Ms. Shereese Alexander
Mentor: Dr. David A. Campbell
Title: Determining Localization and Functional Importance of Dim1B in Trypanosoma Brucei
Left to right: Shereese, Dr. David Campbell, Nancy Sturm
Shereese is graduating senior working under the direction of Dr. David Campbell in the microbiology, immunology, and molecular genetics depart. Her lab works on a number of eukaryotic parasites known as trypanosomes which cause diseases such as trypanosomiasis, leishmaniasis, and African sleeping sickness. Her project focuses on characterizing a proposed methyltransferase protien, Dim 1B in Trypanosoma brucei. This protein is thought to act in such a way as to produce a fully mature and functional ribosomal subunit i n the mitochondria. Her work has shown through RNA interference that Dim 1B is not an essential element for the survival of the insect form of the parasite, but is in fact located in the mitochondrion based on green fluorescent protein fusions. Currently Shereese has applied to many graduate schools around the country in order to get her PhD in microbiology and continue work on infectious diseases.
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Ms. Brianna Burden
Mentor: Dr. Harold Monbouquette Title: Microbiosensor design for use in Parkinson’s disease studies
Brianna Burden began her research career during her second quarter at UCLA in Dr. Arthur Arnold’s laboratory in Physiological Science studying the sex differences in sin3a concentrations in mice. Now in her third year, she is currently studying biochemistry and working in the chemical engineering department in Dr. Harold Monbouquette’s laboratory. She is designing a microbiosensor capable of measuring neurotransmitter levels in living brain tissue. This work is in collaboration with a lab in the neuroscience department studying Parkinson’s disease. This disease is characterized by a decrease in dopamine available for neurotransmission because of neuron degeneration. It is hypothesized that glutamate neurotransmitter binding is increased in Parkinson’s patients. By immobilizing glutamate oxidase on the platinum surface of an electrode, the concentration of this neurotransmitter can be measured. Glutamate can be detected by immobilizing glutamate oxidase in overoxidized polypyrrole which oxidizes glutamate and produces hydrogren peroxide which is oxidized on the electrode and correlated to the concentration of glutamate. Dopamine can be detected through a layer of Nafion which attracts the cation dopamine. Brianna is working to optimize the conditions for the detection of these important neurotransmitters.
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Ms. Tracie Delgado
Mentor: Manuel Penichet M.D. Ph.D.
Title: Delivery efficiency of an IgG3-Avidin fusion protein with biotinylated toxins by transferrin receptor mediated endocytosis.
Left to right: Graduate student, Tracie, Dr. Manuel Penichet
Tracie Delgado is an undergraduate senior majoring in Microbiology, Immunology & Molecular Genetics. This is her 4 th year doing research and she is applying to various Ph.D. programs in microbiology throughout the country. Tracie works under the guidance of Dr. Manuel Penichet. The title of her research is Delivery efficiency of an IgG3-Avidin fusion protein with biotinylated toxins by transferrin receptor mediated endocytosis. The Transferrin Receptor is a type II homodimeric receptor with two functional members, TfR1 and TfR2, They are involved in iron internalization and homeostasis respectively, through Transferrin (Tf) mediated endocytosis. Importantly, increased levels of TfR expression have been previously associated with a number of hematopoietic malignancies. Moreover, the extracellular accessibility and correlation with poor prognosis of the TfR make it an excellent target for the delivery of toxins to malignant tumor cells. Previously, we have genetically fused to chicken avidin a mouse/human chimeric IgG3 targeting the extracellular domain of the human TfR (anti-hu TfR IgG3-Av), and demonstrated the specificity of the anti-hTfR IgG3-Av to TfR1 with no cross-reactivity to cell surface TfR2. Such high specificity in targeting even against close relatives of the receptor, such as TfR2, further ensure its effective targeting in vivo and a decrease in the systemic cytotoxicity common to many non-specific chemotherapeutics. We have previously found that anti-hTfR IgG3-Av facilitates TfR mediated endocytosis of biotinylated toxins, which remain active even after their internalization. Previous studies have also shown that the delivery of these biotinylated molecules elicits an anti-proliferative and pro apoptotic activity in cells expressing high levels of TfR. I intend to test a comprehensive panel of Multiple Myeloma (MM) cell lines, when treated with anti-hTfR IgG3-Av alone or in conjunction with biotinylated chemotoxins, to asses their viability after treatment. Furthermore, because TfR2 may be used by cancer cells as a mechanism of escape from treatment with the anti-hTfR IgG3-Av fusion protein, studying the levels of TfR2 expression in a panel of MM cell lines is also relevant.
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Ms. Thelma Escobar
Alexander van der Bliek
Title: Determining FIS-1 and FIS-2 Function in Mitochondrial Dynamics
left to right: Dr. van der Bliek, Brian Head, Thelma Escobar
Thelma Escobar is a third year student majoring in Molecular Cellular Developmental Biology. She is a first year MARC student and is currently working in a Biological Chemistry laboratory where Mitochondrial Morphology and Dynamics research is being conducted. She entered this lab fall quarter of her sophomore year and is under the supervision of Alexander van der Bliek and her lab mentor Brian Head.
Responsible for the cells' metabolic processes, the mitochondrion has become a very interesting field of study because of its linkage to aging, apoptosis, Alzheimer's, and many other diseases. With Caenorhabditis elegans as a model organism, Alexander van der Bliek’s laboratory is investigating different proteins that are involved in mitochondrial division and fusion. They are interested in the factors that influence mitochondrial division and its determination of mitochondrial shape. Thelma will be analyzing the function and localization of two proteins (Fis-1 and Fis-2) in the mitochondria of C. elegans muscle. Her aim is to over express these two proteins and determine if they play a pivotal role in the division of the mitochondria. Using effective molecular techniques (like Recombinant DNA cloning and TOPO-TA cloning) to create a construct for Fis-1 and Fis-2 genes, she has successfully obtained her clones that include a C. elegans expression vector. To prevent secondary affects once the proteins are over expressed, C. elegans that are RNA interference (RNAi) defective are used. She is currently collecting data for Fis-1 and Fis-2 over expression and analyzing the localization of Fis-1 and Fis-2 in the mitochondria using YFP-Fis1 and YFP-Fis2 constructs that she has created.
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Mr. Johnny Garcia
Mentor: Dr. Araceli Espinosa-Jeffery
Title: CG4 Oligodendrocyte Progenitors Synergize with Trophic Factor TS1 to Enhance Remyelination of the Adult Demyelinated Mouse Brain
Johnny Garcia is a senior majoring in Biology. His journey into scientific research began my 3 rd year, under the guidance of his mentor, Dr. Araceli Espinosa-Jeffery, in the Department of Neurobiology. The title of his current research is ‘CG4 Oligodendrocyte Progenitors Synergize with Trophic Factor TS1 to Enhance Remyelination of the Adult Demyelinated Mouse Brain.’ As part of his research team, he studies oligodendrocytes in the central nervous system (CNS), and the long-term goal of the study is to increase the number of functional oligodendrocytes in the demyelinating adult brain. This work is vital because demyelination is expressed in patients with Multiple Sclerosis, Parkinson’s disease, and Pelizaeus Merzbacher disease. He is currently testing and exploring possible treatments for the demyelinated CNS. The current treatment the lab is working on is grafted central glial-4 (CG4) cells, and a trophic factor termed TS1, via immunocytochemistry and in situ hybridization techniques. Results stemming from work going back to my participation in UCLA’s summer SPUR program, 2004, has shown that when CG4 cells were cografted with TS1 secreting cell line, CG4 cell migration was increased reaching farther demyelinated areas of the brain. Continuing studies in this project will hopefully one day contribute to the treatment of patients suffering from the demyelinating diseases. After graduation, Johnny plans on pursing a career in the biomedical research field.
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Ms. Julie Magallanes
Mentor: Dr. Sabeeha Merchant
Title: Identifying a Crd1/Cth1 containing protein complex that catalyzes the aerobic oxidative cyclase reaction of chlorophyll biosynthesis of Chlamydomonas reinhardtii.
Julie is a graduating senior in biochemistry. She was turned on to research while participating in the Pasadena City College Bridge Program Recombinant DNA Workshop held at UCLA. Since her transfer to UCLA she has interned in 5 labs in departments ranging from neurobiology to autoimmunity. Last summer, Julie was chosen to participate in the Howard Hughes Medical Institutes Exceptional Research Opportunity Program allowing her to study at the University of Pennsylvania, under the guidance of Dr. Morris Birnbaum, who specializes in cellular metabolism, glucose uptake, and Type II Diabetes. She conducted research targeting expression patterns of AMPK, a kinase that senses low cellular energy, within Drosophila melanolgaster embryos. Currently, she is interning in Dr. John Colicelli’s Lab at UCLA studying the RAS/RAF pathway, which is commonly disrupted in breast cancer. She is utilizing siRNA and shRNA to knockdown Rin1, a protein downstream of RAS/RAF, which when disrupted in mammalian cells induces transformation. Following her graduation, Julie will return to the Birnbaum Lab to continue conducting research as she applies for MSTP’s.
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Mr. Edwin A. Paz
Mentor: Dr. John Colicelli
Title: Creating Signal Transduction Probes to Profile Activated Receptor Tyrosine Kinases in Epithelial Tumor Cells
Edwin Paz is a fourth year Microbiology, Immunology & Molecular Genetics student at UCLA. His undergraduate research career began under the direction of Dr. Benjamin Bonavida where he assisted in studying the effects of the antibody Rituximab, and its sensitizing effects on Non-Hodgkin’s Lymphoma Cells. He later joined Dr. Christina Jamieson’s lab where he conducted studies to characterize and detect the levels of the DNA damage sensor, Ataxia Telegactasia Mutated (ATM), to quantify the threshold level at which T cells abandon DNA repair and undergo apoptosis in Dexamethasone treated cells. He is currently working under the guidance of Dr. John Colicelli helping to delineate the specific receptor tyrosine kinases responsible for cancer development in epithelial tumor cells. The objective of this study is to create and purify SH2 domain constructs as probes for evaluating change in RTK activity in tumors and to elucidate the specific receptor tyrosine kinases responsible for cancer development in epithelial tumor cells. By using nanotechnology techniques including Shape Encoded Particles (SEPs) together with different SH2 domain proteins labeled with fluorescent Quantum Dots (Q-dots) it should provide a new level of tumor characterization and may help elucidate specific RTKs responsible for tumorigenesis. Edwin aspires to earn a Ph.D. and to conduct research in the biomedical field while providing future students from inner-city schools with the tools required to excel in the sciences.
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Mr. Jose Rodriguez
Mentor: Dr. Manuel Pinechet
Title: Binding Properties of a Mouse/Human Chimeric IgG3-Avidin Fusion Protein Specific for the Human Transferrin Receptor
Left to right: Gustavo Helguera, Jose Rodriguez, and Manuel Penichet
Jose Rodriguez is a third year biophysics major. He is a first year MARC student and will be applying to Ph.D. programs in BioPhysics and BioEngineering in 2007. He plans to earn a Ph.D. and continue his work with cancer research. The title of his research is ‘Binding Properties of a Mouse/Human Chimeric IgG3-Avidin Fusion Protein Specific for the Human Transferrin Receptor.’ Under the direction of Dr. Manuel Penichet he assisted in developing an antibody fusion protein composed of avidin fused to a mouse/human chimeric IgG3 specific for the human transferrin receptor (TfR). This molecule (anti-hTfR IgG3-Av) exhibits an intrinsic anti-proliferative/pro-apoptotic activity against hematopoietic malignant cells, which can be further enhanced by the addition of biotinylated drugs. However, further studies of the binding properties of anti-hTfR IgG3-Av are required prior to its evaluation in vivo. We have now found that anti-hTfR IgG3-(Av) and its parental antibody (anti-hTfR IgG3) preferentially bind TfR1 over TfR2 as demonstrated by protein and cell ELISA. We also found that the antibodies are able to bind, in a dose dependent manner, a soluble form of the TfR1 (sTfR1) that exists in human blood as a result of proteolysis of the membrane-bound receptor. The lack of binding of these molecules to TfR2 and their binding to sTfR1 is expected to have an impact in their pharmacokinetic properties. Furthermore, using flow cytometry and ELISA we found no competition or binding inhibition between transferrin and the antibodies or between the hemochromatosis protein (HFE, another molecule that binds TfR) and the antibodies, suggesting that Tf and HFE would not interfere with the TfR antibody targeting in vivo. Finally, using flow cytometry we found no evidence of cross-reactivity between our anti-hTfR antibodies and murine TfR, which suggests that mice are not appropriate models for meaningful toxicologic studies or efficacy studies using murine tumors and limits their use to human xenograft tumor models. Our results provide a better understanding of the binding properties of these novel molecules and pave the way for the rational design of future in vitro and in vivo studies aimed for treatment of hematopoietic malignancies such as multiple myeloma.
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Mr. Joshua Sarinana
Mentor: Dr. Alcino J. Silvot
Joshua Sarinana is a 5th year Neuroscience student from the SF Bay Area. Currently he is applying to various Neuroscience PhD programs and is interested in the theoretical aspects of neuronal signaling that mediates memory and learning. Photography is his passion and he loves philosophical discussion. His current research is on the genetic, molecular, and cellular biology of memory and learning in mice. He runs tests to see if activation of protein kinases in specific brain region significantly mediates context fear conditioning (CFC) under the direction of Dr. Alcino J. Silvo.
CFC is a form of association learning and is used as measurement of memory and learning. In this training paradigm mice are placed in a context box and given several foot shocks. Mice naturally freeze to these shocks and with additional application their freezing time increases. The freezing times are measured and used as an index of learning. At a later time point the mouse is reintroduced to the context without the aversive stimulus, and the resultant freezing is the expression of fear memories. I use CFC in several experiments to measure the effect this training paradigm has on the activation of mitogen activated protein kinase (MAPK) in the anterior cingulate cortex (ACC) of mice.
His experiments test the hypothesis that MAPK significantly mediates the initial consolidation of fear memories. Significant increase of MAPK activation is believed to initiate genetic expression of proteins that change neural architecture. It is this change that is thought to be the physical representation of learning. To begin to test our hypothesis mice undergo CFC. After training the ACC of different groups of mice are removed and done at different time points to establish a gradient of MAPK activation. The samples are run on Western blots and the amount of MAPK activation between groups is quantified. Results show MAPK activation in the ACC significantly occurs during CFC. We showed the injection of a MAPK activation inhibitor into the ACC prior to CFC resulted in significantly lower freezing levels. This suggests reduced MAPK activation during CFC results in learning deficits.
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