Contact

Department

Cellular and Integrative Physiology

Crystal Archer, Ph.D.

Postdoctoral Fellow

Personal Statement:

Lab Affiliation: James Stockand, Ph.D.


Research

Dr. Archer’s interest in membrane proteins and ion channels brought her to the graduate program UT Health San Antonio in 2011, where she applied biochemical chemical analyses and structural biology methods to improve the understanding of the molecular mechanism of a potassium ion channel. She earned her PhD in Biochemistry, in June 2017, and soon afterward, joined Dr. Jim Stockand’s laboratory at UT Health San Antonio as a postdoctoral researcher. Her current approach utilizes cell culture and electrophysiology, and biophysical methods to study macromolecular interactions.

Her postdoc research focused on understanding the molecular mechanism of how minor plasma membrane phospholipid PIP2 regulates ENaC (Epithelial Na+ Channel) function. ENaC is an ion channel that is critical for the transport of Na+ and filtered fluid reabsorption through the epithelial lining of many tissues, such as the lungs and kidney. This positions ENaC in a role to balance Na+ reabsorption or Na+ excretion in the kidney to contribute to blood pressure regulation.  ENaC is a trimeric channel comprised of 3 distinct subunits (alpha, beta, and gamma subunits), and each of the 6 intracellular domains of the ENaC behave in a dynamic way to regulate the channel function.  Her work has shown that PIP2 binds 2 distinct sites on the beta and gamma subunits of ENaC. This work was supported by a NIH/T32 Postdoctoral Training Grant and an American Heart Association Postdoctoral Fellowship. Her future goals include understanding whether these sites independently interact with PIP2 or if PIP2 serves as a more complex signaling cofactor to bind both gamma and beta sites on ENaC; Because MLP-1 and Ubiquitin also bind near the PIP2 sites, her future aims expand to the interplay of these cofactors with PIP2 in controlling ENaC activity.

Dr. Archer was awarded the Voelcker Fund Young Investigator Award in 2022 to study how phosphorylation of ENaC plays a key role in regulating AnkyrinG-dependent localization of ENaC to the apical membrane of principal kidney cells.  Understanding the fundamental details of this interaction can serve to improve our understanding of certain ENaC-related genetic diseases and potentially lead to improved therapeutic interventions for blood pressure control for certain patients.  Since this region of ENaC overlaps a ubiquitin binding domain, this research will be expanded in the future to explore how ubiquitin can impact the molecular actions between ENaC and AnkyrinG to control the balance between ENaC trafficking, expression and recycling.

Dr. Archer’s research program also includes a K99/R00 Early Career Award to study how phosphorylation of KCNQ potassium channels can interfere or enhance it activity.  KCNQ channel activity is a key player in regulating neuronal firing, and disfunctions in this channel can lead to neuronal disease such as epilepsy.  We have observed there are at least 1-2 PKC sites on some KCNQ subunits that also overlap calmodulin and PIP2. We are interested in how phosphorylation impacts the interaction between KCNQ and these cofactors, and how fluctuations in calcium also regulate these interactions.  KCNQ2 is of particular interest because it is a “hot spot” for mutations in this PKC-calmodulin-PIP2 domain.  This research is expected to lead to future studies to explore how genetic and somatic mutations impact the molecular interactions with KCNQ channels which may lead to novel therapeutic discoveries.

Lab Members

Lab Pictures:
Lab Members:
Makayla Crawford
Research Assistant-Senior
Bryan Rodrigues
Student Associate
Daniel Nyancho
Medical Student