The research in my laboratory is focused on the effects of mechanical stresses (e.g., those resulting from pressure and flow) on signal transduction, gene expression, and functional behavior of the endothelial cells lining the blood vessels. Endothelial dysfunction can lead to atherosclerosis, which is a major cause of cardiovascular diseases such as myocardial infarction due to the obstruction of coronary arteries. The results of our investigations indicate that the direction of the mechanical stresses plays an important role in the molecular and functional responses in endothelial cells. Stresses with a defined direction, which are seen in the straight part of the arterial tree, lead to events that are protective against atherosclerosis. In contrast, the stresses in arterial branch pointes do not possess clear directions, and the consequent molecular and cellular changes in endothelial cells render these regions prone to atherosclerosis. This presentation will outline the path of evolution of my research direction from my Ph.D. dissertation to the present, together with my formal and informal education and my life in relation to the scientific communities and family. My experience indicates that, while we need to set a direction for our life, we often have to deal with modifying factors that are beyond our control. It is important to have the flexibility to adapt to variations in the external conditions, while being perseverant with our long-term goal. I would like to share with you the seven C's that can be valuable for the achievement of our career goals. That is, we need to have Commitment and Compassion for whatever we choose to do. We should Comprehend what is known and what needs to be done and be Creative in designing and executing our work. It is extremely important to continuously improve our Communication skills and to Cooperate with others. Finally, we must Complete whatever we set out to do. By pursuing what you choose to accomplish with a clear, realistic direction and by using these 7 C's, I am certain that you will have a successful career and a happy life.

Blood comprises many proteins, small molecular weight compounds and cells. It flows in blood vessels in an orderly manner. The blood vessel is covered by a layer of cells, called endothelial cells ( 內皮細胞 ). Endothelial cells are active in producing molecules that prevent blood cells from adhering to blood vessel, blood from clotting and blood vessels from excessive contraction. Blood platelets ( 血小板 ) are unique in that they do not have nuclei. They are highly active and have a tendency toward aggregation. However, under normal condition, platelets flow as an individual cell. Excessive stimulation of platelets leads to blood clotting and thrombosis. The consequence is serious cardiovascular diseases ( 心血管疾病 ) and stroke ( 腦中風 ). Research in my laboratory has shown that platelet reactivity is controlled by a balance between two structurally related small molecular weight compounds generated by two enzymes with similar biochemical characteristics. The compound produced by platelets is called thromboxane and that produced by endothelial cells is prostacyclin. Thromboxane induces aggregation and thrombosis while prostacyclin inhibits both. Aspirin inhibits thromboxane production and therefore is useful in controlling platelet activity. In this presentation, discovery of these compounds and the aspirin development story will be described. The fun of doing basic medical research and translational research will be shared.

In the modern society, drugs are so often misused or abused. Misuse of a drug means that it is taken for the wrong therapeutic indication or with a wrong dosage. Abuse of drugs usually implies that people take them for changing mental status or for other purposes like body-building, physical enhancing, etc. Abuse of a drug may cause toxicity. Toxicity is different depending on acute, frequent or chronic administration. Toxicity is also depending on the route of administration, frequency and dosage of drugs administered, and the duration of the usage. Abuse of drugs may lead to addiction that often produces psychological and/or physical dependence. Tolerance is a phenomenon that frequent use of a drug causes decrease in response. Tolerance to a drug is closely associated with dependence on the drug. Although the frequently abused drugs are mostly acting in the brain, they are more likely produce effects on the other organs as well, since all of them are not specifically just acting on the central nervous system.

This presentation will focus on various aspects of drugs in terms of chemistry, pharmacological properties, toxicity, behavioral effects and health hazards. These drugs include prescription drugs such as morphine, pentobarbital and diazepam, illegal drugs such as heroin, cocaine, methamphetamine, and marijuana, and nonprescription substances such as alcohol, cigarette, and solvents.

In the United States, the mortality from coronary heart disease (CHD) has been declining for the last 30 years- probably because of better treatments (for both disease and risk factors), and more efforts towards primary prevention. However, CHD is still the number two killer. In addition to the well-established CHD risk factors: elevated cholesterol and blood pressure, cigarette smoking, and diabetes, more recently, Obesity and Metabolic Syndrome (MetS) have emerged as novel risk factors. For the development of primary prevention strategies to further reduce CHD mortality and morbidity, it is important to understand factors that are associated with the evolution of CHD risk factors from young adulthood to early middle age.

The Coronary Artery Risk Development in (Young) Adults (CARDIA) Study, is a United States National Heart, Lung, and Blood Institute sponsored multi-center longitudinal study on lifestyles and evolution of cardiovascular risk factors in young adults. The cohort consists of 5,115 black and white men and women, ages18 to 30 in 1985-86 (baseline), with varying socioeconomic status. Six follow-up examinations at Years 2, 5, 7, 10, 15, and 20 have been conducted. This presentation will discuss one of the major public health problems in the United States , i.e., obesity, and several findings in CARDIA that are relevant to the impact of overweight and obesity on the evolution of cardiovascular disease risk factors. In addition, the benefit of a healthy lifestyle during young adulthood on preventing the development of CHD risk factors and subclinical CHD, will also be discussed. In particular, the presentation will include:

•   Trends of CHD mortality in the United States and discussion of two frequently used measures of subclinical CHD
•   Review of CHD risk factors, high blood pressure, high cholesterol, cigarette smoking and diabetes
•   Evolution of the obesity epidemic in the United States
•   Impact of baseline body mass index (BMI) and BMI changes on cardiovascular risk factors and Metabolic Syndrome (MetS)
•   Relationship of MetS in young adulthoods to the development of type-2 diabetes
•   Relationships between baseline CHD risk factors and subclinical CHD 20 years later.
•   Impact of healthy behaviors on ideal risk profile and subclinical CHD.
•   Roles of epidemiologic studies in the reduction of CHD mortality

Results from CARDIA strongly suggest that obesity and weight gain during young adulthood are the major risk factors for MetS and diabetes in middle age. Higher levels of CHD risk factors at baseline are associated with coronary calcium 20 years later. Maintaining a normal weight and adopting a healthy lifestyle during young adulthood helps in retaining an ideal risk factor profile, and also helps in preventing the development of diabetes and subclinical CHD.

When I first heard the story about Isaac Newton and the falling apple, a string of questions came to the head of the 6-year-old. Among many others, I keep wondering why? There were millions of things that falling from the sky each day, and millions of people watching them fall. Why was it Newton discovered gravidity in this one observation? It took me years to finally figured out that it was only a made-up story to show how smart Newton was – that made me to believe only smart people can be scientist - another misery that almost costing my entire professional career.

Although no one would doubt that smart people can make great scientist. The more realistic side is: great scientific achievement was never be made by one smart person. Here, I would like to share with you the story of one hydraulic engineer who worked more than half of his professional life with experts in many other specialties: life scientists, physicians, heart surgeons, through close communication, collaboration, to consolidate on many life saving prostheses and devices.

Atherosclerosis ( 動脈硬化 ), the underlying cause leading to myocardial infarction, stroke and gangrene of extremities, is one of the major medical problems with high morbidity and mortality in developed counties. Substantial studies over the past two decades have revealed that the etiology of atherosclerosis is a complicated process and involves both genetic and environmental factors and their interactions. In addition to many genetic variants which are shown to be associated with disease susceptibilities, a number of risk factors, such as hypercholesterolemia, hypertension, diabetes, inflammation, infection, and smoking, are well-known environmental triggers implicated in the disease development. As the worldwide incidence of cardiovascular diseases continues to increase steadily, fully understanding the pathological mechanisms underlying the disease development at the molecular and genetic levels and developing new approaches for the therapeutic intervention imposes a great challenge in biomedical research. To date, one of the powerful approaches to unravel the complex cellular networks underlying disease development is through analyzing the gene expression profiles of normal and diseased tissues. The identification and characterization of genes that are up or down regulated in the diseased vessels can provide insights into the development and progression of vascular lesions. Among the arrays of disease-associated genes identified, some can be regarded as protective genes as they function to defend or prevent the injured vessels from further deterioration. Advances of our understanding on the functional roles of these protective genes can pave the way for designing better effective strategies to combat disease. In this presentation, I will take our research work as an example to show you how we identified a vasoprotective gene which is induced in vascular lesions and exerts potent protective functions as demonstrated in animal disease models. The clinical significance of the genetic variations of this gene was also revealed in studies showing that a dinucleotide repeat polymorphism in the proximal promoter region is associated with the gene expression level and the susceptibility to coronary heart disease in patients. These findings provide the basis to support its potentials as a therapeutic gene for treating cardiovascular diseases.