Molecular and Cell Signaling Laboratory
Dr. Sylvester’s investigative interest is primarily focused on problems of human development and pregnancy, and includes congenital anomalies and acquired disease. Current studies include population health risk stratification methodology development, epidemiologic disease association studies; molecular and cellular metabolic development mechanistic studies and biomarkers for gut development and adaptation.
The general approach of Dr. Sylvester’s investigative efforts is to combine the study of human clinical and epidemiologic variables along with biologic samples. Model disease organisms are used to pose and test new hypotheses experimentally with a goal of gaining mechanistic insights. The broader objective of these studies is to derive a deeper understanding of human disease and to develop applications for possible new diagnostics and therapeutics focused on diseases of pregnancy and childhood.
A leading line of current investigation is to derive metabolic models (targeted and non-targeted metabolite panels) that quantify human development during pregnancy and in the immediate post-natal period. Using these models the team is looking at ways in which inherent biologic vulnerabilities that are conferred either through modes of inheritance (genetics) or interrupted development (e.g. premature or low birth weight newborns) place newborns at risk for acquired and potentially preventable diseases. This work has high relevance for preventing and treating the causes and consequences of prematurity in the US and throughout the developed world. In addition, the Sylvester laboratory is interested in extending this work to the developing world in an effort to quantify metabolic vulnerability and the problem of stunting (low birth weight and growth during early childhood), its causes and consequences.
In the laboratory, the team is currently investigating the molecular drivers and pathways involved in newborn metabolism. Deregulated metabolism in premature newborns is a likely significant contributor to a category of acquired diseases that are unique and specific to premature newborns (e.g. Necrotizing Enterocolitis, Retinopathy of Prematurity, Respiratory Distress of the Premature and Chronic Lung Disease, Neurodevelopmental Impairment). These diseases are all associated with elevated levels of inflammation that is not specifically initially caused by infectious agents. The Sylvester team is investigating potential common pathways that may be effecting the initiation of these multifactorial acquired diseases.
Dr. Sylvester has worked with an established network of academic children's hospitals and investigators to study the human newborn diseases Necrotizing Enterocolitis. The group has published several papers describing their novel findings of molecular indicators or biomarkers of disease. The group is seeking to establish both molecular indicators of disease as well as biochemical indicators that accurately identify infants most at risk for disease in order to provide clinical strategies to prevent disease onset. Molecules and pathways of interest that have been identified in human specimens are being studied further in experimental models of disease to gain a deeper insight to the specific mechanisms of disease.
We seek to develop novel diagnostic and therapeutic approaches to infant and pediatric disease through a greater understanding of the molecular and cellular biology of human metabolism and inflammation.
Derive a greater understanding of the molecular drivers of human metabolism during pregnancy and fetal-newborn development that are involved in the pathogenesis of disease.
Develop a framework for identifying appropriate risk adjustment and quality indicators to achieve optimal outcomes in the surgical management of newborn congenital anomalies.
Identify the mechanisms of metabolic capacity maturation during human fetal and newborn development.
Develop strategies to target metabolic pathways for therapeutic targeting.
Identify gut-specific biomarkers of injury and adaptation to help clinicians with early diagnosis.
Guozhong Tao- Senior Research Scientist
Dr. Tao received his medical degrees from Liaoning Medical College and China Medical University in China. Dr. Tao next obtained his PhD in Japan from the department of Biochemistry at Akita University School of Medicine. As a postdoctoral fellow, Guozhong came to the US and joined the laboratory of Dr. Bishr Omary at the division of Gastroenterology and Hepatology, Department of Medicine, Stanford University. During his post-doctoral studies, Tao studied the function of intracellular cytoskeletal networks of intermediate filament proteins in health and digestive diseases. In 2008, Dr. Tao transitioned to Dr. Karl Sylvester's lab in the Division of Pediatric Surgery and has been instrumental in leading the studies of developmentally regulated molecular signaling pathways (Wnt, beta-catenin, FOXO) that are integral to the metabolic and injury response of regeneration in a variety of human disease models including: Alcoholic liver disease (ALD), nonalcoholic fatty liver disease (NAFLD), and hepatic ischemia-reperfusion injury (IRI) etc. Recently, Guozhong has been involved in the molecular mechanistic study for Necrotizing Enterocolitis (NEC) in order to understand why premature babies are highly predisposed to the disease. Along with Dr. Sylvester, Ghuozhong has developed novel molecular indicators of gut health and disease (biomarkers).
Zhen Sun- Visiting Research Scholar
Dr. Zhen Sun is a Visiting Scholar in the laboratory through December 2018. She comes from Changzheng Hospital, The Second Military Medical University, Shanghai, China. Zhen received her M.D. in 2001, from Zhenjiang Medical College, Jiangsu, China. The focus of her clinical training is Laboratory Medicine. Zhen also obtained her Master's Degree June 2011 from The Second Military Medical University.
Dr. Sun worked at the Department of Laboratory Diagnostics, Changzheng Hospital for more than ten years. From April 28th, 2015 to December 14th, 2016, she was a Visiting Scientist at The University of Texas Health Science Center at Houston (UTHealth) Medical School, Department of Internal Medicine, and Cardiovascular Medicine.
In December 2016, Dr. Sun entered Dr. Sylvester's laboratory at Stanford University for further research training. She is currently working on the molecular mechanism of Necrotizing Enterocolitis (NEC), the most common and severe intestinal disease among preterm babies. To understand this disease's mechanisms, she conducts animal experiments to investigate differential molecular expression profiling of the key cell signaling pathways between early and late delivery rodent pups. Dr. Sun is also involved in a project that aims to develop blood/fecal biomarker assays for clinical diagnosis of newborn gut adaptation and NEC.