About

Dr. Gina Ann Garcia is a professor at Berkeley School of Education exploring issues of equity and justice in higher education. As an organizational theorist, she seeks to understand how Hispanic-Serving Institutions (HSIs) enact an organizational identity for serving Latine/x students and minoritized populations. She draws on qualitative methods including case studies, interviews, observations, and participatory research methods to explore how organizations change from predominately white to minoritized-serving. Dr. Garcia also examines the experiences of administrators, faculty, and staff within HSIs and the outcomes and experiences of students of color attending these institutions. As a critical scholar, she is race-conscious and equity-minded in her approach, seeking to empower historically marginalized populations and to create liberatory educational experiences in colleges and universities. She and her colleagues coined the term, “servingness” with much of her research interrogating how HSIs come to embody this concept within their organizational structures.

Research topics

• Cell biology
• Computer Science
• Biology
• Chemistry
• Evolutionary biology

Selected publications

• Imaging and Quantifying Mitochondrial Morphology in <i>C. elegans</i> During Aging

  Journal of Visualized Experiments · 2025-01-17 · 6 citations

  articleOpen access

  Mitochondria, important cellular organelles found in most eukaryotic cells, are major sites of energy production through aerobic respiration. Beyond this well-known role as the 'cellular powerhouse,' mitochondria are also involved in many other essential cellular processes, including the regulation of cellular metabolism, proliferation, immune signaling, and hormonal signaling. Deterioration in mitochondrial function during aging or under mitochondrial stress is often characterized by distinct changes in mitochondrial morphology and volume. The nematode C. elegans is an ideal model for studying these changes due to its transparent body and short lifespan, which facilitate live microscopy throughout its lifetime. However, even within the C. elegans field, numerous transgenic constructs and methods for mitochondrial imaging are available, each with its own limitations. Here, single-copy, matrix-localized GFP constructs are presented as a robust and reliable method for imaging mitochondrial morphology in C. elegans. This study specifically focuses on experimentally controllable factors to minimize errors and reduce variability between replicates and across studies when performing mitochondrial imaging during the aging process. Additionally, mitoMAPR is recommended as a robust method to quantify changes in mitochondrial morphology across tissue types during aging.

  PublisherOA PDFDOI

• Beyond genes and environment: mapping biological stochasticity in aging

  GeroScience · 2025-04-29 · 1 citations

  reviewOpen access

  Aging is characterized by extensive variability in the onset of morbidity and mortality, even in genetically identical populations with carefully controlled environments. This points to the important role stochasticity plays in shaping the divergent aging process between individual organisms. Here, we survey how stochastic factors at the level of molecules, cells, tissues, and organisms manifest in and impact the aging process, with a focus on the nematode Caenorhabditis elegans. Findings of stochasticity in C. elegans give additional insights for aspects of aging in the more complex settings of mammals with parallels drawn between organisms when appropriate. The emerging understanding of the stochastic contributors to longevity will enhance research strategies and medical interventions for personalized medicine.

  PublisherOA PDFDOI

• Contrasting Effects of Molecular Crowding on Trinucleotide-Repeat DNA Hairpins

  The Journal of Physical Chemistry B · 2025-10-28

  article

  Trinucleotide-repeat motifs are associated with numerous disorders, and genetic instability arising from these repeat motifs may be related to their propensity to form nonhelical structures. Genetic processing and organization of repeat-containing domains occur within a molecularly crowded environment. To address the influence of molecular crowding on structure formation by trinucleotide-repeat motifs, a single-molecule FRET, DNA hairpin system reveals contrasting effects of crowding on hairpin formation for two different trinucleotide-repeat sequences, CAG and CTG. Molecular crowding causes structure formation by the repeat domains to become more dynamic, with sequence-dependent effects arising from differences in the central mismatch of the trinucleotide-repeat motifs. Crowding conditions promote hairpin formation by accelerating the hairpin closing transition; however, these conditions can also weaken the hairpin structure through crowder size-dependent acceleration of the hairpin opening transition. Molecular crowding shifts the conformational equilibria for repeat sequences away from the hairpin state and toward the unstructured state with increasing NaCl. Temperature-based, single-molecule FRET experiments indicate that molecular crowding has entropic and enthalpic contributions to the folding pathways of these molecules. Molecular crowding can perturb DNA structure formation by mismatch-rich repeat domains and may have an impact on genetic instabilities and their pathological outcomes.

  PublisherDOI

• Abstract 420: On-target mutations confer resistance to WRN helicase inhibitors in Microsatellite Unstable Cancer Cells

  Cancer Research · 2025-04-21

  article

  Abstract Werner helicase inhibitors (WRNi) are in clinical development for treating patients with microsatellite-unstable (MSI) tumors characterized by defective DNA mismatch repair. Here, we investigate the impact of cancer cell evolutionary adaptation on WRN pharmacological inhibition with implications for understanding drug selectivity and potential clinical resistance. Coupling genome-wide CRISPR screens with WRN gene knockout, no suppressors of WRN dependency were identified, underscoring WRN’s essential non-redundant function in MSI cells. Pharmacogenomic screens pinpointed modulators of WRNi sensitivity, including SMARCAL1, linking it to WRN-MSI synthetic lethality. Semi-saturation mutagenesis of WRN and prolonged drug treatment identified on-target WRN mutations driving acquired resistance to multiple WRNi in vitro and in vivo. Specific resistance mutations induce cross-resistance to WRN inhibitors, whereas others preserve sensitivity to alternative WRNi. Our work guides next-generation strategies for targeting MSI cancers, enabling cross-resistance studies to evaluate current and novel WRNi efficacy and informing future clinical trial design. Citation Format: Gabriele Picco, Yanhua Rao, Angham Al Saedi, Samantha J. Walker, Shriram Bhosle, Yang Lee, Sara F. Vieira, Gilberto Valdes Garcia, Kieron May, Francesco Sassi, Mamta Sharma, Cansu Dincer, Inigo Barrio Hernandez, Theo Bell, Anastasia Kavasakali, Maria Garcia-Casado, Ray Shenje, Cuthbert Martyr, Edward Brnardic, Nanhua Deng, Hristina Grigorova Dimitrova, Emre Karakoc, Emma Hitch, Katrina McCarten, Zoe Hewitson, Howard Lightfoot, Syd Barthorpe, Michael P. DeMartino, Phil Landis, Emanuel Gonçalves, Andrea Bertotti, Livio Trusolino, Geeta Sharma, Matthew A. Coelho, Jonathan Houseley, Benjamin Schwartz, Mathew J. Garnett. On-target mutations confer resistance to WRN helicase inhibitors in Microsatellite Unstable Cancer Cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 420.

  PublisherDOI

• Down syndrome with Alzheimer’s disease brains have increased iron and associated lipid peroxidation consistent with ferroptosis

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-02-06

  preprintOpen access

  ABSTRACT INTRODUCTION Cerebral microbleeds (MB) are associated with sporadic Alzheimer’s Disease (AD) and Down Syndrome with AD (DSAD). Higher MB iron may cause iron mediated lipid peroxidation. We hypothesize that amyloid deposition is linked to MB iron and that amyloid precursor protein (APP) triplication increases iron load and lipid peroxidation. METHODS Prefrontal cortex and cerebellum of cognitively normal (CTL), AD and DSAD ApoE3,3 carriers were examined for proteins that mediated iron metabolism, antioxidant response, and amyloid processing in lipid rafts. RESULTS Iron was 2-fold higher in DSAD than CTL and AD. Iron storage proteins and lipid peroxidation were increased in prefrontal cortex, but not in the cerebellum. The glutathione synthesis protein GCLM was decreased by 50% in both AD and DSAD. Activity of lipid raft GPx4, responsible for membrane repair, was decreased by at least 30% in AD and DSAD. DISCUSSION DSAD shows greater lipid peroxidation than AD consistent with greater MBs and iron load. Graphical Abstract Cerebral microbleeds result in increased brain iron and lipid peroxidation in DSAD consistent with ferroptosis as reported for Alzheimer’s disease. Aβ; beta-amyloid peptides, APP; amyloid precursor protein, GCLC; glutathione cysteine ligase catalytic subunit, GCLM; glutathione cysteine modifier subunit, GPx4; glutathione peroxidase 4, HNE; 4-hydroxynonenal. RESEARCH IN CONTEXT Systematic Review: DS is associated with increased microbleeds and brain iron that may be mediated by increased APP from Trisomy 21. To assess potential links between amyloid and iron levels, we examined sporadic and DS with AD brains for amyloid processing and antioxidant enzyme defense in lipid rafts. We further compared DSAD with rare variants of DS: partial and mosaic T21. Interpretation: DSAD brains showed greater oxidation of lipid rafts where APP is processed than sporadic AD. Corresponding decreases in lipid raft antioxidant enzymes, despite increased total levels of these antioxidant enzymes, present a new mechanism for aberrant amyloid processing during AD. Future Directions: Iron chelation therapies in combination with amyloid monoclonals may benefit DSAD.

  PublisherDOI

• Abstract 563: AR-dependent castration-resistant prostate cancer relies on histone methyltransferase KMT2D for cell growth

  Cancer Research · 2025-04-21

  article

  The KMT2D histone H3 lysine 4 (H3K4) methyltransferase plays critical roles in enhancer-regulated gene activation. It is a large multi-domain protein with its C-terminal SET domain being responsible for this activity. High KMT2D expression is associated with reduced patient survival in prostate cancer. Cancer Dependency Map data show a correlation between KMT2D gene dependency and FOXA1 expression in prostate cancer cell lines. FOXA1 is a major regulator of Androgen Receptor (AR) transcription and recent findings showed that KMT2D establishes the chromatin competency to recruit AR and for FOXA1 to activate AR-dependent transcription. Since FOXA1 is predicted to be poorly tractable, we aimed to target the more tractable KMT2D in FOXA1-overexpressing AR-dependent castration-resistant prostate cancer (CRPC). CRPC cell lines with high FOXA1 (FOXA1high) and high AR (ARhigh) and/or AR constitutively active splice variants, such as AR-V7 (AR-V7+) were found to express high levels of KMT2D. KMT2D knockout (KO) reduced cell growth in these cells and in isogenic AR-V7+ 22Rv1 cells lacking full length AR. Additionally, KMT2D KO modulated AR target genes as demonstrated by reduced PSA mRNA and increased mRNA for IGFBP3 and EFNB2. Inactivating SET domain mutations demonstrated that these effects were mediated by KMT2D’s catalytic function thus supporting SET-domain inhibition as the desired target modality. This study highlights the potential of KMT2D as a therapeutic target for AR-dependent CRPC patients with constitutively active AR splice variants who have high unmet medical need due to AR variants being undruggable with currently available therapeutic agents. Citation Format: Angela Bononi, Paul Redford, Weichao Zhang, Gabriella Cifelli, Sungtae Kim, Ian Gao, Kelly Werth, Peter Carman, Gilberto Valdes Garcia, Zane Taylor, Rachel Totoritis, Jess Schneck, Paul Bamborough, Markus Queisser, Georgia Maundrill, Dean Thomas, Hoang Tran, Sarvesh Varma, Biju Mangatt, Michael McCabe, Benjamin Schwartz, Kelly Choi. AR-dependent castration-resistant prostate cancer relies on histone methyltransferase KMT2D for cell growth [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 563.

  PublisherDOI

• Down syndrome with Alzheimer's disease brains have increased iron and associated lipid peroxidation consistent with ferroptosis

  Alzheimer s & Dementia · 2025-06-01 · 6 citations

  articleOpen access

  INTRODUCTION: Cerebral microbleeds (MBs) are associated with sporadic Alzheimer's disease (AD) and Down syndrome with AD (DSAD). Higher MB iron may cause iron-mediated lipid peroxidation. We hypothesize that amyloid deposition is linked to MB iron and that amyloid precursor protein (APP) triplication increases iron load and lipid peroxidation. METHODS: Prefrontal cortex and cerebellum of cognitively normal control (CTL), AD, and DSAD ApoE3,3 carriers were examined for proteins that mediated iron metabolism, antioxidant response, and amyloid processing in lipid rafts. RESULTS: Iron was twofold higher in DSAD than in CTL and AD. Iron storage proteins and lipid peroxidation were increased in the prefrontal cortex. The glutathione synthesis protein GCLM was decreased by 50% in both AD and DSAD. Activity of lipid raft GPx4, responsible for membrane repair, was decreased by at least 30% in AD and DSAD. DISCUSSION: DSAD shows greater lipid peroxidation than AD, consistent with greater MBs and iron load. HIGHLIGHTS: DSAD has increased ferroptotic-related changes compared to sporadic AD. Lipid rafts that process APP have a loss of protective antioxidant enzymes. Partial and mosaic trisomy lowers the amyloid and iron burden.

  PublisherOA PDFDOI

• Iron‐associated lipid peroxidation in Alzheimer's disease is increased in lipid rafts with decreased ferroptosis suppressors, tested by chelation in mice

  Alzheimer s & Dementia · 2025-01-01 · 28 citations

  articleOpen access

  INTRODUCTION: Iron-mediated cell death (ferroptosis) is a proposed mechanism of Alzheimer's disease (AD) pathology. While iron is essential for basic biological functions, its reactivity generates oxidants which contribute to cell damage and death. METHODS: To further resolve mechanisms of iron-mediated toxicity in AD, we analyzed post mortem human brain and ApoEFAD mice. RESULTS: AD brains had decreased antioxidant enzymes, including those mediated by glutathione (GSH). Subcellular analyses of AD brains showed greater oxidative damage and lower antioxidant enzymes in lipid rafts, the site of amyloid processing, than in the non-raft membrane fraction. Apolipoprotein E ε4 carriers had lower lipid raft yield with greater membrane oxidation. The hypothesized role of iron in AD pathology was tested in ApoEFAD mice by iron chelation with deferoxamine, which decreased fibrillar amyloid and lipid peroxidation, together with increased GSH-mediated antioxidants. DISCUSSION: These novel molecular pathways highlight iron-mediated damage to lipid rafts during AD. HIGHLGHTS: Alzheimer's disease (AD) brains have numerous markers for ferroptosis, including increased lipid peroxidation, reduced antioxidant levels, and increased iron storage. Lipid rafts in AD cases have increased oxidative damage and reduced antioxidant enzyme levels and activity which are most severe in apolipoprotein E ε4 carriers. Neuronal markers are correlated with lipid peroxidation, antioxidant defense, and iron signaling proteins suggesting that neuronal loss is linked to these events. Chelation of iron in the early-onset familial AD model reduces iron-mediated lipid peroxidation and fibrillar amyloid.

  PublisherOA PDFDOI

• Transcriptomic analysis of mitohormesis associated with lifespan extension in Caenorhabditis elegans

  GeroScience · 2025-11-04

  articleOpen access

  Abstract Non-lethal exposure to mitochondrial stress has been shown to have beneficial effects due to activation of signaling pathways, including the mitochondrial unfolded protein response (UPR mt ). Activation of UPR mt restores the function of the mitochondria and improves general health and longevity in multiple model systems, termed mitohormesis. In C. elegans , mitohormesis can be accomplished by electron transport chain inhibition, a decline in mitochondrial translation, decreased mitochondrial import, and numerous other methods that activate UPR mt . However, not all methods that activate UPR mt promote longevity. These and other studies have started to question whether UPR mt is directly correlated with longevity. Here, we attempt to address this controversy by unraveling the complex molecular regulation of longevity of the nematode under different mitochondrial stressors that induce mitochondrial stress by performing RNA sequencing to profile transcriptome changes. Using this comprehensive and unbiased approach, we aim to determine whether specific transcriptomic changes can reveal a correlation between UPR mt and longevity. Altogether, this study will provide mechanistic insights on mitohormesis and how it correlates with the lifespan of C. elegans .

  PublisherOA PDFDOI

• Distinct responses to non-autonomous UPRER mediated by glutamatergic and octopaminergic neurons

  Communications Biology · 2025-11-24 · 1 citations

  articleOpen access

  The capacity to deal with stress declines during the aging process, and preservation of cellular stress responses is critical to healthy aging. The unfolded protein response of the endoplasmic reticulum (UPRER) is one such conserved mechanism, which is critical for the maintenance of several major functions of the ER during stress, including protein folding and lipid metabolism. Hyperactivation of the UPRER by overexpression of the major transcription factor, xbp-1s, solely in neurons drives lifespan extension as neurons send a neurotransmitter-based signal to other tissues to activate UPRER in a non-autonomous fashion. Previous work identified serotonergic, dopaminergic, and tyraminergic neurons in this signaling paradigm. To further expand our understanding of the neural circuitry that underlies the non-autonomous signaling of ER stress, we activated UPRER solely in glutamatergic, octopaminergic, and GABAergic neurons in C. elegans and paired whole-body transcriptomic analysis with functional assays. We found that UPRER-induced signals from glutamatergic neurons increased expression of canonical protein homeostasis pathways and octopaminergic neurons promoted pathogen response pathways, while more modest changes were detected in GABAergic UPRER activation. These findings provide further evidence for the distinct role neuronal subtypes play in driving the diverse response to ER stress. Activation of the UPRER in distinct C. elegans neuronal subtypes drives unique organismal outcomes: glutamatergic neurons enhance proteostasis, octopaminergic neurons boost immune defenses and extend lifespan, while GABAergic neurons show modest effects.

  PublisherOA PDFDOI

Frequent coauthors

• Ryo Higuchi‐Sanabria

  University of Southern California

  45 shared

• Andrew Dillin

  University of California, Berkeley

  38 shared

• C. Kimberly Tsui

  Howard Hughes Medical Institute

  24 shared

• Naibedya Dutta

  University of Southern California

  19 shared

• Larry Joe

  University of California, Berkeley

  17 shared

• Hanlin Zhang

  Howard Hughes Medical Institute

  16 shared

• Maxim Averbukh

  University of Southern California

  16 shared

• Athena Alcala

  University of Southern California

  16 shared

Awards & honors

• American Association of Hispanics in Higher Education Book o…