About

Jeremy Garcia, of Hopi/Tewa descent and belonging to the Hospoawungwa (Roadrunner) clan, is an Associate Professor of Indigenous Education in the Department of Teaching, Learning, and Sociocultural Studies at the University of Arizona's College of Education. His research focuses on decolonization, critical Indigenous curriculum and pedagogy, Indigenous teacher education, and critical and culturally sustaining family and community engagement. He supports Indigenous educators by developing curriculum grounded in Indigenous knowledge and values, including work with the Hopi Kuuyi (Water) Curriculum and the Hopi Natwani (traditional farming) curriculum in Arizona. Currently, he collaborates with Hopi educators and the Hopi Cultural Preservations Office to create curriculum related to the history and trauma of the Moquis and Kastiilam peoples. Garcia is also a co-founding Director of the Indigenous Teacher Education Program (ITEP) at the University of Arizona. His recent publication includes a co-edited book titled 'Indigenizing Education: Transformative Research, Theories, and Praxis' (2022). Prior to his current role, he served as an Assistant Professor at the University of Wisconsin-Milwaukee and held a vital role in developing the first Native American Educational and Cultural Center at Purdue University. His background includes experience as an elementary school teacher and parent engagement coordinator on the Salt River Pima-Maricopa Indian Reservation in Arizona. He holds an undergraduate degree in Elementary Education from Northern Arizona University, an M.A. in Curriculum and Instruction from Michigan State University, and a Ph.D. in Curriculum Studies from Purdue University.

Research topics

• Medicine
• Internal medicine
• Biology
• Immunology
• Cancer research
• Oncology
• Endocrinology
• Genetics
• Pathology
• Cell biology

Selected publications

• CYP4F11, an NRF2 Target Gene, Promotes Hepatocellular Carcinoma Cell Growth

  Molecular Carcinogenesis · 2025-05-06 · 2 citations

  article

  Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, is the third leading cause of cancer-related mortality globally. Current systemic therapies for HCC are limited and often exhibit unsatisfactory efficacy, underscoring the need for novel therapeutic approaches. Nuclear factor erythroid 2-related factor-2 (NRF2), a master transcription factor regulating cellular redox and metabolic homeostasis, is frequently overexpressed in HCC due to mutations in NFE2L2/NRF2 or its negative regulator Kelch-like ECH-associated protein 1 (KEAP1), contributing to tumor progression. In this study, we identify CYP4F11, a member of the Cytochrome P450 family, as a direct target gene of NRF2. CYP4F11, primarily expressed in the liver, is crucial in fatty acid oxidation and eicosanoid metabolism. We demonstrate that CYP4F11 expression is driven by NRF2 and is significantly elevated in HCC patients harboring NFE2L2 gain of function or KEAP1 loss of function mutations. Functionally, CYP4F11 promotes HCC cell growth, and reduced expression of CYP4F11 not only suppresses HCC cell proliferation but also enhances sorafenib-induced HCC cell death. Further, NRF2 inhibition sensitizes HCC to sorafenib through downregulation of CYP4F11. These findings position CYP4F11 as a novel contributor to HCC progression and highlight the potential of targeting the NRF2-CYP4F11 axis for HCC treatment.

  PublisherDOI

• Small Molecule Degradation of the microRNA-21 Precursor Rescues Pathogenic Pathways in Cellular Models of Fibrosis

  ACS Chemical Biology · 2025-12-12

  articleOpen access

  MicroRNAs (miRNAs) are short RNA molecules that bind to target mRNAs, resulting in translational repression and gene silencing. Overexpression of microRNA-21 (miR-21) is associated with various human diseases, including autosomal dominant polycystic kidney disease (ADPKD) and pulmonary fibrosis. In this study, a previously described heterobifunctional molecule, TGP-21-RiboTAC, that degrades the miR-21 precursor (pre-miR-21) in triple-negative breast cancer cells was investigated in polycystic kidney cell lines and a lung fibroblast cell line. In the former, TGP-21-RiboTAC degraded pre-miR-21 and derepressed miR-21's downstream targets, programmed cell death 4 (PDCD4) and peroxisome proliferator-activated receptor alpha (PPARα), known drivers of ADPKD. The heterobifunctional molecule also inhibited cyst growth and rescued the metabolic alterations that occur in ADPKD. In the lung fibroblast cell line, MRC-5, TGP-21-RiboTAC also reduced pre- and mature miR-21 levels, rescued transforming growth factor β (TGF-β)-induced repression of SMAD family member 7 (SMAD7), and inhibited cell invasion. Collectively, these studies demonstrate the potential of targeted RNA degradation as therapeutic agents that retard the development of organ fibrosis.

  PublisherOA PDFDOI

• Neurotrauma Biomarkers in Patients With Acute Respiratory Distress Syndrome

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

  articleSenior author

  Abstract RATIONALE: The lung-brain axis has emerged as a significant area of clinical importance with central nervous system and respiratory system injuries demonstrating bi-directional impact. Unfortunately, effective therapeutics for addressing this pathological cross talk remains an unmet need, due in part to the absence of reliable biomarkers that reflect the severity of lung-brain axis disruption. We assessed specific biomarkers in subjects with traumatic brain injury (TBI), a major public health concern affecting 1.4million Americans annually, and subjects with Acute Respiratory Distress Syndrome (ARDS), a life-threatening inflammatory lung injury responsible for more than 10% of ICU admissions each year with a 30-40% mortality. METHODS: Serum collected from TBI subjects (n=63, ∼47y/o, ∼20hr post), ARDS (n=39, ∼52y/o, ∼ day 1), and healthy patients (n=40, ∼50y/o) was analyzed via Meso Scale Discovery ELISA for inflammatory biomarkers (eNAMPT, IL-6, PSGL-1, ANG-2, IL-1β, IL-1RA, TNF-α, S100A8) and neurotrauma biomarkers (Glial fibrillary acidic protein [GFAP], Neuro filament light chain [NFL], Tau). Outliers were removed via ROUT analysis; results were analyzed utilizing Mann-Whitney, Kruskal-Wallis w/ Dunn, and Receiver Operating Characteristic (ROC) Curve analysis. RESULTS: All biomarkers were significantly elevated in TBI patients compared to controls except for PSGL-1 (4xeNAMPT, 21x IL-6, 2x Ang-2, 13x IL-1β,3x IL-1RA, 2x TNF-α, 3x S100A8, 136xGFAP, 9x NFL, 9x Tau). ARDS patients demonstrated significantly elevated levels of all biomarkers compared to controls except for GFAP (8x eNAMPT, 12x IL-6, 5xAng-2, 13x IL-1β, 6x IL-1RA, 1.3xPSGL-1, 3x TNF-α, 3x S100A8, 11x NFL, 5xTau). Comparing ARDS to TBI, IL-6 was significantly higher in TBI subjects (2x)whereas eNAMPT, TNF-α, and Ang-2 were all significantly elevated (2x) in ARDS. GFAP was significantly elevated only in TBI. CONCLUSIONS: The elevations in inflammatory biomarkers in TBI- and ARDS-exposed subjects without neuro trauma reflect shared activation of innate immunity consistent with the observation that 25% of TBI patients develop lung injury (including ARDS) supporting lung brain axis disruption. GFAP appears to be a TBI-specific biomarker with the elevations in NFL and Tau in ARDS subjects potentially reflecting peripheral neurological damage without lung brain axis disruption. Longitudinal studies of well-phenotyped TBI and ARDS subjects are needed to disclose the integrated inflammatory responses and the value of inflammatory biomarker testing to detect bidirectional injuries.

  PublisherDOI

• The transcriptome of CD14 ⁺ CD163 ⁻ HLA-DR ^low monocytes predicts mortality in idiopathic pulmonary fibrosis

  European Respiratory Journal · 2025-12-05 · 1 citations

  articleOpen access

  Background The association between immune-cell-specific transcriptomic profiles and mortality in idiopathic pulmonary fibrosis (IPF) is unknown. Methods We profiled peripheral blood mononuclear cells by single-cell RNA sequencing (scRNA-seq) and investigated which immune-cell-specific transcriptomic profile predicted IPF outcomes consistently. Prognostic accuracy was investigated in peripheral blood mononuclear cells (PBMCs), bronchoalveolar lavage (BAL) and lung tissue. Findings were validated by flow cytometry, analysis of independent scRNA-seq datasets and cellular deconvolution. We investigated the function of this transcriptomic profile and its cellular source in lung tissue (overall sample size, n=1054; IPF, n=555; other, n=499). Connectivity map analysis and LASSO regression were used to identify drug candidates and a subset of genes with prognostic potential, respectively. Results A 230-gene up-score (Pittsburgh PBMC cohort) from CD14 + CD163 − HLA-DR low monocytes predicted mortality in the Chicago PBMC cohort (HR 6.58, 95% CI 2.15–20.13; p=0.001), in BAL pooled analysis (HR 2.20, 95% CI 1.44–3.37; p=0.0003), and negatively correlated with forced vital capacity in lung tissues (ρ= −0.2, p=0.02). Proportions of CD14 + CD163 − HLA-DR low monocytes were higher in progressive versus stable IPF (12.59%, 95% CI 9.66–16.23%, versus 7.61%, 95% CI 6.68–10.21%; p=0.014). High-risk patients with IPF had decreased expression of T-cell co-stimulatory genes (Pittsburgh and Chicago, p<0.01). CD14 + HLA-DR low monocytes had higher expression of profibrotic, proangiogenic and chemotactic factors compared to CD14 + HLA-DR hi monocytes (p<0.05). The 230-gene up-score correlated with the secreted phosphoprotein 1 (SPP1) + fibrosis-associated macrophages gene-score in lung tissues (ρ=0.19, p<2.2e −16 ). Connectivity map analysis identified drug categories to reverse the 230-gene signature. A subset of six genes retained predictive performance (pooled PBMC cohorts HR 4.79, 95% CI 2.58–8.92; p<0.0001). Conclusions The transcriptome of CD14 + CD163 − HLA-DR low monocytes is associated with increased mortality in patients with IPF. Its reversal should be investigated as a precision-based therapy in IPF.

  PublisherOA PDFDOI

• Lung-brain axis-generated inflammatory biomarkers in traumatic brain injury and acute respiratory distress syndrome: Role of mechanical ventilation/stress

  Advances in Biomarker Sciences and Technology · 2025-01-01

  articleOpen accessSenior author

  RATIONALE: The unmet need for effective therapeutic strategies to address the bidirectional perturbation of the lung-brain axis following traumatic brain injury (TBI) or associated with Acute Lung Injury/Acute Respiratory Distress Syndrome (ALI/ARDS) is increasingly recognized. Contributing to this unmet need is the absence of reliable biomarkers that reflect the severity of lung-brain axis disruption. We assessed specific potential lung-brain axis biomarkers in TBI and ALI/ARDS subjects and explored the specific influence of exposure to mechanical ventilation. METHODS: Serum biomarker levels from TBI (n=97) and ARDS subjects (n=39) and healthy controls (n=46) were analyzed (MesoScale Discovery ELISA) utilizing a critical illness lung-brain axis biomarker panel (CILBA) that included DAMPS (eNAMPT, S100A8), inflammatory cytokines (IL-6, IL-1β, IL-1RA, TNF-α), vascular biomarkers (PSGL-1, ANG-2), and neurotrauma biomarkers (GFAP or Glial fibrillary acidic protein, NFL or neurofilament light chain, Tau). RESULTS: TBI and ARDS subjects demonstrated significant elevations in each biomarker (compared to controls) with two exceptions: PSGL-1 was exclusively elevated in ARDS and GFAP exclusively elevated in TBI. Mechanically ventilated subjects exposed exhibited significantly DAMP, vascular and neurotrauma biomarker elevations compared to unexposed subjects. With the exception of GFAP, Ang-2, and S100A8, biomarker elevations were linked to ICU days or mortality. CONCLUSIONS: These results highlight overlapping innate immunity dysregulation as a manifestation of lung-brain axis disruption in both TBI- and ARDS-exposed subjects with amplified dysregulation with mechanical ventilation. Additional longitudinal studies of well-phenotyped TBI and ARDS subjects may substantiate the prognostic value of biomarker analyses in assessing the severity of bidirectional lung-brain axis injuries.

  PublisherDOI

• NEDD4 E3 ligase-catalyzed NAMPT ubiquitination and autophagy activation are essential for pyroptosis-independent NAMPT secretion in human monocytes

  Cell Communication and Signaling · 2025-03-30 · 8 citations

  articleOpen accessSenior author

  salvage pathway. However, increased cellular stress (infection, inflammation, hypoxia) promotes the secretion of extracellular NAMPT (eNAMPT), a TLR4 ligand and damage-associated molecular pattern protein (DAMP) that directly drives amplification of innate immune-mediated inflammatory, fibrotic, and neoplastic responses to influence disease severity. We sought to examine the mechanisms underlying pyroptotic eNAMPT release from human monocytic THP-1 cells, evoked by Nigericin, and non-pyroptotic eNAMPT secretion elicited by lipopolysaccharide (LPS). Our data indicate eNAMPT secretion/release requires NLRP3 inflammasome activation with substantial attenuation by either NLRP3 inhibition (MCC-950) or targeted genetic deletion of key inflammasome components, including NLRP3, caspase-1, or gasdermin D (GSDMD). Pyroptosis-associated eNAMPT release involved cleavage of the pore-forming GSDMD protein resulting in plasma membrane rupture (PMR) whereas non-pyroptotic LPS-induced eNAMPT secretion involved neither GSDMD cleavage nor PMR, verified utilizing non-cleavable GSDMD mutant constructs. LPS-induced eNAMPT secretion, however, was highly dependent upon NAMPT ubiquitination catalyzed by a complex containing the NEDD4 E3 ligase, Hsp90 (a selective chaperone), and intact GSDMD verified by enzymatic inhibition or silencing of NEDD4, GSDMD, or Hsp90. NAMPT ubiquitination and secretion involves autophagy activation as super-resolution microscopy analyses demonstrate NAMPT co-localization with autophagosome marker LC3B and eNAMPT secretion was significantly reduced by targeted ATG5 and ATG7 inhibition, critical components of the autophagy E3-like complex. These studies provide key insights into eNAMPT secretion that may accelerate the development of therapeutic strategies that address unmet therapeutic needs in inflammatory, fibrotic and neoplastic disorders.

  PublisherOA PDFDOI

• Tailored CD4+ lymphocytes expressing human CHAT protein as a novel vasodilator in attenuating RV pressure in PAH animal model

  Translational research · 2025-02-15

  article
  PublisherDOI

• Abstract 3920: The role of humanized monoclonal antibody ALT-100 in reducing cancer-induced bone pain: A murine animal model study

  Cancer Research · 2025-04-21

  article

  Abstract Breast cancer commonly metastasises to the bone promoting a combination of inflammatory and neuropathic mechanisms. This leads to different perceptions of pain with a reported 30-50% of all cancer patients and 75-90% of late-stage patients having cancer-induced bone pain (CIBP). Thus, there is a need for therapeutic interventions to decrease pain caused by the mechanisms of CIBP. Extracellular Nicotinamide Phosphoribosyltransferase (eNAMPT) is a cytokine overexpressed in metastatic breast carcinoma that binds to Toll-like Receptor 4 (TLR4), triggering a signaling cascade through Nuclear Factor kappa beta (NFk-B) and resulting in inflammation, osteoclastogenesis, and severe bone pain. To assess the impact of eNAMPT on CIBP, ALT-100, a monoclonal antibody neutralizing eNAMPT, was tested in a murine CIBP model. The left femur of C57BL/6J female mice was inoculated with EO771 breast cancer cells and allowed 7 days for recovery from tumor growth and the development of cancer-induced pain. Behavioral data were collected to evaluate ALT-100's effectiveness in reducing pain. Four groups were used: sham + saline, sham + ALT-100, cancer + ALT-100, and cancer + saline, with ALT-100 dosed at 4 mg/kg. Pain was assessed on days 0, 7 (pre- and 2 hours post-injection of ALT-100), 10, and 14 using flinching and guarding behavior tests. A two-way ANOVA and Tukey's multiple comparisons test indicated that ALT-100 significantly reduced pain compared to the cancer + saline group. Bone scoring on days 0 and 14 showed no significant differences in bone lesions and fractures between cancer + ALT-100 and cancer + saline groups. To test ALT-100's efficacy in inhibiting osteoclastogenesis in vitro, RAW 264.7 macrophage cells were plated in five groups exposed to different drug combinations: media, eNAMPT, ALT-100, 1:1 eNAMPT + ALT-100, and 1:2 eNAMPT + ALT-100. After 5 days a marker for osteoclastogenesis, Tartrate-Resistant Acid Phosphatase staining, was measured demonstrating that cells treated with ALT-100 + eNAMPT had significantly fewer osteoclasts than those treated with eNAMPT alone. Together these results indicate that ALT-100 inhibits metastatic breast cancer pain and eNAMPT-induced osteoclast differentiation. Citation Format: Nikhil C. Mathur, Ethan Villarroel, Isabella Villarroel, Erfan Bahramnedjad, Sally Dickinson, Joe G. Garcia, Tally Largent-Milnes, Todd W. Vanderah. The role of humanized monoclonal antibody ALT-100 in reducing cancer-induced bone pain: A murine animal model study [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 3920.

  PublisherDOI

• Dysregulated Tricarboxylic Acid Cycle Metabolism Is Associated With Right Ventricular Maladaptation in Pulmonary Vascular Disease

  Journal of the American Heart Association · 2025-05-22 · 7 citations

  articleOpen access

  BACKGROUND: Right ventricular (RV) maladaptation to elevated pulmonary afterload is the primary determinant of outcomes in pulmonary artery (PA) hypertension; however, the pathobiological mechanisms underlying RV decompensation remain poorly understood. METHODS: We performed global untargeted metabolomics on plasma from 55 patients who underwent gold-standard RV-PA coupling measurements using multibeat pressure volume loop assessment in a single-center cohort and from 1027 patients with coupling surrogate measurements in a larger multicenter cohort, the PVDOMICS (Pulmonary Vascular Disease Phenomics) study. Age and sex-adjusted linear regression was performed to identify associations between metabolites and coupling metrics. Additionally, we performed a metabolic flux analysis using gene expression data from RV tissue in an independent cohort of 32 patients. Partial least squares-discriminant analysis was used to identify metabolites and reactions characteristic of the decompensated RV. RESULTS: RV-PA coupling was negatively associated with tricarboxylic acid (TCA) cycle intermediate levels. Specifically, plasma α-ketoglutarate and fumarate were significantly associated with all coupling metrics in both cohorts. Metabolic flux analysis indicated that decompensated RVs exhibited aberrant TCA cycle activity, including reduced acetyl coenzyme A entry and increased lactate elimination, suggesting a shift from the TCA cycle toward glycolysis at the RV tissue level. CONCLUSIONS: We identify an association between circulating TCA cycle intermediate levels and RV-PA uncoupling in 2 independent cohorts, and dysregulated TCA cycle metabolism in decompensated PA hypertension RVs, suggesting that aberrant TCA cycle metabolism could represent a hallmark of RV maladaptation in PA hypertension. Further study of this pathway is warranted to develop novel biomarkers of RV function or RV-targeted therapies.

  PublisherDOI

• eNAMPT Is a Novel DAMP and Therapeutic Target in Human and Murine Pulmonary Fibrosis

  American Journal of Respiratory Cell and Molecular Biology · 2025-03-24 · 10 citations

  articleOpen accessSenior author

  Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disorder without curative therapies, underscoring the critical unmet need for identification of novel therapeutic strategies. eNAMPT (extracellular nicotinamide phosphoribosyltransferase) is a damage-associated molecular pattern protein (DAMP) and TLR4 (Toll-like receptor 4) ligand that contributes to the severity of radiation-induced lung fibrosis and nonalcoholic steatohepatitis-associated hepatic fibrosis. This study investigates eNAMPT as a druggable target in human and preclinical IPF using the eNAMPT-neutralizing ALT-100 monoclonal antibody (mAb). Blood, peripheral blood mononuclear cells (PBMCs), and lung tissues from patients with IPF and from an experimental bleomycin-induced lung fibrosis model in C57Bl6 mice were analyzed. Biochemical and histologic measurements, as well as gene expression through bulk and single-cell RNA sequencing of human PBMCs and murine lung tissues, were performed. Human studies revealed NAMPT expression to be significantly increased in plasma, lung tissues, and PBMCs from subjects with IPF, correlating with disease severity and inversely associated with IPF survival. Bleomycin-exposed mice exhibited increased inflammatory indices associated with lung fibrosis development (including NAMPT levels), as well as physiologic lung stiffening and TGF-β pathway-related protein and gene expression, with each index significantly mitigated in mice receiving ALT-100 mAb. Single-cell RNA sequencing studies demonstrated the ALT-100 mAb to reverse the bleomycin-induced dramatic expansion of alveolar type 2 epithelium and induction of endothelial cell- and epithelial cell-to-mesenchymal/myofibroblast transitions. These finding support the fundamental involvement of eNAMPT/TLR4 signaling pathway in lung fibrosis pathobiology, with eNAMPT neutralization a viable therapeutic strategy to directly address the unmet need for novel IPF treatments.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01HL069340

  NIH · $368k · 2002

• NIH Grant U01HL112696

  NIH · $470k · 2016

• NIH Grant R41HL140741

  NIH · $225k · 2020

• NIH Grant U01HL066583

  NIH · $2.0M · 2006

• NIH Grant P01HL098050

  NIH · $21.9M · 2017

Frequent coauthors

• Roberto F. Machado

  Indiana University – Purdue University Indianapolis

  319 shared

• Viswanathan Natarajan

  University of Illinois Chicago

  255 shared

• Sara M. Camp

  University of Florida

  249 shared

• Jason X.‐J. Yuan

  University of California System

  207 shared

• Alexander D. Verin

  Augusta University Health

  198 shared

• Steven M. Dudek

  University of Illinois Chicago

  192 shared

• Haiyang Tang

  University of Arizona

  192 shared

• Taimur Abbasi

  Massachusetts General Hospital

  189 shared

Education

• MD

  University of Texas Southwestern Medical Center

  1980

• BS

  University of Dallas

  1976