Welcome to ZHOU LAB
Mechanistic studies: We are interested in illuminating novel regulatory mechanisms of signal transduction that remain unresolved in calcium signaling, T cell activation & exhaustion, LLPS, organelle physiology, and DNA demethylation.
Tool development: We are focused on molecular and cellular engineering to enable remote and programmable control over protein activity, cell signaling, gene expression, biomolecular condensation, and CRISPR-mediated (epi)genome editing.
Translational studies: We are also developing calcium channel modulators, smart biologics, and intelligent cell-based therapies that target cancer, immunoinflammatory disorders, and neurodegenerative diseases.
Remote Control Of CAR-T cell therapy
Nature Reviews Bioengineering '23We introduce the use of various physiochemical stimuli, including light, ultrasound, magnetic fields, X-rays, electric fields and small molecules, to control the activity of CAR-T cells against different malignancies. See more...Perturbing TET2 condensation to curtail leukemogenesis
Nature Cell Biology '24 (online)We delineate the molecular mechanims underlying biomolecular condensation of TET2 that fosters a permissive chromatin environment for precise DNA demethylation at specific genomic loci. Disrupting LCI-mediated condensation through genetic or chemogenetic approaches alters genomic binding of TET2, causing promiscuous DNA demethylation and genome reorganization. These changes influence the expression of genes linked to leukemogenesis, effectively curbing leukemia cell proliferation. See more...Perturbing TET2 condensation to curtail leukemogenesis
Nature Cell Biology '24We unveil a low complexity insert (LCI) domain within TET2 that facilitates biomolecular condensation. This interaction fosters a permissive chromatin environment for precise DNA demethylation at specific genomic loci. Pharmacological or genetic perturbation of TET2 liquid-liquid phase separation could influence the expression of genes linked to leukemogenesis, effectively curbing leukemia cell proliferation. See more...TET2 | new functions in blood cell aging
Nature Aging '23We report the role of TET2 in regulating the subnuclear relocalization of heterochromatin in aged hematopoietic stem and progenitor cells (HSPCs), and clarifies a long-standing puzzle by explaining why defects in DNMT and TET enzymes could both lead to clonal hematopoiesis and blood cancer. See more... Highlighted in NA "News & Views"LAMPS | Chromatin reconfiguration with light
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Science Advances '23We collaborated with Dr. Jian Xu's group to develop a Light Activated Macromolecular Phase Separation (LAMPS) toolkit to modulate transcription by reconfiguring chromatin interactions. This new approach enables parallel analyses of changes in gene transcription, chromatin configuration, and macromolecular composition caused by light-induced biomolecular condensation. See more... Reagents available hereNEMO | Ultra-sensitive calcium indicator
Nature Methods '23We report the development of NEMO indicators to report calcium transients with peak SBRs 20-fold larger than the top-of-the-range GCaMP series. NEMO further enables the quantification of absolution calcium concentration with ratiometric or photochromic imaging in mammals and in planta. Reagents available here ER-resident NEMO series available upon requestLiSmore | Optical control of STING
Nature Communications '23We introduce herein the design of an ultra-light-sensitive optogenetic device (designated LiSmore for light-inducible SMOC-like repeats) that selectively and remotely controls STING activation to boost anti-tumor immunity and overcome the tumor suppressive microenvironment. See more...A cover story on optophysiology
Physiological Reviews '22 (cover story)We advocate the concepto of optophysiology to control protein activity, cellular function, and intercellular communications with light, which can accelerate the mechanistic dissection of cell physiology and precision therapy development. See more...A covery story on optogenetic engineering
Trends in Genetics '22 (Cover story)We summarize non-opsin photosensory modules and modular strategies employed for optogenetic engineering, and highlight the latest advances in remote manipulation of gene transcription and (epi)genome engineering. See more...LiCAR-T cells for precision immunotherapy
Nature Nanotechnology '21We present the design of light-switchable CAR T (LiCAR-T) cells that allow photo-tunable activation of T cells with substantially reduced side effects, and set the stage for developing precision medicine to deliver personalized anticancer therapy. See more... Vital RecordcpLOV2 for modular optogenetic engineering
Nature Chemical Biology '21Circularly permuted LOV2 (cpLOV2) is designed to modulate ion channels, anti-CRISPR activity, protein localization, transcriptional outputs, cell suicide and to generate photoactivatable chimeric antigen receptor T cells for lymphoma killing. Vital Record Faculty Opinions Reagents available hereLOCa | Light-operated calcium channel
Nature Communications '21We describe the design of LOCa to modulate aberrant HSPC self-renewal, cell suicide, transcriptional programming, as well as neurodegeneration in a fly model of Alzheimer's Disease. Cell Calcium commentary Reagents available hereOpto-CRAC | Optical control of calcium signaling
Nature Communications '15 & '21; Curr Opin Physiol '20; PLOS Biol '18; Trends in Biotech '17; eLife '15;We engnieer various blue light-responsive photoreceptors into modular domains of STIM1 to deisng Opto-CRAC for optogenetic immmunomodulation in vivo, enabling remote intervention of cancer immunotherapy. See more... Vital Record Photonics News OPTICA Reagents available hereSTIM1beta drives glioblastoma growth
Advanced Science '22 (Cover story)We discovered STIM1β as a novel splicing variant that promote glioblastoma. Compared to pan-STIM inhibition that tends to cause undesired immunosuppressive effects, targeting STIM1β might offer a solution for more precise glioblastoma intervention.pNUT | Optical control of nucleolar targeting
Nucleic Acids Research '22We report a set of photoinducible nucleolus-targeting tools (pNUT1-3) to enable rapid and reversible nucleoplasm-to-nucleolus shuttling. pNUTs allows optical interrogation of nucleolar functions and precise induction of amyotrophic lateral sclerosis associated toxicity in cellular models. See more... Reagents available here.COSMO for chemogenetic control
Advanced Science '21 (Cover story)A genetically encoded caffeine-operated synthetic module (COSMO) is developed to enable versatile chemogenetic manipulation, including caffeine-inducible boosting of nanobodies agasint SARS-CoV-2 to treat COVID-19. See more... Vital Record KBTX Interview Reagents available hereLiPOP | Optical control of necroptosis & pyroptosis
Advanced Science '21 (Cover story)We introduce LiPOPs that enable photoswitchable control over necroptosis or pyroptosis. LiPOPs open new avenues to study the role of non-apoptotic cell death during microbial infection, inflammatory response and cancer immunotherapy. See more... Reagents available hereSunbody & Moonbody | a 'light' touch on antibody
Advanced Biology '21 (Cover story)We develop light-switchable nanobody and monobody to control antibody-antigen interactions, named Sunbody and Moonbody after the Chinese mythological figures Hou Yi the Sun-shooter (后羿射日) and Chang'e the Lady in the Moon (嫦娥奔月). See more... PreLights Reagents available herepiCRAC | Optical inhibition of ORAI channels
JACS '20 (Cover story)Azopyrazole-derived photoswitchable CRAC channel inhibitors (piCRACs) are designed to enable optical inhibition of ORAI channels, and to alleviate thrombocytopenia and hemorrhage in a zebrafish model of Stormorken syndrome in a light-dependent manner. Reagent available hereYZ129 for glioblastoma treatment
Cell Chemical Biology '19 (Cover story)We report the synthesis of a new class of HSP90 inhibitors (YZ129) attacking glioblastoma (magenta sphere). YZ129 targets the calcineurin-NFAT signaling axis and the HSP90 client network. The compounds hold great promise for the development of improved glioblastoma therapy. Research@TAMU Reagent available hereOptoRGK | Optical control of CaV channel
Angewandte Chemie '18 (Cover story)We develop genetically encoded photoswitchable inhibitors (optoRGK) of CaV channels to control calcium-regulated activities in excitable cells. The tool could be adapted to suppress cardiac arrhythmia by light. Vital Record Photonics Media LaserFocusWorld FuturityLiMETER | Optical control of membrane contact sites
Chemical Science '17 (Cover story)We report an optogenetic tool (‘OptoPB’) to enable optogenetic control of protein-lipid interaction and inter-organelle tethering (LiMETER for light-inducible membrane-tethered peripheral ER). NIH Biomedical Beat BioTechniques Vital Record Photonics Media Reagents available hereCiDER | Chemical inducible epigenetic remodeling
JACS '17 (Spotlight article)We engineered a chemical-inducible epigenome remodeling tool, CiDER, to interrogate cellular systems without altering the genetic code, and probe the epigenotype–phenotype relations in mammals. See more... Vital RecordSTIMATE | A novel regulator of the CRAC channel
Nature Cell Biology '15 (N&V highlighted)We apply a two-prongled appraoch by combining proximity proteomics and BiFC to identify STIMATE as a novel regulator of calcium signaling at ER-PM junctions. It provides one of the first proof-of-concept to map the molecular composition of MCS in situ. See more... NCB "News & Views" Reagents avalable here
2024
The Zhou lab are revising/submitting manuscripts with Nature Chemical Biology, Nature Cell Biology, Nature Communications, JACS, Annual Review of Physiology, Current Opinion in Chemical Biology, Medicinal Research Reviews, Clinical and Translational Medicine, and more to be published...
- Congratulations to Xiaoxuan Liu for winning a Poster Award and a Travel Award to attend the FASEB Scientific Research Conference on Channels and Transporters in Immunity!
- A collaboratiev study with Drs. Yuepeng Ke and Junchen Liu on Ras-related proteins was publisehd in JACS.
- A research article entitled "Inhibiting the cGAS-STING pathway in myeloid cells effectively improves myocardial healing related to TET2 deficiency-induced DNA damage response" was accepted by Clinical & Translational Medicine.
- Dr. Yuepeng Ke received a prestigious Cancer Therapeutics Training Program Fellowship to support her innovative research on CAR-T cell therapy against solid tumors!
- The Zhou Lab was awarded a TAMU HSC Seedling Grant to develop intelligent cell-based immunotherapy!
- Congratulations to Dr. Lei Guo for acceptance of a novel study reporting TET2 liquid-liquid phase separation by Nature Cell Biology!
- Congratulations to Xiaoxuan Liu as the recipient of the Finalist Award for Outstanding Research at the 37th SCBA-TX Annual Symposium!
- Congratulations to Dr. Yi-Tsang Lee on his successful defense of his dissertation! He will start his posdtoc career at La Jolla Institute for Immunology.
2023
The Zhou lab published 10+ papers in Nature Methods, Nature Aging, Nature Chemical Biology, Nature Communications, Nature Reviews Bioengineering, Clinical and Translational Medicine, and Science Advances etc.
Dr. Zhou was inducted into the 2023 Class of American American Institute for Medical and Biological Engineering as an AIMBE Fellow. See press release from AIMBE.
The Zhou lab received two NIH R21 grants, and one Translational Research Program Award from the Leukemia & Lymphoma Society to support cancer and immunotherapy research!
Siyao Liu won the Outstanding Presentation Award from the 2023 NCI Allicance for Nanotechnology in Cancer Meeting.
Yi-Tsang Lee and Dr. Tien-Hung Lan attended the 2023 FASEB Science Researcch Conference on Calcium and Cell Function co-chaired by Dr. Zhou at Malahide Ireland to present latest progress in studying calcium signaling.
