Mr. Armin Arshi
Mentor: Dr. Atsushi Nakano
Title: Applications of Biomolecular Scaffolds and Matrix Elasticity in Cardiac Tissue Engineering
Armin Arshi is currently a third year undergraduate Bioengineering major and has been conducting research in the lab of Dr. Atsushi Nakano since February 2009 studying cardiac development.
Current scientific knowledge suggests that cell behavior and morphology is influenced by a combination of intercellular interactions, soluble molecular factors, and insoluble cues. Though difficult to adequately recapitulate in vitro, cell microenvironments appear to be important in stem cell lineage specification. Previous studies suggest that the phenotype, both in morphology and gene expression, of mesenchymal stem cells is extremely sensitive to tissue-level elasticity. With varied substrate stiffness, cells were cultured down a specific lineage trajectory. Soft matrices mimicking brain tissue and rigid matrices resembling collageneous bone, for example, were neurogenic and osteogenic, respectively. The formation of focal-adhesion and cytoskeletal structures is known to influence the wide variation in matrix stiffness for differentiated cells. This mechanism is believed to involve nonmuscle myosin II, whose inhibition completely blocks elasticity-driven lineage specification.
Using carefully engineered biomolecular scaffolds, Armin’s group intends to further this hypothesis and alter pre-deterministic mouse embryonic stem cells in vitro to “push” them down the cardiomyocyte lineage trajectory. By culturing cells in microenvironments of intermediate stiffness, they hope to find a greater yield of cardiac troponin T (cTnT) expression and visibly “beating” cardiomyocytes as compared to standard in vitro tissue culture methods. In addition to delineating the effects of the physical microenvironment on cardiogenesis and other developmental processes, these findings could also have implications in furthering stem cell therapy, by manipulating organotypic explant culture and other means of controlled tissue engineering.
After graduation, Armin intends to pursue a dual MD/PhD degree to facilitate a career in translational research and biomedical industry. He would like to thank the Howard Hughes Undergraduate Research Program, the Gottlieb Foundation, and the entire Nakano lab for supporting his research endeavors, both past and present.
Back to top
Mr. Abhik Banerjee
Mentor: Dr. Julian Martinez
Title:The Roles of Developmental Signaling Pathways in Drosophila melanogaster Tissue Regeneration
Abhik Banerjee is a third year double major in Molecular, Cell, and Developmental Biology and Music Performance. He currently studies the roles of growth signaling pathways in tissue regeneration using the Drosophila melanogaster model system.
While organisms such as the planarian, zebrafish, and cricket display epimorphic regenerative capacity, chickens, humans, and adult Drosophila flies do not display this capacity. However, modern genetic methods, including the ectopic expression of select developmental signaling pathways, have enabled inducible epimorphic regeneration in organisms such as the chicken and Xenopus laevis . In addition, a number of signaling pathways have been shown to be required for regeneration in insects. The Fat/Dachsous pathway is necessary for proper limb regeneration in adult crickets. Similarly, the Jun-Kinase pathway has been linked to Drosophila wing imaginal disc wound healing in vivo. As a result, w e hypothesize that ectopic activation of the JNK and Fat/Dachsous pathways at a later stage in development will promote tissue repair and regeneration in response to injury in Drosophila in vivo and in vitro.
We plan on studying the roles of these pathways using a recently established wing imaginal disc ablation system. This ablation system can induce stage-specific apoptosis of wing imaginal discs, followed by a recovery period in which regeneration occurs. This system can be used in combination with various loss of function alleles or gain of function constructs to study the roles of these pathways in imaginal disc regeneration in vivo. We also plan on over-expressing select components of these signaling pathways and observe their possible effects on imaginal disc regeneration in vitro. In addition to our imaginal disc studies, we also plan to use the adult leg as a model for our regenerative studies. We believe this unique complimentary approach will allow us to identify new candidate genes and targets for future study.
In the future, Abhik plans to pursue a joint MD/PhD program and continue regenerative genetics research. He would like to thank Dr. Julian Martinez, the entire Martinez-Agosto lab, Dr. Clark, Dr. Olson, and the HHURP faculty for their support, advice, and guidance.
Back to top
Mr. Abinav Baweja
Mentor: Dr. John Colicelli
Title: Outflanking BCR-ABL Drug Resistance
Abinav Baweja is a third-year Molecular, Cell, and Developmental Biology major conducting research under the guidance of Dr. John Colicelli in the department of Biological Chemistry. His project is focused on discovering more robust treatments for chronic myelogenous leukemia (CML), in which resistance to current drugs remains an issue. After graduation, Abinav hopes to pursue a research career through an M.D/Ph.D degree.
Previous work in the Colicelli lab has shown that RIN1 binds to the SH2 and SH3 domains of BCR-ABL1, the oncogenic tyrosine kinase in CML. This binding relieves auto-inhibition and enhances kinase activity. Furthermore, drug resistant mutants of BCR-ABL1 remain responsive to kinase stimulation by RIN1. Interestingly, deletion or silencing of RIN1 inhibits oncogenic transformation of cells by BCR-ABL1 and by drug-resistant BCR-ABL1 mutants. Given that RIN1 is expressed in CML cell lines, the RIN1-ABL1 binding interface presents a novel and promising target for CML therapy.
Abinav is currently involved in performing a high-throughput drug screen using TR-FRET (Time-resolved Fluorescence Resonance Energy Transfer) for molecules that can inhibit the functional interaction between RIN1 and ABL1. He expresses the modified forms of RIN1 and ABL1 for the screen in SF9 insect cells using a baculovirus vector. Abinav is trying to investigate whether functionally equivalent truncations of RIN1 can be produced in bacteria, which may increase the efficiency of the assay and yield structural data of the RIN1-ABL1 binding interface.
Abinav would like to thank the Colicelli lab for their support and guidance in pursuing this project.
Back to top
Ms. Ke-Huan Chow
Mentor: Dr. Harold Martinson
Title: The Structural Roles of the Transcription Elongation Complex in the Coupling of pre-mRNA Transcription and Processing.
Ke-Huan Kuo Chow is a third year Molecular, Cell, and Developmental Biology major. She is conducting research under the guidance of Dr. Harold Martinson in the department of Biochemistry. Her lab focuses on uncovering the mechanism by which transcription is coupled to pre-mRNA processing. They work with nuclear extracts that couple pre-mRNA transcription with 3’-end processing without the aid of the crowding agent, PVA.
IIn the past, Dr. Martinson’s laboratory demonstrated that the CPSF transcription factor, when bound to the polymerase body during transcription, disallows the concurrent binding of the CPSF-CstF complex (a complex essential for efficient pre-mRNA cleavage at the poly(A) site). Consequentially, it was proposed that the two cleavage factors bind in a sequential manner: CPSF is recruited to the polymerase first, then CstF binds later in transcription to form the CPSF-CstF complex. Conventionally, the sequential binding was explained by the knowledge that CPSF’s pre-mRNA binding site emerges first during transcription. However, Dr. Martinson’s lab also showed that stripped transcription elongation complex with transcribed poly(A) signal still conducted efficient cleavage in their nuclear extract, despite the fact that CPSF and CstF binding sites were simultaneously available.
Based on the above results, Ke-Huan’s project challenges the conventional view that sequential “binding site emergence” dictates sequential “cleavage factors recruitment”. She tries to demonstrate that it is the intrinsic structure of the transcription elongation complex that dictates the assembly order of the cleavage apparatus. She uses RNaseH protection assays to evaluate protein binding on the pre-mRNA. Since the sequential binding of CPSF and CstF is only believed to occur when transcription is coupled with pre-mRNA processing (as it is in vivo), the findings of this project will hopefully deepen our understanding of the mechanism by which our cells produce their mature mRNA.
Ke-Huan would like to express her deepest gratitude to Dr. Harold Martinson for his unwavering patience and guidance in the past two years. She would also like to thank Benson Ngo and Huimin Zhang for their encouragement, and her family for the never ending support throughout the years. Lastly, she would like to thank the Howard Hughes Medical Institute and the HHURP Staff members for giving her the amazing opportunity to explore research from a different level.
Back to top
Mr. Jonathan Kuo
Mentor: Dr. Craig Merlic
Title: Pd(II) catalyzed coupling of vinyl boronates
Jonathan Kuo is a third year Chemistry major with a Computational Specialization and has been conducting research on organometallics since his second year. Under the supervision of Professor Merlic and Robert Iafe, Jonathan has been investigating Pd(II) catalyzed coupling of vinyl boronates.
Macrocycles are the backbones of countless natural products. One synthetic strategy is to construct a large chain and couple two of the atoms to effectively “close” a ring. This ring-closing step has to overcome unfavorable entropy, so conventional methods of forming carbon-carbon bonds are low yielding or fail all together.
Some of the most powerful methods of forming carbon-carbon bonds require transition metal catalysts. Metals such as nickel and palladium can perform oxidative coupling and effectively form carbon-carbon bonds in even entropically undesirable systems (such as macrocycles). This chemistry is so powerful that it won Heck, Negishi, and Suzuki the Nobel Prize in chemistry in 2010. Most of these reactions occur through a Pd(0) catalyzed mechanism, and require differentiation to install both electrophilic and nucleophilic groups. Manipulating a synthesis to ultimately have both these groups is both time consuming and expensive.
The Merlic Group has shown that Pd(II) can be used to catalyze a similar coupling process, but can operate on two nucleophilic groups. Since differentiation is no longer required, synthesis using Pd(II) is will dramatically enhance the efficiency of macrocycle synthesis. Jonathan has been synthesizing a number of substrates that will demonstrate the utility of Pd(II) catalysis.
Upon graduation, Jonathan intends on pursuing a Ph.D. in organic chemistry. Jonathan would like to thank the Merlic Group for their continued support and guidance as he pursues his research career.
Back to top
Mr. Sung-Ling Lee
Mentor: Dr. Alvaro Sagasti
Identification of minimal enhancer sequences sufficient to drive expression in zebrafish somatosensory neurons
Somatosensory neurons in vertebrates respond to mechanical, thermal, and chemical stimuli. The development and function of somatosensory neurons depend on the expression of specific genes, such as neurotrophin receptors and sensory channels. A number of trk receptors and trp channels are expressed specifically in somatosensory neurons of all vertebrates, suggesting that they are regulated by transcription factors specific to this cell population. To identify these transcription factors, t he promoter regions of these channels and receptors were dissected t o identify the minimal enhancer elements necessary for their expression in somatosensory neurons, and any negative elements. I am “promoter-bashing” the upstream region of known somatosensory genes and using these fragments to create reporter transgenes with the Green Fluorescent Protein (GFP). Initially, two reporter transgenes, one with four kilobases (kb) of the trkA promoter region from pufferfish and the other with five kb of the trpA1a promoter region from zebrafish, were used to drive transient expression of GFP in zebrafish larva. Embryos injected with either transgene expressed GFP specifically in somatosensory neurons. Deletion analysis of the upstream promoter regions in these transgenes revealed that a 250-bp region immediately upstream of the trkA start site and a 2-kb region three kb upstream of the trpA1a start site were sufficient to drive expression of GFP. These two regions contain the sequences essential for the expression of trkA and trpA1a in peripheral sensory neurons and will be further dissected to better define the minimal enhancer regions. The search for potential negative elements will also continue in the sequences excluded by these two regions.
Dean is a junior majoring in Neuroscience. He has been working in Dr. Alvaro Sagasti’s lab since his sophomore year. He plans to pursue a Ph.D. in the biomedical sciences upon graduation. He would like to thank the members of the Sagasti lab for their continued input and especially Dr. Sagasti and graduate mentor Ana Marie Palanca for their unfailing guidance.
Back to top
Mr. Justin Sharim
Mentor: Dr. Peyman Golshani
Title: Cellular Mechanisms of High Frequency Oscillations in the Epileptic Brain
Justin Sharim is presently a junior majoring in Neuroscience. He conducts his research at the David Geffen School of Medicine, Department of Neurology under the guidance of his mentor Dr. Peyman Golshani. Justin has conducted research in Dr. Golshani’s lab since his freshman year. Justin’s current research project focuses on the cellular mechanisms underlying epileptogenesis. Epilepsy is characterized by recurrent, unprovoked seizures. After one episode of status epilepticus (a prolonged seizure), both patients and animal models become predisposed to having seizures later on in their lifetime. Why does this occur? How is the brain rewired after one extended seizure to account for this predisposition?
This rewiring of the brain is observed at the functional network level by recording high frequency oscillations in the hippocampus. Transient bursts of high frequency network oscillations in the 140-200hz frequency band coined ripples have been observed in the non-epileptic brain. These oscillations are normal, and have been said to be responsible for various functions such as consolidating memory and synaptic plasticity. In epileptic models, however, much higher frequency oscillations of 200-600hz, referred to as pathological fast ripples, have been observed. The underlying cause of the pathological high frequency oscillations is still unclear. Justin is currently investigating the underlying cause of these pathological high frequency oscillations using electrophysiological techniques. He records simultaneous field potentials and whole-cell membrane potentials from the hippocampus of epileptic and non-epileptic awake, mobile mice running on a spherical treadmill. Using this approach, Justin aims to demonstrate in vivo which classes of neurons fire synchronously in phase with the bursts of the pathological fast ripples. This knowledge may give rise to finding novel treatments targeting the pathways that create the epileptic state.
Justin would like to thank Dr. Golshani for his ongoing support and invaluable guidance. He would also like to thank the Howard Hughes Medical Institute for the generous funding and the HHURP staff for fostering his research efforts.
Back to top
Mr. William Temple
Mentor: Dr. Benhur Lee
Title: Galectin-1 exposure during the monocyte-derived dendritic cell differentiation results in dendritic cells with a tolerogenic potential
William Temple is a fourth year Microbiology, Immunology, and Molecular Genetics major conducting research under the guidance of Dr. Benhur Lee and Margaret Chang. He began conducting research during the Winter quarter of his freshman year, and has been working on his current project since his second year.
The Lee lab is primarily concerned with elucidating the intricate mechanisms between glycans and dendritic cells in the context of HIV infection; currently William studies dendritic cell immunology.
Dendritic cells (DCs) are sentinels of the immune system, acting as potent antigen presenting cells which regulate immune responses to both exogenous and endogenous signals. Galectin-1 is a galactoside-binding lectin with pleiotropic immunomodulatory functions. We have previously shown that galectin-1 is an endogenous activator of immature human monocyte-derived DCs (MDDCs), triggering their maturation and migration. In addition, galectin-1 is present in peripheral tissues at high concentrations, and thus may affect monocyte to DC differentiation. Here, we show that galectin-1-exposed DCs during the differentiation process result in DCs with a tolerogenic phenotype. Immature DCs differentiated in the presence of galectin-1 specifically display a downregulation of CD83, CD86, and TLR2. This phenomenon is galectin-1 dose-dependent and temporally regulated; reliant upon how long galectin-1 is in the presence of differentiating monocytes. In addition, galectin-1-exposed DCs also upregulate secretion of the anti-inflammatory cytokine IL-10 and decrease levels of proinflammatory IL-12. These MDDCs also retained the ability to uptake antigen and mature in response to classical immunogenic stimuli like lipopolysaccharide (LPS) and polyI:C, however they retained low expression levels of costimulatory molecules and continued to secrete IL-10 but not IL-12. In addition, galectin-1-exposed DCs display an upregulation of PDL-1 and downregulation of MHCII, TLR2, and DCSIGN relative to chemically-induced and untreated DCs. These findings show that monocytes exposed to galectin-1 during the differentiation process possess a cell surface phenotype and functionality consistent with tolerogenic DCs. Thus, galectin-1 has various effects on DC function depending on the differentiation and activation status of the cell.
William would like to thank Dr. Benhur Lee, Margaret Chang, and the rest of the Lee lab for their valuable insight and support. He would also like to thank the Howard Hughes Medical Institute for the generous funding and the HHURP staff for exposing him to novel and exciting research in the biomedical sciences.
Back to top
Ms. Catherine Yao
Mentor: Dr. Hanna Mikkola
Title: Hif-3α as a regulatory factor of hematopoietic stem cell properties
Catherine Yao is a third year Molecular, Cell and Developmental Biology major and Biomedical Research minor. She has been conducting research in Dr. Hanna Mikkola’s lab since winter of her second year. Catherine is currently investigating the intrinsic hypoxia-related factors as possible regulators of the maintenance of hematopoietic stem cell properties.
The ability of the body to replenish its blood system depends on the function of hematopoietic stem cells (HSCs), which possess the unique ability to differentiate into all blood cell types, as well as self-renew to maintain a steady pool of stem cells. HSCs are in high demand for transplantation treatments of various hematological disorders and can be harvested from bone marrow, mobilized peripheral blood, and umbilical cord blood. However, as these sources yield very limited numbers of HSCs, our ultimate goal is to be able to expand HSCs in culture to fill the need for engraftable, HLA-matched stem cells. In order to do so, it is necessary to isolate true HSCs to study the regulatory mechanisms they use for their expansion. Success in this research has been limited by the fact that there are no phenotypic markers to distinguish the purest human HSCs from their immediate downstream progenitors, which can differentiate into either myeloid and/or lymphoid cell types but cannot self-renew.
After analyzing the gene expression of isolated engraftable hematopoietic stem/progenitor cells (HSPCs), we found that the gene for hypoxia-induced factor 3α (hif-3α) is highly upregulated. This is especially intriguing because studies have shown that hif-3α is a transcription factor that regulates the cell’s response to hypoxia, which is crucial in the bone marrow niche to maintain HSC properties. Catherine plans to study whether hif-3α is essential for maintenance of stemness by performing a lenti-viral knockdown of hif-3α and then investigating the hif-3α(-) HSPCs’ capabilities of self-renewal, differentiation, and in vivo engraftment. These experiments will allow us to gain further insight into the cellular mechanisms of hematopoietic stem cells’ unique self-renewal and differentiation abilities and maintenance by its microenvironment. Ultimately, we hope that this information will provide clues to the necessary signaling pathways required to expand HSCs in culture for therapeutic purposes.
After graduation, Catherine plans to pursue a joint MD/PhD program. She would like to thank Dr. Mikkola, advisor Dr. Ira Clark, graduate mentor Sacha Prashad, and the entire Mikkola lab for their expert guidance and support. She would also like to thank the Howard Hughes Medical Institute and the HHURP faculty for this invaluable research opportunity.
Back to top
Mr. Daniel Yazdi
Mentor: Dr. James Bisley
Title: Inhibition of return and priority map guidance for allocation of attention during visual foraging task
Daniel Yazdi is a third year Computational and Systems Biology and Mathematics/Applied Science double major conducting research under the guidance of Dr. James Bisley of the Neurobiology Department. Dr. Bisley’s lab of the Brain Research Institute is primarily interested in the neural mechanisms responsible for the allocation of visual attention. Upon completion of undergraduate studies, Daniel will pursue an MD/PhD.
The lateral intraparietal area (LIP) of the posterior parietal cortex is believed to be responsible for creating a constantly refreshing priority map for covert visual allocation. Contributing bottom-up guidance such as object saliency is combined with top-down object specific feedback in creating the map. It is believed that attention is allocated to the peak of the visual map, which is the location with highest neural activity. In addition, the psychophysical phenomenon of inhibition of return (IOR) describes the slowing of response times to objects already attended during a visual search task, promoting exploration of unsearched areas; an important evolutionary development. IOR is therefore responsible for improving the efficiency of visual search by guiding the oculomotor system to new locations. It has already been shown that the activity of LIP explains efficient visual search by decreasing response times to objects already attended to. As a result, the activity of LIP can explain the efficiency IOR supports. Daniel is particularly interested in using IOR to show that reaction times, a measure of the attentional state of the brain, is directly correlated to activity on a priority map, thereby providing a new interpretation of IOR. He will also further investigate the underlying neural mechanisms of IOR using behavioral and electrophysiological experiments.
Daniel would like to thank Dr. Bisley and the entire lab for their ongoing input, guidance, and support. He has gained invaluable knowledge and experience from time spent in lab. He would also like to thank the Howard Hughes Medical Institute and the Undergraduate Research Scholars Program for their generous funding and support of his research.
Back to top
Ms. Mary Youssef
Mentor: Dr. Paul Mischel
Title: The potential for small molecule inhibitors to target components of intracellular lipid synthesis pathways in an effort to decrease cancer cell proliferation and reduce tumor growth.
Mary Youssef is a third year majoring in Molecular, Cell and Developmental Biology with a minor in Biomedical Research. Her project in the lab of Dr. Paul Mischel explores the potential for small molecule inhibitors to target components of intracellular lipid synthesis pathways in an effort to decrease cancer cell proliferation and reduce tumor growth.
Glioblastoma (GBM) is one of the most deadly cancers, with an average patient survival rate of 12-18 months after diagnosis despite surgery, radiation and chemotherapy, making it increasingly urgent to find new molecular targets and effective drugs. Recently, The Cancer Genome Atlas identified that RTK/PI3K/Akt signaling is activated in about 88% of GBM; this pathway has been recognized as a major driver in promoting malignant cancer cell growth in several cancers. Recently, members of this lab demonstrated that RTK/PI3K/Akt signaling promotes GBM cell growth through sterol regulatory element-binding protein 1 (SREBP-1) mediated fatty acid synthesis, and identified SREBP-1 as a potential molecular target. The purpose of this research is to select effective lipid synthesis inhibitors, and to test their anti-cancer function. Small molecular inhibitor fatostatin was shown to effectively inhibit lipid synthesis, so it is promising to test its anti-cancer function. Experiments will be conducted to determine whether fatostatin treatment can inhibit tumor cell proliferation and increase cell death in vitro, and to establish whether this treatment is more effective in GBM cells with activated EGFR signaling. Further experiments will determine whether fatostatin can produce the same inhibitory effect in vivo. Results of these experiments will be used to translate fatostatin to GBM clinical trials.
In the future, Mary plans to pursue a joint MD/PhD program and continue research in the biomedical sciences. She would like to thank Dr. Paul Mischel, Deliang Guo, her postdoctoral mentor, and the other members of the Mischel Lab for their support and guidance.
Back to top
Ms. Madeline Yung
Mentor: Dr. Jeffrey Miller
Title: Underlying antibiotic resistance in Bacillus anthracis
Madeline Yung is a third-year Neuroscience major conducting research in the lab of Jeffrey H. Miller in the Department of Microbiology, Immunology, and Molecular Genetics. She currently focuses on the mechanisms underlying antibiotic resistance in Bacillus anthracis and works with a variety of knockout strains to determine potential candidates for combination drug therapies. After graduation, Madeline hopes to pursue an M.D./Ph.D and ultimately a career as a research physician.
IIn contrast to its well-documented cousin Escherichia coli, Bacillus anthracis represents a relatively unexplored frontier of bacterial research. However, its lethality underscores the importance of maintaining effective antibiotic treatments even in cases involving resistance. Analyzing the phenotypes of bacterial gene knockouts is crucial to understanding how specific mutations lead to antibiotic resistance. Past projects from the Miller lab such as Garibyan et al. have used a knockout collection of E. coli to investigate mutagenesis pathways in the rpoB gene which resulted in resistance to the antibiotic rifampicin. Additional investigation of Bacillus anthracis papillation mutants has led to the discovery of new mutators and the generation of mutational profiles for genes with ambiguous function. Further characterization of these mutators will lead to a better understanding of bacterial mutagenesis pathways leading to antibiotic resistance.
Madeline is currently involved in the creation of a transposon knockout library similar to the KEIO E. coli collection used in previous lab experiments. The creation of the knockout library involves identifying randomly generated transposon insertion sites in Bacillus anthracis strain Sterne - and thus interrupted genes – for individual knockout strains through Arbitrarily Primed PCR analysis, DNA sequencing, and the NCBI blast database. In addition, she is working to characterize the mutational pathway for mutator strains such as recJ and yycJ. She utilizes the unique phenotype of the nprR gene as an assay to isolate mutants and determines the unique characteristics of the mutators through PCR and DNA sequencing.
Madeline would like to thank Dr. Jeffrey H. Miller, the Miller lab team, and the Howard Hughes Undergraduate Research Program for their support and inspiration.
Back to top
Ms. Lillian Zhang
Mentor: Dr. Hong Wu
Delta-catenin modulation of gamma-secretase function in Alzheimer’s disease
Lillian Zhang is a third year Microbiology, Immunology, and Molecular Genetics major with a minor in biomedical research studying under the direction of Dr. Hong Wu, Dr. Xin Liu, and Mochtar Pribadi in the Department of Molecular and Medical Pharmacology. Specifically, Lillian is studying the role of the neural specific protein, delta-catenin, in amyloid beta peptide formation in Alzheimer’s disease.
It has been previously shown that delta-catenin interacts with presenilin-1, the catalytic subunit of the gamma-secretase complex. The gamma-secretase complex cleaves the amyloid precursor protein (APP) to produce amyloid beta (AB) peptides. Mutations in presenilin-1 cause familial Alzheimer’s disease by increasing the ratio of the abnormal AB-42 peptide to normal AB-40 peptide, resulting in amyloid plaque deposition, a hallmark of Alzheimer’s disease. Our studies suggest that in vivo plaque deposition is considerably amplified in delta-catenin knockout mice, which exhibit significant cognitive deficits. Furthermore, in vitro studies reveal that delta-catenin appears to effectively alter gamma-secretase activity. Based on these observations, we have predicted that delta-catenin influences the production of amyloid beta peptides and serves as a positive modulator of gamma-secretase cleavage of APP.
Lillian would like to thank the Howard Hughes Undergraduate Research Program faculty and scholars, Dr. Ira Clark of the biomedical research minor, and the Howard Hughes Medical Institute for their generous funding and sponsorship. She is especially grateful to Dr. Wu, Dr. Liu, and Mochtar for their support of her research project, and to all the members of the Wu/Liu lab for their guidance and wisdom.