Hepler retired from the Biology Department as the Constantine J. Gilgut and Ray Ethan Torrey Professor Emeritus, although he continues to do research.

[18][19] Hepler did pioneering work in showing the relationship of the microscopic elements of the cytoskeleton to the macroscopic properties of plant growth, development and function.

[13] In late 1962 and early 1963, Hepler tested the newly developed procedure using a glutaraldehyde pre-fix followed by an osmium post-fix to study plant cell structure using an electron microscope.

[36] Building on the earlier work by Sinnott and Bloch,[37] who had shown that wounding the existing tracheary elements in a Coleus stem induced neighboring parenchyma cells to differentiate into new tracheary elements, Hepler showed that cytoplasmic microtubules were localized specifically in the cortical cytoplasm immediately over the bands of new secondary wall thickenings.

This work, along with the studies of Ledbetter and Porter[35] and Green[39] established the importance of cortical microtubules in controlling the alignment of cellulose microfibrils in the cell wall.

[40][41] Further work with Barry Palevitz showed that microtubules were involved in orienting the cellulose microfibrils in the walls of guard cells in a pattern of radial micellation that is necessary for stomatal function.

[42] Hepler, along with the husband and wife team of Dale Callaham and Sue Lancelle, developed a method to achieve rapid freeze fixation of particularly small plant cells that showed that cortical microtubules are closely associated with one another, actin microfilaments, the endoplasmic reticulum and the plasma membrane.

In order to understand how microtubule-organizing centers were generated, Hepler examined the de novo formation of the blepharoplast in the spermatogenous cells of Marsilea vestita.

[56][57] The actin microfilaments had the correct polarity to be part of the actomyosin motor that provides the motive force for cytoplasmic streaming in these giant algal cells.

Hepler's research is currently aimed at finding the ionic and molecular components that make up the pacemaker that regulates the oscillatory growth of pollen tubes.

Subsequently, a pectin methylesterase in the wall results in the de-esterification of the methyl groups that yields carboxyl residues that bind calcium and form calcium-pectate cross-bridges.

The intracellular components that contribute to pollen tube growth include the actin-mediated transfer of Golgi-derived secretory vesicles filled with methylesterified homogalacturonans and pectin methylesterase synthesized on the ER to the growing tip.

[74] The secretion of the vesicles at the growing tip anticipates the increase in growth rate,[75] indicating that the turgor pressure driven intussusception of the methylesterified pectin into the cell wall at the growing tip and its subsequent demethylesterification by pectin methylesterase may relax the cell wall by robbing the load-bearing calcium pectate bonds of its Ca2+.

When the external Ca2+ concentration is above 10 mM, the amount of calcium pectate is so high that the cell wall is too stiff and the pollen tube will not grow.