- Wound Healing and Treatments
- Mesenchymal stem cell research
- Single-cell and spatial transcriptomics
- Dermatologic Treatments and Research
- Cancer Cells and Metastasis
- Cellular Mechanics and Interactions
- Electrospun Nanofibers in Biomedical Applications
- Surgical Sutures and Adhesives
- Organ and Tissue Transplantation Research
- Tissue Engineering and Regenerative Medicine
- Cancer, Hypoxia, and Metabolism
- Digital Imaging in Medicine
- Tendon Structure and Treatment
- 3D Printing in Biomedical Research
- Immune cells in cancer
- Angiogenesis and VEGF in Cancer
- Diabetic Foot Ulcer Assessment and Management
- Reconstructive Surgery and Microvascular Techniques
- Adipose Tissue and Metabolism
- Effects of Radiation Exposure
- Breast Implant and Reconstruction
- Craniofacial Disorders and Treatments
- Extracellular vesicles in disease
- Cancer Genomics and Diagnostics
- Biomedical Ethics and Regulation
Stanford University
2016-2025
Palo Alto University
2012-2024
Creative Commons
2017-2023
California Institute for Regenerative Medicine
2011-2022
Stanford Medicine
2013-2022
Associated Research (United States)
2021
Institute for Stem Cell Biology and Regenerative Medicine
2013-2021
Stanford Health Care
2021
SRI International
2020
Menlo School
2013-2020
Human lung single-cell atlas reveals the complexity and diversity of aberrant cellular populations in pulmonary fibrosis.
Dermal fibroblasts represent a heterogeneous population of cells with diverse features that remain largely undefined. We reveal the presence at least two fibroblast lineages in murine dorsal skin. Lineage tracing and transplantation assays demonstrate single lineage is responsible for bulk connective tissue deposition during embryonic development, cutaneous wound healing, radiation fibrosis, cancer stroma formation. Lineage-specific cell ablation leads to diminished wounds reduces melanoma...
Diabetes is associated with poor outcomes following acute vascular occlusive events. This results in part from a failure to form adequate compensatory microvasculature response ischemia. Since endothelial growth factor (VEGF) an essential mediator of neovascularization, we examined whether hypoxic up-regulation VEGF was impaired diabetes. Both fibroblasts isolated type 2 diabetic patients, and normal exposed chronically high glucose, were defective their capacity up-regulate hypoxia. In...
Skin scarring, the end result of adult wound healing, is detrimental to tissue form and function. Engrailed-1 lineage-positive fibroblasts (EPFs) are known function in but lineage-negative (ENFs) remain poorly characterized. Using cell transplantation transgenic mouse models, we identified a dermal ENF subpopulation that gives rise postnatally derived EPFs by activating expression during healing. By studying responses substrate mechanics, found mechanical tension drives activation via...
The mechanism and magnitude by which the mammalian kidney generates maintains its proximal tubules, distal collecting ducts remain controversial.Here, we use long-term in vivo genetic lineage tracing clonal analysis of individual cells from kidneys undergoing development, maintenance, regeneration.We show that adult undergoes continuous tubulogenesis via expansions fate-restricted clones.Kidneys recovering damage undergo through clones with segment-specific borders, renal spheres developing...
Significance Diabetes is the leading cause of nontraumatic amputations. There are no effective therapies to prevent diabetic ulcer formation and only modestly technologies help with their healing. To enhance wound healing we designed a transdermal delivery system containing FDA-approved small molecule deferoxamine, an iron chelator that increases defective hypoxia inducible factor-1 alpha transactivation in diabetes by preventing iron-catalyzed reactive oxygen stress. This overcomes...
Significance In the skin, tissue injury results in fibrosis form of a scar composed dense extracellular matrix deposited by fibroblasts. Therapies that promote regeneration rather than remain elusive because principles fibroblast programming and response to incompletely understood. Here, we present multimodal -omics platform for study cell populations complex tissue, which has allowed us characterize wound healing fibroblasts across both time space. We identify functionally distinct...
AbstractDiabetic wounds are a significant public health burden, with slow or non-healing diabetic foot ulcers representing the leading cause of non-traumatic lower limb amputation in developed countries. These heal poorly as result compromised blood vessel formation response to ischemia. We have recently shown that this impairment neovascularization results from high glucose-induced defect transactivation hypoxia-inducible factor-1α (HIF-1α), transcription factor regulating vascular...
Abstract Introduction Pathophysiologic changes associated with diabetes impair new blood vessel formation and wound healing. Mesenchymal stem cells derived from adipose tissue (ASCs) have been used clinically to promote healing, although it remains unclear whether impairs their functional therapeutic capacity. Methods In this study, we examined the impact of on murine ASC niche as well potential isolated neovascularization in vitro vivo . A novel single-cell analytical approach was...
Clinically available sources of bone for repair and reconstruction are limited by the accessibility autologous grafts, infectious risks cadaveric materials, durability synthetic substitutes. Cell-based approaches skeletal regeneration can potentially fill this need, adipose tissue represents a promising source development such therapies. Here, we enriched an osteogenic subpopulation cells derived from human subcutaneous utilizing microfluidic-based single cell transcriptional analysis...
Advanced age is associated with an increased risk of vascular morbidity, attributable in part to impairments new blood vessel formation. Mesenchymal stem cells (MSCs) have previously been shown play important role neovascularization and deficiencies these described aged patients. Here we utilize single cell transcriptional analysis determine the effect aging on MSC population dynamics. We identify age-related depletion a subpopulation MSCs characterized by pro-vascular profile. Supporting...
New strategies for skin regeneration are needed to address the significant medical burden caused by cutaneous wounds and disease. In this study, pullulan–collagen composite hydrogel matrices were fabricated using a salt-induced phase inversion technique, resulting in structured yet soft scaffold engineering. Salt crystallization induced interconnected pore formation, modification of collagen concentration permitted regulation size. Hydrogel architecture recapitulated reticular distribution...
Idiopathic pulmonary arterial hypertension (PAH [IPAH]) is an insidious and potentially fatal disease linked to a mutation or reduced expression of bone morphogenetic protein receptor 2 (BMPR2). Because intravascular inflammatory cells are recruited in IPAH pathogenesis, we hypothesized that BMPR2 enhances production the potent chemokine granulocyte macrophage colony-stimulating factor (GM-CSF) response perturbation. When human artery (PA) endothelial deficient were stimulated with tumor...
Fibrocytes are a unique population of circulating cells reported to exhibit characteristics both hematopoietic and mesenchymal cells, play an important role in wound healing. However, putative fibrocytes have been found lose expression surface markers such as CD45 during differentiation, making it difficult track these vivo with conventional methodologies. In this study, distinguish nonhematopoietic without markers, we took advantage the gene vav 1, which is expressed solely on but not other...
Diabetes mellitus (DM) is a metabolic disease frequently associated with impaired bone healing. Despite its increasing prevalence worldwide, the molecular etiology of DM-linked skeletal complications remains poorly defined. Using advanced stem cell characterization techniques, we analyzed intrinsic and extrinsic determinants mouse (mSSC) function to identify specific mSSC niche-related abnormalities that could impair repair in diabetic (Db) mice. We discovered high serum concentrations tumor...
Background: Scarring represents a significant biomedical burden in clinical medicine. Mechanomodulation has been linked to scarring through inflammation, but until now systematic approach attenuate mechanical force and reduce not possible. Methods: The authors conducted 12-month, prospective, open-label, randomized, multicenter trial evaluate abdominoplasty scar appearance following postoperative treatment with the embrace Advanced Scar Therapy device forces on healing surgical incisions....
Adhesions are fibrotic scars that form between abdominal organs following surgery or infection, and may cause bowel obstruction, chronic pain, infertility. Our understanding of adhesion biology is limited, which explains the paucity anti-adhesion treatments. Here we present a systematic analysis mouse human tissues. First, show adhesions derive primarily from visceral peritoneum, consistent with our clinical experience laparotomy rather than laparoscopy. Second, formed by poly-clonal...