About

Melissa Gardner, PhD, is a professor affiliated with the Genetics, Cell Biology & Development department at the University of Minnesota Twin Cities Medical School. Her professional focus is within the fields of genetics, cell biology, and development. Further details about her specific research interests, background, and key contributions are not provided on the page.

Research topics

• Cell biology
• Biology
• Physics
• Genetics
• Endocrinology
• Biophysics
• Biochemistry
• Mechanics

Selected publications

• 17β-Estradiol counteracts pathological microtubule remodeling to enhance right ventricular function in preclinical models

  Journal of Clinical Investigation · 2026-05-07

  articleOpen access
  PublisherOA PDFDOI

• Estradiol pauses microtubule growth without increased incidence of catastrophe events

  Communications Biology · 2025-06-18 · 3 citations

  articleOpen accessSenior author

  Microtubules are long filaments that control cellular structure and influence intracellular transport. The female hormone estrogen has been implicated in alterations to the microtubule network for a variety of cell types. However, the effects of estrogen on individual microtubules are unknown. In this work we systematically investigated a mechanism by which estrogen could alter the length dynamics of individual microtubules. Using multi-line cell assays, cell-free experiments, and computational modeling, we found that estradiol acts to frustrate and pause microtubule growth in cells, independent of estrogen receptor pathways. Specifically, estradiol acts as a switch in which dynamic, growing microtubules were transformed into paused, non-growing microtubules. Estradiol pauses microtubule growth without inducing an increased incidence of catastrophe events, similar to the widely used microtubule poison colchicine. We conclude that estrogen’s ability to limit excessive microtubule proliferation could have important implications for therapeutic approaches in heart disease and breast cancer. Overgrowth of cellular microtubules (MTs) is associated with a range of disease processes. Cellular and biophysical reconstitution experiments reveal that estradiol transforms dynamic, growing MTs into paused, non-growing MTs.

  PublisherOA PDFDOI

• Abstract Wed051: Microtubule Reorganization in Response to Vasoconstrictive Peptides Limits Kinesin-based Transport of the T-tubule Anchoring Protein Junctophilin-2

  Circulation Research · 2025-08-01

  articleSenior author

  Pulmonary arterial hypertension (PAH) is a lethal disease characterized by the remodeling of the distal pulmonary vasculature, largely caused by increased production of vasoconstrictive peptides such as endothelin, leading to hypertension. An examination of cellular events in response to increased endothelin expression has the potential to identify specific therapeutic targets that could ameliorate hypertension in PAH. Microtubules are long filaments that regulate cellular transport within cardiac cells. By utilizing iPSC-derived cardiomyocytes in combination with live-cell confocal microscopy, we found that treatment with endothelin leads to the overproduction of microtubules, which severely limits transportation of the t-tubule anchoring protein Junctophilin-2 (JPH2) throughout the cell (Fig. 1A), thus profoundly disrupting excitation-contraction coupling (p<0.0001). We hypothesized that the pathogenic remodeling of microtubules in endothelin directly reduces the efficiency of JPH2 transport throughout the cell. Consistent with this idea, a microtubule depolymerizing treatment in combination with endothelin restored JPH2 transport throughout the cell and rescued the excitation-contraction coupling in iPSC-derived cardiomyocytes. Thus, we used a cell-free reconstitution assay to examine the mechanism for JPH2 transport throughout the cell. We found that the kinesin Kif5B binds and transports JPH2 on reconstituted microtubules (Fig. 1B). We predicted that “traffic jams” of the Kif5B molecular motor may result from the overproduction of microtubules in endothelin-treated cells, and thus limit JPH2 transport throughout the cell. We will explore this idea using cell-free reconstitution, cell assays with fluorescent motor proteins, and computational modeling. Thus, we will identify and test potential therapeutic targets to facilitate the improved efficiency of JPH2 transport throughout the cell in PAH patients.

  PublisherDOI

• 17β-Estradiol Counteracts Pathological Microtubule Remodeling To Enhance Cardiac Function

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-01-24

  preprintOpen access

  Abstract The female-predominate sex hormone 17β-estradiol exerts cardioprotective effects via multiple mechanisms. Available data demonstrate 17β-estradiol modulates microtubule dynamics in vitro , but its effects on pathogenic microtubule remodeling in pressure-overloaded cardiomyocytes are unexplored. Here, we show 17β-estradiol directly blunts microtubule polymerization in vitro , counteracts endothelin-mediated microtubule remodeling in iPSC-cardiomyocytes, and mitigates microtubule stabilization in pulmonary artery banded right ventricular cardiomyocytes. 17β-estradiol treatment blunts cardiomyocyte and nuclear hypertrophy, restores t-tubule architecture, and prevents mislocalization of connexin-43 in RV cardiomyocytes of pulmonary artery banded rats. These cellular phenotypes are paired with significant improvements in RV function. Thus, we propose 17β-estradiol exerts cardioprotective effects via direct modulation of microtubules in addition to its well ascribed signaling functions.

  PublisherDOI

• Rapid binding to protofilament edge sites facilitates tip tracking of EB1 at growing microtubule plus-ends

  eLife · 2024-02-01 · 2 citations

  articleOpen accessSenior author

  EB1 is a key cellular protein that delivers regulatory molecules throughout the cell via the tip-tracking of growing microtubule plus-ends. Thus, it is important to understand the mechanism for how EB1 efficiently tracks growing microtubule plus-ends. It is widely accepted that EB1 binds with higher affinity to GTP-tubulin subunits at the growing microtubule tip, relative to GDP-tubulin along the microtubule length. However, it is unclear whether this difference in affinity alone is sufficient to explain the tip-tracking of EB1 at growing microtubule tips. Previously, we found that EB1 binds to exposed microtubule protofilament-edge sites at a ~70 fold faster rate than to closed-lattice sites, due to diffusional steric hindrance to binding. Thus, we asked whether rapid protofilament-edge binding could contribute to efficient EB1 tip tracking. A computational simulation with differential EB1 on-rates based on closed-lattice or protofilament-edge binding, and with EB1 off-rates that were dependent on the tubulin hydrolysis state, robustly recapitulated experimental EB1 tip tracking. To test this model, we used cell-free biophysical assays, as well as live-cell imaging, in combination with a Designed Ankyrin Repeat Protein (DARPin) that binds exclusively to protofilament-edge sites, and whose binding site partially overlaps with the EB1 binding site. We found that DARPin blocked EB1 protofilament-edge binding, which led to a decrease in EB1 tip tracking on dynamic microtubules. We conclude that rapid EB1 binding to microtubule protofilament-edge sites contributes to robust EB1 tip tracking at the growing microtubule plus-end.

  PublisherDOI

• Author response: Rapid binding to protofilament edge sites facilitates tip tracking of EB1 at growing microtubule plus-ends

  2024-01-31

  peer-reviewOpen accessSenior author

  Computational modeling combined with biophysical and cellular experiments reveal that rapid binding to incomplete, partial microtubule binding sites facilitates tracking of the end-binding protein EB1 with growing microtubule plus-ends.

  PublisherDOI

• Robust microtubule dynamics facilitate low-tension kinetochore detachment in metaphase

  The Journal of Cell Biology · 2023 · 9 citations

  Senior authorCorresponding
  • Cell biology
  • Biology
  • Genetics

  During mitosis, sister chromatids are stretched apart at their centromeres via their attachment to oppositely oriented kinetochore microtubules. This stretching generates inwardly directed tension across the separated sister centromeres. The cell leverages this tension signal to detect and then correct potential errors in chromosome segregation, via a mechanical tension signaling pathway that detaches improperly attached kinetochores from their microtubules. However, the sequence of events leading up to these detachment events remains unknown. In this study, we used microfluidics to sustain and observe low-tension budding yeast metaphase spindles over multiple hours, allowing us to elucidate the tension history prior to a detachment event. We found that, under conditions in which kinetochore phosphorylation weakens low-tension kinetochore-microtubule connections, the mechanical forces produced via the dynamic growth and shortening of microtubules is required to efficiently facilitate detachment events. Our findings underscore the critical role of robust kinetochore microtubule dynamics in ensuring the fidelity of chromosome segregation during mitosis.

  PublisherOA PDFDOI

• Low tension recruits the yeast Aurora B protein Ipl1 to centromeres in metaphase

  Journal of Cell Science · 2023-07-31 · 6 citations

  articleOpen access

  Accurate genome segregation in mitosis requires that all chromosomes are bioriented on the spindle. Cells monitor biorientation by sensing tension across sister centromeres. Chromosomes that are not bioriented have low centromere tension, which allows Aurora B (yeast Ipl1) to perform error correction that locally loosens kinetochore-microtubule attachments to allow detachment of microtubules and fresh attempts at achieving biorientation. However, it is not known whether low tension recruits Aurora B to centromeres or, alternatively, whether low tension directly activates Aurora B already localized at centromeres. In this work, we experimentally induced low tension in metaphase Saccharomyces cerevisiae yeast cells, then monitored Ipl1 localization. We find low tension recruits Ipl1 to centromeres. Furthermore, low tension-induced Ipl1 recruitment depended on Bub1, which is known to provide a binding site for Ipl1. In contrast, Top2, which can also recruit Ipl1 to centromeres, was not required. Our results demonstrate cells are sensitive to low tension at centromeres and respond by actively recruiting Ip1l for error correction.

  PublisherOA PDFDOI

• Kinesin-14 motors participate in a force balance at microtubule plus-ends to regulate dynamic instability

  Proceedings of the National Academy of Sciences · 2022 · 23 citations

  Senior authorCorresponding
  • Cell biology
  • Biology

  Kinesin-14 molecular motors represent an essential class of proteins that bind microtubules and walk toward their minus-ends. Previous studies have described important roles for Kinesin-14 motors at microtubule minus-ends, but their role in regulating plus-end dynamics remains controversial. Kinesin-14 motors have been shown to bind the EB family of microtubule plus-end binding proteins, suggesting that these minus-end-directed motors could interact with growing microtubule plus-ends. In this work, we explored the role of minus-end-directed Kinesin-14 motor forces in controlling plus-end microtubule dynamics. In cells, a Kinesin-14 mutant with reduced affinity to EB proteins led to increased microtubule lengths. Cell-free biophysical microscopy assays were performed using Kinesin-14 motors and an EB family marker of growing microtubule plus-ends, Mal3, which revealed that when Kinesin-14 motors bound to Mal3 at growing microtubule plus-ends, the motors subsequently walked toward the minus-end, and Mal3 was pulled away from the growing microtubule tip. Strikingly, these interactions resulted in an approximately twofold decrease in the expected postinteraction microtubule lifetime. Furthermore, generic minus-end-directed tension forces, generated by tethering growing plus-ends to the coverslip using λ-DNA, led to an approximately sevenfold decrease in the expected postinteraction microtubule growth length. In contrast, the inhibition of Kinesin-14 minus-end-directed motility led to extended tip interactions and to an increase in the expected postinteraction microtubule lifetime, indicating that plus-ends were stabilized by nonmotile Kinesin-14 motors. Together, we find that Kinesin-14 motors participate in a force balance at microtubule plus-ends to regulate microtubule lengths in cells.

  PublisherOA PDFDOI

• Centromere Tension Measurement in Budding Yeast Mitosis

  Methods in molecular biology · 2022-01-01 · 1 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

Recent grants

• Multi-scale analysis and modeling of acetylation effects on neuronal microtubules

  NIH · $422k · 2017–2020

• Quantitative Analysis and Modeling of Microtubule Structure and Regulation

  NIH · $1.4M · 2013–2019

• Gardner Lab MIRA Proposal: Microtubules and Mitosis

  NIH · $3.4M · 2018–2029

• CAREER: Dissecting the Role of Mechanical Forces in the Regulation of Cytoskeletal Dynamics during Mitosis

  NSF · $400k · 2014–2019

• Computational Modeling and Analysis of Kinetochore Dynamics during Mitosis

  NIH · $410k · 2012–2014

Frequent coauthors

• David J. Odde

  University of Minnesota

  30 shared

• Kerry Bloom

  University of North Carolina at Chapel Hill

  16 shared

• Mark McClellan

  University of Minnesota

  16 shared

• Rebecca R. Goldblum

  University of Minnesota Medical Center

  15 shared

• Courtney Coombes

  12 shared

• Marija Žanić

  Vanderbilt University

  12 shared

• Jonathon Howard

  Yale University

  12 shared

• Taylor A. Reid

  University of Minnesota

  11 shared