Biology

Student Research

 Maria Akopyan in lab with frog on her shoulder.

Maria Akopyan

Abstract —The processes that generate variation in nature have captured the attention of evolutionary biologists since the time of Darwin. Many studies examine the evolution of diversification in closely related or hybridizing species to understand the process by which new species evolve. However, more closely related divergent populations can provide a unique insight into how diversity evolves in nature. The Neotropical red-eyed treefrog (Agalychnis callidryas) exhibits substantial geographic variation on a relatively small spatial scale within Costa Rica and Panama, including differences in color pattern, body size, and skin peptide composition. Genetic analyses indicate ongoing gene flow among phenotypically differentiated populations, providing the opportunity to describe the patterns and processes that are integral to lineage divergence before isolation becomes complete. First, we tested the extent of behavioral premating isolation among differentiated populations by quantifying differences in male and female courtship signals. Our results show that both male advertisement calls and female behavior vary among populations, and that divergence in male signals is coupled with female preference for the local male phenotype. The interplay between male courtship and female responses may facilitate the evolution of local variants in courtship style, thus accelerating premating isolation via assortative mating. Second, we conducted a study of genomic and phenotypic variation across red-eyed treefrog populations, including a central contact zone. Our results indicate the creation of a distinct hybrid population at the contact zone. Association between geographic and genetic distance coupled with disassociation of genetic and phenotypic divergence indicate strong localized selection with high levels of genetic exchange. This study is one of few to characterize genome-wide divergence in a highly admixed intraspecific lineage, allowing us to describe the genomic architecture of diversification and infer whether evolutionary processes are driving and/or constraining divergence. We contribute to a growing body of knowledge on divergence with genetic exchange: gene flow is a dynamic evolutionary process that can simultaneously act as a creative, diversifying, and homogenizing force.

 

Picture of Sa Kim working in a lab

Sa Kim

Pancreatic ductal adenocarcinoma (PDAC) remains one of few malignancies to have single-digit 5-year survival rates at <7%. This dismal prognosis is due in part to the limited ability of clinicians to make pre-metastatic diagnoses and effectively treat localized tumors. Thus, there is a dire need to improve early detection methods and identify new therapeutic targets for abrogating PDAC progression. Integrin alpha 1 (ITGA1) was of primary interest because its high expression in pancreatic cancer precursor lesions which may provide a path toward earlier diagnoses, while targeting its cell surface function may abrogate tumor-stroma interactions known to exacerbate PDAC. Depleting ITGA1 from PDAC cells revealed that it is required for collagen-induced migration and survival. Notably, collagen/ITGA1 signaling promotes the survival of ALDH1-positive stem-like cells and cooperates with TGFβ to drive gemcitabine resistance. Finally, we report that increased ITGA1 expression in PDAC tissue indicates the presence of epithelial-mesenchymal transition (EMT) and that ITGA1 is required for TGFβ/collagen-induced EMT and metastasis. Our data suggest that ITGA1 is a new biomarker for PDAC initiation and, when targeted, can sensitize tumors to available chemotherapies to suppress the growth of pancreatic tumors at primary and metastatic sites. Advisor: Jonathan Kelber

 

Picture of Dani Amoroso

Dani Amoroso

Dudleya is a genus of succulent plants. Many species are restricted to narrow geographic ranges, and many closely related forms live in differing climates. Previously, the Wilson lab found an intriguing set of correlations among nine Dudleya: rare species tended to be smaller and to rush to reproduction, whereas more widespread species tended to delay reproduction and grow larger vegetatively. Dani Amoroso set out to study whether such correlations might represent evolutionary trends across the genus more broadly. She studied 21 species, growing them at a coastal garden and an inland garden and measuring survival though the summer without water. She was able to solidly reject the characterization of Dudleya evolution as following trends. Climate-of-origin was unrelated to survival though the summer, seed size, and mature plant size. Also, seed size did not predict germination rate. Amoroso found that the niches of the species have diverged as evidenced by differences in survival between close relatives, but divergence has been quite idiosyncratic for the various pairs of close relatives. Quite possibly the previous results were caused by divergence between two or a very few lineages in combination with phylogenetic conservatism. Advisor: Paul Wilson.

 

Maria Akopyan

 

Maria Akopyan in lab with frog on her shoulder.

Maria Akopyan

Abstract —The processes that generate variation in nature have captured the attention of evolutionary biologists since the time of Darwin. Many studies examine the evolution of diversification in closely related or hybridizing species to understand the process by which new species evolve. However, more closely related divergent populations can provide a unique insight into how diversity evolves in nature. The Neotropical red-eyed treefrog (Agalychnis callidryas) exhibits substantial geographic variation on a relatively small spatial scale within Costa Rica and Panama, including differences in color pattern, body size, and skin peptide composition. Genetic analyses indicate ongoing gene flow among phenotypically differentiated populations, providing the opportunity to describe the patterns and processes that are integral to lineage divergence before isolation becomes complete. First, we tested the extent of behavioral premating isolation among differentiated populations by quantifying differences in male and female courtship signals. Our results show that both male advertisement calls and female behavior vary among populations, and that divergence in male signals is coupled with female preference for the local male phenotype. The interplay between male courtship and female responses may facilitate the evolution of local variants in courtship style, thus accelerating premating isolation via assortative mating. Second, we conducted a study of genomic and phenotypic variation across red-eyed treefrog populations, including a central contact zone. Our results indicate the creation of a distinct hybrid population at the contact zone. Association between geographic and genetic distance coupled with disassociation of genetic and phenotypic divergence indicate strong localized selection with high levels of genetic exchange. This study is one of few to characterize genome-wide divergence in a highly admixed intraspecific lineage, allowing us to describe the genomic architecture of diversification and infer whether evolutionary processes are driving and/or constraining divergence. We contribute to a growing body of knowledge on divergence with genetic exchange: gene flow is a dynamic evolutionary process that can simultaneously act as a creative, diversifying, and homogenizing force.

Sa Kim

Pancreatic ductal adenocarcinoma (PDAC) remains one of few malignancies to have single-digit 5-year survival rates at <7%. This dismal prognosis is due in part to the limited ability of clinicians to make pre-metastatic diagnoses and effectively treat localized tumors. Thus, there is a dire need to improve early detection methods and identify new therapeutic targets for abrogating PDAC progression. Integrin alpha 1 (ITGA1) was of primary interest because its high expression in pancreatic cancer precursor lesions which may provide a path toward earlier diagnoses, while targeting its cell surface function may abrogate tumor-stroma interactions known to exacerbate PDAC. Depleting ITGA1 from PDAC cells revealed that it is required for collagen-induced migration and survival. Notably, collagen/ITGA1 signaling promotes the survival of ALDH1-positive stem-like cells and cooperates with TGFβ to drive gemcitabine resistance. Finally, we report that increased ITGA1 expression in PDAC tissue indicates the presence of epithelial-mesenchymal transition (EMT) and that ITGA1 is required for TGFβ/collagen-induced EMT and metastasis. Our data suggest that ITGA1 is a new biomarker for PDAC initiation and, when targeted, can sensitize tumors to available chemotherapies to suppress the growth of pancreatic tumors at primary and metastatic sites.

Dani Amoroso

Dani Amoroso

Dudleya is a genus of succulent plants. Many species are restricted to narrow geographic ranges, and many closely related forms live in differing climates. Previously, the Wilson lab found an intriguing set of correlations among nine Dudleya: rare species tended to be smaller and to rush to reproduction, whereas more widespread species tended to delay reproduction and grow larger vegetatively. Dani Amoroso set out to study whether such correlations might represent evolutionary trends across the genus more broadly. She studied 21 species, growing them at a coastal garden and an inland garden and measuring survival though the summer without water. She was able to solidly reject the characterization of Dudleya evolution as following trends. Climate-of-origin was unrelated to survival though the summer, seed size, and mature plant size. Also, seed size did not predict germination rate. Amoroso found that the niches of the species have diverged as evidenced by differences in survival between close relatives, but divergence has been quite idiosyncratic for the various pairs of close relatives. Quite possibly the previous results were caused by divergence between two or a very few lineages in combination with phylogenetic conservatism. Advisor: Paul Wilson.

Nicholas J. Gutierrez

 

Acoustic mating signals play an important role in sexual selection both for identifying species and assessing potential mates. These same signals can vary due to environment or genetics, but how might they vary across a group of related organisms? Using three sister/related species of Gryllus crickets (Gryllus lineaticeps, G. personatus, and G. sp15/‘G. staccato’), I compared male calling song (a sexually selected signal) across all three species in response to environmental (diet) and genetic (family) sources of variation. While environmental factors did have an effect on some body measurements, it did not have an effect on song traits in any of the three species. However, genetic factors did have an effect on song traits vital to identifying and choosing a mate in a consistent pattern of response across all three species, a comparative first for crickets with the potential for other groups of related organisms.

Cathy Soliva

Cathy Soliva recently earned her Master’s Degree in Biology under the guidance of Dr. Cindy Malone, performing her graduate research in the CSUN-UCLA Bridges to Stem Cell Research Program. Cathy studied endometrial regeneration in the laboratory of Dr. Sanaz Memarzadeh at UCLA. Her hypothesis was that there was one cell type rather than two cell types that were the dual progenitor stem cell for the epithelium and stroma in the endometrium. Her study focused on determining whether a specific subset of human endometrial cells that co-expressed several markers for epithelia and stroma were in fact the stem cells responsible for regenerating the endometrium each month in women. These cells are rare, found in the eutopic endometrium and pelvic washings of women with and without endometriosis. Cathy showed that the cells she isolated produced epithelia and stroma when plated as 10,000 cells and as single cells in in vitro cell culture. She showed that these cells regenerated the correct type of epithelial tissue in an in vivo model. Future aims include isolating progenitors from women with and without endometriosis to see if there is a difference between progenitor cells that cause endometriosis and progenitor cells that do not. Cathy began her doctorate program in Physical Therapy here at CSUN last fall. 

Michelle Mojadidi

Michelle Mojadidi

Michelle Mojadidi defended her Master’s Degree Thesis under the guidance of Dr. Cindy Malone, performing her Graduate research in the CSUN-UCLA Bridges to Stem Cell Research Program in the laboratory of Dr. Don Kohn, MD. Michelle studied Sickle Cell Disease (SCD), a blood disorder characterized by defective hemoglobin (HbS) due to a point mutation in the β-globin chain. This mutation causes the red blood cells to sickle under low oxygen conditions and these misshapen blood cells present a danger because they have a tendency to clump together and block small vessels. The β-like chain (Hb) is expressed throughout ontogeny from different genes, with the switching from fetal hemoglobin (HbF) to adult hemoglobin (HbA) during the first 6 months after birth. If this switch is incomplete, high levels of HbF in adults causes a milder clinical manifestation of SCD than adult SCD. If the fetal HB in SCD patients can be increased, their symptoms of SCD can be decreased for a better quality of life. Michelle’s project centers around the proof of principle of manipulating stem cells to persist in expressing HbF by disrupting a known transcriptional repressor, BCL11A. Knockdown of BCL11A using precise artificially engineered nucleases, for example, zinc finger nucleases (ZFNs), transcription activator like nucleases (TALENs) and clustered regulatory interspaced short palindromic repeats (CRISPRs) is an attractive strategy to reactivate HbF and restore mostly functional erythrocytes in patients suffering from SCD. Michelle’s results indicate that ZFN are efficient in human stem cells for genome engineering to knockdown BCL11A and increase persistence of HbF in stem cells compared to TALENs and CRISPR/Cas9.  Michelle is currently employed as a Lab Manager/Research Technician at UCLA, awaiting news from Medical school waitlists.

 

Armen Gharibi

Armen Gharibi’s thesis research is aimed at identifying novel biomarkers and/or therapeutic targets in pancreatic cancer. Because pancreatic cancer progresses in a symptom-free manner, nearly all patients are diagnosed after the tumor has metastasized to other regions in the body. Therefore, discovering and characterizing new regulators of metastasis holds promise for increasing overall patient survival. Prior to Armen’s arrival in Dr. Kelber’s research group, previous trainees had discovered that integrin alpha 1 (ITGA1) is upregulated in pancreatic cancer. Armen has since made the seminal discovery that ITGA1 is required for a complete TGFb-induced epithelial-mesenchymal transition (EMT) – a reprogramming of cancer cells that is a prerequisite for metastasis. To identify potential mechanisms of ITGA1 action during EMT, Armen scoured online databases of cancer patient gene expression signatures. Notably, he discovered that ITGA1 expression was closely tied to specific TGFb response genes that Dr. Kelber’s group has previously studied. Armen is currently preparing a manuscript on his findings with co-first author Sa La Kim (Kelber lab undergraduate) and they will present a poster of their work at the upcoming 2016 AACR conference in New Orleans – their work will likely be published later this year. Armen’s success is rooted in his extensive understanding of the driving mechanisms behind pancreatic cancer, which is highlighted by his first-author review, Cellular and Molecular Aspects of Pancreatic Cancer, that was published in Acta Histochemica earlier this year.

Armin Hojjat

Armin Hojjat is currently earning his Master’s Degree under the guidance of Dr. Cindy Malone, performing his Graduate research in the CSUN-UCLA Bridges to Stem Cell Research Program. Armin is performing gene expression profiling of cardiac cell types during cardiovascular development in Dr. Ardahali at UCLA. Cardiomyocytes are the major cardiac cell type that make up the adult heart. How cardiac stem cells differentiate and proliferate to from an functional heart during embryonic development is largely unknown. To understand the changes that occur at different stages of cardiac development, transcriptional profiling of cells during their progression from an immature progenitor state to terminally differentiated cardiomyocytes was performed. Using transgenic mice, populations of cardiovascular cells at different stages of development are identified by fluorescent markers and isolated. These double transgenic mice were generated by crossing a floxed reporter with cardiac specific-Cre mice (i.e. where Cre recombinase is under the transcriptional control of the promoter of Mesp1, Nkx2.5, or α-MHC; markers that are predominantly expressed during the development of the cardiovascular system). The fluorescent-marked cells were then isolated at respective embryonic time points that correlate with the expression of Mesp1, Nkx2.5, or α-MHC. Gene expression analyses were performed using RNA-seq to identify candidate genes potentially important in mediating differentiation and development of cardiomyocytes. Armin is currently employed by Dr. Ardahali while he finishes up his Master’s degree at CSUN. 

 

Brian (J.R.) Clark

JR Clark and giant sea bassJ.R. is studying the mating behaviors of giant sea bass (Stereolepis gigas). The giant sea bass is the largest bony fish to inhabit the California kelp forest community. Giants have been targeted for both recreational and commercial fishing since the late 1800s, causing numbers to dwindle to the point that they are now on the IUCN Red List as a critically endangered species. Gill nets near shore have been banned, and line fishing for giants has been limited, so giants are now returning to Southern California waters. Remarkably little is known about the life history and behavior of giant sea bass. J.R.’s research on courtship is revealing when, where, and how mating occurs. At the Wrigley Marine Science Center, J.R. made daily SCUBA observations at the historical spawning aggregation site off Goat Harbor. He conducted surveys of giant density morning, afternoon, and evening, recording behaviors on HD video. Giant sea basswere most abundant at Goat Harbor during the afternoon. J.R. learned to sex the species and observed how courting proceeds when fish are in pairs. Soon, J.R. will be describe spawning both visually and acoustically. A thorough understanding of giant sea bass reproductive behavior is essential for the future management of this recovering endangered species. (Advisor Dr. Larry G. Allen

Malachia Hoover

Malachia Hoover

Malachia Hoover has been working on a project relevant to pancreatic cancer. Pancreatic cancer is the fourth leading cause of cancer-related deaths. Newly diagnosed pancreatic cancer patients on average survive less than a year. Notably, there are virtually no biomarkers to aid in early detection of this disease or in predicting its therapy responsiveness. Identifying and validating such biomarkers is hampered by the fact that researchers have limited access to fresh tumor tissue for screening RNA. Banking fresh-frozen tumor samples has proven very challenging. In contrast, formalin-fixed paraffin-embedded (FFPE) samples are routinely collected by pathologists, and substantial archives of FFPE tissues are linked to clinical data. It would, therefore, be great to develop a method for harvesting high-quality RNA from FFPE samples. To this end we have established a collaboration with Claremont BioSolutions, a company that has recently pioneered nucleic acid extraction. We are testing their new micro-homogenizer on FFPE samples.  Malachia has demonstrated that the addition of micro-homogenization upstream of FFPE RNA extraction significantly improved total RNA yield, purity, and the length of recovered sequences. Our long-term goal is to optimize these methods to gain critical insights into gene signatures that govern pancreatic cancer progression, metastasis, therapy responsiveness, and disease outcome. (Advisor: J. Kelber).

Anasheh Ghazarian

Anasheh GhazarianAnasheh Ghazarian is studying what agents facilitate binding between cells. A variety of lectins facilitate binding. Anasheh added sugars to the mix, and certain of these sugars (most notably D-melezitose) inhibit the binding. In other words, the sugars and the lectins interact. She has studied a variety of sugars at a variety of concentrations. This is part of a series of studies searching for promising therapeutic anti-infectivity and anti-cancer reagent. (Advisor: Steve Oppenheimer)

Megan Agajanian

Megan AgajanianMegan Agajanian is studying breast cancer—how cells from this class of solid tumors divide and move. Previously, the Kelber lab found that the protein PEAK1 was associated with several aspects of human cancer progression and resistance to anti-tumor therapies. Now, Megan is working with breast cancer cells in which she has modified PEAK1 protein levels to test its function in more detail. She has discovered that increased levels of PEAK1 in these cells promotes cell motility/movement—an approximation of cell invasion potential. Her studies have also revealed that PEAK1 mediates transforming growth factor (TGF) signaling and the ability of this class of growth factors to induce a regulated, orderly transition from one cell type to another: PEAK1 promotes a more aggressive cellular phenotype. Megan's results are the first to provide evidence that PEAK1 is involved in TGF signaling in cells. (Advisor: Jonathan Kelber)

Jason Warner

Jason WarnerThe ability to survive freezing temperatures is a severe selective pressure faced by organisms living at high elevations. Many ectothermic vertebrates have adaptations to cope with the challenges imposed by extreme cold, such as the ability to supercool (maintain fluids as fluid below 0° C). Jason Warner is studying cold-hardiness in a group of lizards that live in the Andes. He has measured several cold-hardiness parameters for six species of lizards in the genus Liolaemus, collected along an elevation range from 1550 to 4075 m in northwestern Argentina. Lizards from high elevations have turned out to be more susceptible to ice formation and show a trend to tolerate freezing events of longer duration than their lower elevation relatives. Jason is making his comparisons in the context of the evolutionary tree by which the six lizards are related. On the tree, it seems that the capacity to supercool is conservative rather than convergent. Furthermore, all of Jason's study species were able to supercool to some extent. Thus, the ability to cope with cold temperatures seems ancestral for the lineage as a whole and may have allowed for multiple independent invasions of high elevation by members of the genus. Maybe the geographic distribution of the capacity to withstand freezing is not so much reflective of natural selection in-a-place, as the movement of hearty species to extraordinary elevations. (Advisor: Dr. Robert Espinoza)

Sabrina Uppal

Sabrina UppalSabrina Uppal is using neuronal stem cells in an attempt to repair memory in neurotoxin hippocampal-lesioned rats. She started off by implanting rats with cyclosporine pumps, an immunosupressant, to prevent stem cell implantation rejection. Then she used a neurotoxin to damage the hippocampus of the rats' brains, and a week later she implanted stem cells into the area of damage (live stem cells in a treatment group, and dead stem cells in a control group). Two weeks following stem cell implantation, she conducted a series of memory tests. Sabrina found that live stem cell implantation improved performance in learning and spatial memory tests. Currently, Sabrina is in the process of sectioning the rat brains, and using immunihistochemical staining them for presence of stem cells, degree of their multiplication, differentiation and their phenotypic characteristics they develop in the rat hippocampus. The hippocampus is one of the first areas of the brain damaged by diseases such as Alzheimer's and epilepsy. The results of this study are exciting as they identifies the potential of neuronal stem cells in restoratative therapies for neurodegenerative disorders. (Advisor: Dr. Randy Cohen)

Chris Nosala

Chris NosalaChris Nosala undertook two studies on the implications of small biochemical alterations. (1) Epigenetic mechanisms have been shown to control gene expression and can permanently silence a gene. Chris investigated the role of epigenetic mechanisms in the stage-specific silencing of the gene VpreB. This gene must be expressed and extinguished at specific stages for the healthy development of cells of the immune system. Chris reactivated VpreB after inhibiting epigenetic mechanisms in cells for which VpreB is normally silenced. (2) Chris also explored the effects on substrate specificity of single point mutations in the active site of the enzyme dCK. dCK is the rate limiting step for the salvage of several nucleotides as an alternative to de novo nucleotide synthesis. By making his three mutations, Chris was able to successfully increase dCK’s specificity for the thymidine analog L-FMAU, which is used in medical imaging PET scans. Chris also confirmed previous results that the three mutations can broaden dCK’s specificity for thymidine. Chris begins a Ph.D. program this Fall (2012) at UC Davis. (Advisor: Dr. Cindy Malone, and Chris did the other half of his work through the CSUN-UCLA Bridges stem cell program)

Alissa Luken

Alissa LukenAn evolutionary reversal is when a character state in a derived lineage reverts back to what was previously an ancestral state. Alissa Luken is testing whether reversals drag along inefficiencies as bagage. She is studying geckos. Geckos are descended from ancestrally diurnal lizards, most gecko species are nocturnal, and several gecko lineages have independently reversed to diurnality. Alissa is testing whether reversals to diurnality in geckos are associated with a return to performance levels of typical diurnal lizards or whether their long history of nocturnality has compromised gecko performance. She hypothesized that diurnality in geckos would be associated with higher sprint performance at warmer temperatures (as for typical diurnal lizards) and a decrease in performance at lower temperatures compared to closely related nocturnal geckos. She sprinted 30 gecko species at five temperatures and recorded maximum sprint speed. While 21 of the gecko species had typical performance curves (i.e., slow sprints at the low and at high body temperature and fast sprints at intermediate body temperature), two species had performance curves that continued to increase with temperature, two species had curves that increased initially and then reached a plateau, and five species had wavey curves. So far, she has found no difference in temperature-dependent sprint speed between the nocturnal and diurnal geckos; more data are to be analyzed soon. (Advisor: Dr. Robert Espinoza)

Lynnea Waters

Lynnea WatersLynnea Waters just graduated with a B.S. in Molecular and Cellular Biology. While at CSUN, she studied regulation of genes implicated in Mantle Cell Lymphoma. Specifically, she studied the promoter region of NcoA4, a transcriptional co-regulator that binds to certain transcription factors. NcoA4 exists as two alternatively spliced isoforms (alpha or beta). Differential expression of NcoA4 has been associated with many cancers. In prostate cancer, the beta form increases proliferation, whereas the alpha form suppresses proliferation. Lynnea started with a bioinformatic search in which she identified putative transcription factor binding sites. She found the NcoA4 putative promoter region to be 42% identical and 57% conserved among humans and rodents. Next, the putative 1332 bp NcoA4 promoter region was amplified by PCR, subcloned into a cloning vector, and then directionally subcloned into a reporter vector. Transient transfection showed a 40% increase in transcriptional activity of the 1332 bp putative NcoA4 promoter region over a no-promoter control vector. Finally, a deletion series of the NcoA4 putative promoter region was constructed by restriction digest and re-ligation using both endogenous and created restriction sites to test successively smaller constructs by transient transfection. Significant differences in transcriptional activity among the promoter deletion constructs identified the core promoter fragment. Lynnea is entering a Ph.D. program this Fall (2012) at UCLA. (Advisor: Dr. Cindy Malone)

Angelica Zavala Lopez

Angelica Zavala LopezAngelica Zavala Lopez is studying the effect of a warming climate on flatworms in Carpinteria Salt Marsh. Her flatworms are parasites with a complex life cycle moving from snail hosts to fish hosts to bird hosts and back to snails. Angelica has found that a little bit of warming makes the parasite emerge from the snail faster than normal but more warming tends to halt emergence. After the parasites have emerged and are free-living, their survival is also temperature dependent, with an intermediate optimal temperature bracketed by temperatures that are too cool or too hot. Finally, the probability that a parasite will be able to infect a fish is also temperature dependent. Angelica is studying three species of flatworms. She hypothesizes that the three have different responses to temperature, so if the salt marsh warms, the composition of the parasite community will change correspondingly. (Advisor: Dr. Cheryl Hogue)

Tannaz Faal

Roo WisidagamaTannaz Faal recently earned her M.S. She studied Glioblastoma Multiforme (GBM), a type of brain cancer. Previously, GBM had been broken down into four distinct types that differ from each other based on unique genetic mutations, rate of tumor growth, and response to treatment. Some cancer cells have stem-cell properties such as the ability to give rise to multiple cell types and the maintenance of self-renewal. It is believed that the GBM cancer cell population is resistant to radiation and the chemotherapy drug TMZ. TMZ eradicates cells by alkylating their DNA. Working with patient-derived GBM stem-like cell cultures, Tannaz showed that the cultures separate into different response groups. Additionally, Tannaz also show that expression of the DNA repair enzyme MGMT, which removes TMZ induced DNA alkylation, infers GBM culture resistance to TMZ. Tannaz successfully identified groups of her GBM cultures that differ from each other based on their response to treatment. These data will be used in classify cultures into one of the four GBM subgroups. Additionally, identifying the cell type of origin for GBM will also provide important insight on how to combat this cancer to develop more targeted cancer therapy. Tannaz began a Ph.D. program this fall (2012) at the UC Irvine. (Advisor: Dr. Cindy Malone through the CSUN-UCLA Bridges stem cell program)

Roo Wisidagama

Roo WisidagamaHypoxia (5% oxygen) stimulates embryonic stem-cell self renewal. Others have shown that hypoxia inducible factor 2 alpha (HIF2alpha) up regulates OCT4, a gene associated with pluripotency, and also increases the efficiency of reprogramming differentiated cells. These results suggest that hypoxia might impair the differentiation of stem cells. However, Roo Wisidagama's research shows HIF1alpha expression promotes stem-cell differentiation. Knocking down expression of HIF1alpha or its binding partner, aryl hydrocarbon receptor nuclear translocator (ARNT), inhibits the early induction of five genes involved in differentiation. Knocking down HIF1alpha or ARNT also impaired embryo formation. Conversely, Roo found that expression of a stabilized HIF1alpha (in 21% oxygen) leads to enhanced developmental gene induction. Combined, her data show a previously unanticipated role for HIF1alpha in promoting early stem-cell differentiation in hypoxia. (Advisor: Dr. Cindy Malone through the CSUN-UCLA Bridges stem cell program)

Kristina Stott

Kristina StottCaulobacter crescentus' beta-ketoacyl ACP synthase FabH is essential for growth and division. Therefore, Kristina Stott is studying DNA replication regulation in a FabH mutant. Kristina hypothesized that the inability of Caulobacter to produce de novo fatty acids induces a starvation condition that leads to the activation of SpoT. SpoT is a regulatory enzyme that synthesizes the alarmone ppGpp, which orchestrates an appropriate transcriptional response to survive starvation. She has found that, when blocking de novo fatty acid biosynthesis, the transcription or accumulation of cell cycle master regulators that regulate DNA replication are altered in a SpoT-dependent manner. Understanding how lipid biosynthesis integrates with the control of the cell cycle master regulators will be an important addition to our understanding of cell cycle progression. Furthermore, understanding more about how bacteria replicate may reveal novel antibiotic targets. (Advisor: Dr. Sean Murray)

Brooke Van Kummer

Brooke Van KummerBrooke Van Kummer is studying the effects of aerobic exercise on a mutant strain of rat that suffers from ataxic symptoms; kind of like the resting tremor and rigidity associated with Parkinson’s disease. She and co-workers have found that moderate treadmill exercise reduces brain cell degeneration, delays motor dysfunction, and increases the rat’s lifespan. Recently, Brooke hypothesized that since a protein called Brain-Derived Neurotrophic Factor (BDNF) is known to be important in neuronal cell survival and growth, inhibiting the action of this protein by targeting the receptor it uses (TrkB) to exert its effects ought to counter the exercise-induced neuroprotection previously found. She took mutant rats and administered the drug K252a, a known receptor activity inhibitor, or she administered a control solution. The rats were then placed on a regimen of exercise. Mutant rats receiving K252a exhibited significant declines in motor function, and examination of the brain revealed decreases in cell survival. The successful blocking of the protective effect of exercise using K252a suggests that the neuroprotective benefits of exercise directly affect a signal cascade involving the TrkB receptor. (Advisor: Dr. Randy Cohen)

Lena Ayala Coleman

Lena Ayala ColemanLena Ayala Coleman is studying a grand transect of 3000 m in elevation in Sequoia National Park in terms of the community composition of the mosses. Mosses have a very different underlying biology than vascular plants. For example, mosses are able to dry out and become dormant during the summer drought of lowland California. Because of their distinctive biology, Lena does not expect moss niche relations to be similar to those of vascular plants. She has been finding that for mosses that occur in dry sites there is greater species richness down low than in the high country, whereas for mosses that occur in wet sites the reverse pattern is being found. Another results is that certain families of mosses (Pottiaceae) are very important in the lowlands, whereas other famiies (Mniaceae) are very important at higher elevations. Reproductive strategies also change. Most of the species with specialized asexual diaspores that are green occur at intermediate elevations in the Giant Sequoia zone. (Advisor: Dr. Paul Wilson)

Anya Brown

Anya BrownCoral reefs around the world are in danger of changing from being dominated by corals to being dominated by algae. It is said that the algae outcompete the coral; however, the mechanisms of this interaction are unknown. Several hypotheses purport to explain how algae outcompete corals. (1) Possibly physical abrasion occurs when an alga rubs up against a coral and scrapes off tissue. (2) Possibility algae release noxious chemicals. (3) Or possibly algae release photosynthates that allow microbes to grow and they in turn alter the oxygen available to a coral. Anya Brown is studying how the physical force of water flow may influence the mechanism of competition and thereby the outcome of interactions between corals and algae. She has been comparing microhabitats with lower and higher water flow. In lower flow conditions, where water and chemicals are retained longer, algal turf wins more often than in higher flow conditions where chemicals are flushed away more quickly. Anya’s next steps will be to identify how the oxygen microenvironment changes in different flow speeds by placing coral-algal interactions within a flume and measuring oxygen concentrations with a miniature oxygen probe designed specifically for this purpose. Only by understanding the mechanism and what factors influence the mechanisms of competition will we be able predict what the reefs of the future will look like. (Advisor: Dr. Robert Carpenter)

Denita Weeks

Denita WeeksDenita Weeks studies the thermal biology of the world’s southernmost gecko, Homonota darwinii. Environmental temperature plays an important factor in the life of all organisms. In ectotherms, environmental temperature is a key component to regulating body temperature. This limits the geographic distribution of ectoterhmic species. Traditionally, geckos are known to live in warm tropical climates. Yet, H. darwinii is a nocturnal gecko that occurs across a wide distribution of Argentina, exposing it to climates ranging from warm to very cool. Denita’s study aims to synthesize physiological measurements with climatic information to characterize the current distribution and activity time for H. darwinii. Ultimately, she will use temperature predictions for the year 2100 to show how climate change could affect geographic distribution. Early data suggest that this species differs in performance ability and thermal tolerances across its distribution indicating potential shifts in distribution and activity time following climate change. (Advisor: Dr. Robert Espinoza)

Joshua Shipp

Joshua ShippJoshua Shipp studies heterospecific communication, especially communication between birds and mammals regarding predation risk. His study system is the California ground squirrel (Spermophilus beecheyi) and four co-occurring species of birds; Joshua is interested in how squirrels react to alarm and song calls from these four species. Field playbacks of bird call recordings have been carried out at two different locations near the Loma Linda Hills in Southern California. Results so far suggest that squirrels do indeed respond to the bird alarm calls with increased vigilance, while song calls do not provoke this same response. These results, including the possibility that song calls actually calm squirrels by representing an absence of predation risk, are an important addition to the relatively new and unexplored realm of bird-mammal communication. (Advisor: Dr. Tim Karels)

Maggie Johnson

Maggie JohnsonMaggie Johnson is interested in understanding how higher concentrations of carbon dioxide in the ocean will affect growth of an important species of alga in tropical coral-reef ecosystems. Crustose coralline algae (CCA) are calcified encrusting algae that serve important ecosystem functions in coral reefs. Maggie studies how ocean acidification affects growth and calcification of one important reef building species of CCA, Hydrolithon onkodes. Her research is being done in Moorea, southern Taiwan, and Hawaii, where she has found that higher concentrations of CO2 decrease growth rates of H. onkodes. Maggie is also investigating how slower rates of CCA growth and calcification under ocean acidification conditions translate into susceptibility to grazing by herbivorous sea urchins. Maggie’s research will shed light on the consequences of carbon dioxide emissions for tropical coral reef ecosystems, and provide insight into how community composition of coral reefs may change in the coming decades. (Advisor: Dr. Robert Carpenter)

Estenia Haley

Estenia HaleyEstenia Haley is studying mating behaviors of the camel cricket Pristoceuthophilus marmaratus. Camel crickets have some interesting special features. The males have a big bend in the hind tibia, two spines on the hind femur, and tubercules on the upper dorsal region of the abdomen. There has been no previously published work on behavior in the genus Pristocethaphilus or on the functions of the males’ special features. Estenia’s observations have shown that males use their hind legs to fight other males. They also use their legs to coerce females during mating, but it seems they are more likely to coerce previously mated females compared to virgin ones. In field crickets, males attract potential mates acoustically, by using their wings to make chirping sounds. Camel crickets do not have wings, so how do they attract their potential mates? Estenia’s study suggests that the males use the tubercules to release chemical cues to attract females. These results inform the study of male-male competition and conflict between males and females over mating. (Advisor Dr. Dave Gray)

Jocelyn Holt

Jocelyn HoltJocelyn Holt is studying the endangered species Pentachaeta lyonii. As its population declines and has either low density or stray individuals not in a patch of flowers, do pollinator services also decline? Is the species in danger of imploding upon itself reproductively? Jocelyn has measured pollinator visitation and seed production in plants growing in patches of varying density and on plants in pots deployed at varying densities from a natural patch. So far, the pollination news is mostly good. The plants seem to be well served by pollinators, and the flowers appeal broadly to many species of bees and flies in the community. Probably other factors, such as competition from alien grasses, are more responsible for declines in this endangered's species reproductive output. (Advisors: Drs. Paul Wilson, Christy Brigham)

Carly Ryan

Carly (Wil) RyanCarly Ryan works with the encrusting, colonial hydrozoan Hydractinia to study the evolution of phenotypic plasticity, that is, the ability for a genotype to produce more than one phenotype across different environments. These animals occur exclusively on the shells of hermit crabs in the intertidal mudflats of the eastern United States and have been used previously as a model system for understanding the development of animal vascular systems. Through experiments in the lab and at field sites across the Gulf of Maine Carly has found that changes in the environment can alter how these individuals grow—either arranging their vascular tissue as a continuous sheet or as discrete branches. These different growth forms can have wide-ranging consequences on various ecologically important traits like growth rate, metabolic efficiency, and competitive ability. Since an individual can only express one phenotype at a time, there is a complicated balance between responding morphologically to one environmental signal, like reduced oxygen, and maintaining a phenotype that is also adaptive for feeding, competing, and the colony's other concerns. Carly's work focuses on understanding how these selective forces interact to maintain a diversity of colony forms within populations. (Advisor: Dr. Steve Dudgeon)

Nicholas Colvard

Nicholas ColvardNicholas Colvard studies the photophysiological and growth response of scleractinian coral to their light microenvironment. As coral cover is declining on tropical reefs, largely from thermal stresses causing bleaching events and ocean acidification degrading reef structure, macroalgae has been preempting the newly available space on the benthos. These changes in macroalgae cover over the benthos influence the spectral composition of the light microenvironments around scleractinian corals. However, little is known of the interaction this macroalgae has on the light harvesting efficiency for the corals that persist through these pressures. Colvard completed two field studies, one in Moorea, and one in southern Taiwan in the spring and summer of 2009. He found there is a difference in the spectral composition of the light environment on a heavily grazed surface compared to a substratum dominated by macroalgae. This difference in spectral quality of the benthos had a significant influence on the photophysiological response of corals incubated on artificial surfaces mimicking these environments. These findings will help scientists to better understand how corals response to the changing environment around them, as well as help to forecast the future state of tropical reefs with the threat of climate change. (Advisor: Dr. Peter J. Edmunds)

Chris Bowman-Prideaux

Chris Bowman-PrideauxChris Bowman-Prideaux is studying the population ecology of the federally endangered plant, Braunton’s milkvetch (Astragalus brauntonii). The greatest threat to this plant is habitat fragmentation and loss due to land-use changes. This plant is found in isolated populations that vary in distance with some populations isolated by more than 31 miles to the nearest known population. Bowman-Prideaux has conducted a demography study examining both vegetative and reproductive characteristics of six populations and found evidence of phenotypic differences between populations. He is currently conducting common-garden and reciprocal-transplant experiments to see if these differences are the result of plasticity or genetic divergence among the populations. This research will help to better understand this species and how to effectively manage those populations. (Advisor: Dr. Paula Schiffman)

Stella Swanson

Stella SwansonStella Swanson’s research is on sea urchins on the coral reefs of Moorea, French Polynesia. By controlling the growth of macroalgae, a known competitor for space and sunlight with corals, certain species of sea urchins can maintain a healthy coral reef. There are five main species of sea urchins that live on Moorean reefs, and her research is focused on determining the relative importance of each for maintaining the coral reef. It appears that there is a gradation of importance in terms of herbivory. Those species belonging to the family Diadematidaceae seem to be the most influential, grazing heavily at distances of meters from their holes. Other species such as Echinometra mathaei and Echinostrephus aciculatus are largely confined in their influence to the area within and in close proximity to their burrows. This research has broader implications in the development of management plans, which will be important tools in protecting delicate coral reef ecosystems. (Advisor Dr. Robert Carpenter)

Wyndee Haley

Wyndee HaleyWyndee Haley is interested in ethology and in birds. Her supervisor works on flowers. So, she is doing her thesis on hummingbird foraging decisions. The thesis is motivated by the phenomenon that flowers adapted to hummingbird pollination have a consistent suite of characters, including the production of copious but dilute nectar, red colors, and lower lips that are small or folded out of the way. Hypotheses have long come to mind explaining this phenomenon, but past tests of those hypotheses have failed to substantiated them. For example, hummingbirds visiting feeders have a strong preference for concentrated nectar, not dilute nectar. Wyndee has constructed arrays of artificial flowers that more closely resemble real flowers (like those of Penstemon). This is allowing her to test those hypotheses under more natural yet experimental conditions. Wyndee hopes that her results can be discussed along with those from similar experiments on bee behavior. (Supervisor: Dr. Paul Wilson)

Dawn Bailey

Dawn BaileyDawn Bailey's research focuses on the importance of predators on populations of fish within Marine Protected Areas (MPAs). She is investigating whether an accumulation of large predatory fish in MPAs causes increased mortality among juveniles, and smaller fishes, and thus alters the size structure of fish communities. Dawn works in the kelp forest communities of southern California (primarily at Catalina Island), focusing on the dominant fish-eating predator, the kelp bass (Paralabrax clathratus). Her investigation so far suggests that fish communities inside the MPA are distinguishable from those outside the MPA by the presence of both large predatory species and disproportionately few individuals of small species and size classes. The goal of Dawn's research is to provide a basis for more realistic predictions of how MPAs may affect marine fish communities. (Advisor: Dr. Mark Steele)

Ann Dorsey

Ann DorseyAnn Dorsey is comparing the physiological ecology of nine races of Dudleya (right photo), a genus that has radiated into a large number of species in southern California. Some of the forms Ann is studying are listed as endangered species and are restricted to a few coastal sites, whereas others are common at many local sites. The races differ in life-history traits such as the propensity to flower the first year (rare ones) or to grow large before flowering (common ones). Ann is going on to test for differences in photosynthesis and growth through the seasons at inland and coastal sites and depending on whether she provides supplemental watering or not. (Supervisor: Dr. Paul Wilson)

Chris Chabot

Chris ChabotChris Chabot employs genetic markers to determine the level of connectivity among globally distributed populations of the tope (Galeorhinus galeus) (right photo)- a medium sized shark listed as vulnerable by the IUCN. Until recently (1946-1994), California tope populations were considered to be declining due to historic overfishing. However, more recent observations indicate that populations appear to be rebounding, but with no clear indication as to the source of new individuals (local populations vs. distant populations). In order to answer this question, Chris compared tope DNA from Argentina, Australia, California, Peru, South Africa, and the U.K.. His research has shown that tope populations are not connected, therefore increasing numbers off of the California coast must be due to local population growth and not migrants from distant populations. (Supervisor: Dr. Larry Allen)

Lut Hang (Alex) Li

Lut Hang (Alex) LiLut Hang (Alex) Li is studying the effects of pocket gopher (Thomomys bottae) disturbances on grassland community composition in Santa Monica Mountains National Recreation Area. He is testing the hypothesis that there is a link between the timing and density of soil disturbance and the relative abundances of native and invasive non-native plants. Alex is simulating gopher disturbance (right photo) at different times and intensities using a soil auger (left photo). He then monitors the changes in plant species composition within his disturbed plots and compares them with undisturbed controls. The results of Alex’s study will add to our understanding of how a grassland’s natural disturbance regime can facilitate the persistence of disturbance-adapted invasive annual plants. (Advisor: Dr. Paula M. Schiffman)

Tarja Sagar

Tarja SagaTarja Sagar is studying the niches of mosses (right photo) in the Santa Monica Mountains. First, she developed an identification guide to the 112 species. Then, she compared the species' microhabitat preferences and the assemblages that occur in various sites across the Mountains. Now, she is relating that information to biogeographic ranges. As part of our partnership with the Santa Monica Mountains National Recreation Area, she is also employed by the Park - she monitors rare vascular plants as her day-job. (Advisor: Paul Wilson)

Hollie Putnam

Hollie PutnamHollie Putnam is investigating the effects of changes in ocean temperature on coral physiology. Most of her research takes place on the island of Moorea, French Polynesia (near Tahiti), where she is conducting manipulative experiments to test the effects of daily fluctuations in temperature on common reef corals. The other portion of Hollie’s research takes place in St. John (United States Virgin Islands) and Taiwan, where she is examining the effects of thermal microclimates and fluctuating temperature on corals of different species and life stage. Hollie’s research investigates the response of corals to thermal stressors, which are a critical aspect of coral bleaching, especially in light of global climate change. (Advisor: Dr. Pete Edmunds)

Jolene Pucci

Jolene PucciJolene Pucci has been studying the effects of invasive plants on a native endangered sunflower, Pentachaeta lyonii (right photo) in the Santa Monica Mountains near Los Angeles, California in association with the National Park Service. She designed and implemented field experiments to test her hypothesis that invasive plants are a cause of population declines in this endangered plant. Jolene found that three non-native plant groups reduce P. lyonii’s reproductive potential. She also demonstrated that habitat manipulations improved conditions for P. lyonii persistence. Jolene’s research provides a significant contribution for making science-based management decisions for recovery of the species. (Advisor: Paula Schiffman)

Stephanie Talmage

Stephanie TalmageStephanie Talmage conducts her research on a brown algal species, Sargassum mangarevense, in Moorea, French Polynesia. Her work addresses how water motion and herbivory can alter the distribution and responses of a tropical macroalgal species in a coral reef environment. Stephanie’s research suggests that this seaweed allocates resources differentially across abiotic and biotic gradients, and that trade-offs between algal life functions fluctuate across reef habitats. (Advisor: Bob Carpenter)

Joanne Moriarty

Joanne MoriartyJoanne Moriarty is investigating reproduction in bobcats living among the small remnants of habitat within the suburban sprawl of Los Angeles. As in many US cities, rapid growth has destroyed, fragmented and pocketed much of the natural habitat, and bobcats in these areas now face many new obstacles. In partnership with the Santa Monica Mountains National Recreation Area, Joanne is measuring female home range selection and survival of kittens, to determine if bobcat populations are viable in this increasingly fragmented landscape. (Advisors: Paul Wilson and Ray Sauvajot)