About

Sangmoo Jeong is an assistant professor in the Department of Chemical and Biomolecular Engineering at Johns Hopkins University, with a secondary appointment at the Oncology Center and a core membership at the Institute for NanoBioTechnology. His research interests include metabolic dysfunctions, extracellular vesicles, and biosensors, with a focus on understanding how metabolic dysfunctions link to major diseases such as cancer. His lab develops technologies to detect metabolic biomarkers and dysfunctions and investigates the underlying mechanisms of these processes. Jeong received his Bachelor of Science degree in electrical engineering from the Korea Advanced Institute of Science and Technology (KAIST) in Korea, and his Master of Science and PhD in electrical engineering from Stanford University. He completed postdoctoral research at Massachusetts General Hospital/Harvard Medical School with Ralph Weissleder and Hakho Lee, as well as at Memorial Sloan Kettering Cancer Center with Kayvan Keshari. His notable awards include the NIH Pathway to Independence Award (K99/R00), the Hollis Brownstein Research Award from the Leukemia Research Foundation, and the NIH Maximizing Investigators’ Research Award (R35).

Research topics

• Biochemistry
• Cancer research
• Chemistry
• Biology
• Medicine
• Biophysics
• Internal medicine

Selected publications

• Hypoxia restores the acidosis-induced inhibition of cancer cell dissemination

  Cell Reports · 2026-02-01 · 1 citations

  articleOpen access

  = 6.4) suppresses cell proliferation, metabolism, dissociation from tumor spheroids, and migration in vitro as well as extravasation in chick embryos and mice. Acidosis acutely inhibits motility by downregulating the activity of sodium-hydrogen exchanger isoform-1 (NHE1), which in turn suppresses phosphatidylinositol 3-kinase (PI3K)/Akt. PI3K/Akt inhibition blocks Yes-associated protein (YAP) translocation to the nucleus, reducing NHE1 and integrin-linked kinase (ILK) expression. The resulting reduction in NHE1-/ILK-dependent migration and ATP production is rescued by hypoxia across cell types. While certain cancer cells can adapt to long-term (>3 weeks) acidosis and acquire an aggressive phenotype, acidosis-induced adaptation is not universal and depends on the cell's ability to restrain reactive oxygen species overproduction via fatty acid oxidation.

  PublisherDOI

• Chronic alcohol exposure drives inflammaging and transposon derepression in hematopoietic stem progenitor cells

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-12-26

  articleOpen access

  Abstract Chronic alcohol use can cause pancytopenia and diminished immune responses against pathogens. However, its underlying molecular mechanisms remain unclear. Furthermore, whether chronic alcohol consumption directly induces inflammation in human hematopoietic stem progenitor cells (HSPCs) or whether it affects aging hematopoiesis differently is unknown. To examine how chronic alcohol use influences HSPCs, we performed single-cell RNA-seq in murine and human HSPCs and single-cell ATAC-seq in aged murine HSPCs following alcohol exposure. In the native murine bone marrow, chronic alcohol exposure primed HSPCs to differentiate into myeloid cells and to exhibit heightened inflammation, DNA damage, and epigenetic reactivation of transposable elements (TEs) in an age-dependent manner. Alcohol-exposed aged long-term hematopoietic stem cells (LT-HSCs) displayed increased chromatin accessibility at TE-containing loci correlated with aberrant TE transcription. This transposon derepression was associated with the accumulation of dsRNAs in aged bone marrow cells, and activation of innate immune pathways, perpetuating HSC inflammaging. Furthermore, we identified two epigenetically distinct LT-HSC clusters, LT-HSC1 and LT-HSC2, with the LT-HSC2 cluster expanding in response to chronic alcohol consumption, resembling activated HSCs. In xenotransplanted human HSPCs, chronic alcohol feeding resulted in a significant myeloid bias, heightened inflammation, upregulation of double-stranded RNA (dsRNA) sensors, activation of type I interferon responses, and increased expression of endogenous retroviruses. Despite these molecular alterations, we did not observe a decrease in long-term repopulation capacity in either human or murine HSCs. This suggests that HSC function may recover following alcohol cessation. However, previous chronic alcohol exposures imprint murine HSPCs to exhibit long-term myeloid bias and reduced cell cycle entry upon bacterial LPS challenge. Our data illuminate potential interactions between alcohol and aging that can reinforce inflammaging and epigenetic dysregulation in HSPCs. Keypoints Aging perpetuates alcohol-induced myeloid bias, inflammation, DNA damage, and TE upregulation in murine HSPCs Prior chronic alcohol consumption does not affect long-term repopulation but causes persistent myeloid bias and inefficient stress responses after LPS challenge Chronic alcohol consumption alters chromatin accessibility in TE-overlapping regions Chronic alcohol consumption promotes myeloid bias, inflammation, and upregulation of endogenous retroviruses in xenotransplanted human HSPCs. Graphical Abstract

  PublisherOA PDFDOI

• Dietary serine restriction increases venetoclax efficacy in Acute Myeloid Leukemia

  Blood · 2025-11-03

  articleOpen accessSenior author

  Abstract Acute myeloid leukemia (AML) is a highly aggressive hematologic malignancy with relapse rates exceeding 50% and long-term survival below 30% at 5 years. The anti-apoptotic protein BCL-2 is upregulated in over 80% of patients at diagnosis and about 90% at relapse, making it a potent therapeutic target. Venetoclax (VEN), a selective BCL-2 inhibitor, is FDA-approved for AML treatment. However, nearly 25% of patients do not respond to VEN-based therapy, and more than half of initial responders eventually relapse, often exhibiting venetoclax resistance. Mechanisms of this resistance include upregulation of alternate anti-apoptotic proteins (e.g., MCL-1, BCL-xL) and metabolic adaptations, including increased glycolysis and fatty acid oxidation. Thus, identifying targetable metabolic vulnerabilities that can potentiate VEN efficacy is essential for improving AML outcomes. One such vulnerability is serine and glycine metabolism, which supports nucleotide biosynthesis and cell proliferation in various cancers. We found that AML cells are highly sensitive to exogenous serine depletion; MV4-11, MOLM-13, NOMO-1, and THP-1 cells exhibited reduced proliferation rates of 0.50, 0.81, 0.61, and 0.74, respectively, after 72 hours of culture in serine-free media. This was accompanied by upregulation of serine synthesis pathway (SSP) enzymes, including phosphoglycerate dehydrogenase (PHGDH). In contrast, glycine depletion had no effect on proliferation or SSP activation. Notably, we observed that AML cells preferentially imported serine and exported glycine under regular media conditions, indicating active SSP and reliance on one-carbon metabolism. Importantly, isotope tracing analysis with mass spectrometry revealed that VEN markedly impaired SSP flux, as evidenced by reduced fractional enrichment of serine (m+3) and glycine (m+2) in both MV4-11 and MOLM-13 cells cultured in [U-13C] glucose media. This effect may be mediated by ATF4, a key transcriptional activator of SSP enzymes, which was downregulated by VEN and accompanied by decreased mRNA levels of PHGDH. These findings suggest that VEN-treated cells become increasingly dependent on exogenous serine. Consistent with this hypothesis, serine deprivation significantly sensitized AML cells to VEN. For instance, the IC50 for MOLM-13 decreased from 50.93 μM to 11.92 μM, and for MV4-11 from 63.36 μM to 9.03 μM under serine-depleted conditions. This sensitization was reflected in increased cell death and early apoptosis across both VEN-responsive (MV4-11, MOLM-13) and less responsive (NOMO-1, THP-1) cell lines. To investigate the mechanism underlying this synergy, we examined metabolic adaptations under combined treatment. VEN impaired mitochondrial respiration, with a compensatory increase in glycolysis, as evidenced by elevated glycolytic ATP production. Serine depletion further increased mitochondrial stress, resulting in loss of membrane potential and reduced maximal respiratory capacity. Mechanistically, loss of serine exacerbates VEN-induced energy stress by diverting glycolytic intermediates toward SSP. This disruption of cellular energy homeostasis was confirmed by a significant decrease in intracellular ATP levels, with approximately 43% reduction in MOLM-13 cells and 36% in MV4-11 cells compared to untreated controls in complete media. To test this synergy in vivo, we xenografted NSG mice with MV4-11 cells and assigned them to four Groups: (1) regular diet + vehicle, (2) regular diet + VEN, (3) serine/glycine-free (-SG) diet + vehicle, and (4) -SG diet + VEN. Mice on the -SG diet exhibited significantly delayed AML progression and reduced leukemic burden compared to those on the regular diet. Disease progression in Groups 2 and 3 was comparable, with average survival extended to 50 days versus 38 days in Group 1. Remarkably, all mice in Group 4 (-SG diet + VEN) remained alive at day 60, the time of the abstract submission. In summary, our findings identify serine metabolism as a critical metabolic vulnerability in AML. Targeting serine availability synergizes with venetoclax to induce profound ATP stress and leukemic cell death. This strategy offers a novel therapeutic paradigm in which dietary interventions, rather than additional chemotherapeutics, can be leveraged to enhance therapeutic efficacy while minimizing chemo-mediated systemic toxicity.

  PublisherOA PDFDOI

• Self‐Nourishing and Armored Probiotics via Egg‐Inspired Encapsulation

  Advanced Healthcare Materials · 2025-03-19 · 4 citations

  articleOpen accessSenior authorCorresponding

  The gut microbiota plays an essential role in regulating overall physiology, including metabolism and neurological and immune functions. Therefore, their dysregulation is closely associated with metabolic disorders, such as obesity and diabetes, as well as other pathological conditions, including inflammatory bowel diseases, cancer, and neurological disorders. Probiotics are commonly used to maintain a healthy gut microbiome, but their oral delivery is inefficient mainly due to their poor stability in the harsh gastrointestinal (GI) environment. This work presents an innovative encapsulation strategy, inspired by the natural structure of an egg, for the effective oral delivery of probiotics, termed PIE (Probiotics-In-Egg). The PIE technology is based upon encapsulating probiotics with phosvitin and ovalbumin derived from egg yolk and egg white, respectively. PIE exhibits significantly enhanced survival and proliferation in a simulated GI tract, as well as the ability to neutralize harmful reactive oxygen species (ROS) and sustain in nutrient-depleted conditions. Moreover, when administered orally in mouse models, PIE demonstrates excellent bioavailability and enhanced colonization in the GI tract. This egg-inspired encapsulation technology has great potential as a practical and effective platform for oral delivery of probiotics, which can significantly help maintain a healthy gut microbiome.

  PublisherOA PDFDOI

• ALDH9A1 deficiency as a source of endogenous DNA damage that requires repair by the Fanconi anemia pathway

  The Journal of Cell Biology · 2025-05-03 · 8 citations

  articleOpen access

  The Fanconi anemia (FA) DNA repair pathway is required for the repair of DNA interstrand cross-links (ICLs). ICLs are caused by genotoxins, such as chemotherapeutic agents or reactive aldehydes. Inappropriately repaired ICLs contribute to hematopoietic stem cell (HSC) failure and tumorigenesis. While endogenous acetaldehyde and formaldehyde are known to induce HSC failure and leukemia in FA patients, the effects of other toxic metabolites on FA pathogenesis have not been systematically investigated. Using a metabolism-focused CRISPR screen, we found a synthetically lethal interaction between ALDH9A1 and the deficiency of the FA pathway. Combined deficiency of ALDH9A1 and FANCD2 causes genomic instability, apoptosis, and decreased hematopoietic colony formation. Fanca-/-Aldh9a1-/- mice exhibited an increased incidence of ovarian tumors. A suppressor CRISPR screen revealed that the loss of ATP13A3, a polyamine transporter, resulted in improved survival of FANCD2-/-ALDH9A1-/- cells. These findings nominate high intracellular polyamines and the resulting 3-aminopropanal and acrolein as sources of endogenous DNA damage in patients with FA.

  PublisherOA PDFDOI

• Engineered extracellular vesicles for In Vivo gene therapy in sickle cell disease

  Blood · 2025-11-03

  articleSenior author

  Abstract Sickle Cell Disease (SCD) is a genetic blood disorder that affects over 100,000 persons in the U.S. and 20 million people worldwide. Sickled red blood cells (RBCs) tend to clump together, leading to vessel blockages known as vaso-oclusive crises (VOCs). VOCs can be extremely painful and significantly impact the quality of life for SCD patients. According to the Sickle Cell World Assessment Survey, patients experience an average of 5.3 VOCs per year, with 33% requiring hospitalization. Additionally, they miss over 1 day of work per week and face an estimated lifetime burden of $1.7 million in medical costs. In 2023, the FDA approved two gene therapies for SCD: Casgevy and Lyfgenia. While promising, these therapies are prohibitively expensive (over $2 million) and require intensive procedures, such as hematopoietic stem progenitor cell (HSPC) isolation and myeloablative conditioning, as well as lengthy hospitalization. Here, we present an alternative therapeutic strategy to address the limitations of the current gene therapies. We have developed a cost-effective in vivo gene therapy delivery system using engineered extracellular vesicles (EVs). Extracellular vesicles are membrane limited particles secreted by cells. They are used as a mode of intercellular communication and can transport various biological agents between cells, including proteins, RNAs and DNAs. EVs are an attractive delivery vehicle due to their ability to avoid host clearance and travel into difficult to reach areas such as the bone marrow. Our EVs are designed to efficiently and selectively deliver CRISPR-Cas9 ribonucleoprotein (RNP) complexes for BCL11A gene silencing to HSPCs, particularly those with erythroid lineage bias, for effective in vivo gene therapy. To maximize the loading efficiency of Cas9 RNP complexes into our EVs, we generated EV-producing cells to overexpress Cas9 bound to CD63 via a photocleavable linker (PhoCl). Since CD63 is highly expressed on EV membranes, the fusion protein CD63-PhoCl-Cas9 facilitates the enrichment of Cas9 RNP complexes into EVs. This is superior to other conventional methods, including electroporation which is currently used in Casgevy. Furthermore, the use of PhoCl enables the release of RNP complexes into the cytoplasm of EV-recipient cells. Our confocal imaging analysis showed that Cas9 is highly enriched in endosomes and multivesicular bodies (MVBs), the intracellular compartments where EVs are formed, in our EV-producing cells engineered to express CD63-PhoCl-Cas9. To maximize the delivery efficiency to HSPCs for gene therapy, we generated EVs expressing stem cell factor (SCF), the ligand of the c-KIT receptor. SCF exists in two isoforms: a soluble form and a transmembrane form. Given that c-KIT is highly expressed on HSPCs with erythroid lineage bias, by expressing the transmembrane SCF on EVs, we can significantly enhance the efficiency of EV-mediated delivery to c-KIT+ HSPCs. We engineered HEK293T cells to overexpress the transmembrane SCF and confirmed SCF localization to the plasma membrane with confocal microscopy. Western blot analysis confirmed that EVs isolated from our SCF overexpressed cells also expressed SCF. To investigate the c-KIT targeting efficacy of our SCF-EVs, we compared the uptake levels between cells with varying c-KIT expression. We compared Jurkat and HEL cells, which had 21% and 98% c-KIT expression respectively when quantified using flow cytometry. We treated Jurkat and HEL cells with GFP+-SCF-EVs. Both cell lines showed a non-zero, time dependent increase in EV uptake. Notably, HEL cells had a greater than twofold increase in SCF-EVs compared to Jurkat cells (p=0.0153). To further explore the rate of SCF-EV uptake by c-KIT+ cells, we generated 3 c-KIT knockdown (KD) cell lines of HEL using shRNA, all of which had reduced median c-KIT fluorescence intensity by over 50% (p<0.0001). We used the KD clones to confirm that a higher c-KIT expression enhances SCF-EV uptake. Our therapeutic strategy represents a new paradigm for the targeted, in vivo delivery of CRISPR-Cas9 RNP complexes to HSPCs. Our innovative approach has the potential to serve as a foundational technology for a safer, more accessible, and non-viral gene therapy applicable to a broad range of genetic disorders. The successful completion of this project will generate critical proof-of-concept data and enable us to pursue further translational development for in vivo gene therapy for SCD.

  PublisherDOI

• Data from E-Cadherin Induces Serine Synthesis to Support Progression and Metastasis of Breast Cancer

  2024-09-04 · 1 citations

  preprintOpen accessSenior author

  <div>Abstract<p>The loss of E-cadherin, an epithelial cell adhesion molecule, has been implicated in metastasis by mediating the epithelial–mesenchymal transition, which promotes invasion and migration of cancer cells. However, recent studies have demonstrated that E-cadherin supports the survival and proliferation of metastatic cancer cells. Here, we identified a metabolic role for E-cadherin in breast cancer by upregulating the <i>de novo</i> serine synthesis pathway (SSP). The upregulated SSP provided metabolic precursors for biosynthesis and resistance to oxidative stress, enabling E-cadherin<sup>+</sup> breast cancer cells to achieve faster tumor growth and enhanced metastases. Inhibition of phosphoglycerate dehydrogenase, a rate-limiting enzyme in the SSP, significantly and specifically hampered proliferation of E-cadherin<sup>+</sup> breast cancer cells and rendered them vulnerable to oxidative stress, inhibiting their metastatic potential. These findings reveal that E-cadherin reprograms cellular metabolism, promoting tumor growth and metastasis of breast cancers.</p><p><b>Significance:</b> E-Cadherin promotes the progression and metastasis of breast cancer by upregulating the <i>de novo</i> serine synthesis pathway, offering promising targets for inhibiting tumor growth and metastasis in E-cadherin–expressing tumors.</p></div>

  PublisherDOI

• Supplementary Data from E-Cadherin Induces Serine Synthesis to Support Progression and Metastasis of Breast Cancer

  2024-09-04

  preprintOpen accessSenior author

  <p>Supplementary data</p>

  PublisherDOI

• Extracellular Vesicles Derived from Adipose-Derived Mesenchymal Stem Cells Alleviate Apoptosis and Oxidative Stress of Retinal Pigment Epithelial Cells Through Activation of Nrf2 Signaling Pathway

  Journal of Ocular Pharmacology and Therapeutics · 2024-10-25 · 5 citations

  article

  Purpose: To examine the potential protective effects of adipose-derived mesenchymal stem cell-derived extracellular vesicles (ASC-EVs) on ARPE-19 cells exposed to hydrogen peroxide (H 2 O 2 ) stress and to evaluate their ability to delay retinal degeneration in Royal College of Surgeons (RCS) rats. Methods: ARPE-19 cells were pre-treated with ASC-EVs for 24 h, followed by exposure to 200 μM H 2 O 2 for an additional 24 h. RCS rats received an intravitreal injection of phosphate-buffered saline in one eye and ASC-EVs in the other eye. Results: ASC-EV pretreatment significantly protected against H 2 O 2 in the Cell Counting Kit-8 assay and was also effective in the lactate dehydrogenase-release assay. It notably reduced early apoptosis (Annexin V-fluorescein isothiocyanate/propidium iodide assay) and late apoptosis (Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling assay), while significantly decreasing intracellular reactive oxygen species, glutathione levels, and superoxide dismutase activity. NFE2L2 , HMOX1 , and NQO1 mRNA levels, along with Nrf2, HO-1, and NQO1 protein levels, were significantly elevated with ASC-EV pretreatment. Compared with ARPE-19-derived EVs, 11 miRNAs were upregulated and 34 were downregulated in ASC-EVs. In RCS rats, intravitreal injections of ASC-EVs led to significant preservation of the outer nuclear layer and photoreceptor segments, along with increased nuclear Nrf2 expression and elevated HO-1 and NQO1 levels in the inner retina. Eyes that received intravitreal injections of ASC-EVs demonstrated significantly preserved electroretinography a- and b-wave amplitudes at 1 week post-injection, though this effect faded by 2 weeks. Conclusions: ASC-EVs mitigated apoptosis and oxidative stress in ARPE-19 cells subjected to H 2 O 2 exposure and temporarily slowed retinal degeneration in RCS rats via Nrf2 pathway activation by miRNAs.

  PublisherDOI

• Microneedle Patch for Sustained Delivery of Hydroxyurea and L-Glutamine for Sickle Cell Treatment

  Blood · 2024-11-05 · 1 citations

  articleSenior author

  Sickle cell anemia (SCA) is a genetic blood disorder in which the red blood cells have a sickled shape due to a mutation in hemoglobin. The sickle-shaped red blood cells can cause blockages in blood vessels, leading to various complications, such as vaso-occlusive crises (VOCs), acute chest syndrome, stroke, and organ damage. In 2023 the FDA approved two genetic therapies to cure SCA. However, these therapies are expensive and as a result, patients are more likely to choose treatments that manage their SCA and reduce VOCs. Currently, there are only two FDA-approved management treatments for SCA: hydroxyurea and L-glutamine. Unfortunately, these treatments require daily or twice daily dosages and have severe side effects, a major challenge for patients to comply with daily administration. To address this problem, I propose a novel approach: a microneedle patch for the sustained release of these drugs over a week. I expect that this innovative therapeutic strategy will directly improve patient compliance and quality of life. Microneedle (MN) patches are a novel and non-invasive method of transdermal drug delivery. They consist of a patch backing and MN tips that are inserted into the skin. Passive transdermal drug delivery is limited by the outermost layer of the skin, the stratum corneum. MN patches overcome this limitation by disrupting the stratum corneum and reaching the lower layers of the epidermis for drug administration. MN patches have been shown to significantly reduce severe side effects, such as ulcers, nausea and muscle pain, by providing consistent drug release and bypassing hepatic metabolism. Our MN patch is made of gelatin methacrylol (GelMA) and PLGA, both of which are biocompatible and biodegradable. This allows the patch to degrade over a period of one week, with negligible adverse reaction and discomfort when applied the skin. The MN patch is designed to meet the FDA recommended dose of hydroxyurea (10 to 40 mg/kg/day) and L-glutamine (5 to 15 g/dose). The synthesis of the MN patch is done by first combining two solutions: (1) GelMA and PLGA (40:60 ratio) in 90% dioxane solution and (2) hydroxyurea and L-glutamine in 5% water solution. The mixture is added to a PDMS mold in a layer-by-layer method, with centrifugation between layers to remove air bubbles. After 5-minute UV curing, the patch is left to dry overnight and ready for use. Our device has achieved the required mechanical force of 0.3N to penetrate the stratum corneum. The MN tips have a height of 600 µm to remain in the viable epidermis and avoid contact with nerves. We have also demonstrated that the MN design has a linear release profile when loaded with L-glutamine. Moreover, we have developed a mass spectrometry-based technology to quantify hydroxyurea concentration in solution. This method enables sensitive and quantitative analysis of the release profile of hydroxyurea from the MN patch in both in vitro and in vivo settings. Our optimized device will be tested on the Townes mouse models, and its therapeutic efficacy will be presented at the 2024 ASH Annual Meeting.

  PublisherDOI

Recent grants

• Hyperpolarized Micro-NMR for Quantitative Analysis of Metabolism in Leukemia Stem Cells

  NIH · $255k · 2018–2020

Frequent coauthors

• Moonjung Jung

  35 shared

• Kayvan R. Keshari

  Memorial Sloan Kettering Cancer Center

  31 shared

• Andrew J. Ewald

  29 shared

• Robert D. Leone

  Johns Hopkins Medicine

  29 shared

• Denis Wirtz

  Johns Hopkins Medicine

  23 shared

• Κωνσταντίνος Κωνσταντόπουλος

  Johns Hopkins University

  23 shared

• Jung-Woo Kim

  Seoul National University

  23 shared

• Roozbeh Eskandari

  Albert Einstein College of Medicine

  22 shared

Labs

• JeongLab@JHUPI

Education

• PhD, Electrical Engineering

  Stanford University

  2013

• BS, Electrical Engineering

  Korea Advanced Institute of Science and Technology

  2007

Awards & honors

• NIH Pathway to Independence Award (K99/R00)
• Hollis Brownstein Research Award (Leukemia Research Foundati…
• NIH Maximizing Investigators’ Research Award (R35)