Ruhma Syeda, Ph.D.

Dr. Syeda’s long term research interests focus on the physiological and pathophysiological implications of ion channel gating  with respect to health and disease. She has received rigorous training in the fields of chemical biology, molecular neuroscience and biophysics.

Membrane biology and ion channels first came to her attention during undergraduate studies at Karachi University, where she earned a B.Sc in Chemistry and an M.Sc in Physical Chemistry. Based on the fundamental role that ion channels play in health and disease, Dr. Syeda found them to be captivating and promising research opportunities. She then earned her D.Phil. under the mentorship of Prof. Hagan Bayley at the University of Oxford focusing on Chemical Biology. As a Clarendon Scholar graduate student, she worked on a novel technique called droplet lipid bilayers and refined the technique to produce membrane proteins by cell-free in vitro transcription and translation inside the nanoliter droplets. This research led to important applications of the system, as demonstrated by the rapid screening of blockers and modulators against a viral potassium channel. Due to the success of the project, she earned the Eli Lilly Award for outstanding postgraduate research studies.

As a postdoctoral fellow in the laboratory of Prof. Mauricio Montal, she brought the droplet-bilayer system to UC San Diego and further developed the technique to address how neuronal proteins sense voltage across the cell membrane. She studied the effect of gating modifiers such as lipid monolayer composition, anti-depressants, neurotoxins, and anti-epileptics on voltage gated potassium channels. As a postdoctoral fellow in the laboratory of Ardem Patapoutian, her research focused on the gating of the mechanosensory cation channel PIEZO and the volume-regulated anion-channel Swell1. PIEZO channels respond to physical stimuli such as pressure, shear stress and perturbations in membrane tension, while Swell proteins are regulated by change in cell volume. 

Two ion channels, TRP and PIEZOs received the spotlight when the 2021 Nobel Prize in Physiology or Medicine was awarded for the discovery of molecular sensors of temperature change (TRP) and mechanical stimuli (PIEZO). Dr. Syeda’s work showed for the first time that PIEZOs are a bona fide ion channel that responds directly to mechanical stimuli and is also chemically modulated by small molecule Yoda1, identified by screening ~3 million compounds. These findings were highlighted in Nobel Prize Scientific Background describing discoveries of receptors for temperature and touch, in 2021.

PIEZOs are now known to be critical sensors of touch and pain (somatosensation), volume regulation (osmosensation), shear stress (cardiovascular tone), baroreception, proprioception, and respiratory physiology, and may have other functions yet to be discovered. The research projects in Syeda lab are designed under the umbrella of PIEZO-dependent mechanotransduction and have three major components: i) Structure-function relationship and biophysical analysis of PIEZOs permeation and gating mechanism(s). ii) PIEZO’s physiological roles and mechanism(s) in various cell types. (iii) Pathophysiology and channelopathies with the intent of identifying missense mutations and expand phenotypic spectrum of PIEZO-related disorders. The team has reported the major advancements in peer-reviewed publications, validating the successful launch of all three avenues and shows continuity in the research to address important questions in the mechanobiology field.