About

Huanghe Yang, PhD, is the Principal Investigator of the Yang Lab. He completed his Bachelor of Science in Chemistry at Zhengzhou University in 1995, followed by a Master of Science in Chemistry at the Dalian Institute of Chemical Physics in 2021 under the advisement of Tao Zhang. He earned his PhD in Biomedical Engineering from Washington University in St. Louis in 2008, where he was advised by Jianmin Cui. Subsequently, he conducted postdoctoral research in Physiology at UCSF/HHMI in 2015, mentored by Lily Jan. Throughout his career, Dr. Yang has received several prestigious honors and awards, including the NIH Pathway to Independence Award in 2014, the Whitehead Scholar Award in 2015, the NIH Director's New Innovator Award in 2018, the Duke Science & Technology SPARK Award in 2023, the NIGMS MIRA Award in 2024, the Paul F. Cranefield Award from the Society of General Physiologists in 2025, and the Early Career Mentoring Award in Basic Science from the Duke School of Medicine. These accolades reflect his significant contributions to his field and his commitment to mentoring the next generation of scientists.

Research topics

• Biochemistry
• Biology
• Chemistry
• Genetics
• Cell biology

Selected publications

• BPS2026 – How forces reshape membranes: The PIEZO1-TMEM16F cascade in health and disease

  Biophysical Journal · 2026-02-01

  article1st authorCorresponding
  PublisherDOI

• Cannabidiol Inhibits PIEZO Channels to Mitigate Red Blood Disorders

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-01-24

  articleOpen accessSenior authorCorresponding

  Abstract Hyperactivity of the mechanosensitive ion channel PIEZO1 promotes pathologic Ca²⁺ overload in red blood cells (RBCs), driving dehydration, TMEM16F-dependent phosphatidylserine (PS) exposure, microparticle shedding, and increased thrombotic and vaso-occlusive risks in hereditary xerocytosis (HX) and sickle cell disease (SCD). However, clinically deployable PIEZO inhibitors to treat these blood disorders are lacking. Here we report that cannabidiol (CBD), a non-psychoactive cannabinoid commonly used in SCD patients for pain management, inhibits PIEZO1 activity and restores aberrant mechanotransduction in HX and SCD RBCs. Micromolar concentrations of CBD blocks PIEZO1 currents and suppresses PIEZO1-mediate Ca²⁺ entry. In HX and SCD RBCs, CBD attenuates PIEZO1-TMEM16F coupling, thereby reducing PS exposure, microparticle release, thrombin generation, RBC-endothelium adhesion, and sickling. Beyond RBCs, CBD also blocks PIEZO2 currents and PIEZO2-dependent mechanical sensation in mice, suggesting broader effects of CBD-mediated PIEZO inhibition on nociceptive functions. Together, our findings identify CBD as a potent PIEZO inhibitor that restores calcium and membrane homeostasis, supporting the repurposing of CBD or the development of CBD-derived, PIEZO-selective analogs as a promising disease-modifying strategy for SCD, HX, and other PIEZO-mediated mechanosensing disorders. Highlights CBD inhibits PIEZO channels and disrupts the PIEZO1-TMEM16F axis in diseased RBCs CBD shows a therapeutic window to prevent PS exposure and translational promise for HX and SCD

  PublisherOA PDFDOI

• Targeting <scp>PIEZO1</scp> ‐ <scp>TMEM16F</scp> Coupling to Mitigate Sickle Cell Disease Complications

  American Journal of Hematology · 2025-10-08 · 1 citations

  articleSenior authorCorresponding

  ABSTRACT A deeper understanding of sickle cell disease (SCD) pathophysiology is critical for identifying novel therapeutic targets. A hallmark of SCD is abnormal phosphatidylserine (PS) exposure on sickle red blood cells (RBCs), which contributes to anemia, thrombosis, and vaso‐occlusive crises (VOC). However, the mechanisms underlying this excessive PS exposure remain unclear. Here, we identify TMEM16F, a Ca 2+ ‐activated lipid scramblase, as a key mediator of PS exposure downstream of Ca 2+ influx through the mechanosensitive channel PIEZO1 in sickle RBCs. Electrophysiology, imaging, and flow cytometry reveal that deoxygenation‐induced sickling activates PIEZO1, triggering Ca 2+ entry, TMEM16F activation, and PS exposure. This cascade promotes PS + microparticle release, thrombin generation, and RBC adhesion to endothelial cells. Notably, partial PIEZO1 inhibition with benzbromarone, an anti‐gout drug, suppresses these effects. Our findings define a previously unrecognized mechanotransduction pathway in sickle RBCs and propose a unique therapeutic strategy to mitigate hypercoagulability and vaso‐occlusion associated with SCD.

  PublisherDOI

• Targeting PIEZO1-TMEM16F Coupling to Mitigate Sickle Cell Disease Complications

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-05-31 · 3 citations

  preprintOpen accessSenior authorCorresponding

  Abstract A deeper understanding of sickle cell disease (SCD) pathophysiology is critical for identifying novel therapeutic targets. A hallmark of SCD is abnormal phosphatidylserine (PS) exposure on sickle red blood cells (RBCs), which contributes to anemia, thrombosis, and vaso-occlusive crises (VOC). However, the mechanisms underlying this excessive PS exposure remain unclear. Here, we identify TMEM16F, a Ca 2+ -activated lipid scramblase, as a key mediator of PS exposure downstream of Ca 2+ influx through the mechanosensitive channel PIEZO1 in sickle RBCs. Electrophysiology, imaging and flow cytometry reveal that deoxygenation-induced sickling promotes PIEZO1 activation, triggering Ca 2+ entry, TMEM16F activation, and PS exposure. This cascade enhances PS + microparticle release, thrombin generation, and RBC adhesion to endothelial cells. Notably, partial PIEZO1 inhibition with benzbromarone, an anti-gout drug, suppresses these changes. Our findings thus define a previously unrecognized mechanotransduction pathway in sickle RBCs and propose a unique therapeutic strategy to mitigate hypercoagulability and vaso-occlusion associated with SCD. Brief Summary Enhanced PIEZO1 activation in sickle red blood cells promotes TMEM16F scramblase-mediated phosphatidylserine exposure and subsequent sickle cell disease complications. Disrupting this coupling presents a potential therapeutic strategy.

  PublisherOA PDFDOI

• BPS2025 - Dynamic regulation of membrane lipid asymmetry: Mechanisms, molecular tools, and physiological functions

  Biophysical Journal · 2025-02-01

  articleSenior author
  PublisherDOI

• PIEZO1 Drives Trophoblast Fusion and Placental Development

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-03-26 · 2 citations

  preprintOpen accessSenior authorCorresponding

  Abstract PIEZO1, a mechanosensor 1,2 in endothelial cells, plays a critical role in fetal vascular development during embryogenesis 3,4 . However, its expression and function in placental trophoblasts remain unexplored. Here, we demonstrate that PIEZO1 is expressed in placental villus trophoblasts, where it is essential for trophoblast fusion and placental development. Mice with trophoblast-specific PIEZO1 knockout exhibit embryonic lethality without obvious vascular defects. Instead, PIEZO1 deficiency disrupts the formation of the syncytiotrophoblast layer in the placenta. Mechanistically, PIEZO1-mediated calcium influx activates TMEM16F lipid scramblase, facilitating the externalization of phosphatidylserine, a key “fuse-me” signal for trophoblast fusion 5,6 . These findings reveal PIEZO1 as a crucial mechanosensor in trophoblasts and highlight its indispensable role in trophoblast fusion and placental development, expanding our understanding of PIEZO1’s functions beyond endothelial cells during pregnancy.

  PublisherOA PDFDOI

• Structural and functional basis of mechanosensitive TMEM63 channelopathies

  Neuron · 2025-06-05 · 10 citations

  articleOpen access
  PublisherOA PDFDOI

• PIEZO1 drives trophoblast fusion and placental development

  Nature Communications · 2025-07-26 · 5 citations

  articleOpen accessSenior author

  PIEZO1, a mechanosensor in endothelial cells, plays a critical role in fetal vascular development during embryogenesis. However, its expression and function in placental trophoblasts remain unexplored. Here, we demonstrate that PIEZO1 is expressed in placental villus trophoblasts, where it is essential for trophoblast fusion and placental development. Mice with trophoblast-specific PIEZO1 knockout exhibit embryonic lethality without obvious vascular defects. Instead, PIEZO1 deficiency disrupts the formation of the syncytiotrophoblast layer in the placenta. Mechanistically, PIEZO1-mediated calcium influx activates TMEM16F lipid scramblase, facilitating the externalization of phosphatidylserine, a key “fuse-me” signal for trophoblast fusion. These findings reveal PIEZO1 as a crucial mechanosensor in trophoblasts and highlight its essential role in regulating trophoblast fusion and placental development, expanding our understanding of PIEZO1’s functions beyond endothelial cells during pregnancy. Here they show that PIEZO1, a force-sensing ion channel, is important for trophoblast fusion during placental development. It triggers calcium entry that activates the TMEM16F lipid scramblase, allowing cells to merge and support fetal development.

  PublisherOA PDFDOI

• BPS2025 - An activator mimics the effects of a BK channelopathy mutation by targeting its allosteric pathway to open the pore

  Biophysical Journal · 2025-02-01

  article
  PublisherDOI

• Calcium-activated ion channels drive atypical inhibition in medial habenula neurons

  Science Advances · 2025-03-19 · 3 citations

  articleOpen accessSenior authorCorresponding

  Nicotine is an addictive substance that poses substantial health and societal challenges. Despite the known links between the medial habenula (MHb) and nicotine avoidance, the ionic mechanisms underlying MHb neuronal responses to nicotine remain unclear. Here, we report that MHb neurons use a long-lasting refractory period (LLRP) as an unconventional inhibitory mechanism to curb hyperexcitability. This process is initiated by nicotine-induced calcium influx through nicotinic acetylcholine receptors, which activates a calcium-activated chloride channel (CaCC). Owing to high intracellular chloride levels in MHb neurons, chloride efflux through CaCC, coupled with high-threshold voltage-gated calcium channels, sustains MHb depolarization near the chloride equilibrium potential of -30 millivolts, thereby enabling LLRP. Concurrently, calcium-activated BK potassium channels counteract this depolarization, promoting LLRP termination. Our findings reveal an atypical inhibitory mechanism, orchestrated by synergistic actions between calcium-permeable and calcium-activated channels. This discovery advances our understanding of neuronal excitability control and nicotine addiction.

  PublisherDOI

Recent grants

• Advancing mechanistic understanding of membrane ion and lipid transport

  NIH · $1.4M · 2024–2029

• Manipulating TMEM16F lipid scramblase to understand the transbilayer phospholipid transport phenomenon

  NIH · $2.2M · 2017–2022

• Ca2+ activated TMEM16 channels and their physiological roles in the brain

  NIH · $117k · 2014–2016

Frequent coauthors

• Shuang‐Nan Zhang

  Institute of High Energy Physics

  81 shared

• Subir Bera

  University of Calcutta

  81 shared

• John K. Gallos

  Aristotle University of Thessaloniki

  81 shared

• Michael J. Krische

  The University of Texas at Austin

  81 shared

• Kuan‐Hao Su

  81 shared

• Yinghui Li

  Northwest University

  81 shared

• Zhizhong Sun

  Northwest Institute of Eco-Environment and Resources

  81 shared

• Yuan Zhang

  81 shared

Labs

• Yang LabPI

Education

• PhD, Biomedical engineering

  Washington University in Saint Louis

  2008

• MS

  Dalian Institute of Chemical Physics

  2001

• BS, Chemistry

  Zhengzhou University

  1995

Awards & honors

• NIH Director's New Innovator Award
• Pathway to Independence Award (K99/R00)