About
Activity
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Today Melissa R. Michelson and I held the third BIO 101 diversity in science panel - part of our series to encourage student success in and interest…
Today Melissa R. Michelson and I held the third BIO 101 diversity in science panel - part of our series to encourage student success in and interest…
Liked by Dina Buitrago Silva
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I am pleased to present the latest work from our lab deposited in bioRXiv, a human heart-macrophage assembloid model powered by self-organization…
I am pleased to present the latest work from our lab deposited in bioRXiv, a human heart-macrophage assembloid model powered by self-organization…
Liked by Dina Buitrago Silva
Experience & Education
Volunteer Experience
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UCSF chapter* Event Coordinator, Executive Board Memeber
SACNAS
- 5 years
•Plan, budget, and support events surrounding community building, outreach, professional development workshops, and networking opportunities
•Maintain social media accounts (e.g. SACNAS@UCSF Twitter)
•Maintain relationships with SFSU BUILD for NSF workshops, Science & Health Education Partnership (SEP), the Multicultural Resource Center at UCSF and other campus organizations
•Lead panels for various science groups discussing scientific journey and current research (e.g. undergrads and…•Plan, budget, and support events surrounding community building, outreach, professional development workshops, and networking opportunities
•Maintain social media accounts (e.g. SACNAS@UCSF Twitter)
•Maintain relationships with SFSU BUILD for NSF workshops, Science & Health Education Partnership (SEP), the Multicultural Resource Center at UCSF and other campus organizations
•Lead panels for various science groups discussing scientific journey and current research (e.g. undergrads and high schools in the bay area)
•Coordinating/supporting events with campus groups (e.g. Black Excellence in STEM (BE-STEM))
•Planning and leading annual SACNAS board retreats
•Fully organize and lead the RCO graduate division fair on Gathertown platform (2020) with all RCO campus groups
•Support and lead discussions for the yearly Diversity Breakfast with the Graduate Division during multiple interview weekends -
Event Coordinator
Centro Civico Colombiano
- 1 year 9 months
Social Services
•Planning events to bring Colombian community together in NYC local venues
•Run the annual Pageant (2015), recruitment of candidates and teaching basic pageantry techniques
•Booking venues and negotiating pricing/event details with high stake holders
•Promoting free ESL classes for immigrants in Queens, NY
•Coordinating and promoting citizenship exam classes for the community
•Participate in discussions around the improvement of the nonprofit and bringing new ideas as the…•Planning events to bring Colombian community together in NYC local venues
•Run the annual Pageant (2015), recruitment of candidates and teaching basic pageantry techniques
•Booking venues and negotiating pricing/event details with high stake holders
•Promoting free ESL classes for immigrants in Queens, NY
•Coordinating and promoting citizenship exam classes for the community
•Participate in discussions around the improvement of the nonprofit and bringing new ideas as the youngest member -
Volunteer
Cell Motion Laboratories
- 9 months
Education
•Show elementary and middle school students living and nonliving samples through a microscope on the Bio Bus (mobile science lab)
•Walk through scientific hypotheses and make observations with students
•Mentoring K-12 students on the BioBus in NYC low-income areas
•Lead a short lesson on the BioBus on several topics including basic ecosystem concepts, model organisms, and detailing science as a career
Publications
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Haploinsufficiency underlies the neurodevelopmental consequences of SLC6A1 variants
American Journal of Human Genetics
Heterozygous variants in SLC6A1, encoding the GAT-1 GABA transporter, are associated with seizures, developmental delay, and autism. The majority of affected individuals carry missense variants, many of which are recurrent germline de novo mutations, raising the possibility of gain-of-function or dominant-negative effects. To understand the functional consequences, we performed an in vitro GABA uptake assay for 213 unique variants, including 24 control variants. De novo variants consistently…
Heterozygous variants in SLC6A1, encoding the GAT-1 GABA transporter, are associated with seizures, developmental delay, and autism. The majority of affected individuals carry missense variants, many of which are recurrent germline de novo mutations, raising the possibility of gain-of-function or dominant-negative effects. To understand the functional consequences, we performed an in vitro GABA uptake assay for 213 unique variants, including 24 control variants. De novo variants consistently resulted in a decrease in GABA uptake, in keeping with haploinsufficiency underlying all neurodevelopmental phenotypes. Where present, ClinVar pathogenicity reports correlated well with GABA uptake data; the functional data can inform future reports for the remaining 72% of unscored variants. Surface localization was assessed for 86 variants; two-thirds of loss-of-function missense variants prevented GAT-1 from being present on the membrane while GAT-1 was on the surface but with reduced activity for the remaining third. Surprisingly, recurrent de novo missense variants showed moderate loss-of-function effects that reduced GABA uptake with no evidence for dominant-negative or gain-of-function effects. Using linear regression across multiple missense severity scores to extrapolate the functional data to all potential SLC6A1 missense variants, we observe an abundance of GAT-1 residues that are sensitive to substitution. The extent of this missense vulnerability accounts for the clinically observed missense enrichment; overlap with hypermutable CpG sites accounts for the recurrent missense variants. Strategies to increase the expression of the wild-type SLC6A1 allele are likely to be beneficial across neurodevelopmental disorders, though the developmental stage and extent of required rescue remain unknown.
Other authorsSee publication -
The full spectrum of OCT1 (SLC22A1) mutations illuminates the bridge between drug transporter biophysics and pharmacogenomics
Molecular Cell
Mutations in transporters can impact an individual’s response to drugs and cause many diseases. Few variants in transporters have been evaluated for their functional impact. Here, we combine saturation mutagenesis and multi-phenotypic screening to dissect the impact of 11,213 missense single-amino-acid deletions, and synonymous variants across the 554 residues of OCT1, a key liver xenobiotic transporter. By quantifying in parallel expression and substrate uptake, we find that most variants…
Mutations in transporters can impact an individual’s response to drugs and cause many diseases. Few variants in transporters have been evaluated for their functional impact. Here, we combine saturation mutagenesis and multi-phenotypic screening to dissect the impact of 11,213 missense single-amino-acid deletions, and synonymous variants across the 554 residues of OCT1, a key liver xenobiotic transporter. By quantifying in parallel expression and substrate uptake, we find that most variants exert their primary effect on protein abundance, a phenotype not commonly measured alongside function. Using our mutagenesis results combined with structure prediction and molecular dynamic simulations, we develop accurate structure-function models of the entire transport cycle, providing biophysical characterization of all known and possible human OCT1 polymorphisms. This work provides a complete functional map of OCT1 variants along with a framework for integrating functional genomics, biophysical modeling, and human genetics to predict variant effects on disease and drug efficacy.
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Describing inhibitor specificity for the amino acid transporter LAT1 from metainference simulations
Biophysical Journal
The human L-type amino acid transporter 1 (LAT1; SLC7A5) is a membrane transporter of amino acids, thyroid hormones, and drugs such as the Parkinson's disease drug levodopa (L-Dopa). LAT1 is found in the blood-brain barrier, testis, bone marrow, and placenta, and its dysregulation has been associated with various neurological diseases, such as autism and epilepsy, as well as cancer. In this study, we combine metainference molecular dynamics simulations, molecular docking, and experimental…
The human L-type amino acid transporter 1 (LAT1; SLC7A5) is a membrane transporter of amino acids, thyroid hormones, and drugs such as the Parkinson's disease drug levodopa (L-Dopa). LAT1 is found in the blood-brain barrier, testis, bone marrow, and placenta, and its dysregulation has been associated with various neurological diseases, such as autism and epilepsy, as well as cancer. In this study, we combine metainference molecular dynamics simulations, molecular docking, and experimental testing, to characterize LAT1-inhibitor interactions. We first conducted a series of molecular docking experiments to identify the most relevant interactions between LAT1's substrate-binding site and ligands, including both inhibitors and substrates. We then performed metainference molecular dynamics simulations using cryoelectron microscopy structures in different conformations of LAT1 with the electron density map as a spatial restraint, to explore the inherent heterogeneity in the structures. We analyzed the LAT1 substrate-binding site to map important LAT1-ligand interactions as well as newly described druggable pockets. Finally, this analysis guided the discovery of previously unknown LAT1 ligands using virtual screening and cellular uptake experiments. Our results improve our understanding of LAT1-inhibitor recognition, providing a framework for rational design of future lead compounds targeting this key drug target.
Other authorsSee publication -
Deorphaning a solute carrier 22 family member, SLC22A15, through functional genomic studies
The FASEB Journal
The human solute carrier 22A (SLC22A) family consists of 23 members, representing one of the largest families in the human SLC superfamily. Despite their pharmacological and physiological importance in the absorption and disposition of a range of solutes, eight SLC22A family members remain classified as orphans. In this study, we used a multifaceted approach to identify ligands of orphan SLC22A15. Ligands of SLC22A15 were proposed based on phylogenetic analysis and comparative modeling. The…
The human solute carrier 22A (SLC22A) family consists of 23 members, representing one of the largest families in the human SLC superfamily. Despite their pharmacological and physiological importance in the absorption and disposition of a range of solutes, eight SLC22A family members remain classified as orphans. In this study, we used a multifaceted approach to identify ligands of orphan SLC22A15. Ligands of SLC22A15 were proposed based on phylogenetic analysis and comparative modeling. The putative ligands were then confirmed by metabolomic screening and uptake assays in SLC22A15 transfected HEK293 cells. Metabolomic studies and transporter assays revealed that SLC22A15 prefers zwitterionic compounds over cations and anions. We identified eight zwitterions, including ergothioneine, carnitine, carnosine, gabapentin, as well as four cations, including MPP+, thiamine, and cimetidine, as substrates of SLC22A15. Carnosine was a specific substrate of SLC22A15 among the transporters in the SLC22A family. SLC22A15 transport of several substrates was sodium‐dependent and exhibited a higher Km for ergothioneine, carnitine, and carnosine compared to previously identified transporters for these ligands. This is the first study to characterize the function of SLC22A15. Our studies demonstrate that SLC22A15 may play an important role in determining the systemic and tissue levels of ergothioneine, carnosine, and other zwitterions.
Other authorsSee publication -
Gonadal Hormones Rapidly Enhance Spatial Memory and Increase Hippocampal Spine Density in Male Rats
Endocrine Society
Previous studies showed acute estradiol (E2) treatment to ovariectomized female rats enhances memory, and thus our project aimed at replicating this phenomenon in males. We hypothesized that testosterone (T) treatment, not E2, would enhance memory in males and increase spine density in the hippocampal CA1 region. The protocol involved injecting male rats with E2 or T followed by assessment of memory through the object placement test. Using Golgi impregnation, we assessed the rapid effects of E2…
Previous studies showed acute estradiol (E2) treatment to ovariectomized female rats enhances memory, and thus our project aimed at replicating this phenomenon in males. We hypothesized that testosterone (T) treatment, not E2, would enhance memory in males and increase spine density in the hippocampal CA1 region. The protocol involved injecting male rats with E2 or T followed by assessment of memory through the object placement test. Using Golgi impregnation, we assessed the rapid effects of E2 and T of hippocampal spine density in the CA1 region and dentate gyrus. Our behavioral and physiological results showed that acute T and E2 improved spatial recognition memory in males. Our findings have implications for treating neurodegenerative diseases and aging processes associated with memory loss through gonadal hormone replacement therapies.
Other authorsSee publication
Honors & Awards
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Quantitative Biosciences Consortium DEI Award
QBC at UCSF
For my DEI work in revising and redesigning admissions practices within the Pharmaceutical Sciences and Pharmacoogenomics PhD program at UCSF to increase equity through transparency and clarity. Read more here: https://graduate.ucsf.edu/news/celebratory-symposium-graduate-division’s-jedi-leadership-course
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Pharmacy Graduate Program Fellowship
UCSF School of Pharmacy
The fellowship awards $15,000 to for tuition and stipend
and is a contingent on continued good standing with the Pharmaceutical
Sciences and Pharmacogenomics (PSPG) Graduate program. -
Student Trainee Grant Award for ASCPT meeting
American Society for Clinical Pharmacology and Therapeutics
ASCPT grant award to fully fund my attendance to the ASCPT meeting in 2022.
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American Epilepsy Society Research Award (Grant)
American Epilepsy Society
This is a research award in the amount of 20K granted for a year to work on functionally characterizing missense mutations in the SLC6A1 gene (GABA Transporter). This work is a collaboration between Kathy Giacomini's Lab and Stephan Sander's lab.
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Theodora Salmon Award for Excellence in Biological Sciences
CUNY Hunter College
Award recipients are nominated by professors in the Department of biological sciences at Hunter College. These students show great dedication and understanding in biology through their grades and/or participation outside of class (e.g. extensive research).
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Women in Science Mildred Dresselhaus Scholar
CUNY Hunter College
Scholarship award dedicated to women pursuing careers in science and continuing their education in graduate school.
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10th Health Disparities Conference 2017 Undergraduate Award Recipient
Xavier University of Louisiana, College of Pharmacy
2017 Student Poster Competition, March 16-17, 2017, NOLA
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National Science Foundation Graduate Research Fellowship Program (NSF GRFP)
National Science Foundation
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Penn Honors Diversity (PHD) Symposium Travel Award
University of Pennsylvania
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SACNAS Presentation Award 2016 (Pharmacology Division)
Society for Advancement of Chicanos/Hispanics and Native Americans in Science (SACNAS)
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SACNAS Travel Award
SACNAS
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The Scholarship & Welfare Fund
CUNY Hunter College
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NIGMS-RISE Scholar
CUNY Hunter College
Languages
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Spanish
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Organizations
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Society for Advancement of Chicanos/hispanics and Native Americans in Science (SACNAS)
Member
- Present -
American Society for Pharmacology and Experimental Therapeutics
member
- Present -
Pharmacogenomics Research Network
Member
More activity by Dina
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Thrilled to share with you all that my graduate school work has been published in the American Journal of Human Genetics, titled "Haploinsufficiency…
Thrilled to share with you all that my graduate school work has been published in the American Journal of Human Genetics, titled "Haploinsufficiency…
Shared by Dina Buitrago Silva
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