About

Danielle Narae Choi is an Associate Professor of Landscape Architecture at the Harvard Graduate School of Design. Her research and teaching examine landscape design as a cultural practice that brings technology, infrastructure, and ecology into dialogue with public life. Her current book project, Design Beyond Nature: Interior Landscapes and the Infrastructure of Life, investigates iconic climate-controlled landscapes of the Northern Hemisphere, focusing on how cultivated plants, engineered soils, and life-support technologies are intertwined in cycles of growth, dependence, and decay. These landscapes are constructed to exceed natural capacities, exposing and frustrating illusions of human control. Her ongoing research includes investigating infrastructural breaches of continental divides in North America, such as watershed diversions by canal, tunnel, and pipe, and their implications for the concept of genius loci in landscape architecture. Choi's work explores the everyday, incremental work of design, construction, and stewardship as material practices that redefine the ethical, professional, and aesthetic boundaries of landscape architecture amid climate change. She has published essays and articles in various academic and professional journals and magazines, and has led studios and seminars at the GSD addressing topics in design, technology, and landscape history. Before her academic appointment, she practiced professionally with Topotek in Berlin and Michael Van Valkenburgh Associates in New York, shaping complex projects and leading multidisciplinary teams. Choi also serves on the Harvard University Design Advisory Committee and was appointed a commissioner of the Boston Civic Design Commission in 2026.

Research topics

• Biochemistry
• Nanotechnology
• Organic chemistry
• Materials science
• Biology
• Ecology
• Chemistry
• Cell biology

Selected publications

• Binge drinking triggers VGLUT3-mediated glutamate secretion and subsequent hepatic inflammation by activating mGluR5/NOX2 in Kupffer cells

  Nature Communications · 2025-07-01 · 2 citations

  articleOpen access

  Glutamate, a crucial player in hepatic amino acid metabolism, has been relatively unexplored in immune cell activation. We show in a study with male mice that hepatic glutamate accumulates in vesicles of perivenous hepatocytes through vesicular glutamate transporter 3 (VGLUT3), regulated by the aryl hydrocarbon receptor upon chronic alcohol intake. Additional binge drinking triggers the exocytosis of glutamate by altering the intracellular Ca2+ level, stimulating metabotropic glutamate receptor 5 (mGluR5) and subsequent NADPH oxidase 2 (NOX2)-mediated ROS production in Kupffer cells (KCs). This interaction between hepatocytes and KCs is facilitated by pseudosynapse formation, arising from alcohol-induced ballooning of perivenous hepatocytes. Genetic or pharmacological interference of mGluR5 or NOX2 in KCs alleviates alcohol-related steatohepatitis (ASH). Analysis of patient samples confirmed some of the findings from mice, showing that plasma glutamate concentration and VGLUT3 levels correlate with ASH development. Conclusively, our findings highlight glutamate storage and release in mediating ASH, particularly through the pseudosynapse between hepatocytes and KCs. The mechanisms for disease progression in alcohol-related steatohepatitis are incompletely understood. Here the authors report that binge drinking on top of chronic alcohol consumption in mice triggers the release of glutamate by hepatocytes, leading to liver inflammation via mGluR5/NOX2 -mediated reactive oxygen species production in Kupffer cells.

  PublisherOA PDFDOI

• Metabolic Sparks in the Liver: Metabolic and Epigenetic Reprogramming in Hepatic Stellate Cells Activation and Its Implications for Human Metabolic Diseases

  Diabetes & Metabolism Journal · 2025-05-01 · 10 citations

  reviewOpen accessSenior author

  The liver plays a fundamental role in metabolic homeostasis, integrating systemic fuel utilization with the progression of various metabolic diseases. Hepatic stellate cells (HSCs) are a key nonparenchymal cell type in the liver, which is essential for maintaining hepatic architecture in their quiescent state. However, upon chronic liver injury or metabolic stress, HSCs become activated, leading to excessive extracellular matrix deposition and pro-fibrotic signaling, ultimately positioning them as key players in liver pathology. Emerging evidence highlights the critical roles of metabolic reprogramming and epigenetic regulation in HSCs activation. HSCs activation is driven by both intrinsic fuel metabolism reprogramming and extrinsic metabolic cues from the microenvironment, while the metabolic intermediates actively reshape the epigenetic landscape, reinforcing fibrogenic transcriptional programs. In this review, we summarize recent advances in understanding how metabolic and epigenetic alterations drive HSCs activation, thereby shaping transcriptional programs that sustain fibrosis, and discuss potential therapeutic strategies to target these interconnected pathways in human metabolic diseases.

  PublisherOA PDFDOI

• Rapid Eye Movement Sleep-Suppressing Antidepressant Use is Associated With Enhanced Survival in Amyotrophic Lateral Sclerosis

  American Journal of Respiratory and Critical Care Medicine · 2025-05-01

  article

  Abstract RATIONALE Patients with weakened inspiratory muscles are vulnerable to sleep disordered breathing, most acutely during rapid eye movement (REM) sleep. Pharmacological suppression of REM sleep has been found to improve sleep disordered breathing and nocturnal hypoxemia in patients with Duchenne muscular dystrophy as well as in patients with restrictive chest wall disease and nocturnal hypoventilation. To our knowledge, this approach has not been investigated in amyotrophic lateral sclerosis (ALS), the most common form of motor neuron disease. METHODS We queried the TriNetX Research network (Cambridge, MA), which aggregates the electronic health record (EHR) and claims-derived data of over 132 million patients (primarily in the US) for patients diagnosed with ALS (ICD-10-CM G12.21) and prescribed riluzole (RxNorm 35623) between 09/2003 – 09/2023. We defined a REM-inhibited cohort in which patients were prescribed one of several antidepressant medications associated with the suppression of REM sleep in the 3 years preceding inclusion criteria, as well as a non-REM-inhibited cohort who received antidepressants not linked to REM suppression, excluding patients who received prescriptions from both classes. The primary outcome was 2-year survival, analyzed using Kaplan-Meier methodology with log-rank testing and hazard ratios estimated using Cox proportional hazards models. Propensity score matching was performed using age, race, and gender. RESULTS We identified 17,444 patients with ALS who met inclusion criteria, 2,492 (14.3%) of which made up the REM-inhibited cohort and 365 (2.1%), the non-REM-inhibited cohort. Two-year Kaplan-Meier survival was significantly higher in the REM-inhibited group prior to propensity score matching (47.18% vs 41.06%, log-rank p=0.027; Figure 1), with a hazard ratio of 1.21 (95% CI 1.022 – 1.433). This survival benefit trend persisted but did not reach significance after matching (48.13% vs 41.06%, log-rank p=0.072; HR 1.23, 95% CI 0.981 – 1.547). Preserved proportionality (p=0.442) suggested a consistent treatment effect throughout follow-up. CONCLUSION To our knowledge, this is the first study examining differential survival in ALS patients receiving REM-inhibiting versus non-REM-inhibiting antidepressants. The observed survival benefit aligns with findings from other neuromuscular disorders, where REM sleep suppression ameliorates nocturnal respiratory dysfunction. While our investigation was limited by its retrospective nature and potential confounding factors inherent to EHR data, the results suggest that pharmacologically targeting a period of known vulnerability in ALS may have meaningful clinical impact. These findings justify prospective trials of REM-targeted interventions, particularly given the limited treatment options currently available for ALS.

  PublisherDOI

• Engineered Cell‐Derived Nanovesicles with CAR and PH20 for Enhanced Targeted Photodynamic Cancer Therapy and Tumor Microenvironment Modulation (Adv. Funct. Mater. 25/2025)

  Advanced Functional Materials · 2025-06-01

  articleOpen access

  Engineered Cell-Derived Nanovesicles In article number 2418138, Wooram Park, Hee Ho Park, and co-workers introduce engineered cell-derived nanovesicles (CNVs) equipped with chimeric antigen receptors (CAR) and PH20 hyaluronidase. These nanovesicles enhance targeted photodynamic therapy (PDT) by improving tumor penetration and modulating the tumor microenvironment. The combined approach demonstrates improved therapeutic efficacy in overcoming tumor-associated barriers, presenting a promising strategy for effective cancer treatment.

  PublisherOA PDFDOI

• “Good” fats, bad news: HDL-delivered vitamin E shields tumors from ferroptosis

  Signal Transduction and Targeted Therapy · 2025-09-01 · 1 citations

  articleOpen access1st authorCorresponding
  PublisherOA PDFDOI

• The crossroad between mitochondrial architecture and metabolism

  Biochimica et Biophysica Acta (BBA) - Bioenergetics · 2024-08-26

  article
  PublisherDOI

• Engineered Cell‐Derived Nanovesicles with CAR and PH20 for Enhanced Targeted Photodynamic Cancer Therapy and Tumor Microenvironment Modulation

  Advanced Functional Materials · 2024-12-31 · 3 citations

  article

  Abstract Photodynamic therapy (PDT) is a promising cancer treatment, but its clinical use is limited by nontargeted photosensitizers (PS) that accumulate in normal tissues, causing adverse effects, and poor penetration in tumor tissues due to the dense extracellular matrix (ECM). Here an innovative approach is presented using cell‐derived nanovesicles (CNVs) engineered with chimeric antigen receptor (CAR) and hyaluronidase PH20 to enhance targeted PDT. The CAR–PH20 CNVs, loaded with the photosensitizer pheophorbide a (PheoA), specifically target HER2‐expressing tumor cells and degrade hyaluronic acid in the tumor microenvironment (TME), improving tumor penetration and drug distribution. In vitro and in vivo experiments demonstrate increased reactive oxygen species (ROS) generation, improved tumor retention, and enhanced therapeutic efficacy compared to conventional methods. When combined with laser irradiation, these CNVs induce significant tumor cell apoptosis and inhibit tumor growth in mouse models, while minimizing toxicity to normal tissues. This platform offers a promising strategy for targeted, TME‐modulating PDT with improved efficacy, and reduced side effects, marking a significant advance in nanodrug‐based cancer therapies.

  PublisherDOI

• Effect of RNF113A deficiency on oxidative stress-induced NRF2 pathway

  Animal Cells and Systems · 2024-05-11 · 10 citations

  articleOpen access

  expression levels, leading to decreased glucose uptake reactions and lower intracellular glucose levels. These alterations potentially caused a reduction in ROS scavenging activity. Taken together, our findings suggest that the loss of RNF113A promotes oxidative stress-mediated activation of the NRF2 pathway, providing novel insights into RNF113A-associated human diseases.

  PublisherOA PDFDOI

• A microbiota-derived metabolite, 3-phenyllactic acid, prolongs healthspan by enhancing mitochondrial function and stress resilience via SKN-1/ATFS-1 in C. elegans

  Nature Communications · 2024-12-30 · 24 citations

  articleOpen access

  The mechanisms underlying the impact of probiotic supplementation on health remain largely elusive. While previous studies primarily focus on the discovery of novel bioactive bacteria and alterations in the microbiome environment to explain potential probiotic effects, our research delves into the role of living Lactiplantibacillus (formerly known as Lactobacillus) and their conditioned media, highlighting that only the former, not dead bacteria, enhance the healthspan of Caenorhabditis elegans (C. elegans). To elucidate the underlying mechanisms, we conduct transcriptomic profiling through RNA-seq analysis in C. elegans exposed to GTB1, a strain of Lactiplantibacillus plantarum or 3-phenyllactic acid (PLA), mimicking the presence of key candidate metabolites of GTB1 and evaluating healthspan. Our findings reveal that PLA treatment significantly extends the healthspan of C. elegans by promoting energy metabolism and stress resilience in a SKN-1/ATFS-1-dependent manner. Moreover, PLA-mediated longevity is associated with a novel age-related parameter, the Healthy Aging Index (HAI), introduced in this study, which comprises healthspan-related factors such as motility, oxygen consumption rate (OCR), and ATP levels. Extending the relevance of our work to humans, we observe an inverse correlation between blood PLA levels and physical performance in patients with sarcopenia, when compared to age-matched non-sarcopenic controls. Our investigation thus sheds light on the pivotal role of the metabolite PLA in probiotics-mediated enhancement of organismal healthspan, and also hints at its potential involvement in age-associated sarcopenia. These findings warrant further investigation to delineate PLA's role in mitigating age-related declines in healthspan and resilience to external stressors.

  PublisherOA PDFDOI

• Unraveling the role of the mitochondrial one-carbon pathway in undifferentiated thyroid cancer by multi-omics analyses

  Nature Communications · 2024-02-08 · 34 citations

  articleOpen access

  The role of the serine/glycine metabolic pathway (SGP) has recently been demonstrated in tumors; however, the pathological relevance of the SGP in thyroid cancer remains unexplored. Here, we perform metabolomic profiling of 17 tumor-normal pairs; bulk transcriptomics of 263 normal thyroid, 348 papillary, and 21 undifferentiated thyroid cancer samples; and single-cell transcriptomes from 15 cases, showing the impact of mitochondrial one-carbon metabolism in thyroid tumors. High expression of serine hydroxymethyltransferase-2 (SHMT2) and methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is associated with low thyroid differentiation scores and poor clinical features. A subpopulation of tumor cells with high mitochondrial one-carbon pathway activity is observed in the single-cell dataset. SHMT2 inhibition significantly compromises mitochondrial respiration and decreases cell proliferation and tumor size in vitro and in vivo. Collectively, our results highlight the importance of the mitochondrial one-carbon pathway in undifferentiated thyroid cancer and suggest that SHMT2 is a potent therapeutic target.

  PublisherOA PDFDOI

Frequent coauthors

• Seong Ho Choi

  46 shared

• Jin Seok Heo

  Samsung Medical Center

  45 shared

• Nika N. Danial

  Harvard University

  25 shared

• In Woong Han

  Sungkyunkwan University

  20 shared

• Jin Seok Heo

  20 shared

• Cheol Yong Choi

  Sungkyunkwan University

  19 shared

• Kee‐Taek Jang

  Sungkyunkwan University

  18 shared

• Kee Taek Jang

  14 shared

Labs

• Harvard Graduate School of Design - Landscape ArchitecturePI

Education

• Ph.D., Landscape Architecture

  Harvard Graduate School of Design

  2010

• M.A., Landscape Architecture

  Harvard Graduate School of Design

  2006

• B.A., Environmental Design

  University of California, Berkeley

  2003

Awards & honors

• Jacob Weidenman Award for excellence in design