Student Profiles Archive - Howard Hughes Undergraduate Research Program 2012-2013
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.
| Ms. Kimberly Loo
Ms. Kimberly Loo
Mentor: Dr. William Lowry
Title: Elucidating the Developmental Maturity of Pluripotent Stem Cell Neural Progenitor Cells
Kimberly Loo is a third year Molecular, Cell, and Developmental Biology major with a minor in Biomedical Research. She has been conducting research under the guidance of Dr. William Lowry since winter quarter of her second year. Kimberly’s current research project focuses on elucidating the developmental maturity of pluripotent stem cell neural progenitor cells.
Human pluripotent stem cells (hPSCs) have the potential to differentiate into many cell types, yet it is not known how similar the process of PSC in vitro development reflects the in vivo process. The Lowry lab has recently found that both human embryonic stem cells and human induced pluripotent stem cells make cells that are more similar to cells found only very early in fetal development. From this work, our lab identified a set of 105 genes whose expression appears to distinguish mature tissue derived cells from those generated from hPSCs. Among some of the differences observed between hPSC progeny and their respective natural counterparts is one set of genes thought to only be expressed in early embryos, and a second set of genes “maturity or specification” genes that fail to be properly induced during in vitro differentiation.
Kimberly aims to perform transfection experiments on PSC-neural progenitor cells to overexpress a set of the “maturity or specification genes” in attempts to successfully manipulate the gene expression of genes misexpressed between PSC derivatives and their natural counterparts to yield more mature, functional cells that both mimic tissue derived cells and functionally replace cells that are lost in disease or injury.
Kimberly is extremely grateful to Dr. William Lowry, biomedical research minor advisor Dr. Ira Clark, graduate student mentor Michaela Patterson, and the entire Lowry lab for their patience, continued guidance, and unwavering support. She would also like to thank the Howard Hughes Medical Institute and the HHURP faculty for this amazing opportunity.
| Shannon Wongvibulsin
In Photo from Left to Right: Stephanie Reed, Shannon Wongvibulsin, Dr. Benjamin Wu
Ms. Shannon Wongvibulsin
Mentor: Dr. Benjamin Wu
Title: 3D-Printed Sugar Preforms for Scaffold Creation in Aqueous Environments
Shannon Wongvibulsin is a third year undergraduate minoring in biomedical research, majoring in bioengineering, and performing research in Dr. Benjamin Wu's lab. Because of Shannon's interest in biomedical research, she has been a member of Dr. Wu's lab since the summer before her freshman year at UCLA. While projects of the Wu Lab range from the study of cell interactions with appetite bone matrix to dermal wound healing, they all center upon the study of biomimetic environments for the ultimate goal of tissue repair.
After working with 3D printing and developing a technique which allows 3D printed sugar preforms to serve as positive molds for infusion of aqueous-based scaffold solutions, such as chitosan-alginate, Shannon is currently working on implementing this system to create chitosan-alginate scaffolds with two zones, one that facilitates bone growth and one that facilitates cartilage growth. The long-term aim of this project is the creation of chitosan-alginate scaffolds with zonal micro- and macro-architecture for cartilage and bone regeneration. Additionally, these two zones of the scaffold will be created to have different pore sizes, larger pores for the bone region and smaller pores for the cartilage region; channels to facilitate the influx of endogenous progenitor cells will also be incorporated into the design of the preform.
Shannon would like to thank all her research mentors for enriching her undergraduate education with the opportunity for hands on experience in solving current biomedical challenges. After graduation, she hopes to pursue an MD-PhD dual degree and contribute to the medical field both as a physician and a member of the research community.
| Daniel Wong
In Photo from Left to RightName of people in picture (from left to right): Daniel Wong and Dr. Julian A. Martinez-Agosto
Mr. Daniel Wong
Mentor: JULIAN ANTONIO MARTINEZ
Title: The Role of Pico, The Drosophila MRL Protein, in Growth Regulation
Daniel Wong is a junior at UCLA, majoring in Molecular, Cell, and Developmental Biology with a minor in Biomedical Research. Since March 2011, he has been working in the Martinez-Agosto laboratory in the department of Human Genetics. His current project investigates the molecular mechanism through which pico, the Drosophila MIG-10/RIAM/lamellipodin (MRL) protein, regulates systemic larval growth.
Control of tissue and organismal size is coordinated by a number of intracellular growth signal transduction pathways that respond to various extracellular cues. While these growth regulatory mechanisms are crucial to the normal growth and development of animals, dysregulation of these pathways can lead to overgrowth diseases such as cancer. Therefore, elucidating the points in growth signaling pathways at which dysregulation occurs is essential for the development of therapeutic strategies to treat and prevent disease processes such as tumorigenesis.
Daniel’s project seeks to characterize the role that MRL proteins play in the communication of these growth regulatory pathways. MRL proteins comprise a specific class of molecular adaptors that connects upstream events, for example, the binding of a ligand to a surface receptor, to downstream targets whose activation brings about a cell response, such as the initiation of proliferation. Using Drosophila melanogaster as a model to study and characterize MRL proteins, Daniel aims to illuminate the role of pico in the regulation of systemic larval growth through examining the link that Pico has to two specific growth signaling pathways: the PI3K/Akt/TOR pathway and insulin signaling.
Daniel would like to thank Dr. Julian Martinez-Agosto for his continued guidance in the laboratory, and Daniel greatly appreciates the generosity and support from the Gottlieb Foundation and the Howard Hughes Undergraduate Research Program. Finally, Daniel is grateful to Dr. Ira Clark, Dr. John Olson, the HHURP faculty, and the URC for their encouragement in his research endeavors.
| Kevin Wang
Mr. Kevin Wang
Mentor: Peter Bradley
Title: Functional Characterization of a Novel Toxoplasma Inner Membrane Complex Protein IMC18
Kevin Wang is a 3rd year Microbiology, Immunology, and Molecular Genetics major with a minor in Biomedical Research. He currently conducts research in Dr. Peter J. Bradley’s laboratory. The Bradley’s Lab mainly studies the cell biology and protein functions of an obligate intracellular parasite called Toxoplasma gondii. Kevin’s research focuses on a novel protein that localizes to a compartment that has shown to be essential in T. gondii’s survival, the Inner Membrane Complex.
Apicomplexans are a large phylum of obligate intracellular parasites that cause substantial medical and veterinary disease worldwide. In humans, the two most important apicomplexans are Toxoplasma gondii. and Plasmodium falciparum, the causative agent of malaria. T. gondii infects about one third of the human population, making it one of the most successful parasites on Earth. Infection occurs by ingestion of encysted forms of the parasite from contaminated undercooked meat or feline feces. Even though T. gondii infects a large number of humans, it only causes disease in those that are immunocompromised, such as AIDS/HIV patients and congenitally infected neonates. Current therapies can limit the infection but are unable to clear the latent forms of the parasite. The drug treatments are also often toxic and thus new therapies are needed. In addition, T. gondii’s ease of manipulation and its available genetic tools permit it to serve as a model organism for other apicomplexans that are less genetically amenable.
One unique aspect of these parasites is their unusual method of cellular division known as endodyogeny in which daughter parasites are formed inside of the mother and ultimately consume the mother to release the daughter cells. Construction of daughter parasites is dependent upon an internal membrane system known as the inner membrane complex (IMC). The IMC is composed of membrane stacks supported on a network of intermediate filaments that grows throughout this internal division process. While the IMC is critical for parasite replication as well as host invasion, little is known about the protein components of the IMC and how they function in division. Kevin’s project at Dr. Bradley’s lab focuses on a novel IMC protein (denoted IMC18) that he recently discovered and localized utilizing a protein tagging method. He plans to further characterize the protein by determining its function, as well as identifying its possible interacting partners. Together, this research will provide new insight into the protein content and function of the IMC.
Kevin would like to pursue a Ph.D degree in either Microbiology or Molecular Sciences in the future after he graduated. He would like to thank Dr. Peter J. Bradley for always being there and guiding him through his project and his research. Kevin would also like to thank the Biomedical Research minor, the Howard Hughes Undergraduate Research Program, and the Bradley lab to provide him the opportunity and the chance to explore research on multiple levels.
| Mericien Venzon
Ms. Mericien Venzon
Mentor: MICHAEL EDWARD ALFARO
Title: Phylogenomic Study of Coral Reef Fish Faunas using ultra-conserved DNA elements (UCEs)
Mericien Venzon is a 3rd year Pre-Computational Systems and Biology major. After taking an introductory biology course with Dr. Michael Alfaro last fall, she discovered her interest and enthusiasm for evolutionary biology. She has been working in the lab of Dr. Alfaro in the department of Ecology and Evolutionary Biology since the spring quarter of her second year. Her current research project employs a new phylogenomic method that uses target enrichment and massively parallel sequencing of >1300 ultra-conserved DNA elements (UCEs) to investigate hypotheses regarding the evolutionary relationships and histories of coral reef fish faunas.
Coral reefs are home to over half of all the ocean’s fish species, yet the evolutionary history of these species remains as one of the most longstanding problems in vertebrate systematics. UCE’s represent a new set of genetic markers that more efficiently identify and isolate ideal regions of genomes for comparative analysis, better matching the capacity of next generation sequencing technologies. As the first application of UCEs to this group, Mericien aims to generate a more resolved phylogeny that will enable further investigations regarding the biogeographic history and tempo of diversifications of both reef and non-reef lineages. After sampling the 10 core reef associated fish families, Mericien’s long term goals include increasing the density of sampling within these groups as well as extending this method to 22 additional poorly studied reef clades.
Aside from phylogenomics, Mericien’s broader research interests include molecular evolution, disease ecology and evolution, and bioinformatics. After graduation, she plans to pursue an MD-PhD degree and ultimately hopes to use evolutionary medicine to develop new approaches to disease pathology and treatment. Mericien would like to thank Dr. Michael Alfaro for recognizing her potential, for his daily mentorship, the opportunity to learn in his lab, and above all, for introducing her to the endless possibilities in the world of evolution and computational biology. She would also like to extend her gratitude to Bernard Kim, her previous graduate student research mentor, her fellow members of the Alfaro lab, and her family for all their continued support. Finally, she would like to extend her gratitude to the URC Sciences and the Howard Hughes Medical Institute for providing opportunities in undergraduate research.
| Jennifer Pena
Ms. Jennifer Peña
Mentor: Dr. Elisa Hallem
Title: Innate Immune Response of Drosophila to Entomopathogenic Nematode Infection
Jennifer Peña is a third year Microbiology, Immunology and Molecular Genetics major. She has been in the lab of Dr. Elissa Hallem in the department of Microbiology, Immunology and Molecular genetics since January 2012. Jennifer is investigating Drosophila’s innate immune response to entomopathogenic nematode infection.
Parasitic nematode infection is a major health problem worldwide. Over one hundred species of nematodes are parasites of humans and a quarter of the world’s population is infected with parasitic nematodes. However, as little is known about a host’s immune response after infection, it is important to find a model system in which to investigate innate immunity to parasitic infection. Mammalian-parasitic nematodes and insect-parasitic nematodes have very similar modes of infection, both actively seek out and infect their host using chemosensory cues. Due to these similarities, entomopathogenic nematodes (EPNs), in conjunction with Drosophila melanogaster, can be used to establish a model system to study host immune response to parasitic nematode infection.
The goal of this study is to establish a model system for investigating the immune response to nematode infection and then to characterize the insect immune response to nematode infection. To do this Drosophila melanogaster were infected with the EPN Steinernema carpocapsae. Experiments were done using a natural infection assay. Using this method Jennifer is investigating survival rates, melanization and antimicrobial peptide expression in Drosophila larvae that have been exposed to EPNs.
Jennifer would like to thank Dr. Hallem, Dr. Zarate and Dr. Hasson for their mentorship and support. She would also like to thank HHURP, UC LEADS and URC sciences office for the research opportunities they have provided.
| Joon Ha Lee
Mr. Joon Ha Lee
Mentor: ELISSA A HALLEM
Title: Olfactory Plasticity in Entomopathogenic Nematodes
Joon Ha Lee is a third year Neuroscience major and has been working in Dr. Elissa Hallem's lab in the Microbiology, Immunology, and Molecular Genetics department since June 2011. The lab is interested in the neurobiology of olfaction in nematodes, and Joon's project focuses on the effect of environmental conditions on the olfactory preference of entomopathogenic nematodes.
Olfaction is a critical component of host-seeking behavior in parasitic nematodes to locate potential hosts, but little is known about how these parasites respond to olfactory cues and the neurons mediating olfactory response. Entomopathogenic nematodes (EPNs), used as model systems for studying host-seeking behavior, are closely related to human-parasitic nematodes such as Strongyloides stercoralis, and have much potential in agriculture as biocontrol agents for insect pests and disease vectors. Joon's work in the Hallem lab so far has shown that although the infective juveniles of EPNs are developmentally arrested prior to infection of a host, their response to odorants appears to be plastic and influenced by environmental cues such as temperature and time. Joon aims to characterize the environmental condition-dependent changes in EPN olfactory behavior. Furthermore, he plans to identify neurons responsible for olfactory response, and ultimately identify chemosensory genes that are differentially expressed at different cultivation temperatures. This work will provide insight into how environmental conditions can influence behavior and improve EPNs' efficacy as biocontrol agents.
After graduation, Joon plans to pursue a Ph.D. program. He would like to thank Dr. Hallem and everyone in the Hallem lab for their guidance and support. He would also like to thank the Howard Hughes Medical Institute and the Holmes O. and Margaret R. Miller Scholarship for their generous funding and support of his research.
| Ashley Yeon Joo Kim
Mentor: Dr. Hanna K. A. Mikkola
Title: Elucidating the effect of VEGF-A levels during multipotent hematopoietic stem cell development
Ashley is a third year majoring in Molecular, Cell, and Developmental Biology. She has been conducting research in Dr. Mikkola's lab since her freshman year. Her first project investigated c-Met-dependent multipotent labyrinth trophoblast progenitors and their contribution to the hematopoietic microenvironment. Currently, Ashley is studying the differential requirement for the vascular endothelial growth factor (VEGF-A) levels on the development of hematopoietic stem cells (HSC).
A major bottleneck in enabling a broader use of HS transplantation in regenerative medicine is the inability to robustly generate true HSCs in vitro. This challenge can be overcome through a better understanding of the dynamic signaling environment that directs HSC fate during embryogenesis.
The VEGF signaling pathway is widely studied for its vital role in vasculogenesis and angiogenesis. In the embryo, the VEGF receptor Flk-1 is expressed in the mesoderm; the Flk-1+ mesoderm must properly migrate to hemogenic sites in order to establish the hemogenic endothelium, where self-renewing HSCs and lineage-restricted hematopoietic progenitors emerge. Our preliminary data on heterozygous Vegf embryos has suggested that fine-tuning of the level of VEGF-A may be crucial for the specification of multipotent HSC fate. We now aim to investigate the effect of homozygous VEGF deletion on embryonic hematopoiesis in mice models, using conditional gene-targeting strategy to bypass lethality. The comparative analysis of the half and full reductions of VEGF will help elucidate the significance of its proper dosage during multiple hematopoietic waves, and provide insight into a mechanism that dictates the emergence of true HSC.
| Mr. Jacob Borrajo
Mr. Jacob Borrajo
Mentor: Dr. Tatiana Segura
Title: Spatially Controlled Bioactive Signal Incorporation to Guide Stem Cell Fate in Hydrogels
Jacob is a Chemical and Biomolecular Engineering major with a concentration on Bioengineering and is conducting research under the guidance of Dr. Tatiana Segura in the department of Chemical and Biomolecular Engineering. He is interested in engineering biomaterials to direct stem cell differentiation. As stem cell fate can be influenced by bioactive signals in the extracellular matrix (ECM), engineering cell instructive biomaterials that mimic ECMs is of great value to the fields of tissue engineering and regenerative medicine.
Hydrogels are networks of hydrophilic polymer chains that can be used as tissue culture systems that mimic the natural stem cell niche. Because hydrogels have mechanical properties similar to natural tissues and can be functionalized with bioactive signals, hydrogels are promising platforms to direct stem cell differentiation. Jacob aims to develop a hydrogel system which can be spatially functionalized with bioactive signals via departure of protecting photolabile pendant moieties and enzyme-assisted bioconjugation. It is hoped that such a hydrogel system will allow for the photopatterning of complex biochemical patterns and gradients to imitate in vivo cell microenvironments. If spatial control of bioactive signal incorporation is possible in two dimensions with photomasks, then it would be highly desirable to use two-photon excitations in order to have three-dimensional spatial control. Such a hydrogel system would have importance in the fields of tissue engineering and regenerative medicine, as it would present the opportunity to have three-dimensional control of stem cell fate in a three-dimensional culture.
Jacob would like to thank Dr. Tatiana Segura, the Segura group, Howard Hughes Undergraduate Research Program, URC - Sciences, and the support of his family. He would also like to express his reverence towards the elegant and beautiful natural universe.
| Ms. Jennifer Chyu
Ms. Jennifer Chyu
Mentor: Dr. Robb MacLellan
Title: Characterizing the therapeutic potential of induced pluripotent stem cell derived cardiovascular progenitor cells
Jennifer Chyu is a third year Molecular, Cell, and Developmental Biology major with a minor in Biomedical Research who has been in the lab of Dr. Robb MacLellan in the department of cardiology since June 2011. Jennifer is investigating the potential for induced pluripotent stem cell (iPSC)-derived cardiovascular progenitor cells (CPCs) to regenerate the myocardium.
Over a billion adult cardiomyocytes are lost following myocardial infarction (MI). As there is little to no natural mechanism for cardiac regeneration, the MacLellan lab would like to characterize the iPSC-derived CPC, a multipotent cell committed to the cardiac lineage, and its therapeutic potential for cardiac repair following MI.
To do this, MI will be induced in mice and species matched GFP+-iPSCs will be cultured to induce differentiation into CPCs. The cells will then undergo fluorescence-activated cell sorting (FACS) for CPCs. Recovered CPCs are suspended in pro-survival cocktail (PSC; Laflamme, M. et al 2007) with a hyaluronan-heparin-collagen hydrogel that is hypothesized to better support cell survival and engraftment than PSC alone. 21 days after intramyocardial cell transplantation, an echocardiogram will be performed to assess for recovery and normalization of the EF. The hearts will be harvested for immunostaining and confocal imaging to assess the GFP+ cells for engraftment and integration into the healthy myocardium as well as differentiation into cardiomyocytes. Furthermore, we will isolate the GFP+ cardiomyocytes to assess their functionality by patch clamp to confirm that their action potentials are indicative of healthy adult cardiomyocytes.
After graduation, Jennifer plans to pursue a career in academic medicine. She would like to thank Dr. MacLellan and Dr. Ali Nsair for their support of her research endeavors, as well as Dr. Tamara Horwich, Dr. Ira Clark, and the entire MacLellan lab for their advice, guidance, and mentorship.
| Mr. Jaideep Dudani
Mr. Jaideep Dudani
Mentor: Dr. Di Carlo Dino
Funding: HHMI Honorary
Title: High-throughout Cellular Sample Preparation Through Rapid Inertial Solution Exchange (RInSE)
Jaideep Dudani is currently a third year Bioengineering major, Biomedical Research minor working in the Microfluidic Biotechnology lab directed by Professor Di Carlo since March 2010. He has been working on developing a microfluidic system to replicate numerous macroscale lab procedures in a microscale device for increased automation in sample preparation of cell-based assays.
A high-throughput, miniaturized device that can replicate manual procedures has numerous clinical and research applications. For example, single-cell analysis has numerous clinical applications, but there is a lack of adequate measurement tools in a clinical setting. Additionally, tools such as flow cytometers have limited ability for detecting low-affinity interactions and often require numerous preparatory steps. This tool would allow us to automate the steps required upstream of analytical schemes, thereby making cell based diagnostics possible in clinical environments and the study of previously inaccessible kinetic interactions.
IIn this technology, cells and large particles are transferred from the sample solution to an exchange solution and ordered into a single stream due to inertial force phenomenon (the expertise of the Di Carlo laboratory). This can be used upstream of laser interrogation for fluorescent assays and immunophenotyping. Additionally, the ability to rapidly transfer the cells to another solution can be used for kinetic studies of interactions that occur at small timescales. Jaideep and other group members will more heavily explore these applications.
Jaideep intends on pursuing graduate school in the field of Bioengineering, hoping to develop tools of value beyond the bench top. He would like to thank Daniel Gossett, Henry Tse, Professor Di Carlo, and the rest of the Di Carlo lab. Additionally, he would like to express his gratitude towards the Howard Hughes Medical Institute and the URC - Sciences office.
| Ms. Amy Wisdom
Ms. Amy Wisdom
Mentor: Dr. Rhonda Wisdom
Title: understanding mechanisms in central nervous system inflammation and degeneration
Amy Wisdom is a third year Neuroscience major conducting research under the guidance of Dr. Rhonda Voskuhl of the Neurology department. Her current project focuses on understanding mechanisms in central nervous system inflammation and degeneration.
Multiple sclerosis (MS) is an autoimmune disease characterized by demyelination and axonal degeneration and currently does not have an effective treatment. The goal of the Voskuhl lab is to find novel anti-inflammatory and neuroprotective agents to halt the progression of MS. Thus far, two different agents have reached clinical trials in MS patients based on basic research done in the Voskuhl lab.
Estrogen has documented neuroprotective effects in both MS and the mouse model experimental autoimmune encephalomyelitis (EAE), including mitigation of clinical symptoms and attenuation of neurodegeneration and inflammation. These effects are mediated by estrogen receptors α and β. Recently, the Voskuhl lab demonstrated through cell-type gene disruption experiments that the ability of estrogen to prevent inflammation in the central nervous system (CNS) is dependent on ERα. These findings reveal a unique cellular mechanism for estrogen-mediated CNS protective effects by signaling through astrocytes. Further experiments are being conducted to determine the efficacy of a highly selective ERβ ligand in neuroprotection and decreased inflammation, and to establish the mechanism of this treatment. Results of these experiments will be used to translate an estrogen receptor ligand to MS clinical trials.
After graduation, Amy plans to pursue a joint MD/PhD program and continue research in the biomedical sciences. She would like to thank Dr. Voskuhl, her graduate mentor Rory Spence, and the other members of the Voskuhl lab for their guidance and support. She would also like to thank the Howard Hughes Medical Institute for the generous funding and the HHURP staff for their support.
| Mr. David Yao
Mr. David Yao
Mentor: Dr. Yi Yao
Title: determining the role of glial-like cells in common neurological disorders such as Rett Syndrome (RTT)
David Yao is a 3rd year neuroscience major conducting research in the laboratory of Dr. Yi Sun. The Sun Lab studies the molecular and epigenetic mechanisms underlying stem cell dynamics and the cellular changes induced by neuronal activity. David's research focuses on determining the role of glial-like cells in common neurological disorders such as Rett Syndrome (RTT), by modeling them in vitro with stem cells.
RTT, an X-linked Autism Spectrum Disorder, is caused by a mutation in the Methyl CpG binding protein 2 (MeCP2) gene. MeCP2 binds to methylated DNA, modulating transcription by modifying the neighboring chromatin structure. RTT mice harboring mutations in MeCP2 that abrogate its ability to bind methylated DNA develop asymptomatically over a month after birth, until RTT-symptoms suddenly manifest alongside regressive neurodevelopmental potential. These animals die prematurely within 10 weeks of age. Histological pathologies of both post-mortem murine and human RTT brains are significant for decreased density in dendritic arborization and smaller neural nuclei. This, and other evidence suggests that glial cells like astrocytes may be implicated in RTT. To confirm and study their role in the RTT phenotype, we are establishing a protocol for the transdifferentiation of fibroblasts to induced-astrocytes (iAs), and hypothesize that RTT patient fibroblasts that are transdifferentiated into iAs will display a defect in supporting neuronal dendritic growth when cultured onto neurons. Modeling human RTT in vitro using cell culture-based systems and techniques may overcome previous limitations in studying RTT with murine models. Establishing a protocol for the induction of astrocytes from stem cells will also be useful for exploring other neurological disorders that involve glial like cells.
Upon graduating, David aims to apply for the joint M.D/Ph.D Medical Scientist Training Program (MSTP) in preparation for a career in academia. David would like to thank Dr. Yi Sun, the entire Sun Lab, the HHURP, as well as Dr. Ira Clark and Dr. Rafael Romero for their encouragement, advice, and guidance.
| Ms. Mary Youssef
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 fourth 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.