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Sara Bolivar Wagers

Undergraduate Major: Biomedical Sciences Major

Future Plans: Enroll in a MD/PhD program

Sara Bolivar Wagers

Sara Bolivar Wagers was born in Bogota, Colombia and moved to the United States at the age of ten. She is majoring in Molecular Biology and Microbiology. Sara has participated in Stanford Summer Research Program/Amgen Scholars Program and the DAAD RISE program in Germany. Her goal is to become a physician, specifically a pediatrician, and scientist with a focus on translational research. Her passion is to help others through medicine and use research to improve medical treatment. Her research interests strongly involve infectious diseases. After graduation, Sara plans to earn her MD/PhD.

Title: Analysis of potential interaction partners of the HIV host restriction factor SAMHD1

Conducted at the Paul Ehrlich Institute - Federal Institute for Vaccines and Biomedicines, Langen Germany as part of the German Academic Exchange Service (DAAD) Research Internships in Science and Engineering (RISE).

Mentors: Dr. Renate Koenig, Paul Ehrlich Institute, Langen, Germany

Abstract: Recent studies discovered Sterile alpha motif (SAM) and HD domain-containing protein 1 (SAMHD1) to be a Human Immunodeficiency Virus-1 (HIV-1) restriction factor in non-cycling myeloid and resting CD4+ T cells. HIV-2 and Simian Immunodeficiency Virus (SIV) have the accessory Vpx protein which counteracts the function of SAMHD1 by leading to ubiquitin-proteosomal dependent degradation. SAMHD1 depletes the pool of deoxynucleoside triphosphates (dNTPs) available in the cell necessary for reverse transcription, thereby preventing viral replication. Restriction by SAMHD1 only occurs in non-cycling cells and is independent of its expression level. The underlying mechanism of SAMHD1 regulation is not yet understood. A recent mass spectroscopy analysis provided insights into a potential SAMHD1 interaction. The aim of this study was to verify potential interaction partners of SAMHD1. We cloned the genes of potential interaction partners into expression plasmids and wanted to verify the interaction with SAMHD1 via Co-immunoprecipitation assays. The genes of interest in this study were a WD repeat domain containing protein, cyclin dependent kinase, and a phosphatase. This information will help understand the cellular function of SAMHD1 and its ability to restrict HIV-1 infection.

Title: A Systematic Review of Immunodeficiency-related Vaccine Derived Poliovirus Cases Worldwide

Awards: 2013 SACNAS Travel Award and SACNAS Undergraduate Student Poster Presentation Awardee

Conducted at Stanford University as part of the Stanford's Summer Research Program (SSRP) and the AMGEN Scholars Program

Mentors: Dr. Yvonne Maldonado, Dr. Marisa Holubar, and Dr. Nita Srinivas, Stanford University

Co-author: Jean Guo

Abstract: In 1988, the World Health Organization unveiled a plan to eradicate poliomyelitis. Worldwide vaccine strategies rely upon Oral Poliovirus Vaccine (OPV) because it is cost efficient, easy to deliver, and can increase herd immunity. OPV has successfully decreased wild type poliovirus, but as we are nearing eradication new problems related to OPV use are emerging. Patients with immunodeficiencies have a weak immune response to OPV, a live attenuated vaccine. They can have prolonged intestinal replication of the vaccine virus which forms new mutated virulent strains known as vaccine-derived polioviruses (VDPVs) that can cause paralysis identical to wildtype virus. This phenomenon may prevent polio eradication as it can reintroduce paralysis-causing mutants into polio-free communities. Despite the recognition that immunodeficiency-related Vaccine Derived Poliovirus (iVDPVs) jeopardize eradition, its determinants are still not well understood. We are conducting a systematic review of all recorded cases of iVDPVs from the 1970's to present. We have developed search strings for scientific databases to detect all previously published iVDPV cases. We will evaluate trends such as age, vaccine history, immune disorder, gender, and percent divergence of the virus. We hypothesize the patient's type of immunodeficiency and location of residence will be the main risk factors for formation of iVDPVs. Additionally, we propose that the increase in iVDPVs recorded in the last decade, especially in middle and low income countries, may be due to increased surveillance technologies. This study will inform vaccine strategies and global policies necessary to accomplish polio eradication.

Title: Shedding of Sabin Oral Poliovirus Vaccine (OPV) in Siblings of OPV Vaccinated Zimbabwean Infants

Conducted at Stanford University as part of the Stanford's Summer Research Program (SSRP) and the AMGEN Scholars Program

Mentors: Dr. Yvonne Maldonado, Dr. Marisa Holubar, Stanford University

Abstract: Transmission of vaccine-related polioviruses occurs through fecal shedding of oral poliovirus vaccines (OPV), allowing for the continued circulation and development of OPV mutant strains. In this study, we present data regarding OPV shedding in siblings of OPV vaccinees in order to study secondary household transmission. We collected demographic information and processed 142 stool samples from 90 siblings of OPV vaccinees living in Chitungwiza, Zimbabwe. Stool samples were collected a month after the vaccinees received their first, second, and third OPV doses. We used RNA extraction, reverse transcription, and real-time PCR to detect oral polioviruses.

Results: The median age of the siblings was 8 years (range 1-24 years). 8% (7) were siblings of HIV positive vaccinees, 92% (83) were siblings of HIV negative vaccinees. Households had a mean of 1.69 family members less than 5 years of age, 74% (67) had a working toilet, and 98% (88) had tap water in their homes. The prevalence of OPV shedding was 4.4% (4). Of the four siblings who shed OPV, one was a sibling of HIV positive vaccinee. This sibling shed all three OPV serotypes. Seven of the ten isolated serotypes had the mutation associated with vaccine associated paralytic poliomyelitis (VAPP).

Conclusions: Overall, Zimbabwean siblings of recently OPV vaccinated infants showed low prevalence of OPV shedding. This signifies that secondary transmission of OPV is minimal and is unlikely to jeopardize polio eradication.

Title: Measuring the genetic effects of a recent population bottleneck of the keystone urchin species, Diadema antillarum

Conducted at the University of Central Florida as part of the Research and Mentoring Program

Mentors: Dr. Linda Walters, and Dr. Eric Hoffman

Co-author: Lauren Smith

Abstract: When a species undergoes a mass mortality event that reduces its genetic diversity, known as a genetic bottleneck, the effects on the surviving populations are of considerable interest. Diadema antillarum, the long-spined sea urchin, is a keystone species in Caribbean coral reefs for its role in consuming macroalgae. In 1983, the species underwent a disease-induced bottleneck event causing a 98% population reduction. The absence of D. antillarum negatively impacted corals, causing algal biomass to increase 22-439% across reef zones within 16 months. Recently, D. antillarum has shown a slow, progressive comeback in many regions. Many studies have evaluated the ecological importance of D. antillarum, but genetic studies have yet to utilize more comprehensive and sensitive methods. We examined how the bottleneck event affected the current genetic diversity of D. antillarum, using individuals collected from 13 populations across the Caribbean, including populations in the U.S. Virgin Islands, the Florida Keys, Jamaica, Brazil, and Belize. We optimized microsatellite primers for eleven loci and used these markers to analyze the genetic diversity between these locations. Preliminary results show high genetic diversity in the analyzed populations which is unexpected in a species recovering from a bottleneck event. Fixation index (FST) values were very low, indicating low genetic differentiation between populations, possibly due to high gene flow and ocean currents. Our findings will contribute to the knowledge on genetic consequences of a massive die-off in a widespread species, which will help find ways to protect keystone species such as D. antillarum.