Ruhma Syeda, Ph.D. Titles and Appointments Assistant Professor Endowed Title W.W. Caruth, Jr. Scholar in Biomedical Research School Medical School Department Neuroscience Graduate Programs Molecular Biophysics, Neuroscience Biography 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. Research Interest Cellualr and Acellular Molecular Studies Electrophysiology Ion Channel Structure-Function Mechano - Sensation and Transduction Mechano Pathologies Rare Genetic Disorders and Channelopathies Publications Featured Publications Analysis of pressure activated Piezo1 open and subconductance states at a single channel level. Ullah G, Nosyreva ED, Thompson D, Cuello V, Cuello LG, Syeda R, J Biol Chem 2024 Mar 107156 PIEZO1 loss-of-function compound heterozygous mutations in the rare congenital human disorder Prune Belly Syndrome. Amado NG, Nosyreva ED, Thompson D, Egeland TJ, Ogujiofor OW, Yang M, Fusco AN, Passoni N, Mathews J, Cantarel B, Baker LA, Syeda R, Nat Commun 2024 Jan 15 1 339 A Novel Computational Biomechanics Framework to Model Vascular Mechanopropagation in Deep Bone Marrow. Zhao YC, Zhang Y, Jiang F, Wu C, Wan B, Syeda R, Li Q, Shen B, Ju LA, Adv Healthc Mater 2023 Mar 12 8 e2201830 TMEM16F and dynamins control expansive plasma membrane reservoirs. Deisl C, Hilgemann DW, Syeda R, Fine M, Nat Commun 2021 08 12 1 4990 Physiology and Pathophysiology of Mechanically Activated PIEZO Channels. Syeda R, Annu Rev Neurosci 2021 Jul 44 383-402 A mechanosensitive peri-arteriolar niche for osteogenesis and lymphopoiesis. Shen B, Tasdogan A, Ubellacker JM, Zhang J, Nosyreva ED, Du L, Murphy MM, Hu S, Yi Y, Kara N, Liu X, Guela S, Jia Y, Ramesh V, Embree C, Mitchell EC, Zhao YC, Ju LA, Hu Z, Crane GM, Zhao Z, Syeda R, Morrison SJ, Nature 2021 Mar 591 7850 438-444 Identification and functional characterization of the Piezo1 channel pore domain. Nosyreva ED, Thompson D, Syeda R, J Biol Chem 2020 Dec Dabbling with Piezo2 for mechanosensation. Syeda R Proc. Natl. Acad. Sci. U.S.A. 2017 Nov Piezo1 Channels Are Inherently Mechanosensitive. Syeda R, Florendo MN, Cox CD, Kefauver JM, Santos JS, Martinac B, Patapoutian A Cell Rep 2016 Nov 17 7 1739-1746 The Sensorless Pore Module of Voltage-gated K+ Channel Family 7 Embodies the Target Site for the Anticonvulsant Retigabine. Syeda R, Santos JS, Montal M J. Biol. Chem. 2016 Feb 291 6 2931-7 Results 1-10 of 21 1 2 3 Next Last Honors & Awards The Welch FoundationResearch Grant (2018-2021) American Heart AssociationScientist Development Grant (2017-2019) Eli Lilly AwardOutstanding Postgraduate Student (2008) Lincoln College Senior ScholarUniversity of Oxford (2008-2010) Clarendon ScholarshipFully funded D.Phil program (2007-2010) Lady Noon Foundation AwardTo Pursue D.Phil in Chemical Biology (2007-2010)