About

Jason Karpac, PhD, is an Associate Professor at Texas A&M University Naresh K. Vashisht College of Medicine. His laboratory, the Karpac Lab, is broadly interested in the origins of signaling networks that provide animals with metabolic flexibility and the capacity to balance energy homeostasis. These ancient signaling networks, under intense evolutionary pressure, respond to and are shaped by diverse inputs such as nutrient availability, pathogens, and aging. Dr. Karpac primarily uses the fruit fly Drosophila melanogaster as a genetic model to investigate the function and integration of these signaling networks across multiple levels of biological organization, including molecules, cells, tissues, inter-organ communication, organismal physiology, and aging.

Research topics

• Cell biology
• Genetics
• Biology
• Computational biology
• Biochemistry
• Neuroscience
• Immunology

Selected publications

• NF-κB restrains nutrient-dependent transcription programs through chromatin modulation in <i>Drosophila</i>

  Nucleic Acids Research · 2026-01-14

  articleOpen accessSenior author

  The co-evolution of immune and metabolic systems has endowed immune signaling pathways with distinct control of cellular metabolism. Innate immune transcription factors, such as nuclear factor κB (NF-κB), have thus emerged as key regulators of adaptive metabolic responses to changes in diet and nutrition. Utilizing chromatin accessibility genomics, we found that Drosophila NF-κB (Relish) can restrain nutrient-dependent metabolic transcriptional programs that control cellular catabolism of energy substrates, divergent from the protein's canonical role as a transcriptional activator. NF-κB/Relish restricts chromatin accessibility through modulating histone acetylation at metabolic target gene loci, which restrains metabolic gene transcription and blocks excessive activation of nutrient-dependent metabolic programs. Targeted genetic screening revealed that histone deacetylase 6 interacts with NF-κB/Relish at NF-κB DNA regulatory motifs to limit chromatin accessibility and repress metabolic transcriptional programs. These results highlight that innate immune transcription factors can epigenetically restrain cellular catabolism to fine-tune nutrient-dependent metabolic adaptation.

  PublisherDOI

• Diacylglycerol metabolism drives host-pathogen responses during enteric infection in <i>Drosophila</i>

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-09-02

  preprintOpen accessSenior authorCorresponding

  Lipid metabolism is fundamental to cellular homeostasis, supporting energy storage, membrane architecture, and cellular signaling. Beyond these canonical roles, lipids have emerged as critical regulators of host immunity. Here, we define a lipid-driven mechanism that governs host-pathogen interactions by impacting pathogen clearance and thus infection outcomes. Exploiting Drosophila, we show that enteric infection triggers robust accumulation of neutral lipids, and specifically 1,2-diacylglycerols (DAGs), in the midgut. Disruption of DAG biosynthesis or lipid transport in midgut enterocytes (ECs) impairs lipid accumulation and reduces host survival. Conversely, dietary lipid supplementation enhances lipid storage and improves survival. Mechanistically, these lipid-dependent responses regulate defecation, thereby controlling bacterial clearance from the midgut. DAGs can act as signaling lipids that activate protein kinase C (PKC), and DAG accumulation in ECs correlates with elevated PKC activity and calcium signaling in midgut visceral muscle (VM), promoting VM contraction, midgut motility, and expulsion of pathogens via defecation. Together, our findings reveal a previously unrecognized role for DAG metabolism in shaping host defenses.

  PublisherOA PDFDOI

• NF-κB restrains nutrient-dependent transcription programs through chromatin modulation in <i>Drosophila</i>

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-26 · 1 citations

  preprintSenior authorCorresponding

  The co-evolution of immune and metabolic systems has endowed immune signaling pathways with distinct control of cellular metabolism. Innate immune transcription factors, such as nuclear factor κB (NF-κB), have thus emerged as key regulators of adaptive metabolic responses to changes in diet and nutrition. Utilizing chromatin accessibility genomics, we found that Drosophila NF-κB (Relish) can restrain nutrient-dependent metabolic transcriptional programs that control cellular catabolism of energy substrates, divergent from the protein's canonical role as a transcriptional activator. NF-κB/Relish restricts chromatin accessibility through modulating histone acetylation at metabolic target gene loci, which restrains metabolic gene transcription and blocks excessive activation of nutrient-dependent metabolic programs. Targeted genetic screening revealed that histone deacetylase 6 (HDAC6) interacts with NF-κB/Relish at NF-κB DNA regulatory motifs to limit chromatin accessibility and repress metabolic transcriptional programs. These results highlight that innate immune transcription factors can epigenetically restrain cellular catabolism to fine-tune nutrient-dependent metabolic adaptation.

  PublisherDOI

• Inter-organ communication in Drosophila: Lipoproteins, adipokines, and immune-metabolic coordination

  Current Opinion in Cell Biology · 2025-04-06 · 4 citations

  reviewOpen accessSenior authorCorresponding

  Inter-organ communication networks are essential for maintaining systemic homeostasis in multicellular organisms. In Drosophila melanogaster, studies of adipokines and lipoproteins reveal evolutionarily conserved mechanisms coordinating metabolism, immunity, and behavior. This mini-review focuses on two key pathways: the adipokine Unpaired 2 (Upd2) and lipoprotein-mediated signaling. Upd2, a leptin analog, mediates fat-brain communication to regulate insulin secretion, sleep, and feeding behavior. Recent work has uncovered an LC3/Atg8-dependent secretion mechanism for Upd2, linking nutrient sensing to systemic adaptation. Lipoproteins, particularly ApoLpp and LTP, function beyond lipid transport, orchestrating neural maintenance and immune responses. During infection, macrophage-derived signals trigger lipoprotein-mediated lipid redistribution to support host defense. Additionally, muscle tissue emerges as an unexpected mediator of immune-metabolic coordination through inter-organ signaling. These findings highlight the intricate cross-talk between organs required for organismal survival and suggest therapeutic strategies for metabolic disorders.

  PublisherDOI

• Mutant APC reshapes Wnt signaling plasma membrane nanodomains by altering cholesterol levels via oncogenic β-catenin

  Nature Communications · 2023-07-19 · 19 citations

  articleOpen access

  Although the role of the Wnt pathway in colon carcinogenesis has been described previously, it has been recently demonstrated that Wnt signaling originates from highly dynamic nano-assemblies at the plasma membrane. However, little is known regarding the role of oncogenic APC in reshaping Wnt nanodomains. This is noteworthy, because oncogenic APC does not act autonomously and requires activation of Wnt effectors upstream of APC to drive aberrant Wnt signaling. Here, we demonstrate the role of oncogenic APC in increasing plasma membrane free cholesterol and rigidity, thereby modulating Wnt signaling hubs. This results in an overactivation of Wnt signaling in the colon. Finally, using the Drosophila sterol auxotroph model, we demonstrate the unique ability of exogenous free cholesterol to disrupt plasma membrane homeostasis and drive Wnt signaling in a wildtype APC background. Collectively, these findings provide a link between oncogenic APC, loss of plasma membrane homeostasis and CRC development.

  PublisherOA PDFDOI

• Data from Long-Chain n-3 Fatty Acids Attenuate Oncogenic KRas-Driven Proliferation by Altering Plasma Membrane Nanoscale Proteolipid Composition

  2023-03-31

  preprintOpen access

  &lt;div&gt;Abstract&lt;p&gt;Ras signaling originates from transient nanoscale compartmentalized regions of the plasma membrane composed of specific proteins and lipids. The highly specific lipid composition of these nanodomains, termed nanoclusters, facilitates effector recruitment and therefore influences signal transduction. This suggests that Ras nanocluster proteolipid composition could represent a novel target for future chemoprevention interventions. There is evidence that consumption of fish oil containing long-chain n-3 polyunsaturated fatty acids (n-3 PUFA) such as eicosapentaenoic acid (EPA, 20:5&lt;sup&gt;Δ5,8,11,14,17&lt;/sup&gt;) and docosahexaenoic acid (DHA, 22:6&lt;sup&gt;Δ4,7,10,13,16,19&lt;/sup&gt;) may reduce colon cancer risk in humans, yet the mechanism underlying this effect is unknown. Here, we demonstrate that dietary n-3 PUFA reduce the lateral segregation of cholesterol-dependent and -independent nanoclusters, suppressing phosphatidic acid-dependent oncogenic KRas effector interactions, via their physical incorporation into plasma membrane phospholipids. This results in attenuation of oncogenic Ras-driven colonic hyperproliferation in both &lt;i&gt;Drosophila&lt;/i&gt; and murine models. These findings demonstrate the unique properties of dietary n-3 PUFA in the shaping of Ras nanoscale proteolipid complexes and support the emerging role of plasma membrane-targeted therapies.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Significance:&lt;/b&gt; The influence of dietary long chain n-3 polyunsaturated fatty acids on plasma membrane protein nanoscale organization and KRas signaling supports development of plasma membrane-targeted therapies in colon cancer.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Graphical Abstract:&lt;/b&gt; &lt;a href="http://cancerres.aacrjournals.org/content/canres/78/14/0000/F1.large.jpg" target="_blank"&gt;http://cancerres.aacrjournals.org/content/canres/78/14/3899/F1.large.jpg&lt;/a&gt;. &lt;i&gt;Cancer Res; 78(14); 3899–912. ©2018 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;

  PublisherDOI

• Supplemental Figure Legends from Long-Chain n-3 Fatty Acids Attenuate Oncogenic KRas-Driven Proliferation by Altering Plasma Membrane Nanoscale Proteolipid Composition

  2023-03-31

  preprintOpen access

  &lt;p&gt;Contains the legend text for supplemental figures 1, quantitative pERK analysis images.Supplemental figures 2, pERK Western. Supplemental figures 3, Drosophila corn oil FLIM-FRET.&lt;/p&gt;

  PublisherDOI

• Supplemental Figures from Long-Chain n-3 Fatty Acids Attenuate Oncogenic KRas-Driven Proliferation by Altering Plasma Membrane Nanoscale Proteolipid Composition

  2023-03-31

  preprintOpen access

  &lt;p&gt;Contains Supplemental Figure 1, photomicrographs of cells demonstrating the method for determining quantitative pERK levels. Supplemental Figure 2, pERK, ERK, and Ras western images. Supplemental Figure 3, charts representing data from FLIM-FRET experiments on corn oil fed drosophila.&lt;/p&gt;

  PublisherDOI

• Supplemental Figures from Long-Chain n-3 Fatty Acids Attenuate Oncogenic KRas-Driven Proliferation by Altering Plasma Membrane Nanoscale Proteolipid Composition

  2023-03-31

  preprintOpen access

  &lt;p&gt;Contains Supplemental Figure 1, photomicrographs of cells demonstrating the method for determining quantitative pERK levels. Supplemental Figure 2, pERK, ERK, and Ras western images. Supplemental Figure 3, charts representing data from FLIM-FRET experiments on corn oil fed drosophila.&lt;/p&gt;

  PublisherOA PDFDOI

• Supplemental Tables from Long-Chain n-3 Fatty Acids Attenuate Oncogenic KRas-Driven Proliferation by Altering Plasma Membrane Nanoscale Proteolipid Composition

  2023-03-31

  preprintOpen access

  &lt;p&gt;Contains Supplemental Table 1, drosophila diet fatty acid composition. Supplemental Table 2, mouse diet composition. Supplemental Table 3, mouse diet fatty acid composition. Supplemental Table 4, incorporation of exogenous fatty acids into murine colonic crypt membrane phospholipids. Supplemental Table 5, incorporation of exogenous corn oil fatty acids into Drosophila gut membrane phospholipids.&lt;/p&gt;

  PublisherDOI

Recent grants

• Stress signaling in Insulin Producing Cells

  NIH · $150k · 2009–2011

• Foxo/NFkB Interactions in the Regulation of Metabolic Homeostasis

  NIH · $1.7M · 2016–2021

Frequent coauthors

• Mohamed Mlih

  Texas A&M University

  18 shared

• Xiao Zhao

  Shanghai First People's Hospital

  16 shared

• Heinrich Jasper

  16 shared

• Robert S. Chapkin

  Texas A&M University

  13 shared

• Natividad R. Fuentes

  The University of Texas MD Anderson Cancer Center

  11 shared

• Ian A. Prior

  10 shared

• Spencer T. Behmer

  Texas A&M University

  10 shared

• Trevor J. Steele

  10 shared

Labs

• The Karpac LabPI