layer will not be parallel to the spin of the electrons from the first layer. The magnetic field from the rotated layer will exert a torque on the spins of unpaired carrier electrons traveling through the device and therefore cause them to flip and align with the field. The flipping requires extra energy, and the increase in the threshold energy raises the resistance of the device. MATLAB programs that she has created in the past simulate and analyze several quantum mechanical phenomena, including tunneling effects and eigenstates of potential wells. In order to study the dynamics of a dual spin valve, she will be numerically solving and analyzing the Landau Lifshitz Gilbert equation using similar MATLAB programs. She plans to continue her research through a PhD program, hoping to contribute to the development of quantum information processing. Rina would like to thank Litton, URC/CARE, and Professor Jiang for their kind support.

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Mr. Jason Kang
Mentor: Dr. Genhong Cheng
Funding: Wasserman Scholar
Title:
The role of TRAF3 in the regulation of the innate immune system and antiviral responses

(Left to right:) Dr. Jane Deng, Jason, and Dr. Genhong Cheng

Jason Kang is a senior at UCLA majoring in the field of Microbiology, Immunology, and Molecular Genetics. For the past year and a half, he has been working with Drs. Genhong Cheng and Supriya Saha on the role of t umor necrosis factor receptor-associated factor 3 (TRAF3) in the regulation of the innate immune system and antiviral responses. In recent years, understanding the innate immune response and the recognition of the presence of virus by mammalian cells has become the focus of numerous scientific studies, and much progress has been made in the characterization of the pathways of Toll-like receptors (TLRs) and their responses to viral infection. Upon viral infection, type I interferons (IFNs), a family of cytokines, are produced and secreted by mammalian cells. T umor necrosis factor receptor-associated factor 3 (TRAF3) was identified as a critical molecule required for the induction of type I IFNs but not inflammatory cytokines in response to viral infection. Despite these findings, it remains unclear how TRAF3 regulates the transcription of type I IFNs. The focus of this project is to identify which regions of the TRAF3 molecule are required for the production of type I IFNs. Also, the study will attempt to answer questions about the differences between TRAF3 and related molecules in the TRAF family, such as TRAF2. Ultimately, this knowledge is important for elucidating the pathways used by the immune system to fight viral infection and will hopefully contribute to the development of vaccines and cures for viral pathogens. After graduating, Jason will take a year to continue research before attending medical school and pursuing a career in international medicine. Jason would like to thank the Wasserman family for the generosity, and would also like to thank Dr. Genhong Cheng, Dr. Jane Deng, Eric Pietras, and the Cheng lab for their guidance, support, and passion for scientific research.

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Ms. Jennifer Kaplan
Mentor: Dr. Patricia Phelps
Funding: Hilton Scholar
Title: Does the presence of noradrenergic axons below the lesion site in paraplegic adult rats provide evidence of axon regeneration?

Jenny Kaplan is a fourth year Neuroscience major. Under the guidance of Dr. Patricia E. Phelps and graduate student Aya Takeoka, she studies spinal cord regeneration following complete transection (SCI) in the rat model. Dr. Phelps’ lab uses Olfactory Ensheathing Glia (OEG) transplantations to promote axonal regeneration across the lesion site in paraplegic rats. OEGs are unique glial cells found in the olfactory epithelium and in the olfactory bulb and ensheathe the axons of the olfactory sensory neurons as they travel from the epithelium through the cribiform plate and into the central nervous system (CNS). As OEGs are naturally found in both the central and peripheral nervous systems and surround axons as they project into the CNS, they may be the ideal candidate to facilitate regeneration following SCI. One criterion often used to evaluate axon regeneration across the lesion site is the presence of noradrenergic axons in the spinal cord tissue caudal to the lesions site. When analyzing caudal spinal cord tissue from a previous study, we noticed noradrenergic axons in the caudal spinal cord in both OEG and media-injected rats. The existence of these axons in the lesioned media-injected controls, where we expected little to no regeneration, was puzzling. The goal of Jenny’s project is to determine if noradrenergic nerve fibers associate with blood vessels in the caudal stump of OEG, and media-injected paraplegic rats. If the axons are associated with blood vessels, she will establish whether or not they enter the spinal cord from the periphery. Our data has the potential to elucidate the validity of noradrenergic axons as markers of regeneration in spinal cord injured rats. After graduating from UCLA this spring, Jenny plans to attend medical school. She would like to thank everyone in the Phelps lab, especially Aya Takeoka and Dr. Phelps for their guidance. She would also like to expresses her sincere appreciation to the Diane A. and Henry H. Hilton Scholarship Fund for their support of her research.

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Mr. William Kim
Mentor: Dr. Utpal Banerjee
Funding: Rose Hills Scholar
Title:
Characterization of the role of hypoxia and the canonical Notch signaling pathway in lineage specification during Drosophila larval hematopoiesis


William is a transfer student, finishing up his third year at UCLA as a Molecular, Cell, and Developmental Biology major. Since his first year at UCLA, he has been part of the HHMI funded UCLA Undergraduate Research Consortium in Functional Genomics (URCFG) where undergraduate researchers utilized a P-element screen to identify genes required for Drosophila eye development. As he continued through the program, he participated in a project to develop a novel screen for nuclear encoded mitochondrial genes, which has been published in Genetics. William is currently working in Dr. Utpal Banerjee’s Lab with Dr. Tina Mukherjee to study Drosophila hematopoiesis. He is also in the process of applying to different MD/Ph.D programs in order to pursue a career in biomedical research. As a physician-scientist, he plans on studying the relationship between stem cells and cancer in hopes of further elucidating and adding on to current knowledge of how they function, which will ultimately lead to a better understanding of cell biology and provide new avenues in the fight against cancer. William would like to thank the Howard Hughes Medical Institute and Dr. Utpal Banerjee for truly enriching his UCLA experience through URCFG and would also like to thank Mrs. Lew Wasserman and Mr. Casey Wasserman and the Rose Hills Foundation for their generosity.

Abstract:Hypoxia Inducible Factor-1 α (Hif-1 α), a key component of the hypoxia-induced pathway, has been implicated in the maintenance of several types of mammalian stem cells, including hematopoietic stem cells. Misregulation of this pathway has been shown to result in the onset of various blood related illnesses, such as leukemia. However, due to limitations in in vivo approaches along with the inaccessibility of the mammalian hematopoietic stem cell niche, the role of the hypoxia-induced pathway and its regulators remains to be fully deciphered. In Drosophila, hematopoiesis parallels mammalian blood cell development in that several molecular aspects have been evolutionarily conserved, allowing Drosophila to be used as a relevant model system for human health. For this study, gain/loss-of-function strategies were utilized to characterize the role of Hif-1 α during Drosophila larval hematopoiesis. Immunohistochemical staining for Similar, the Drosophila homolog of mammalian Hif-1 α, in larval lymph glands indicates its expression in crystal cells, which are similar to mammalian melanocytes. Loss of Sima function results in a smaller lymph with fewer crystal cells, whereas the PSC and the MZ do not seem to require proper sima function. Converse experiments using sima gain-of-function results in larger lymph glands; loss of medullary zone markers, tep4 and ROS; expansion of crystal cell number; and often times formation of melanotic tumors. These preliminary results indicate a novel role for Sima in lineage specification during larval hematopoiesis.

 

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Ms. Janet Lee
Mentor: Dr. Chenato Lin
Funding: Rose Hills Scholar
Title:
Uncovering the Signal Transduction Pathway of Cryptochrome2 in Arabidopsis thaliana

Janet Lee is a fourth year Molecular, Cell, and Developmental Biology major. She has been conducting research in Dr. Chentao Lin’s laboratory since Fall of 2004.

The laboratory’s studies involve the photoreceptor cryptochrome in the model organism Arabidopsis thaliana . To date, the exact mechanism through which cryptochromes function in response to light is still unclear.

Cryptochrome 2 (cry2) function and degradation is dependent on blue light. It has been hypothesized that the phosphorylated cry2 is the active photoreceptor and the unphosphorylated cry2 is inactive. However, it is also possible that the active cry2 triggers phosphorylation and inactivates the photoreceptor. At this point, it is still uncertain whether cry2 is active in the phosphorylated or unphosphorylated state. Janet’s research project will resolve these competing hypotheses and allow a better understanding of the mechanisms and physiological roles of cryptochrome blue light-dependent phosphorylation. She will be investigating the structure-function relationship of cryptochromes by analyzing how mutations of selected amino acids affect cryptochrome cellular localization, stability, and activity. This will be achieved by site-directed mutagenesis to change serine residues to either alanine to block phosphorylation or to aspartic acid to mimic phosphorylation. If the serine residues that were exchanged for aspartic acid residues activate the protein, then the active cryptochromes are in the phosphorylated state. In contrast, if the serine residues that were exchanged for alanine result in an active protein, then the active cryptochromes are in the unphosphorylated form. Changes in protein phosphorylation affect the structure and activity of a protein, so the results obtained from this experiment will allow a better understanding of how cry2 functions and interacts with other proteins.

Janet would like to thank the researchers in the Lin Laboratory for their guidance and the Wasserman family for their support.

 

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Mr. Kenny Lin
Mentor: Dr. Christopher Colwell
Funding: Van Trees Scholar
Title: The Role of the NR2B Subunit and NMDA Receptor in Circadian Rhythm

Kenny Lin is a fourth year Psychobiology Major and a Neuroscience Minor. He currently works in Dr. Christopher Colwell’s Laboratory of Circadian Rhythm.

Circadian rhythm is the 24-hour cycle of physiological processes that are associated with sleep, hunger, and metabolism. Within the suprachiasmatic nucleus (SCN), a cluster of cells in the brain associated with circadian rhythm, exists the multimeric NMDA (N-methyl-D-aspartic acid) receptor protein. This receptor protein has already been discovered to be significantly involved with a signal transduction cascade of light-induced phase shifts. In other words, light, such as light from the sun, causes a series of reactions in which the NMDA receptor protein is involved. Proteins are comprised of subunits. The NR2B subunit of the NMDA receptor proteins has been found to be the dominantly active one at night. This NR2B subunit can be blocked by the antagonist ifenprodil.

Kenny has been conducting electrophysiology experiments where the effects of ifenprodil on NMDA currents are recorded. This includes testing different concentrations of the drug and recording how they produce systematic differences in NMDA current inhibition. He has also been designing protocols to determine if ifenprodil can be effectively washed out after SCN cells have undergone drug treatment. Another antagonist is currently being researched and once obtained, Kenny will continue to perform whole cell recordings to further contribute to understanding of the NR2B subunit.

Kenny would like to thank Dr. Colwell for the opportunity to learn electrophysiology and contribute to circadian research, as well as being a supportive and all-around great mentor. He would also like to thank Katie for introducing him to fried chicken Wednesdays, Analyn for sharing in the “fun” that comes with making internals, and Louisa for “culturing” him.

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Ms. Anne Liu
Mentor: Dr. Jeffrey H. Miller
Funding: Rose Hills Fellow
Title: High throughput screening of the Escherichia coli gene knockout collection for mutator and hyper recombination phenotypes

Anne Liu is a second year Mircobiology, Immunology and Molecular Genetics major under the mentorship of Dr. Jeffrey H. Miller since her first year, winter quarter at UCLA.

E. coli strains are fascinating in that after they are mutated, they are able to develop unique DNA repair strategies to counteract mutagenesis. Anne is focused on three long-term goals to study and discover these novel mutational pathways, mutation avoidance and DNA repair systems. In the long run, this work on bacteria can be correlated to cancer cells. If cancer cells are able to adopt the effective DNA repair strategies, then they, too, will successfully revert back to their normal states.

Anne’s MIMG 199 project is directed on DNA repair systems using a set of 4,000 Japanese E. coli strains. Referred to as the complete knockout collection, each strain has one gene knocked out and contains only the second half of the lacZ gene. The knockouts are recombined with a donor 36609 strain that has a frameshift mutation in the second half of the lacZ gene. Successful knockout recombinants (possessing functional lacZ gene) receive the first half of the 36609 lacZ gene without the mutation. The matings are printed onto minimum glucose, Xgal, Pgal, Uracil, Kan and Tet indicator plates by the Deutz Cryo-replicator. This time-saving instrument is a crucial part of the newly developed high throughput printing and screening method. After 3-4 days, the plates display growing colonies of blue papillae over a white background. Certain knockouts have higher recombination levels (hyper recs with upregulation) and others have lower levels (rec minus). Currently Anne is developing a method to quantitively assay the blue expression to pinpoint the knockouts with high recombination frequencies and to study the genes involved in suppressing hyper recombination.

Of the genes knocked out, only a limited number have known protein functions. This study also provides the valuable opportunity to discover novel proteins and their mutational avoidance strategies.

Anne would like to express her heartfelt thanks towards her donors, the URC/CARE directors and staff and her lab mentor and colleagues for fueling her strong research passion.

 

 

 

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Ms. Revana Lukman
Mentor: Dr. Denise Feil
Funding: Wasserman Scholar
Title: Caregiver Focus Group Study on Barriers to Diabetes Care in Dementia

Revana Lukman is a fourth year Psychobiology major and Gerontology minor. She is currently working at the Veteran’s Affair Medical Center under the mentorship of geriatric psychiatrist Dr. Denise Feil. She is working on an IRB approved qualitative study of “Caregiver Focus Groups on Barriers to Diabetes Care in Dementia” that demonstrates the importance of qualitative approach to information gathering.

Diabetes and cognitive impairment both are rising in epidemic proportions. In addition, results from 10 population-based longitudinal studies on type-2 diabetes and cognitive dysfunction confirmed an increased risk of cognitive decline and dementia from diabetes. Cognitive Impairment in diabetic patients is associated with functional impairment, poorer self-care and high health and social services use. Dr. Feil’s current focus group study on caregivers will help explain the difficulties in diabetes care for elderly with dementia. The identified themes will help in the long term goal of model development that addresses these barriers to pilot test interventions. Revana will be comparing the barriers of caregiving, specifically investigating the levels of difficulty in providing care among women’s roles. She hypothesizes that daughters may face a struggle for control and thus confront psychological balance of power that wife caregivers might not have.

Revana finds the integration of biology, medicine, psychology, and sociology to be a fascinating approach, especially in the study of aging. Revana is also currently involved in the Mobile Clinic Project at UCLA as a caseworker, and is a research associate with the Stroke Study Student Research Program. She would like to give a special thanks to Dr. Denise Feil for her guidance and mentorship—for demonstrating what it truly means to be a caring and compassionate physician.




Ms. Aleksandra Sasha Lukyanets
Mentor: Dr. H. Pirouz Kavehpour
Funding: Mason Scholar
Title: Engineering Biomimetric Corneal Constructs

Aleksandra is a fourth year Aerospace Engineering student under the guidance of Professor H. P. Kavehpour in the UCLA Complex Fluids and Interfacial Physics Laboratory. She is contributing to a multidisciplinary collaboration with Northeastern University, funded by NIH regarding the surface preparation and modification of glass substrates for collagen alignment. The creation of an artificial cornea requires a proper, perfectly parallel alignment of a number of collagen molecules which is difficult due to their long and slender shape. However, collagen’s hydrophilic nature may be used to achieve this with the use of a properly prepared substrate of varying surface energy. Glass is a hydrophilic substance which Aleksandra will be coating with HMDS, a self-assembling monolayer with hydrophobic properties. Additionally, a layer of AZ5214 E IR Photoresist will be spin coated over the layer of HMDS. The substrate will then be covered with a mask containing a desired pattern and subject to a UV light. After a bath in an AZ400K/water solution, the mask pattern will be etched onto the surface, creating a hydrophobic surface with hydrophilic channels. Once coated onto the surface, the collagen will be forced to align with the hydrophilic channels, creating the necessary arrangement for the manufacturing of corneal constructs.

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Mr. David Luong
Mentor: Dr. Craig Merlic
Funding: Wasserman Scholar
Title: Macrocyclizations with Palladium Catalyzed Coupling Reactions

David is a fourth year biochemistry student. Under the guidance of Dr. Craig Merlic, he has been researching the use of palladium(II) as a catalyst for coupling reactions. Palladium is known as a catalyst in a number of coupling reactions, such as Suzuki coupling. Many of these reactions occur through a palladium (0) mechanism, and require the differentiation of end groups into nucleophilic and electrophilic components. These reactions require numerous manipulations to differentiate nucleophilic and electrophilic terminals of the chain in order for coupling to proceed. However, it has been shown that palladium (II) can also catalyze coupling reactions, but without the restrictions that Pd (0) faces. Palladium (II) coupling of pinacol vinylboronates can enhance the efficiency of the synthesis of macrocycles, a class of molecules that often have biological activity. Most commonly, macrocycles are known as antibiotics, although many have other functions, such as immunosuppressives as well. Macrocyclizations reactions present the most efficient method of synthesizing these complex molecules. Coupling of vinylboronates can not only occur with trans-vinylboronates, but also with cis-vinylboronates. Currently a number of model substrates are being developed to demonstrate macrocyclization under a variety of conditions, in order to show the efficacy and versatility of this method. David would like to thank Dr. Merlic and the rest of the members of the Merlic group, as well as the Wasserman family for their support.

 

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Ms. Megan Matal
Mentor: Dr.
Pirouz Kavehpour
Funding: Wasserman Scholar
Title: Experimental Study of the Spreading of Thin Precursor Films Using Fluorescence Microscopy

Megan is a fourth year student majoring in Aerospace Engineering. Working in the complex fluids lab under the guidance of Dr. Kavehpour, Megan is studying the spreading of thin precursor films on wetted surfaces. Small droplets of wetting fluid with a diameter on the order of about 1mm are driven to spread by capillary force. For these wetting fluids, a microscopic film, which is known as the precursor film, exists in front of the moving contact line. The structure of this thin film has been studied theoretically but previous experimental investigations were limited by the resolution required to capture the complete scope of this feature. Theory predicts that the precursor film expands at a different rate than the droplet. To non-invasively measure the evolution of the profile of a spreading droplet near the moving contact line, Megan uses a total internal reflection fluorescence microscopy (TIR-FM) system. The TIR-FM is able to take very high resolution pictures which are saved to a computer for analysis. Megan’s research will lead to an experimental understanding of slow moving liquids that are of considerable importance in a variety of industrial applications such as the coating processes, soldering technology, and the printing of inks. After graduating, Megan hopes to attain a career as a leader in the Aerospace field before returning to graduate school. Finally, Megan would like to thank Dr. Kavehpour and the Wasserman family for their generous support.

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Ms. Melinda McBride
Mentor: Dr. Wenyuan Shi
Funding: Hilton Scholar
Title: (Beta)D-Allose-Mediated Inhibition of Fruiting Body Formation in Myxococcus xanthus

(left to right) Nena Chavira, Melinda and Dr. Wenyuan Shi

Melinda (Mindy) McBride is a fourth-year Microbiology, Immunology, and Molecular Genetics major who is currently researching Myxococcus xanthus in the laboratory of Dr. Wenyuan Shi.

Myxococcus xanthus is a “social” soil bacterium species that undergoes a developmental program requiring intercellular communication. When starved of amino acids, members of Myxococcus xanthus communicate with each other, synchronize their movements, and aggregate into fruiting body structures that produce spores. In prior studies, bD-allose, a rare sugar, was found to inhibit fruiting body formation and a genome-wide mutagenesis screen via miniHimar1 transposon insertion was conducted to better understand the genetic basis for the inhibition. By BLAST analysis, it was discovered that the gene glcK (encoding a glucokinase) is required for bD-allose inhibition activity, providing evidence that bD-allose may need to be phosphorylated in order to inhibit fruiting body formation. GlcK is present in an operon that includes three other genes: an oxidoreductase, thiol peroxidase (tpx), and a phosphoglucomutase (alg C). To determine which genes in the identified operon are responsible for sensitivity to bD-allose, Mindy will continue operon analysis with in-frame deletions to target each gene specifically and ensure that there are no polar effects of the transposon mutagenesis. She will characterize the phenotypes of the in-frame deletion mutants. These studies, along with ongoing investigations of other mutants from the original mutagenesis screen in the Shi lab, may reveal molecular mechanisms for intercellular development and regulation as well as information about the role of sugars in prokaryotes.

Mindy hopes to pursue a career in research and explore her interest in public health. She would like to thank Hilton for endowing her scholarship, Dr. Shi for providing the research opportunity and offering encouragement, Nena Chavira for giving continual support and guidance, and other members of the Shi lab for contributing to her overall research experience.

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Mr. Leeron Morad
Mentor: Dr. Gouping Fan
Funding: Alcott Scholar
Title: Deriving neural precursors from embryonic stem cells

From left to right are Dr. Gouping Fan, Leeron Morad, and Yin Shen (grad student)

A potential life-saving application of stem cell technology is its ability to regenerate the nervous system following accident or disease. Leeron Morad has set out to help understand this possibility a bit more.

Morad is a 4 th year Microbiology, Immunology, and Molecular Genetics major. He began his research under the direction of Dr. Gouping Fan in early 2006 with the intent of learning about human embryonic stem cells. He works closely with the graduate students in the laboratory who are always happy to offer him help and answer his questions.

As the first step for his research project, Morad is seeking to compare different techniques for neural precursor differentiation of both human and mouse embryonic stem cells; he wants to find procedures that are most efficient for deriving each of the major neural cell lineages.

As a second step, Morad hopes to engraft these cell types into mice lacking certain parts of their nervous system to see if the cells which he helped differentiate can repair or regenerate these parts.

Morad’s research will contribute to the understanding of the potential for stem cell therapy in cases such as stroke, and injury.

In addition to his research, Morad is the president of a pro-Israel student group and frequently takes long sunset-walks on the beach.

 

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Mr. Lin Naing
Mentor: Dr. Reggie Edgerton
Funding: Wasserman Scholar
Title: Recovery of both standing and stepping abilities in complete spinal mice after robotic training

Lin Naing is a fourth-year senior neuroscience honors student. His curiosity in spinal cord injury and stroke inspired him to join Dr. Edgerton’s neuromuscular laboratory at UCLA. His initial project is primarily concerned with different robotic training paradigms and their relative effectiveness to the recovery of spinal cord-transected mice, with the long-term goal of providing cost-effective physical therapy with maximal recovery outcomes to spinal cord injured and stroke patients. During his junior year, he conducted and presented an independent study for two consecutive quarters for the paper entitled, “Effects of assist-as-needed robotic training on adult spinal cord-transected mice compared with fixed robotic training.” His further interest in spinal cord research led to the second project in summer 2006 concerning with the recovery of the standing ability in spinal mice. He is now conducting his senior honors research project dealing with the in-depth analysis of both standing and stepping recovery outcomes using robotic training paradigms. He believes that his research will contribute to the advancement of current physical therapies available to stroke and spinal cord injured patients in the nation.

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Mr. Christopher Ng
Mentor: Dr. Jacob Schmidt
Funding: Alcott Scholar
Title:
Microfluidic Device for Automated Lipid Bilayer Membrane Formation with Integrated Proteins

Chris Ng is a third-year undergraduate bioengineering major. Since the summer of 2006, he has been working in the lab of Dr. Jacob Schmidt. A major research focus in Dr. Schmidt’s lab is the exploration of devices functionalized by membrane proteins. These compact, versatile proteins can be manufactured to pump analytes, sense touch and temperature, or transduce energy. One application would be the utilization of molecular-specific transport to create detection or purification devices. Other applications include mechanical, acoustic, and thermal sensors. A shortcoming that has slowed research and prevented widespread application of powerful membrane proteins involves the difficult fabrication of lipid membranes. Chris will be working on a microfluidic device for membrane formation that relies on extracting organic solvent (poly­dimethy­lsiloxane) from a lipid solution. His research will involve designing a built-in faraday cage around a microscope to conduct measurements, discovering the optimal variables for PDMS bonding, and working on an organic droplet generator. A LabView program needs to be designed to control solenoid valves, which direct flow rates into the droplet generator. An optimal lipid droplet size and frequency is essential for membrane formation. Chris will graduate in 2008 and plans to pursue a Ph.D. in bioengineering.

 

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Ms. Kathy Ngo
Mentor: Dr. Yung-Ya Lin
Funding: Rose Hills Scholar
Title: Positive Contrast Visualization of SPIOs via Non-Linear Feedback in High-Field NMR

Kathy Ngo is a second-year majoring in Biochemistry. Under the guidance of Dr. Yung-Ya Lin since Spring 2006, she has been working on developing a novel technique for positive contrast visualization of superparamagnetic iron oxides (SPIOs) using Magnetic Resonance Imaging (MRI). Upon finishing her undergraduate degree, she hope to study biophysics in graduate school and pursue a career in stem cell research using molecular imaging as a tool for cell visualization and cell-cell interactions. She would also like to thank Dr. Lin for his patience, spirits, encouragement, and guidance throughout the project. Finally, she would like to extend her gratitude towards the Rose Hills Foundation for their generous financial support of this research project and all her peers in the research group.

SPIO nanoparticles used as contrast agents have shown great promise in cell visualizing in MR imaging methods, including the detection of liver and spleen lesions. The unusual large magnetic moment of these particulates allow them to serve as effective relaxation enhancers at very dilute concentrations, making them advantageous over other contrast agents such as Gd-DTPA. With a large magnetic moment, these magnetic particles prove to be a powerful tool in cell-tracing, lesions tracking, and tumor detection. In contrast to gadolinium chelates which brightens the local signal intensity by shortening of T 1, SPIOs act as negative contrast agents due to signal dephasing induced magnetic field inhomogeneity caused by nearby water molecules. A major drawback to negative contrast agents is that these agents cannot be distinguished from a signal void in the image. Although positive contrast imaging may still be achieved by T 1 weighting, it is not as effective due to competing T 1 and T 2 effects. More recent positive imaging methods using SPIO nanoparticles have been developed which includes spectrally-selective excitation, image subtraction, separating off and on-resonance spins using data processing, and gradient compensation. These previously mentioned methods, nevertheless, show limitations in sensitivity and contrast due to field inhomogeneity, bandwidth size of pulse sequence and frequency shifts. Recent methods incorporated the use of nonlinear feedback fields to enhance contrast in MR imaging.

By extending this principle, Kathy has confirmed that positive contrast results in the presence of radiation damping: the inner regions of the sample showed a higher magnetization than the outer regions or solvent molecules. Radiation damping is a macroscopic reaction field due to the coupling of receiver coil with the bulk magnetization. The field is fed back to the spins via an induced current in the receiver coil. Due to the insensitivity of the radiation damping field to the spatial distribution of the magnetization and its dependency on the mean transverse magnetization, different magnetization configurations with the same net transverse magnetization produce the same radiation field everywhere in the sample, hence such reaction fields can be used for contrast enhancement in sample with small differences in resonance frequencies. A 179 o RF pulse initially prepares the magnetization in an unstabilized state, tipping it in the transverse magnetization plane. The radiation damping field then modulates M z causing the transverse magnetization to grow faster in the inner region than the outer region, with a dependence only on resonance frequencies. The group has just recently discovered that it is possible to exploit the dephasing effect due to SPIOs, by coupling it with a RD field and a very weak Continuous Wave (CW) to generate positive contrast. Along with one of the graduate students in the lab, Jon Furuyama, they are determining the dynamics of why this is possible and determining parameters to maximize contrast enhancement through mathematical simulations. Kathy will demonstrate a proof-of-principle both in vitro and in vivo. In experimental conditions, nonetheless, other consideration must be taken into account such as relaxation due to T 2* effects, making the spins near the nanoparticles dephase even faster.











                 


Ms. Angela Nguyen
Mentor: Dr. Yibin Wang
Funding: Wasserman Scholar
Title:
Functional Characterization of Sprouty and Spred as Negative Modulators in Cardiac Growth

Angela is a 3 rd year majoring in psychobiology this year. She is currently conducting research at the UCLA Medical School with Dr. Yibin Wang, a passionate specialist in the study of heart disease as well as a supportive mentor for student research. She is sincerely grateful for Dr. Yibin Wang as well as all the lab members who have helped her develop her research background. She greatly appreciates their time, help, and most importantly, their motivational nature. The inspiration that she has received from the lab and her own experiences have convinced her that dedicating her time to research, in hopes of helping others through biological advancement is not only worthwhile…but meaningful in every aspect.

Angela would also like to express her sincere gratitude to the Wasserman family for their kindness and generous support. She would also like to thank Dr. Cramer and the entire URSP scholarship committee for providing her with this opportunity. Last but not least, she would also like to express her utmost appreciation and gratitude to her dearest family members and friends for always wishing her the best in life, and for their constant motivation and love. As a token of gratitude for everyone’s encouragement and support, Angela promises to continue striving to accomplish her goals in the future.

Research Topic:

Promoting cell proliferation in cardiac cells may provide beneficial methods to achieve tissue repair and treatment of heart failure. On the other hand, the negative regulators to cell proliferation may serve as targets to treat cancer.

In terminally differentiated state, adult cardiac muscle cells develop hypertrophy (enlargement of cell size) rather than cell proliferation upon growth stimulation. As a result, no adult ventricular muscle cell line has been established in culture. The lack of proliferative response to growth stimulation can be attributed to potent negative regulation of growth signaling in heart muscle cells. Identifying the molecular nature and functional mechanism of these negative regulatory genes will have potential implication in both cardiac and cancer biology.

 

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Ms. Lauren O'Laughlin
Mentor: Dr. Larry Simpson
Funding: Sparks Scholar
Title:
Investigating the Properties of LC8 in Leishmania tarentolae

Lauren is a 5th year MIMG major with a French minor.  She has been working in the Simpson lab since March of 2006.  Her project involves investigating the activity of LC8, one protein in the L-complex in Leishmania parasites.  The L-complex is the enzymatic center for the phenomenon known as RNA-editing, which involves post-transcriptional, pre-translational changes in the RNA.  In Leishmania, these changes are U insertion and/or U deletion at various editing sites in the mRNA.  Most of the proteins of the L-complex have been identified, but their individual functions and how they work together is still an incomplete picture.  The Simpson lab has charged itself with completing this picture of the L-complex to better understand the mechanism behind RNA editing.

Lauren's protein, LC8, has a diverged RNAse III motif, indicating that it may have some cleavage properties.  Lauren has worked to express and isolate recombinant LC8 from both a bacterial and insect vector, and now is testing the protein with full-round editing assays, both for the insertion and deletion model.  She is currently working on harvesting whole L-complex from a culture of Leishmania tarentolae to use as a positive control in her assays for LC8. 

Lauren hopes to identify the function of LC8 by the end of the school year before going on to pursue her PhD in human genetics in the fall of 2007.




Mr. Ariel Ourian
Mentor: Dr. Michael Bryer-Ash
Funding: Wasserman Scholar
Title: The Role of Focal Adhesion Kinase (FAK) in Glycogen Synthesis, and in the Regulation Akt/PKB, GSK-3 and Glycogen Synthase

From left to right: Dr. Michael Bryer-Ash, Ariel Ourian

Ariel Ourian is a fourth year Biology Major. For over a year, he has been working with Dr. Michael Bryer-Ash within the Division of Endocrinology, Diabetes and Hypertension, at the David Geffen Medical School at UCLA. Ariel’s area of interest is a particular protein called Focal Adhesion Kinase (FAK) and its correlation with the insulin pathway and Type II Diabetes. FAK is located within in the focal adhesion complex, a site where several integrin pathway signaling proteins cluster. The insulin pathway is responsible for both glycogen synthesis and glucose uptake into cells through an intricate mechanism that is still not fully understood. In the Bryer-Ash lab, mutant FAK constructs were over-expressed in HepG2 hepatoma cells to show that FAK is involved in insulin-mediated stimulation of glycogen synthesis and acts to promote insulin action downstream of PI3-K by a specific interaction with GSK-3β and Akt/PKB, proteins found in the insulin signaling pathway. Ariel is currently trying to establish the function of FAK in glycogen synthesis in vivo, using tissues isolated from FAK knock out and wild type animals. If FAK plays a regulatory role in glycogen synthesis, reduced amounts of insulin-stimulated glycogen should be observed in the tissues of the FAK knock out animals. Additionally, he hopes to find a probable mechanism of FAK regulation, in vivo, by determining concentrations of proteins in the insulin signaling pathway, including IRS1, IRS2, GSK-3β Akt/PKB, and GSb, in both FAK knock out and wild type animals.

Ariel plans to attend medical school after taking a year off after graduation to teach at a local high school, continue his research, and travel. He would like to thank the Wasserman family for their generosity, Dr. Bryer-Ash and Diane Huang for their continued support of his research endeavors.

 

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Ms. Tina Keun Park
Mentor: Dr. Ting-Ting Wu
Funding: Rose Hills Scholar
Title: Sufficiency of DNA replication and Role of Viral trans-factors for Expression of Late Genes in a Gammaherpsvirus

Tina Keun Park is in her third year at UCLA, and working on obtaining a degree in Molecular Cell Developmental Biology. After graduation, she plans to attend medical school where she will be trained to become a medical doctor and also continue with research to acquire Ph. D. in the field of biology. She began to work under the guidance of Dr. Wu in her sophomore year and now her training and discipline has prepared her to become a more independent researcher. Through research, she has not only obtained technical training but also gained ability to walk through the steps to think critically, to plan effectively, and to draw logical conclusions. She is really pleased to be selected as one of the recipients of the Rose Hills Scholarship.

Her laboratory is using murine gammaherpesvirus-68 as a model system to study replication and pathogenesis of tumor-associated herpesvirus. Coupling of viral late gene expression to genome replication is a hallmark of productive infection by DNA viruses. However, the regulation of late gene expression in herpesviruses remains largely uncharacterized. It has previously been shown that ORF30 and ORF 34 are trans-factors required for expression of late gene by showing that mutant virus with nonfunctional ORF 30 and 34 fail to produce late gene products. Now they want to study further mechanism of how these trans-factors control the expression of late genes. Also, it has previously been shown that DNA replication is necessary for the induction of late gene expression. This leads to a new question, "then is DNA replication sufficient to activate late promoters?" Her goal for this year is to identify the mechanism of how the trans-factors affect expression of late gene and to wrap up the question "is DNA replication sufficient to activate late promoters?" The ultimate goal of her projects is to get a better understanding of the virus life cycle and pathogenesis of tumor-associated virus.

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Mr. Michael Rome
Mentor: Dr. Peter Bradley
Funding: Mason Scholar
Title:
Characterization of a novel rhoptry protein in Toxoplasma gondii


Michael Rome is a senior Molecular, Cell, and Developmental Biology (MCDB) major. Michael is interested in fundamental biochemical processes such as protein modification and protein-protein interactions. He is currently conducting research in the laboratory of Dr. Peter Bradley (MIMG). Dr. Bradley studies how the obligate intracellular parasite Toxoplasma gondii invades and co-opts its host cells. Toxoplasma gondii is an Apicomplexan parasite that causes central nervous system disorders in individuals who have compromised immune systems and disease in congenitally infected neonates. Toxoplasma possesses complex and specialized organelles called rhoptries, located at the apical end of the organism. These organelles, which make up the apical complex, are thought to be involved in invasion, attachment, and formation of the parasitophorousvacuole in which the parasite resides in the cytoplasm of its host. Michael’s specific project involves characterizing a rhoptry protein (protein 0114) unique to Toxoplasma. He is using to two approaches to address his objective. The first approach is to produce antibodies against a recombinant portion of protein 0114 and use these antibodies to localize the Toxoplasma protein by immunofluorescence assays. The second approach is to examine the function of the protein by gene knockout technology. Overall, Michael feels that this work is important because this protein may be used as a potential drug target for individuals infected with the parasite. In the future, Michael plans to attend graduate school in the field of biochemistry/molecular biology.

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Ms. Audrey Ross
Mentor: Dr. Kendall N. Houk
Funding: Van Trees Scholar
Title:
Substituent Control of the Cyclohexyl-Cyclopentylmethyl Radical Rearrangement

Audrey Ross is a fourth year chemistry major, and has been involved with experimental and theoretical research under the guidance of Professor Kendall N. Houk since her second year. Her project began with the observation of a cyclohexyl to cyclopentylmethyl rearrangement by Syngenta Corporation.  This unusual phenomenon prompted a theoretical study from which it was concluded that the macrocycle’s substituent groups were able to facilitate an intramolecular radical process to the more strained product. 

The possibility of a general rearrangement was then approached using density functional theory, which has shown that certain groups alpha to the radical are able to reverse the typical thermodynamics and favor the cyclopentylmethyl over the cyclohexyl radical.  As the proposed acyclic intermediate is analogous to a 5-hexenyl radical, it was expected that ring closure to the 5-membered product could be favored due to an earlier transition state and kinetic factors.  It was found that not only was the radical favored thermodynamically, but this ring closure had the kinetic advantage of a lower transition state barrier.  It has also been found that the energetic penalty of ring opening of the cyclohexyl intermediate is significantly reduced by the presence of certain groups at the beta position.  Following the discovery of groups that stabilize the necessary transition state structures, theoretical treatment has revealed trends in which substituents will allow rearrangement.  From these data along with radical stabilization energies, an experimental model was designed. 

Preliminary experimental work on has shown that despite an enormous thermodynamic preference for a rearranged product, more facile reactions can preempt rearrangement.  Kinetic studies of the current model will be used determine if the product distribution may be altered.  Additionally, other substrates with lesser ring opening barriers will be considered.

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Profiles of Students