Faculty2016-07-08T07:55:56-07:00

Faculty

Young-Kwon Hong

Young-Kwon Hong

Professor of Surgery;Chief, Division of Basic Sciences
Surgery
1450 Biggy St. NRT6501 Health Sciences Campus Los Angeles

Lymphatic endothelial cell RXRa is critical for 9-cis-retinoic acid-mediated lymphangiogenesis and prevention of secondary lymphedema FASEB J. 2023 01; 37(1):e22674. . View in PubMed

Aqueous outflow channels and its lymphatic association: A review Surv Ophthalmol. 2022 May-Jun; 67(3):659-674. . View in PubMed

Perfusable micro-vascularized 3D tissue array for high-throughput vascular phenotypic screening Nano Converg. 2022 Apr 08; 9(1):16. . View in PubMed

Prolymphangiogenic Effects of 9-cis Retinoic Acid Are Enhanced at Sites of Lymphatic Injury and Dependent on Treatment Duration in Experimental Postsurgical Lymphedema Lymphat Res Biol. 2022 12; 20(6):640-650. . View in PubMed

Delta-like ligand-4 regulates Notch-mediated maturation of second heart field progenitor-derived pharyngeal arterial endothelial cells J Cell Mol Med. 2022 10; 26(20):5181-5194. . View in PubMed

Dose-response relationship of pulmonary disorders by inhalation exposure to cross-linked water-soluble acrylic acid polymers in F344 rats Part Fibre Toxicol. 2022 04 08; 19(1):27. . View in PubMed

Fibrillin-1 mutant mouse captures defining features of human primary open glaucoma including anomalous aqueous humor TGF beta-2 Sci Rep. 2022 06 23; 12(1):10623. . View in PubMed

PROX1, a Key Mediator of the Anti-Proliferative Effect of Rapamycin on Hepatocellular Carcinoma Cells Cells. 2022 01 27; 11(3). . View in PubMed

Pro-resolving lipid mediators in traumatic brain injury: emerging concepts and translational approach Am J Transl Res. 2022; 14(3):1482-1494. . View in PubMed

Subconjunctival Lymphatics Respond to VEGFC and Anti-Metabolites in Rabbit and Mouse Eyes Invest Ophthalmol Vis Sci. 2022 09 01; 63(10):16. . View in PubMed

VE-Cadherin: A Critical Sticking Point for Lymphatic System Maintenance: Role of VE-Cadherin in Lymphatic Maintenance Circ Res. 2022 01 07; 130(1):24-26. . View in PubMed

Piezo1-Regulated Mechanotransduction Controls Flow-Activated Lymphatic Expansion Circ Res. 2022 07 08; 131(2):e2-e21. . View in PubMed

Structural Confirmation of Lymphatic Outflow from Subconjunctival Blebs of Live Human Subjects Ophthalmol Sci. 2021 Dec; 1(4). . View in PubMed

From Bench to Bedside: The Role of a Multidisciplinary Approach to Treating Patients with Lymphedema Lymphat Res Biol. 2021 02; 19(1):11-16. . View in PubMed

Aqueous humour outflow imaging: seeing is believing Eye (Lond). 2021 01; 35(1):202-215. . View in PubMed

Tetracyclines improve experimental lymphatic filariasis pathology by disrupting interleukin-4 receptor-mediated lymphangiogenesis J Clin Invest. 2021 03 01; 131(5). . View in PubMed

Serial intravital imaging captures dynamic and functional endothelial remodeling with single-cell resolution JCI Insight. 2021 05 24; 6(10). . View in PubMed

Terminating Cancer by Blocking VISTA as a Novel Immunotherapy: Hasta la vista, baby Front Oncol. 2021; 11:658488. . View in PubMed

Lymphatic Proliferation Ameliorates Pulmonary Fibrosis after Lung Injury Am J Pathol. 2020 12; 190(12):2355-2375. . View in PubMed

Functional, structural, and molecular identification of lymphatic outflow from subconjunctival blebs Exp Eye Res. 2020 07; 196:108049. . View in PubMed

Ras Pathways on Prox1 and Lymphangiogenesis: Insights for Therapeutics Front Cardiovasc Med. 2020; 7:597374. . View in PubMed

Ischemia and reperfusion injury in superficial inferior epigastric artery-based vascularized lymph node flaps PLoS One. 2020; 15(1):e0227599. . View in PubMed

Organogenesis and distribution of the ocular lymphatic vessels in the anterior eye JCI Insight. 2020 07 09; 5(13). . View in PubMed

The Lymphatic Cell Environment Promotes Kaposi Sarcoma Development by Prox1-Enhanced Productive Lytic Replication of Kaposi Sarcoma Herpes Virus Cancer Res. 2020 08 01; 80(15):3130-3144. . View in PubMed

Prevention of postsurgical lymphedema via immediate delivery of sustained-release 9-cis retinoic acid to the lymphedenectomy site J Surg Oncol. 2020 Jan; 121(1):100-108. . View in PubMed

Small Peptide Modulation of Fibroblast Growth Factor Receptor 3-Dependent Postnatal Lymphangiogenesis Lymphat Res Biol. 2019 Feb; 17(1):19-29. . View in PubMed

Mesenchymal Stromal Cells Isolated from Irradiated Human Skin Have Diminished Capacity for Proliferation, Differentiation, Colony Formation, and Paracrine Stimulation Stem Cells Transl Med. 2019 09; 8(9):925-934. . View in PubMed

Meningeal lymphatic vessels at the skull base drain cerebrospinal fluid Nature. 2019 08; 572(7767):62-66. . View in PubMed

GATA2 controls lymphatic endothelial cell junctional integrity and lymphovenous valve morphogenesis through miR-126 Development. 2019 11 05; 146(21). . View in PubMed

A Pre-clinical Animal Model of Secondary Head and Neck Lymphedema Sci Rep. 2019 12 04; 9(1):18264. . View in PubMed

Piezo1 incorporates mechanical force signals into the genetic program that governs lymphatic valve development and maintenance JCI Insight. 2019 03 07; 4(5). . View in PubMed

YAP and TAZ Negatively Regulate Prox1 During Developmental and Pathologic Lymphangiogenesis Circ Res. 2019 01 18; 124(2):225-242. . View in PubMed

Exosomes as a Communication Tool Between the Lymphatic System and Bladder Cancer Int Neurourol J. 2018 Sep; 22(3):220-224. . View in PubMed

Human Acellular Dermis as Spacer for Small-Joint Arthroplasty: Analysis of Revascularization in a Rabbit Trapeziectomy Model Plast Reconstr Surg. 2018 09; 142(3):679-686. . View in PubMed

Endothelial lineage-specific interaction of Mycobacterium tuberculosis with the blood and lymphatic systems Tuberculosis (Edinb). 2018 07; 111:1-7. . View in PubMed

Postnatal development of lymphatic vasculature in the brain meninges Dev Dyn. 2018 05; 247(5):741-753. . View in PubMed

Advances in Renal Cell Imaging Semin Nephrol. 2018 01; 38(1):52-62. . View in PubMed

Context-dependent functions of angiopoietin 2 are determined by the endothelial phosphatase VEPTP Proc Natl Acad Sci U S A. 2018 02 06; 115(6):1298-1303. . View in PubMed

Complementary Wnt Sources Regulate Lymphatic Vascular Development via PROX1-Dependent Wnt/ß-Catenin SignalingCell Rep. 2018 10 16; 25(3):571-584. e5. . View in PubMed

Deregulation of HDAC5 by Viral Interferon Regulatory Factor 3 Plays an Essential Role in Kaposi's Sarcoma-Associated Herpesvirus-Induced Lymphangiogenesis mBio. 2018 01 16; 9(1). . View in PubMed

Lymphatic exosomes promote dendritic cell migration along guidance cues J Cell Biol. 2018 06 04; 217(6):2205-2221. . View in PubMed

Impaired angiopoietin/Tie2 signaling compromises Schlemm's canal integrity and induces glaucoma J Clin Invest. 2017 Oct 02; 127(10):3877-3896. . View in PubMed

Rapamycin reversal of VEGF-C-driven lymphatic anomalies in the respiratory tract JCI Insight. 2017 Aug 17; 2(16). . View in PubMed

ORAI1 Activates Proliferation of Lymphatic Endothelial Cells in Response to Laminar Flow Through Krüppel-Like Factors 2 and 4 Circ Res. 2017 Apr 28; 120(9):1426-1439. . View in PubMed

Laminar flow downregulates Notch activity to promote lymphatic sprouting J Clin Invest. 2017 Apr 03; 127(4):1225-1240. . View in PubMed

Toward in vivo two-photon analysis of mouse aqueous outflow structure and function Exp Eye Res. 2017 05; 158:161-170. . View in PubMed

Genetic and neuronal regulation of sleep by neuropeptide VF Elife. 2017 11 06; 6. . View in PubMed

Development and Characterization of A Novel Prox1-EGFP Lymphatic and Schlemm's Canal Reporter Rat Sci Rep. 2017 07 17; 7(1):5577. . View in PubMed

Deep tissue analysis of distal aqueous drainage structures and contractile features Sci Rep. 2017 12 06; 7(1):17071. . View in PubMed

Topical Fibronectin Improves Wound Healing of Irradiated Skin Sci Rep. 2017 06 20; 7(1):3876. . View in PubMed

Intestinal Enteroendocrine Lineage Cells Possess Homeostatic and Injury-Inducible Stem Cell ActivityCell Stem Cell. 2017 07 06; 21(1):78-90. e6. . View in PubMed

Rapamycin up-regulates triglycerides in hepatocytes by down-regulating Prox1 Lipids Health Dis. 2016 Feb 27; 15:41. . View in PubMed

Aberrant Activation of Notch Signaling Inhibits PROX1 Activity to Enhance the Malignant Behavior of Thyroid Cancer Cells Cancer Res. 2016 Feb 01; 76(3):582-93. . View in PubMed

Limited versus total epithelial debridement ocular surface injury: Live fluorescence imaging of hemangiogenesis and lymphangiogenesis in Prox1-GFP/Flk1::Myr-mCherry mice Biochim Biophys Acta. 2016 10; 1860(10):2148-56. . View in PubMed

Prevention of Postsurgical Lymphedema by 9-cis Retinoic Acid Ann Surg. 2016 08; 264(2):353-61. . View in PubMed

Efficient Assessment of Developmental, Surgical and Pathological Lymphangiogenesis Using a Lymphatic Reporter Mouse and Its Embryonic Stem Cells PLoS One. 2016; 11(6):e0157126. . View in PubMed

DeepCAGE transcriptomics identify HOXD10 as a transcription factor regulating lymphatic endothelial responses to VEGF-C J Cell Sci. 2016 07 01; 129(13):2573-85. . View in PubMed

A Model of Lymphangioleiomyomatosis in a Three-Dimensional Culture System Lymphat Res Biol. 2015 Dec; 13(4):248-52. . View in PubMed

DeepCAGE Transcriptomics Reveal an Important Role of the Transcription Factor MAFB in the Lymphatic Endothelium Cell Rep. 2015 Nov 17; 13(7):1493-1504. . View in PubMed

Intravital imaging of intestinal lacteals unveils lipid drainage through contractility J Clin Invest. 2015 Nov 02; 125(11):4042-52. . View in PubMed

Simultaneous in vivo imaging of blood and lymphatic vessel growth in Prox1-GFP/Flk1::myr-mCherry mice FEBS J. 2015 Apr; 282(8):1458-1467. . View in PubMed

TH2 cells and their cytokines regulate formation and function of lymphatic vessels Nat Commun. 2015 Feb 04; 6:6196. . View in PubMed

Prox1 expression in the endolymphatic sac revealed by whole-mount fluorescent imaging of Prox1-GFP transgenic mice Biochem Biophys Res Commun. 2015 Jan 30; 457(1):19-22. . View in PubMed

A lymphatic defect causes ocular hypertension and glaucoma in mice J Clin Invest. 2014 Oct; 124(10):4320-4. . View in PubMed

Lymphatic regulator PROX1 determines Schlemm's canal integrity and identity J Clin Invest. 2014 Sep; 124(9):3960-74. . View in PubMed

CXCR2 inhibition enhances sulindac-mediated suppression of colon cancer development Int J Cancer. 2014 Jul 01; 135(1):232-7. . View in PubMed

Thrombospondin-2 overexpression in the skin of transgenic mice reduces the susceptibility to chemically induced multistep skin carcinogenesis J Dermatol Sci. 2014 May; 74(2):106-15. . View in PubMed

Preferential lymphatic growth in bronchus-associated lymphoid tissue in sustained lung inflammation Am J Pathol. 2014 May; 184(5):1577-92. . View in PubMed

Control of retinoid levels by CYP26B1 is important for lymphatic vascular development in the mouse embryo Dev Biol. 2014 Feb 01; 386(1):25-33. . View in PubMed

Novel characterization and live imaging of Schlemm's canal expressing Prox-1 PLoS One. 2014; 9(5):e98245. . View in PubMed

Localization and proliferation of lymphatic vessels in the tympanic membrane in normal state and regeneration Biochem Biophys Res Commun. 2013 Oct 25; 440(3):371-3. . View in PubMed

Protective role of the lymphatics from sepsis Blood. 2013 Sep 26; 122(13):2143-4. . View in PubMed

Interleukin-8 reduces post-surgical lymphedema formation by promoting lymphatic vessel regeneration Angiogenesis. 2013 Jan; 16(1):29-44. . View in PubMed

Novel biomarkers of arterial and venous ischemia in microvascular flaps PLoS One. 2013; 8(8):e71628. . View in PubMed

Lymphatic reprogramming by Kaposi sarcoma herpes virus promotes the oncogenic activity of the virus-encoded G-protein-coupled receptor Cancer Res. 2012 Nov 15; 72(22):5833-42. . View in PubMed

Interleukin-8 and its receptor CXCR2 in the tumour microenvironment promote colon cancer growth, progression and metastasis Br J Cancer. 2012 May 22; 106(11):1833-41. . View in PubMed

The new era of the lymphatic system: no longer secondary to the blood vascular system Cold Spring Harb Perspect Med. 2012 Apr; 2(4):a006445. . View in PubMed

9-cis retinoic acid promotes lymphangiogenesis and enhances lymphatic vessel regeneration: therapeutic implications of 9-cis retinoic acid for secondary lymphedema Circulation. 2012 Feb 21; 125(7):872-82. . View in PubMed

Opposing regulation of PROX1 by interleukin-3 receptor and NOTCH directs differential host cell fate reprogramming by Kaposi sarcoma herpes virus PLoS Pathog. 2012; 8(6):e1002770. . View in PubMed

The Primo Vascular System Detection of the Primo Vessels in the Rodent Thoracic Lymphatic Ducts. 2012. . View in PubMed

Interleukin-8 is associated with proliferation, migration, angiogenesis and chemosensitivity in vitro and in vivo in colon cancer cell line models Int J Cancer. 2011 May 01; 128(9):2038-49. . View in PubMed

Visualization of lymphatic vessels by Prox1-promoter directed GFP reporter in a bacterial artificial chromosome-based transgenic mouse Blood. 2011 Jan 06; 117(1):362-5. . View in PubMed

Novel discovery of LYVE-1 expression in the hyaloid vascular system Invest Ophthalmol Vis Sci. 2010 Dec; 51(12):6157-61. . View in PubMed

Akt/Protein kinase B is required for lymphatic network formation, remodeling, and valve development Am J Pathol. 2010 Oct; 177(4):2124-33. . View in PubMed

Kaposin-B enhances the PROX1 mRNA stability during lymphatic reprogramming of vascular endothelial cells by Kaposi's sarcoma herpes virus PLoS Pathog. 2010 Aug 12; 6(8):e1001046. . View in PubMed

An exquisite cross-control mechanism among endothelial cell fate regulators directs the plasticity and heterogeneity of lymphatic endothelial cells Blood. 2010 Jul 08; 116(1):140-50. . View in PubMed

Direct transcriptional regulation of neuropilin-2 by COUP-TFII modulates multiple steps in murine lymphatic vessel development J Clin Invest. 2010 May; 120(5):1694-707. . View in PubMed

Heterogeneity and plasticity of lymphatic endothelial cells Semin Thromb Hemost. 2010 Apr; 36(3):352-61. . View in PubMed

The Molecular Mechanism of Tumor Lymphangiogenesis Molecular Mechanisms to Targeted Therapy. 2010. . View in PubMed

The origin of Kaposi sarcoma tumor cellsKaposi sarcoma. A model of oncogenesis. 2010; 123-138. . View in PubMed

Phosphate-buffered saline-based nucleofection of primary endothelial cells Anal Biochem. 2009 Mar 15; 386(2):251-5. . View in PubMed

Prox1 physically and functionally interacts with COUP-TFII to specify lymphatic endothelial cell fate Blood. 2009 Feb 19; 113(8):1856-9. . View in PubMed

Current understanding of lymphatic system development Endothelial Biomedicine. 2007; 1533-1567. . View in PubMed

Prox1 promotes lineage-specific expression of fibroblast growth factor (FGF) receptor-3 in lymphatic endothelium: a role for FGF signaling in lymphangiogenesis Mol Biol Cell. 2006 Feb; 17(2):576-84. . View in PubMed

Alcian blue staining method to visualize bonghan threads inside large caliber lymphatic vessels and x-ray microtomography to reveal their microchannels Lymphat Res Biol. 2006; 4(4):181-90. . View in PubMed

Role of Notch signal transduction in Kaposi's sarcoma-associated herpesvirus gene expression J Virol. 2005 Nov; 79(22):14371-82. . View in PubMed

Up-regulation of the lymphatic marker podoplanin, a mucin-type transmembrane glycoprotein, in human squamous cell carcinomas and germ cell tumors Am J Pathol. 2005 Mar; 166(3):913-21. . View in PubMed

Ultraviolet B irradiation of human skin induces an angiogenic switch that is mediated by upregulation of vascular endothelial growth factor and by downregulation of thrombospondin-1 Br J Dermatol. 2005 Jan; 152(1):115-21. . View in PubMed

Development of the lymphatic vascular system: a mystery unravels Dev Dyn. 2004 Nov; 231(3):462-73. . View in PubMed

Function of Drg1/Rit42 in p53-dependent mitotic spindle checkpoint J Biol Chem. 2004 Sep 10; 279(37):38597-602. . View in PubMed

Induction of cutaneous delayed-type hypersensitivity reactions in VEGF-A transgenic mice results in chronic skin inflammation associated with persistent lymphatic hyperplasia Blood. 2004 Aug 15; 104(4):1048-57. . View in PubMed

Lymphatic reprogramming of blood vascular endothelium by Kaposi sarcoma-associated herpesvirus Nat Genet. 2004 Jul; 36(7):683-5. . View in PubMed

VEGF-A promotes tissue repair-associated lymphatic vessel formation via VEGFR-2 and the alpha1beta1 and alpha2beta1 integrins FASEB J. 2004 Jul; 18(10):1111-3. . View in PubMed

Ultraviolet B-induced skin angiogenesis is associated with a switch in the balance of vascular endothelial growth factor and thrombospondin-1 expression J Invest Dermatol. 2004 Jan; 122(1):201-8. . View in PubMed

An N-terminal 80 kDa recombinant fragment of human thrombospondin-2 inhibits vascular endothelial growth factor induced endothelial cell migration in vitro and tumor growth and angiogenesis in vivo J Invest Dermatol. 2003 Dec; 121(6):1536-43. . View in PubMed

Prox1, master regulator of the lymphatic vasculature phenotype Cell Tissue Res. 2003 Oct; 314(1):85-92. . View in PubMed

T1alpha/podoplanin deficiency disrupts normal lymphatic vasculature formation and causes lymphedema EMBO J. 2003 Jul 15; 22(14):3546-56. . View in PubMed

Identification of vascular lineage-specific genes by transcriptional profiling of isolated blood vascular and lymphatic endothelial cells Am J Pathol. 2003 Feb; 162(2):575-86. . View in PubMed

Prox1 is a master control gene in the program specifying lymphatic endothelial cell fate Dev Dyn. 2002 Nov; 225(3):351-7. . View in PubMed

Activation of the tie2 receptor by angiopoietin-1 enhances tumor vessel maturation and impairs squamous cell carcinoma growth Am J Pathol. 2002 Apr; 160(4):1381-92. . View in PubMed

Non-disruptive PNA-FISH protocol for formalin-fixed and paraffin-embedded tissue sections Biotechniques. 2001 Sep; 31(3):472475-6. . View in PubMed

PNA interference mapping demonstrates functional domains in the noncoding RNA Xist Proc Natl Acad Sci U S A. 2001 Jul 31; 98(16):9215-20. . View in PubMed

Thrombospondin-2 plays a protective role in multistep carcinogenesis: a novel host anti-tumor defense mechanism EMBO J. 2001 Jun 01; 20(11):2631-40. . View in PubMed

Development of two bacterial artificial chromosome shuttle vectors for a recombination-based cloning and regulated expression of large genes in mammalian cells Anal Biochem. 2001 Apr 01; 291(1):142-8. . View in PubMed

Murine Xist RNA isoforms are different at their 3' ends: a role for differential polyadenylation Gene. 2001 Mar 21; 266(1-2):131-7. . View in PubMed

The essential function of Not1 lies within the Ccr4-Not complex J Mol Biol. 2000 Oct 20; 303(2):131-43. . View in PubMed

A revision of the human XIST gene organization and structural comparison with mouse Xist Mamm Genome. 2000 Mar; 11(3):220-4. . View in PubMed

Tetracycline-resistant gene cassette designed for construction of mutant libraries of a target gene Biotechniques. 1999 Oct; 27(4):682-5. . View in PubMed

A new structure for the murine Xist gene and its relationship to chromosome choice/counting during X-chromosome inactivation Proc Natl Acad Sci U S A. 1999 Jun 08; 96(12):6829-34. . View in PubMed

Single base discrimination of CENP-B repeats on mouse and human Chromosomes with PNA-FISH Mamm Genome. 1999 Jan; 10(1):13-8. . View in PubMed

Dr. Hong obtained his Ph.D. in Microbiology at the University of California, Davis. He then studied global genetic and epigenetic regulations in mouse embryonic stem cells at the Harvard Institute of Human Genetics during his post-doctoral fellowship. In 2001, he was recruited as an Instructor at the Cutaneous Biology Research Center, Massachusetts General Hospital, and Harvard Medical School. After 5 years, he joined the Department of Surgery, Keck School of Medicine in 2005. Dr. Hong is a Professor of Surgery and affiliated with Norris Comprehensive Cancer Center. He also serves as the Director of Translational and Basic Science Research of Surgery Department and supervises all basis and translational research in the department. His main research interest is to understand the molecular and cellular controls of tissue fluid homeostasis in health and disease, including cancer, vascular malformation, brain fluid outflow, inflammation, viral infection, and wound healing, and to translate the knowledge to benefit human health. Dr. Hong received numerous awards for his outstanding research accomplishments, including the Seungman Cha Young Scientist Award, the STOP CANCER Award, Margaret E. Early Medical Research Foundation Young Investigator Award, James H. Zumberge Innovation Research Award, Concern Foundation Young Scientist Award, American Heart Association Award, The Wright Foundation Young Investigator Award, The U.S. Department Of Defense Congressionally Directed Medical Research Programs Breast Cancer Idea Award, March Of Dime Birth Defect Foundation Scholar Award, and American Cancer Society Research Scholar Award. Dr. Hong has trained and mentored more than 80 students (high school, undergraduate, graduate, and medical school), post-doctoral fellows, surgical residents, visiting scholars, and junior faculty members during the past 15 years at the Keck School of Medicine.

The research interests in the Hong laboratory are listed below.

1. Lymphatic Development and Differentiation
Although Hippocrates simultaneously discovered the blood and lymphatic system, the lymphatic system has been extremely understudied despite its vital role in human health and diseases, compared to the blood vascular system. About 100 years ago, Sabin proposed that lymphatics are generated from the blood vascular system. This Sabin’s theory has recently been confirmed using newly discovered molecular and cellular markers and research tools. We are interested in how various signal pathways control lymphatic development and differentiation. A better understanding of lymphatic development and differentiation will significantly help to treat many human diseases related to the lymphatic system.

2. Organ-On-Chips
We have recently launched an Organ-On-Chips program. Collaborating with other biomedical engineer groups, we aim to grow blood and lymphatic vessels on a chip to investigate the mechanisms of physiological and pathological angiogenesis and lymphangiogenesis. This new technology is powerful as it enables us to study the biology of vascular development and differentiation and models our organs and tissues for many biomedical and therapeutic purposes.

3. Development of Lymphedema Therapy
Surgery-related lymphedema is the leading morbidity that is associated with breast cancer survivors. To date, non-invasive therapeutic approaches are unavailable for this disfiguring, painful and demoralizing illness. We have recently published the therapeutic efficacy of retinoic acid against surgery-associated lymphedema in the prestigious journal Circulation. Our study found that retinoic acid could regenerate damaged lymphatic system and prevent potential lymphedema using animal models. We aim further to confirm this new therapy in rats and large animals and eventually bring it to clinical trials. Because retinoic acids have been extensively studied for their medicinal properties and are already used in clinics for other diseases, the new approach presents great promise and hope to patients suffering from surgery-associated lymphedema.

4. Fluid Homeostasis and Outflow Facility in the Eye
The lymphatics play essential roles in tissue fluid homeostasis in the interstitial space. Similarly, Schlemm’s canal (SC), a specialized vascular structure in the eye, controls the fluid homeostasis of the eye's anterior chamber. SC is an endothelium-lined channel that encircles the margin of the cornea and drains the aqueous humor from the anterior chamber of the eye into the circulation through collector channels. As the intraocular pressure (IOP) is closely correlated with the aqueous humor outflow (AHO), SC plays a key role in regulating IOP in the eye. When the draining function of SC becomes compromised, the IOP could be dramatically elevated and damage the ocular nerve, possibly causing glaucoma. Directly connected to the aqueous vein, SC has long been thought to be a venous extension, whose inner wall is lined by blood vascular endothelial cells (BECs). Interestingly, SC has also been known to display molecular, structure, and functional features of lymphatic vessels, which are responsible for draining the interstitial fluids into the circulation. During development, lymphatic endothelial cells (LECs) are differentiated from BECs and this BEC-to-LEC fate reprogramming process is exquisitely controlled by a homeodomain transcription factor Prox1. Recently, my group, together with a vascular biology group in Korea, has published an exciting study, demonstrating that lymphatic regulator PROX1 determines SC integrity and identity. In addition, we have collaborated with other groups in two other studies on SC's development and maintenance. We are thrilled to utilize our expertise to understand better how fluid homeostasis and intraocular pressure are controlled in healthy and glaucoma eyes. We are interested in defining the molecular mechanism by which fluid flow directs the development and maintenance of SC through the shear stress regulator, Klf4. Our experience and resource would contribute to advancing the knowledge of the molecular controls of intraocular pressure with therapeutic implications for glaucoma.

5. Stem Cell Research
We study the molecular mechanism underlying the vascular differentiation of embryonic stem (ES) and adipose-derived stem cells (ADSC) with three goals. (a) to acquire a better understanding of the embryonic and postnatal genetic program that specifies vascular and lymphatic endothelial cells, (b) to develop technology that allows maximal differentiation efficiency for 3-D printing of organs, and (c) to acquire the clinical-grade vascular building blocks to treat vascular diseases, including vascular malformation and lymphedema.

6. Cancer Development and Metastasis
The majority of cancers recruit and invade lymphatic vessels for their metastasis. We are interested in how breast and colon cancers interact with lymphatic vessels to promote their metastasis. Our preliminary data suggest that tumor-induced tissue pressure could play a previously unidentified role in their spread. Separately, various pathogens, such as Kaposi sarcoma herpes virus (KSHV), directly infect vascular endothelial cells and cause neoplasm in HIV- and organ transplant patients. We are studying the molecular and cellular interactions between the host and the pathogens.
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