Student Profiles Archive - Howard Hughes Undergraduate Research Program 2014-2015
Here you will find information about past and present students funded through scholarships administered by the Undergraduate Research Center - Sciences. We are proud of the achievements of our research scholars.
Please click on the program year to get information about the supported students, their mentors and their research projects.
| Albert Yen
Faculty Mentor: Dr. Dean Ho
Funding Source: Silva Trust
Project Title: A Nanodiamond-Embedded Mucoadhesive Patch for the Treatment of Oral Cancer
Albert Yen is a third-year bioengineering major who has been conducting research in the laboratory of Dr. Dean Ho since the first quarter of his sophomore year. Driven by an interest in bionanotechnology, Albert is currently working on the development of a nanodiamond-based drug delivery system for the treatment of oral cancer.
Celecoxib (Cxb) is a non-steroidal anti-inflammatory drug with the potential to treat oral cancer. In order to deliver Cxb into oral cancer lesions in a localized, sustained, and non-invasive manner, Albert intends to synthesize a biodegradable and mucoadhesive buccal hydrogel patch embedded with nanodiamond-Cxb complexes. Nanodiamonds (NDs) are carbon nanoparticles that serve as effective drug carriers due to their surface functionality, biocompatibility, and drug sequestration capability. Furthermore, in vivo studies performed with doxorubicin-loaded NDs and mice mammary tumors have shown that ND-drug conjugates bypass drug resistance mechanisms found in chemoresistant cancer cells. Thus, it is believed that ND-Cxb will overcome Cxb-resistant oral cancer cells. Ultimately, the patch can be directly applied to an oral cancer lesion, allowing for localized and sustained release of ND-Cxb into the lesion as the hydrogel degrades over time.
After graduation, Albert plans to obtain a Ph.D. in bioengineering and pursue a career in translational research. He would like to thank Dr. Ho for his guidance and for providing him with the opportunity to conduct laboratory research. He would also like to thank Kangyi Zhang, his graduate mentor, for his endless patience and invaluable advice. Finally, Albert would like to thank the Howard Hughes Medical Institute, the Undergraduate Research Center, and the rest of the Ho Lab for supporting his research endeavors.
| David Shia
Pictured, left to right: Dr. Michael E. Jung, David Shia, Dr. Brian T. Chamberlain
Faculty Mentor: Dr. Michael E. Jung
Funding Source: Gottlieb
Title: Synthesis of a Fluorinated [3.1.0] Bicyclic Nucleoside Mimetic
David is currently a fourth year at UCLA majoring in Molecular, Cell, and Developmental Biology. He began work with the Jung group in January of 2012 in the Department of Chemistry and Biochemistry. His current project looks at synthetic routes towards a total synthesis of fluorinated bicyclo[3.1.0]hexane nucleoside mimetics, which have shown promise as antiviral and chemotherapeutic agents and may also be candidates for antisense therapies.
Nucleoside analogues have emerged as promising potential treatments for a wide variety of disease. Currently, there are a number of nucleoside analogues marketed, including the anti-HIV drug AZT, anti-hepatitis B drug Tenofovir, and anti-cancer drug Gemcitabine. The promiscuity of viral polymerases allows the uptake and incorporation of select analogues into growing nucleic acid polymers, effecting premature chain termination that can slow the proliferation of viral infection. Due to differences in structure of eukaryotic polymerases and viral reverse transcriptases, nucleoside analogues can be designed that will only be recognized by viral polymerases. Less selective analogues have also been used as cytotoxic agents that can effectively slow the progression of certain cancers.
David continues his work on the synthesis of a fluorinated bicyclo[3.1.0]hexane nucleoside analogue through a synthetic route that takes advantage of a key ruthenium catalyzed ring metathesis followed by oxidative rearrangement and Simmons-Smith cyclopropanation to yield the core bicyclic structure. Currently, we are working toward the stereoselective incorporation of fluorine to the 3-carbon of the core structure.
David would like to extend his gratitude towards Dr. Jung for providing the opportunity to engage in this undergraduate research experience. He would also like to thank Dr. Brian Chamberlain, all current members of the Jung lab, former members Dr. Mikhail Guzaev and Dr. Felix Perez, and his family for all of their continued support. Lastly, David thanks the URC Sciences, Howard Hughes Undergraduate Research Program faculty, and the Gottlieb family for providing the new avenues to facilitate his research.
| Katherine Sheu
Mentor: Dr. Guoping Fan
Title: Regulation of DNA Methylation in Post-Mitotic Neurons of the Mouse Brain
Katherine Sheu is third year undergraduate majoring in Molecular, Cell, and Developmental Biology. Spurred by an interest in epigenetics and neuroscience, she joined the Fan Lab in the winter of her freshman year. The Fan Lab focuses on epigenetic regulation in stem cells, neuronal function and neural development.
One contributor to epigenetic regulation is DNA methylation, a chemical modification of cytosine which involves the addition of a methyl group most commonly to CpG dinucleotides. DNA methylation is commonly studied in cell differentiation, plays a central role in development and in cancer cells, and is associated with phenomena such as X-inactivation and imprinting. Katherine intends to continue her work using a mouse model to investigate DNA methylation activity which has also been suggested to occur in post-mitotic cells, such as in neurons, where active DNA methylation turnover may play a role in regulating gene expression and affecting learning and memory. Methylation activity in the nervous system is especially clinically important to study since some mental retardation diseases such as Rett Syndrome are due to mutations that affect the reading or writing of the epigenome. Because methylation has traditionally been considered a relatively static mark on DNA, with only maintenance methylation occurring in dividing cells, the possibility of active methylation activity in non-dividing neurons may provide some insight into neuronal plasticity.
Katherine would like to thank Dr. Fan and all members of the Fan Lab for their encouragement and excellent guidance. She would also like to thank the faculty of the Howard Hughes Undergraduate Research Program and the Biomedical Research Minor for their support.
| Michael Reitman
Faculty Mentor: Dr. S. Thomas Carmichael
Funding Source: Gottlieb
Title: Characterization of Recovery and Remyelination Mechanisms after White Matter Stroke
Michael Reitman is a fourth year UCLA Neuroscience major conducting research in the laboratory of Dr. S. Thomas Carmichael. Through volunteer work at the Stanford Behavioral and Functional Neuroscience Laboratory before his arrival at UCLA, Michael developed an interest in investigating the function and disorders of the central nervous system. In February 2012 Michael joined the Carmichael lab in the department of Neurology, which focuses on translational research into mechanisms of repair after stroke, and investigates the proteins involved in repair and recovery of white matter tissue following subcortical ischemic stroke.
Although white matter stroke accounts for up to a quarter of all stroke subtypes, the proteins and mechanisms by which recovery after stroke occurs has yet to be thoroughly explored. One of the main reasons for the lack of research in this area is the absence of a model which can reliably create the isolated white matter lesion characteristic of this stroke subtype. However, in the last few years the Carmichael lab has developed a mouse model using the nitric oxide synthase inhibitor N5-(1-iminoethyl)-L-ornithine (L-NIO) which can reliably produce more clinically relevant and localized subcortical ischemia. Using this model, and a list of proteins of interest from RNA sequencing data, Michael's project aims to use immunohistochemical techniques to investigate protein expression and location in and around the lesion area at various time points post-stroke. Through these methods Michael plans on identifying key proteins involved in remyelenation and repair with the long-term goals of identifying molecular pathways and therapeutic targets related to subcortical ischemic white matter stroke.
Michael would like to thank his faculty mentor Dr. Carmichael, as well as his current postdoctoral fellow mentor Dr. Shira Rosenzweig and the rest of the Carmichael lab, for their invaluable support, guidance, and knowledge. He would also like to express his gratitude to the URC and the Howard Hughes Undergraduate Research Program for the encouragement of his research interests and for the generous opportunities they have provided.
| Dianne Lumaquin
Pictured: Megan Hoban, Dianne Lumaquin, and Dr. Donald B. Kohn
Mentor: Dr. Donald B. Kohn
Project Title: Comparison of TAL Effector Nucleases and the CRISPR/Cas9 Nuclease System to Correct the Sickle Cell Disease Mutation
Dianne Lumaquin is a third year undergraduate at UCLA majoring in Microbiology, Immunology, and Molecular Genetics (MIMG) with a minor in Biomedical Research. Since August 2013, she has been an undergraduate researcher in the laboratory of Dr. Donald B. Kohn under the Departments of MIMG and Pediatrics. Under the mentorship of graduate student Megan Hoban, she is conducting a comparison of site-specific genome editing technologies to correct the sickle mutation of the beta-globin gene in hematopoietic stem cells.
Sickle cell disease is the result of an amino acid substitution of valine for glutamic acid in the beta-subunit of hemoglobin due to a point mutation in the gene. Transcription Activator-Like Nucleases (TALEN) and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 nuclease system are genome editing technologies containing a site-specific DNA binding domain and endonuclease component. TALEN and CRISPR/Cas9 can target and correct the sickle mutation when delivered alongside a corrected donor template. Previously designed and constructed TALEN and CRISPR/Cas9 plasmids have demonstrated targeted cleavage and gene modification at the beta-globin gene in cell lines. Dianne's project focuses on in vitro transcription of TALEN and CRISPR/Cas9 plasmids into functional mRNA, and determining which genome editing technology produces the highest gene modification rate as well as lowest toxicity and off-target activity in hematopoietic stem cells.
Dianne would like to thank her faculty mentor Dr. Kohn and her graduate student mentor Megan Hoban for their support and guidance throughout all of her endeavors. She would also like to thank Dr. Caroline Kuo, Dr. Zulema Romero, Dr. Roger Hollis, and the rest of the Kohn Lab for their continued support. Dianne would like to express her gratitude to the URC Sciences, Howard Hughes Undergraduate Research Program faculty, the Biomedical Research Minor faculty, and the CARE/MSD Scholars Program for providing the opportunities and encouragement to pursue her research interests.
| Laura Liu
Mentor: Dr. Ting-Ting Wu
Title: Characterizing the Significance of ORF34 in Gamma-Herpesviruses’ Late Gene Regulation
Laura is a junior majoring in Biochemistry with a minor in Biomedical Research. She started working in research early on in her freshman year in the Molecular and Medical Pharmacology department. Her work focuses on understanding late gene expression in the gammaherpes-virus by characterizing Open Reading Frame 34 in the virus.
Kaposi’s Sarcoma-associated Herpesvirus (KSHV) and Epstein-Barr Virus (EBV) are two human gamma-herpesviruses associated with cancers in immuno-compromised patients. Like all herpesviruses, progression of gene expression during lytic replication consists first of immediate early genes, followed by early genes, and finally late genes. The late genes encode structural components of virions and their expression is essential for the completion of the viral lytic cycle. In hopes of eventually developing a strategy to prevent persistent infection and identify potential targets to inhibit prior to virion production, late genes will be analyzed. Late gene expression can only occur after DNA replication has been completed so it is hypothesized that there exists a link between the two processes. There are currently six known viral Open Reading Frames (ORFs) that are part of the late gene complex and ORF 34 is one of those six. Laura will be identifying an interaction between ORF 34 and a component of the DNA replication complex in the hopes of determining a linkage. Mutations on ORF 34 will be made once an interaction is confirmed to determine which amino acids in the sequence are essential for this interaction.
Upon graduation, Laura intends to pursue a Ph.D. in graduate school. Laura would like to thank Dr. Ting-Ting Wu and Dr. Ren Sun, as well as the members of the Sun Lab for giving her the opportunity to work under their guidance. She would also like to thank URC Sciences and the Howard Hughes Undergraduate Research Program for their generous support.
| Ashley Yeon Joo Kim
Mentor: Dr. Hanna K. A. Mikkola
Funding Source: Regent's Scholar Award
Title: Integrin Alpha-8 Marks Cardiac Progenitors Arising from Murine Embryonic Stem Cells in vitro
Ashley is a fourth year in the MCDB major. She joined the Mikkola Lab during winter of her freshman year, and she has contributed to the identification of a novel population of progenitor cells giving rise to the interface of the placenta, an organ crucial for not only pregnancy but also hematopoiesis, and the mechanism that sustains these progenitors (http://dx.doi.org/10.1016/j.devcel.2013.10.019 ). Following this, Ashley has also worked to help characterize surface protein LYVE-1 as a differential marker of the transient-definitive wave of hematopoiesis during embryogenesis. This year Ashley began her third project in the lab investigating a potential marker of cardiogenic precursors arising ectopically from the hemogenic endothelium in an Scl-knockout model (see below).
More than 22 million people in the world suffer from heart failure, and each year one in four deaths in the US is due to heart disease. Regenerating a population of patient's heart cells that die after a myocardial insult is a major challenge due to the quiescence state of cardiomyocytes. Therefore the ability to engineer engraftable cardiomyocytes in great numbers from pluripotent stem cell sources would have a profound impact on cardiac regenerative medicine.
The stem cell leukemia gene encodes a basic helix-loop-helix transcription factor SCL/TAL1 which is known to regulate the development of hematopoietic stem cells. Previously our lab discovered that loss of Scl causes ectopic cardiomyogenesis in the yolk sac hemogenic endothelium and that a large sub-population of the CD31+PDGFRa+ cells (ectopic endothelial-derived cardiac cells) in Scl-deficient endothelium expressed integrin-alpha 8 (ITGA8). Following these studies, Ashley aims to show that the formation of ITGA8+ cells can be reproduced in vitro using mouse embryonic stem cells and that they can differentiate into mature cardiomyocytes in culture.
The first aim is to optimize a cardiac differentiation protocol to establish means of deriving cardiomyocytes from ES cells. Wild-type, Scl-knockout, and Scl-inducible mouse embryonic stem cells will be infected using viral vectors that contain cardiac troponin-GFP reporter to allow visual detection of cardiomyocyte formation. Once the system is established, this platform will be used to characterize kinetics of ITGA8 expression by flow cytometry. By FACS, ITGA8+ cells arising from Scl-knockout ES cell culture will be isolated and tested for their ability to form cardiomyocytes.
Ashley would like to thank Dr. Mikkola for making all her endeavors and achievements possible through all the encouragements and superb mentorship. She would also like to thank her lab members, especially Masaya, Lydia, and Edo for their kind guidance and support. In the fall of 2015, Ashley will be entering a medical-scientist training program to pursue an MD/PhD.
| Vincent Huang
Mentor: Dr. Atsushi Nakano
Title: Investigating the Role of Hematopoietic Cells in Coronary Artery Development
Vincent is a third year majoring in Molecular, Cellular and Developmental Biology with a minor in Biomedical Research. His curiosity with stem cell derived cardiomyocytes and the process of heart development led him to join Dr. Atsushi Nakano’s MCDB lab in the fall of 2013. His current project is examining how hematopoietic cells influence coronary artery development by regulating the process of epicardial epithelial to mesenchymal transition (EMT).
Coronary artery disease is the most common cause of death worldwide (~7 million died in the last year) and the most common form of heart disease. The cause of the disease is the gradual accumulation of atherosclerotic plaque within the arteries that supply oxygen to the heart. An emerging new concept for coronary artery treatment is the de novo formation of coronary arteries to replace the diseased coronary arteries. A critical step towards developing such treatments requires gaining a comprehensive understanding of the relatively new field of coronary artery formation and the process of epicardial EMT.
Recently, Vincent and his mentors showed that hematopoiesis deficient mice (Runx1-/- and Vav1-DTA mice) exhibited abnormal coronary artery formation and reduced epicardial EMT. Previously, a population of hematopoietic cells have been shown to be derived from the heart and a substantial portion of them appear to reside in the heart. Subsequently, the project Vincent is currently working on aims to determine the role of hematopoietic cells in regulating coronary artery formation and the signaling pathways responsible for regulating epicardial EMT by analyzing epicardial protein and gene expression profiles in hematopoiesis deficient mice. Such novel findings will contribute to our understanding of coronary artery development and may eventually lead to uncovering of therapeutic targets for coronary artery disease treatment.
Vincent would like to thank his faculty mentor, Dr. Atsushi Nakano, as well as his post-doctoral fellow mentors, Dr. Haruko Nakano and Dr. Gentian Lluri, and the rest of the Nakano Lab, for providing immeasurable support, guidance and an intellectually thriving research environment. He would also like to thank the Gottlieb Foundation, the Biomedical Research Minor and the Howard Hughes Undergraduate Research Program for the providing him with additional research resources and the wonderful opportunity to pursue his scientific research interests.
| Kimberly Hoi
Faculty Mentor: Dr. David Teplow
Funding Source: Judith Smith Award
Project Title: Identification of key regions and residues controlling Abeta folding and assembly
Kimberly Hoi is a fourth year undergraduate majoring in Neuroscience with a minor in Biomedical Research. Her curiosity in the mechanisms underlying neurodegenerative diseases, Alzheimer's disease in particular, led her to join Dr. David Teplow's laboratory in the Department of Neurology at UCLA in October 2012. She is currently working on a project aiming to identify the specific amino acids responsible for controlling the biophysical and biochemical properties of oligomer formation of the amyloid beta-protein (Abeta).
Neurotoxic oligomers formed by Abeta in the brain are thought to play a key role in the etiology of Alzheimer's disease (AD), and are therefore attractive therapeutic drug targets for AD therapy. In order to develop knowledge-based drug therapies that target these oligomers, the biophysical and structural characteristics of the protein must be well understood. Kimberly's project involves studying the physical biochemistry of Abeta monomer folding and assembly using D-amino acid substitutions. By implementing several different techniques to observe how D-amino acid substitutions affect Abeta oligomerization, secondary structure, morphology, and fibril formation kinetics, she hopes to identify specific amino acids important in controlling the formation of Abeta40 and Abeta42, the most physiologically abundant isoform and the most toxic isoform, of Abeta, respectively.
Kimberly would like to thank the members of the Teplow laboratory for their continuous support and guidance as her undergraduate education is enriched by the opportunity to participate in research. She would also like to extend her gratitude to the Biomedical Research minor advisors for their constant encouragement to pursue a career in research, and finally the HHURP and UC LEADS faculty. Upon graduation, Kimberly aims to pursue her doctorate in biomedical sciences.
| Dewal Gupta
Faculty Mentor: Dr. Dino Di Carlo
Funding Source: Wasserman
Title: High Throughput Cell Viability Assay using Deformability Cytometry
Dewal is currently a third year at UCLA majoring in computational and systems biology. He currently works in Dr. Di Carlo's lab in the Bioengineering department with microfluidic devices. His current project focuses on deformability cytometry and how epigenetic modifications to the DNA structure can be detected using deformability.
Microfluidics is a large field and generally deals with the behavior and manipulation of cells and fluids at a micro-scale level. One of the most important tools recently developed is the deformability cytometry. Deformability cytometry works by stretching cells at a junction while a high-speed camera records the elasticity of each cell as it passes through. It is high-throughput and has the capability of analyzing approximately 1,000 to 3,000 cells per second. It has been shown there are significant differences in the deformability of live and dead cells, differentiated stem cells, cancer cells, and many other cell populations. Therefore, deformability cytometry can be used as an efficient and high-throughput cell viability assay. Currently, Dewal is experimenting with different designs and methods to sort cells based on viability without the need of staining or labeling. His project looks to detect the epigenetic modifications of certain drugs on cancer cells, and how these changes can be quantified using deformability cytometry. By using the deformability cytometer, it will become much easier and cheaper to quantify viable cells and measure the effectiveness of DNA modifying drugs on specific cell populations.
Dewal would like to thank Dr. Di Carlo, the Di Carlo lab, and the Undergraduate Research Scholars Program, the Howard Hughes Undergraduate Research Program and the Wasserman Scholarship for supporting his research endeavors. He is very grateful for their guidance and support that he has received over the past few years.
| Arbor Dykema
Mentor: Dr. Utpal Banerjee
Arbor is a third year undergraduate majoring in Microbiology, Immunology, and Molecular Genetics with a minor in Biomedical Research. Her interest in immunology with respect to cell development led Arbor to join the Banerjee Lab in the department of Molecular and Cell Developmental Biology during winter of her second year. She has been working on the identification of a variety of hematopoietic pathways in Drosophila melanogaster and how certain stimuli cause a reactive cascade within the organisms to affect blood development. Currently, Arbor is working with Dr. Carrie Spratford, a postdoctoratal fellow in the Banerjee Lab, on a signaling pathway mediating overgrowths in tumorous tissue and the lymph gland, the major hematopoietic organ in Drosophila.
Cancerous tumors are aggressive, invasive tissues that elicit devastating effects on living organisms. During mammalian tumorigenesis, the quickly proliferating primary tumor creates a particular microenvironment through recruitment of bone marrow cells to the target site (Egeblad et al., 2010). This recruitment relies on an unknown signaling pathway between the original tumor site and the organ serving as a source for progenitor (undifferentiated) cells. This source of blood progenitors in Drosophila is the lymph gland. Previous studies, done by Dr. Carrie Spratford, have shown that activating tumors in the wing disc (through a wing disc specific gene driver, dpp-GAL4) causes a phenotype in which the lymph gland exhibits premature differentiation and develops a thick casing. The lymph gland does not express dpp; therefore, this phenotype is nonautonomous. The lymph gland is responding to stress from a separate organ, in this case the tumorous wing disc. This signaling mechanism is still unknown, but by investigating candidate molecules from RNA sequencing data and comparing results from activating tumors in various tissues, Arbor will investigate this tumor signaling pathway, identify which molecules are involved in this pathway, and observe how the lymph gland is receiving these signals. The overall goal of Arbor’s project is to establish a clear understanding of the signaling pathway that allows for communication between other organs and the lymph gland.
Arbor would like to thank Dr. Banerjee for the opportunity to research in his laboratory as well as for his consistent guidance. She would also like to thank Dr. Carrie Spratford for all of her assistance and support. Arbor has recently joined the Howard Hughes Undergraduate Research Program (HHURP) and is thankful for the encouragement and instruction from the faculty and her peers. Arbor would also like to thank Dr. Ira Clark and the rest of the Biomedical Research Minor faculty members for their dedication to undergraduate research and continued support throughout her undergraduate career.
| Joseph Conovaloff
Pictured left to right: Dr. David B. Teplow, Joseph Conovaloff, Dr. Eric Y. Hayden
Faculty Mentor: Dr. David B. Teplow
Funding Source: Gottlieb
Title: Isolation and Characterization of Amyloid Beta-Protein Oligomers
Joseph Conovaloff is a fourth year neuroscience major, minoring in biomedical research. He has been doing research in the Teplow laboratory since June 2012, under the direct mentorship of Dr. Eric Y. Hayden. The Teplow lab focuses on studying and understanding the amyloid beta-protein (Ab), a protein heavily implicated in causing Alzheimer's disease (AD).
AD is a neurodegenerative disorder that can lead to difficulty in performing basic tasks, forgetfulness, and eventually death. Currently in the United States, over 5 million people have AD. This is estimated to increase to at least 15 million by 2050, amounting to over $1 trillion in healthcare costs. In AD, small clumps (oligomers) of Ab are responsible for the death of brain cells. To develop effective therapeutic agents for AD, it is necessary to understand how these oligomers form and to determine their three-dimensional structures. Medicinal chemists can then design specific agents that bind to the atoms that control this clumping phenomenon. Oligomers contain small numbers of Ab proteins, but no single type exists. Oligomers may contain two, three, or more individual Ab proteins (monomers). In addition, these oligomers can convert from one to another by losing or gaining monomers, making oligomer structure determination very difficult. Joseph has helped to develop a method of isolating these individual oligomers that contain different numbers of monomer units in one complex, and is now working on characterizing each individual oligomer through different studies. These will provide a knowledge base for therapeutic agents against the most toxic species of Ab. As there are numerous disease that involve amyloid proteins, this process of isolating oligomers could provide insight into isolating oligomers associated with other diseases, such as Parkinson's disease.
Joseph is a part of the Howard Hughes Undergraduate Research Program (HHURP) at UCLA, and is extremely grateful for the HHURP faculty's support and guidance. He would also like to thank Drs. Ira Clark and Rafael Romero and the Biomedical Research Minor for their encouragement and dedication to promoting undergraduate research.
| Iris Bachmutsky
Pictured: Maria Lazaro, Dr. Dan Geschwing, Iris Bachmutsky
Faculty Mentor: Dr. Dan Geschwind
Title: ASD Electrophysiology Characterized by Mouse Model CNTNAP2
Iris Bachmutsky is a third year neuroscience major, minoring in bioinformatics. She has been doing research in the Geschwind laboratory since June 2012, and in the Golshani laboratory since March 2014, both under the mentorship of PhD candidate Maria Lazaro. The Geschwind lab is interested in assessing the role of genetics in a wide array of neuropsychiatric disorders and neurological disease. The Geshwind and Golshani labs are working together to determine whether the Cntnap2 KO mouse line, a model of Autism Spectrum Disorder (ASD), has regional and electrophysiological deficits.
A significant proportion of autism cases, now occurring at a frequency of 1 in every 68 individuals in the United States, are thought to be genetic. The genetic mouse model of autism recapitulates the triad of deficits that characterizes ASD: impairments in language, social interactions, and repetitive or restrictive behaviors. The Cntnap2 KO mouse further displays a decrease in excitatory neurotransmission, decreased neuronal synchronization, neuronal migration deficits, as well as a decrease in the total number of PV interneurons.
The current findings support the hypothesis that Cntnap2 KO mice will therefore display regional alterations in cortical connectivity, which ultimately alter brain network activity and disrupt behavior. Iris is helping to characterize the regional behavior of the KO mouse using local field potentials (LFP), taking gamma frequency power and coherency particularly into account. Further, Iris is searching for the biochemical and morphological changes that would cause these physiological and network deficits. Subsequent insight into the Cntnap2 KO model may resolve the connection between known electrophysiological changes and larger-scale behavioral deficits. The analyses may even lead to a general increase in the understanding and comparison of circuit level dynamics, or a new avenue for therapeutic application.
Iris is exceedingly grateful to her fellow lab members in the Golshani and Geschwind labs for their advice and help, and in particular to Maria Lazaro for her continued mentorship. Additionally, Iris would like to thank the Howard Hughes Undergraduate Research Program (HHURP) at UCLA for its help in facilitating her research and the HHURP faculty for their support.