We investigate the roles of angiopoietin-like protein 4 (ANGPTL4), a matricellular protein and also a redox modulator, in tissue repair, metastasis and NAFLD. Leveraging on physiologically relevant in vitro and animal models, we address key knowledge gaps to understand the pathogenesis of the disease and to develop rapid molecular diagnostics. Using a multi-disciplinary approach, we adjust cellular and acellular microenvironments to improve treatments.

METABOLIC DISORDERS (Metabolic-dysfunction Associated Steatotic Liver Disease, MASLD)
MASLD is an impending epidemic that affects 30% of the population worldwide. There is no FDA-approved treatment for MASH. Oxidative stress plays a central role in the pathogenesis of MASLD. We have developed a novel MASLD model with humanized gut microbiome that recapitulates the various transitory stages of human MASLD and extrahepatic comorbidities. We are currently investigating the relationship between gut microbes and the redox imbalance in the liver.

TARGETING METASTASIS
Metastasis accounts for more than 90% of cancer mortality. Once metastasis occurs, surgical excision of the primary tumor no longer guarantees disease free survival and the probability of cancer relapse in distal organs increases significantly. Our findings have established several paradigms in oxidative stress-driven metastasis. Our current interest aims to decipher the mechanisms that regulate and coordinate the different networks during metastasis.

TISSUE REPAIR
Excessive oxidtaive stress is detrimental to tissue repair. We focus on chronic skin wounds and inflammation-associated pulmonary injury (acute respiratory distress syndrome, ARDS), which currently does not have effective treatments.
Effective management of these problems will require better understanding of the healing process to allow the creation of a salubrious environment conducive to healing. Our lab has worked extensively to understand the interplay among different cell types, contributing to redox imbalance.

US 2018/0199327 A1: Angiopoietin-like 4 as Diabetic Wound Healing Agent and Anti-Scarring Agent (2019)
Abstract: A method and a pharmaceutical composition for increasing wound healing in an individual in need thereof, the method comprising administering an angiopoietin like 4 (ANGPTL4) polypeptide or a therapeutically active fragment thereof.

US 2015/0368331 A1: Angiopoietin-Related Protein 4 (CANGPTL4) As A Diagnostic Biomarker For Acute Lung Damage (2018)
Abstract: The invention relates to the C-terminal fragment of angiopoietin-related protein 4 [cAngptl4] as a diagnostic marker for viral and bacterial pneumonia; anti-angiopoietin-related protein 4 therapeutic antibodies, and the use of anti-angiopoietin-related protein 4 antibodies in the treatment of viral and bacterial pneumonia.

US 2016/0053268 A1: Antiproliferative Agent (2018)
Abstract: The invention provides an antibody specific to the ANGPTL4 protein capable of neutralizing proliferation and methods of making and using the same. The antibody of the invention is further directed to the C terminal region of the protein and may be capable of neutralizing cell proliferation and treating cancer. The antibody may be monoclonal and/or humanized antibody.

US 2015/0196616 A1: Angiopoietin-like 4 as Diabetic Wound Healing Agent and Anti-Scarring Agent (2018)
Abstract: A method and a pharmaceutical composition for increasing wound healing in an individual in need thereof, the method comprising administering an angiopoietin like 4 (ANGPTL4) polypeptide or a therapeutically active fragment thereof.