Alumni RMI Scholars

Rocio’s project that examined the role of a planar cell polarity protein during mammary gland development. As a core planar cell polarity (PCP) protein, Vangl2 functions in uniformly orienting cells in a sheet of epithelium. One way PCP proteins such as Vangl2 accomplish this regulation is by aligning each cell’s cilia.  Rocio will evaluate whether Vangl2 functions in this manner in the breast. In order to investigate this question, Rocio is working to improve the staining of the primary marker for cilia, acetylated tubulin, by testing different dilutions of the antibody. Once this is completed, she will stain 5 week wild type (WT) tissue with Vangl2 and acetylated tubulin and look for co-localization. She will also compare cilia positioning in WT and Vangl2 knockout (KO) tissue.

Alex is currently designing and engineering a device that will simplify the immobilization of specific receptor molecules on a magnetic chip. The magnetic chip’s system is based on GMR (Giant Magnetic Sensor), and with the help of paramagnetic nanobeads, one can detect the presence of a specific protein/molecule. Ideally, we would test and detect multiplex proteins on a single chip by transferring a solution to a specific region on the sensor array. However, the current method is rather challenging and inefficient. With the help of this device, researchers will be able to detect multiplex proteins more efficiently and accurately. Read about Alex’s project at the Harvard-MIT Broad Institute Summer Research Program in Genomics. View Alex’s ISMB 2014 Poster presentation Investigating large sequence variants in drug resistant Mycobacterium tuberculosis

She also explored the issues of DNA ownership and genetic privacy. In the age of computers, she looked at legislative solutions to the question “do we want the government to have our genome?”

Ochoa worked on mammary gland development, with the aim of understanding the biology of breast cancer. One in 10 women develop breast cancer during their lifetime, making it one of the leading cancer-related deaths of women in the western world.

In her first paper, “Genetic modification and  egalitarianism: distinguish and distribute,” Lopez illustrated the difference between “preventative” gene therapy and “enhancement” gene therapy. She described the threat genetic engineering poses in a society with an unequal distribution of health care. In her second paper, “Three types of cloning and the necessity to regulate,” Lopez defined and evaluated DNA cloning, reproductive cloning, and therapeutic cloning. She referred to current legislation in the US and examines the results of the California Advisory Committee of Human Cloning.

Tekeste worked to understand a critical step in the process where information in DNA is read and then used in cells. The step is called pre-mRNA splicing, and errors in this process are responsible for a large number of human genetic diseases. Shewit focused on the structural analysis of an early phase of the spliceosome, called E complex.

In his first paper, “Future consequences for potential persons and our parental obligations regarding human germline engineering,” Rojas argued for the therapeutic use of genetic engineering while evaluating a broad range of possible applications and concerns. In this paper he examined parents’ responsibilities to their children in an age of germline engineering. In his second paper, “Somatic cell gene therapy: a leap in technology and reassessment of values,” Rojas compared somatic cell gene therapy with traditional medicine in order to dispel fears and examine the present values and definitions of “healthy.”

Arciniega studied sea otters, Enhydra lutris ssp, known as a “keystone species” because they have a strong influence on diversity of near-shore marine communities. Unfortunately, sea otters were hunted almost to extinction and population sizes have dramatically decreased in the past 50 years. Information about the amount and distribution of genetic variation is vital for implementing effective conservation efforts. Martha’s project involves adding variable markers to the microsatellites already in use for sea otters. Microsatellites–DNA sequences that include tandem-repeated base pairs–are used to determine the relatedness between individuals and among populations. Microsatellites can provide information about population history, genetic drift, mate choice and migration. This project will provide enough statistical power to reconstruct pedigrees and investigate levels of differentiation between otter populations in California, Alaska and Russia. The pedigrees will show the lineages of sea otters that are closely related or part of the same family. A more complete knowledge regarding otter pedigrees will help marine scientists understand patterns of dispersal as well as past historical demography. 

In Fall 2015 and Winter 2016, she worked on a project, “Parallel  evolution & adaptive genomics of the steelhead summer ‘ecotype’ in multiple populations in Oregon and California.

Dicochea examined how architectural modifications to a general purpose processor design can increase the computational performance of current genome sequencing algorithms. Scientific applications such as those necessary in the genomic sciences are heavily data parallel. Thus, the issues addressed in the design of a CPU for scientific applications must take into account additional parameters above what is specified for a general purpose processor. Rigo’s research project seeks to explore those parameters. His goal is the design and fabrication of a microprocessor architecture aimed at providing very high computational performance on very large genomic data sets. He also hopes to introduce a new suite of benchmarks to the computer architecture community that will enable researchers to quantify the performance of genomic applications on their processor designs.

Pamela studies a key component of the molecular mechanism whereby arsenic, a naturally occurring toxic metal, leaches into drinking water aquifers. Arsenic contaminated drinking water is tasteless and odorless, and therefore hard to detect. Arsenic gets into the natural water system because in natural sediments low in oxygen and rich in arsenic and carbon, microbes generate energy by reducing arsenic instead of oxygen during cellular respiration. The reduced form of arsenic is water soluble, and thus can seep into drinking water aquifers. Pamela’s research aims at understanding exactly which aspects of microbial respiration impact the mobilization of this toxin.

All three human pathogenic Yersinia species, Y. pseudotuberculosis, Y. enterocolitica, and Y. pestis utilize a needle-like apparatus called a type three secretion system (T3SS) that is required for virulence. The T3SS forms a pore in the membrane of host cells and injects Yersinia effector proteins into the host cell cytoplasm. Once inside the host cell, these effector proteins disrupt the host immune response to Yersinia infection. YopD is a T3SS translocator protein involved in the post-transcriptional regulation of yop synthesis and pore formation in host cell membranes, both of which are directly linked to the effective translocation of effector proteins into the host cell cytosol. Groups have identified and described several discrete functional domains on YopD that are involved in chaperone binding, membrane interactions, and the translocation of Yersinia effector proteins. Despite these efforts, the central region of YopD between amino acids 150-227 (YopD150-227) remains largely uncharacterized. Walter’s research aims to identify the role that YopD150-227 plays in Yersinia pseudotuberculosis infection. Understanding the function of this domain will generate a more comprehensive picture of YopD in the context of Yersinia virulence and host-pathogen interactions.

Through his unique, interdisciplinary research, Geralde developed new nanopore-based technology for sequencing DNA and RNA. He focused on addressing weaknesses in current alpha-hemolysin-based sensor technology developed at UCSC to improve its effectiveness. You can read about his research in a 2011 paper that he co-authored with other members of his research team: “Distinct complexes of DNA polymerase I (Klenow fragment) for base and sugar discrimination during nucleotide substrate selection”. Garalde received his Ph.D. in 2011 and now works as a research scientist at Oxford Nanopore Technologies in Oxford, UK.

Lares studied a novel RNA gene occurring in a segment of the human genome that has evolved with surprising rapidity between the chimpanzee and the human genomes. She used x-ray crystallography to investigate the structure and possible function of this RNA gene.

Dassah worked on the mechanism for pre-mRNA splicing. Almost all higher eukaryotic mRNA molecules give correct genetic information only after the introns (non-coding regions) are spliced out of the RNA and the exons (protein-coding regions) are joined in the cell nucleus. Many heredetary diseases are caused by disorders in the splicing process.

Tissues are distinctly engineered to carry out a given function. The breast (or murine mammary gland) is an example of this, forming a network of bi-layered ducts that terminate in alveoli formed during pregnancy. These specialized structures have an outer layer of myoepithelial cells that will contract during lactation to squeeze milk from an inner layer of polarized epithelial cells. In order to generate this system of ducts, the mammary gland undergoes growth by branching; therefore, mechanisms involved in branch formation define mammary architecture. Diseases, such as breast cancer, often result in highly unorganized tissues; therefore, understanding the genes that regulate the overall architecture of the mammary gland could aid in understanding breast cancer pathology and identify potential therapeutic targets. Recent studies have identified genes involved in establishing proximal-distal (planar) polarity in epithelial cells as regulators of branching morphogenesis, however the mechanism of their action is currently unknown. Prestina’s project aims to understand how the core planar cell polarity (PCP) gene Vangl2 regulates branching in the mammary gland by investigating changes in mammary morphology in Vangl2 mutant mice, identifying regulators of Vangl2 and determining how VANGL2 cooperates with other PCP proteins to promote mammary development. Smith’s studies will provide insight into the mechanisms that function to establish the architecture of the mammary gland and elucidate a novel role for planar cell polarity in tissue morphogenesis.

Soriano worked on developing a program to evaluate the output of various computer algorithms for predicting local protein structure.

Richard’s research focuses on how early life manganese exposure disrupts DNA methylation patterns in dopamine receptor genes, which alters prefrontal cortex dopamine function and ultimately leads to deficits in attention. He aims to determine the mechanistic basis for how oxidative stress may alter a gene’s DNA methylation “blueprint” to cause altered protein expression. These DNA changes can be heritable, and this mechanism can span a wide range of fields such as environmental toxicology, nature, and nutrition.

Margarita utilized photoactive metal complexes that deliver nitric oxide (NO) to DNA bases and eventually to selected oligonucleotides. Because DNA damage is a hallmark of programmed cell death or apoptosis, their group is interested in the interaction between NO and other reactive nitrogen species with specific nucleobases. She uses HPLC techniques and UV-Vis spectroscopy in characterizing the initial products of NO-mediated DNA damage.

In the spring of 2011 she published a paper on an additional research project that investigated the physiological roles of carbon monoxide (CO) in neurotransmission,vasorelaxation, and cytoprotective activities.
Inorganic Chemistry 2011, 50(7), 3127-3134. Link: https://doi.org/10.1021/ic2000848

Update: In August of 2013, Margaria completed all the requirements of her graduate research training and filed her dissertation. Congratulations, Dr. Gonzales!

Hector’s research focused on developing therapeutic strategies for diagnosing and treating breast cancer.

Update: Hector received his Ph.D. in 2010 and is currently a post doctoral researcher in the Michael German lab at the University of California, San Francisco. The German lab is interested in identifying genetic factors that influence diabetes by identifyingthe genes that regulate the transition of stem cells to mature pancreatic beta-cells. Pancreatic beta-cells are the body’s sole provider of insulin. By understanding the role of these factors inbeta-cell production the German research team is developing novel strategies for curing diabetes. Congratulations, Dr. Macias! We look forward to your future contributions to biomedical science.

With Carol Rohl, Samayoa worked to expand and improve modeling methods for predicting 3-dimensional protein structure. The project is called, “Homology-based modeling with Rosetta and NMR data.” He then participated in an interdisciplinary projects with advisors Kevin Karplus and Fitnat Yildiz: “A bioinformatic analysis of simple repeats and small proteins in Vibrio cholerae El Tor.”

Olano worked on developing an immunoassay for prostate-specific antigen and also designing a biomarker using quantum dots for detecting ovarian cancer. Both assays employed a spectrophotometric technique called surface-enhanced Raman scattering (SERS).

The ion channel is used to capture and examine one molecule of DNA at a time. The interaction of double-stranded DNA or single-stranded DNA with the channel can readily be observed via changes in an electrical current through the channel. De Guzman observes and studies double-stranded-DNA ends fraying and reforming in a channel—an important step in biological processes. In HIV infection, for example, DNA fraying is necessary for HIV DNA to be spliced into human host DNA.

LEARN MORE about the Nanopore Project at UC Santa Cruz

Andrew uses the nematode C. elegans as a model to study the role of the SUMOylation pathway in preventing somatic cells (e.g., muscle, neurons, intestine) from acquiring germ cell (eggs and sperm) characteristics. Germ cells and somatic cells are fundamentally different: while somatic cells are differentiated and mortal, germ cells retain the ability to develop into any cell type (called ‘totipotency’) and are immortal from generation to generation. Knutson found that removing the highly conserved SUMOylation pathway causes somatic cells to express germline proteins. The SUMOylation pathway modifies many nuclear proteins, thereby affecting their activity and function. Knutson employs genome-wide techniques, including microarray analysis and ChIP-seq technology, to assess how removing the SUMOylation pathway affects gene expression and to determine where SUMOylated proteins reside in the genome. His studies will elucidate mechanisms that control genome organization and development and how those mechanisms contribute to distinguishing germ and somatic identities.

Publication: Comparative effects of histone deacetylase inhibitors on p53 target gene expression, cell cycle and apoptosis in MCF-7 breast cancer cells.
Oncol Rep. 2012 Mar;27(3):849-53. doi: 10.3892/or.2011.1590. Epub 2011 Dec 12.
PMID: 22159450

How bacteria metabolize a solid mineral externally is of interest to microbiologists and geologists. Reyes investigated how bacteria metabolize iron minerals using the model bacterium Shewanella sp. strain ANA-3. The precise steps involved in bacterial metabolism of the iron mineral are not known, however, several hypotheses have been proposed. One hypothesis is that the bacterium metabolizes the iron using proteins inside the cell and sitting on the cell surface. These cytochrome proteins are thought to pass electrons from inside the cell to the iron mineral outside the cell. All organisms possess cytochrome proteins, and animals and plants use them in oxygen metabolism. In certain bacteria, these cytochrome proteins are composed of multiple residues that allow for the passage of electrons, a feature not common in animals and plants. The goal of her project is to determine why these bacterial cytochromes require multiple residues to pass electrons from inside the cell to iron minerals outside the cell. By altering the genetic material of ANA-3, she has eliminated specific regions of a cytochrome involved in iron metabolism in hopes of discovering which components enable this protein to pass electrons to the mineral outside the cell.

Reyes received her doctorate in 2011 and is  currently a research fellow at the Hanse-Wissenschaftskolleg Institute for Advanced Study in Bremen, Germany. Her research is supported in part by a fellowship from the J. William Fulbright Foundation, and an International Research Fellowship from the National Science Foundation.

Reed combined qualitative research methods with surveys of physicians, geneticists, and researchers at UCSF and Stanford University to examine the implications of how race, especially for people of mixed race, is included and accounted for in genomic research.

Riggs worked to better understand what happens during the last phase of cell division in animals, using Drosophila melanogaster (the fruit fly) as a model. He is looking at the phase where the plasma membrane constricts to form two daughter cells.

Bacterial pathogens are a major cause of mortality worldwide, yet we know little about how these organisms adapt to habitats outside of the human host. Vibrio cholerae, the causative agent of the severe diarrheal disease cholera, is an excellent model system to study environmental adaptation because it must survive in aquatic habitats for prolonged periods between outbreaks. Temperature is a critical environmental signal governing the occurrence of V. cholerae, and cholera outbreaks are highly correlated with sea surface temperature.  However, it is unknown how V. cholerae senses and responds to temperature change or how this response impacts environmental survival and infectivity of this pathogen.  Loni’s research aims to identify the regulatory networks responsible for temperature adaptation in V. cholerae and determine their impact on the environmental survival of this pathogen.      

Hansen studied information visualization interfaces that allow biologists to look at and easily query visual representations of biological information. The interfaces are used for information such as phylogeny charts, chromosomes, genes, and sequence alignments. For example, a user could start with a phylogeny chart, then click on “fly” to get a sub-chart that lists different species of flies. The user could then click on “Drosophila melanogaster ” to get a picture of fruit fly chromosomes. Clicking on a chromosome of interest would bring up a zoomed-in view showing which genes have been mapped. The user might also be able to click on notes to see the full text of annotations researchers may have attached.