About

Alisa Huffaker received her Ph.D. from the Institute of Biological Chemistry at Washington State University and continued her postdoctoral training there in plant defense signaling. She joined the section of Cell and Developmental Biology at UC San Diego in 2014. Her research centers on plant peptide signals, known as Peps, which regulate broad spectrum plant defense responses against pathogens and herbivores. Her work involves studying the interaction of Plant Elicitor Peptides (Peps) and their receptors (PEPRs), which coordinate plant immunity by perceiving foreign molecules associated with attacking microbes and herbivores, leading to complex defense responses. Dr. Huffaker's research also explores the role of endogenous peptides like AtPep1 in Arabidopsis and their orthologs in other plant species, including maize, to understand how these signals enhance resistance to various biotic stresses. Her current efforts focus on studying Pep-PEPR ligand-receptor interactions, characterizing downstream signaling components, and developing Pep-based strategies to improve plant immunity against pathogens and pests.

Research topics

• Biology
• Genetics
• Computational biology
• Cell biology
• Biochemistry
• Botany

Selected publications

• Overexpression of <i>AtPROPEP6</i> enhances <i>Arabidopsis thaliana</i> resistance to Southern root-knot nematode <i>Meloidogyne incognita</i>

  Plant Signaling & Behavior · 2026-02-08

  articleOpen access

  as a paralog contributing to plant defense against nematodes.

  PublisherDOI

• Overexpression of <i>AtPROPEP6</i> enhances <i>Arabidopsis thaliana</i> resistance to Southern root-knot nematode <i>Meloidogyne incognita</i>

  Figshare · 2026-01-01

  articleOpen access

  Plant elicitor peptides (Peps), derived from PROPEP protein precursors, are stress-induced signaling molecules that enhance plant immunity. While previous studies of Pep-mediated immune signaling in <i>Arabidopsis thaliana</i> have focused on the roles of <i>AtPROPEP1–3</i> genes in bacterial and fungal resistance, this study identifies the <i>AtPROPEP6</i> gene as a contributor to defense against the Southern root-knot nematode (<i>Meloidogyne incognita)</i>. <i>In silico</i> promoter analysis revealed enrichment of W box motifs, suggesting potential regulation by WRKY transcription factors associated with plant immune responses. Unlike other <i>PROPEP</i> gene family members, <i>AtPROPEP6</i> shows specific upregulation in response to ascr#18, a nematode-derived molecular pattern, but not to other pathogen elicitors. Transgenic constitutive overexpression of <i>AtPROPEP6</i> in <i>A. thaliana</i> significantly reduced gall formation and total nematode numbers and delayed nematode development. These phenotypes correlated with <i>AtPROPEP6</i> transcript abundance in three independent transgenic lines and were accompanied by elevated basal <i>AtPR1a</i> expression. Although <i>AtPROPEP6</i>-overexpressing plants exhibited shorter roots, the extent of root length reduction did not align with transgene expression levels, and the number of root tips available for infection remained unchanged. Our findings expand the repertoire of defense-associated <i>A. thaliana PROPEP</i>s beyond <i>AtPROPEP1–3</i> and identify <i>AtPROPEP6</i> as a paralog contributing to plant defense against nematodes.

  PublisherDOI

• Discovery of the rosalexin pathway expands the modular network of maize diterpenoid chemical defenses

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-04-17

  articleOpen access

  Abstract The evolutionary expansion of specialized metabolism has shaped the ability of plants to adapt to combined pathogen, pest, and other environmental pressures. For instance, the duplication and divergence of ancestral gibberellin pathway genes have given rise to specialized kauralexin and dolabralexin diterpenoids in maize ( Zea mays ) that serve as core components of disease resistance and stress adaptation. Here, we describe the biosynthesis and elicited production of rosalexins as a previously unrecognized component of the maize chemical defense network. By integrating genomics-enabled gene discovery, combinatorial enzyme assays, and AI-assisted enzyme mechanistic studies we show that maize rosalexin biosynthesis proceeds via a distinct 5-rosanol scaffold formed by the pairwise activity of two diterpene synthases, ZmTPS38/CPS2/AN2 and ZmTPS42/KSL1, recruited from gibberellin metabolism. Further oxygenation by the promiscuous P450 enzyme, ZmCYP71Z18, yields epoxyrosanol that, in turn, can undergo epoxide ring opening to form trihydroxyrosanol. Epoxyrosanol, but not 5-rosanol or trihydroxyrosanol, display strong inhibitory activity on fungal pathogen growth in vitro , highlighting the contribution of the epoxide group to antibiotic efficacy. Large variation in rosalexin presence and abundance exists across maize genotypes due to expansive ZmTPS42/KSL1 gene sequence variation and pseudogenization. Transcriptomics and targeted metabolomics demonstrated the pathogen-elicited accumulation of rosalexins in maize lines featuring functional ZmTPS42/KSL1 genes. However, no dominant pathogen resistance phenotype was observed in association with rosalexin abundance. These collective findings expand our knowledge of how multiple interconnected diterpenoid pathways arose in maize via duplication of hormone-metabolic genes and enable the utilization of a common precursor to form modular chemical defense layers. Significance Statement Plant diterpenoids play critical roles in crop development, stress defense and ecological adaptation. In maize, diterpenoids serve as key components of chemical defenses against pests and diseases with direct impact on crop immunity and vigor. Enzymes of the diterpene synthase and cytochrome P450 families largely drive diterpenoid chemical diversity. This study reports the discovery and characterization of the pathway forming rosalexin diterpenoids in maize. Pathogen-elicited accumulation and in vitro antifungal activity of rosalexin metabolites supports a physiological function in maize chemical defense.

  PublisherDOI

• Overexpression of <i>AtPROPEP6</i> enhances <i>Arabidopsis thaliana</i> resistance to Southern root-knot nematode <i>Meloidogyne incognita</i>

  Open MIND · 2026-01-01

  article

  Plant elicitor peptides (Peps), derived from PROPEP protein precursors, are stress-induced signaling molecules that enhance plant immunity. While previous studies of Pep-mediated immune signaling in <i>Arabidopsis thaliana</i> have focused on the roles of <i>AtPROPEP1–3</i> genes in bacterial and fungal resistance, this study identifies the <i>AtPROPEP6</i> gene as a contributor to defense against the Southern root-knot nematode (<i>Meloidogyne incognita)</i>. <i>In silico</i> promoter analysis revealed enrichment of W box motifs, suggesting potential regulation by WRKY transcription factors associated with plant immune responses. Unlike other <i>PROPEP</i> gene family members, <i>AtPROPEP6</i> shows specific upregulation in response to ascr#18, a nematode-derived molecular pattern, but not to other pathogen elicitors. Transgenic constitutive overexpression of <i>AtPROPEP6</i> in <i>A. thaliana</i> significantly reduced gall formation and total nematode numbers and delayed nematode development. These phenotypes correlated with <i>AtPROPEP6</i> transcript abundance in three independent transgenic lines and were accompanied by elevated basal <i>AtPR1a</i> expression. Although <i>AtPROPEP6</i>-overexpressing plants exhibited shorter roots, the extent of root length reduction did not align with transgene expression levels, and the number of root tips available for infection remained unchanged. Our findings expand the repertoire of defense-associated <i>A. thaliana PROPEP</i>s beyond <i>AtPROPEP1–3</i> and identify <i>AtPROPEP6</i> as a paralog contributing to plant defense against nematodes.

  DOI

• A multifunctional sesquiterpene synthase integrates with cytochrome P450s to reinforce the terpenoid defense network in maize

  The Plant Journal · 2025-11-01

  articleOpen access

  Terpenoids, the largest and most structurally diverse class of plant natural products, play essential roles in maize defense and ecological interactions. In this study, we identified and functionally characterized a sesquiterpenoid-based defense pathway in maize centered on α-santalenoic acid, a pathogen-inducible sesquiterpenoid antibiotic. Using a combination of metabolite-based genome-wide association studies (mGWAS), linkage mapping, and heterologous expression assays, we identified ZmTPS9 as a multiproduct terpene synthase that primarily produces α-santalene and β-bisabolene. Sequence analysis and site-directed mutagenesis revealed that threonine at position 413 is critical for enzyme activity, with its deletion resulting in a complete loss of enzyme activity. The sesquiterpene hydrocarbons produced by ZmTPS9 are further oxidized by three cytochrome P450 monooxygenases, ZmCYP71Z16, ZmCYP71Z18, and ZmCYP71Z19, to yield antimicrobial metabolites including α-santalenoic acid, zealexin D1 (ZD1), and zealexin D2 (ZD2). Together, these findings demonstrate a convergent biosynthetic strategy in maize, where multiproduct terpene synthases and promiscuous P450s collaboratively generate a flexible and robust terpenoid defense network.

  PublisherOA PDFDOI

• Field Evaluation of Experimental Maize Hybrids for Resistance to the Fall Armyworm (Lepidoptera: Noctuidae) in a Warm Temperate Climate

  Insects · 2024-04-19 · 4 citations

  articleOpen access

  The polyphagous fall armyworm (FAW), Spodoptera frugiperda, has become an invasive pest worldwide in recent years. To develop maize germplasm with multiple pest resistance and understand genetic inheritance, 12 experimental hybrids (six pairs of reciprocal crosses) with diverse genetic backgrounds and four commercial checks were examined for FAW resistance in 2013 and 2014. The experiment utilized a randomized complete block design with four replications as the block factor. FAW injury on maize plants was assessed at 7 and 14 d after the artificial infestation at the V6 stage, and predatory arthropod taxa and abundance on maize seedlings were recorded 7 d after the infestation. Spodoptera frugiperda resistance varied significantly among the 16 hybrids. Two reciprocal crosses (‘FAW1430’ × ‘Oh43’ and ‘CML333’ × ‘NC358’) showed the least FAW injury. Eleven arthropod predators [i.e., six coleopterans, three hemipterans, earwigs (dermapterans), and spiders (or arachnids)] were also recorded; the two most common predators were the pink spotted ladybeetle, Coleomegilla maculata, and the insidious flower (or minute pirate) bug, Orius spp. Predator abundance was not correlated to FAW injury but varied greatly between 2013 and 2014. Principal component analysis demonstrated that, when compared with FAW resistant (or Bt-transgenic) checks (‘DKC69-71’, ‘DKC67-88’, and ‘P31P42’), five pairs of the reciprocal crosses had moderate FAW resistance, whereas a pair of reciprocal crosses (‘NC350’ × ‘NC358’ and NC358 × NC350) showed the same FAW susceptibility as the non-Bt susceptible check ‘DKC69-72’. Both parents contributed similarly to FAW resistance, or no maternal/cytoplasmic effect was detected in the experimental hybrids.

  PublisherOA PDFDOI

• Maize Terpene Synthase 8 (ZmTPS8) Contributes to a Complex Blend of Fungal-Elicited Antibiotics

  Plants · 2023-03-01 · 6 citations

  articleOpen access

  In maize (Zea mays), fungal-elicited immune responses include the accumulation of terpene synthase (TPS) and cytochrome P450 monooxygenases (CYP) enzymes resulting in complex antibiotic arrays of sesquiterpenoids and diterpenoids, including α/β-selinene derivatives, zealexins, kauralexins and dolabralexins. To uncover additional antibiotic families, we conducted metabolic profiling of elicited stem tissues in mapping populations, which included B73 × M162W recombinant inbred lines and the Goodman diversity panel. Five candidate sesquiterpenoids associated with a chromosome 1 locus spanning the location of ZmTPS27 and ZmTPS8. Heterologous enzyme co-expression studies of ZmTPS27 in Nicotiana benthamiana resulted in geraniol production while ZmTPS8 yielded α-copaene, δ-cadinene and sesquiterpene alcohols consistent with epi-cubebol, cubebol, copan-3-ol and copaborneol matching the association mapping efforts. ZmTPS8 is an established multiproduct α-copaene synthase; however, ZmTPS8-derived sesquiterpene alcohols are rarely encountered in maize tissues. A genome wide association study further linked an unknown sesquiterpene acid to ZmTPS8 and combined ZmTPS8-ZmCYP71Z19 heterologous enzyme co-expression studies yielded the same product. To consider defensive roles for ZmTPS8, in vitro bioassays with cubebol demonstrated significant antifungal activity against both Fusarium graminearum and Aspergillus parasiticus. As a genetically variable biochemical trait, ZmTPS8 contributes to the cocktail of terpenoid antibiotics present following complex interactions between wounding and fungal elicitation.

  PublisherOA PDFDOI

• 9,10-KODA, an α-ketol produced by the tonoplast-localized 9-lipoxygenase ZmLOX5, plays a signaling role in maize defense against insect herbivory

  Molecular Plant · 2023-07-11 · 30 citations

  articleOpen access
  PublisherOA PDFDOI

• A role for ethylene signaling and biosynthesis in regulating and accelerating <scp>CO₂</scp>‐ and abscisic acid‐mediated stomatal movements in Arabidopsis

  New Phytologist · 2023-03-30 · 30 citations

  articleOpen access

  Summary Little is known about long‐distance mesophyll‐driven signals that regulate stomatal conductance. Soluble and/or vapor‐phase molecules have been proposed. In this study, the involvement of the gaseous signal ethylene in the modulation of stomatal conductance in Arabidopsis thaliana by CO 2 /abscisic acid (ABA) was examined. We present a diffusion model which indicates that gaseous signaling molecule/s with a shorter/direct diffusion pathway to guard cells are more probable for rapid mesophyll‐dependent stomatal conductance changes. We, therefore, analyzed different Arabidopsis ethylene‐signaling and biosynthesis mutants for their ethylene production and kinetics of stomatal responses to ABA/[CO 2 ]‐shifts. According to our research, higher [CO 2 ] causes Arabidopsis rosettes to produce more ethylene. An ACC‐synthase octuple mutant with reduced ethylene biosynthesis exhibits dysfunctional CO 2 ‐induced stomatal movements. Ethylene‐insensitive receptor (gain‐of‐function), etr1‐1 and etr2‐1 , and signaling, ein2‐5 and ein2‐1 , mutants showed intact stomatal responses to [CO 2 ]‐shifts, whereas loss‐of‐function ethylene receptor mutants, including etr2‐3;ein4‐4;ers2‐3 , etr1‐6;etr2‐3 and etr1‐6 , showed markedly accelerated stomatal responses to [CO 2 ]‐shifts. Further investigation revealed a significantly impaired stomatal closure to ABA in the ACC‐synthase octuple mutant and accelerated stomatal responses in the etr1‐6;etr2‐3 , and etr1‐6 , but not in the etr2‐3;ein4‐4;ers2‐3 mutants. These findings suggest essential functions of ethylene biosynthesis and signaling components in tuning/accelerating stomatal conductance responses to CO 2 and ABA.

  PublisherOA PDFDOI

• Shielding the oil reserves: the scutellum as a source of chemical defenses

  PLANT PHYSIOLOGY · 2022-02-03 · 5 citations

  articleOpen access

  The cereal scutellum is a hub for diverse specialized defense metabolism and pathway discovery.

  PublisherOA PDFDOI

Recent grants

• CAREER: Decoding differential protein phosphorylation patterns at the nexus between biotic and abiotic stress responses

  NSF · $500k · 2020–2027

Frequent coauthors

• Eric A. Schmelz

  University of California, San Diego

  118 shared

• Peter E. A. Teal

  Center for Medical, Agricultural and Veterinary Entomology

  70 shared

• Hans T. Alborn

  Center for Medical, Agricultural and Veterinary Entomology

  63 shared

• Martha Vaughan

  National Center for Agricultural Utilization Research

  61 shared

• Shawn A. Christensen

  Brigham Young University

  45 shared

• Nicole J. Dafoe

  Slippery Rock University

  41 shared

• Xinzhi Ni

  Agricultural Research Service

  28 shared

• L. H. Allen

  22 shared

Labs

• Alisa Huffaker LabPI