NF-kB seminar at Chinese University of Hong Kong

Today, I accompanied the Onwon Trading Co. team to a seminar for researchers at The Chinese University of Hong Kong.  The talk was given by Chandra Mohan, PhD of Merck Biosciences on the topic “NF-kB Activation: The Link Between Chronic Inflammation and Diseases.”

First, a little about the CUHK and the lab we visited.  The Centre for Research into Circulating Fetal Nucleic Acids is one of five focus areas at the university, headed by Prof. Dennis Y.M. Lo.

Prenatal diagnosis is an indispensable component of health care. Definitive diagnostic methods in current use, e.g., amniocentesis, are invasive and pose a risk to the unborn child. In 1997, Prof. Dennis Lo and his team discovered, for the first time in the world, the presence of cell-free fetal DNA in the plasma of pregnant women, offering new possibilities for non-invasive prenatal diagnosis. The team has further pioneered many diagnostic applications, a number of which are now used clinically by many centers globally. The center consists of a multidisciplinary group of local and international researchers to address a number of high-profile unsolved questions in the field of circulating fetal nucleic acids, including non-invasive molecular methods for the diagnosis of fetal Down syndrome. Its ultimate goal is to make safe prenatal diagnosis available to citizens around the world and to promote the development of expertise in molecular diagnostics in this region.

Read more at http://www.lihs.cuhk.edu.hk/index.html.

Now, an overview of Dr. Mohan’s talk on NF-kB.

Inflammation, a normal physiological response to injury or infection, results the activation of several pro-inflammatory genes and the release of pro-inflammatory cytokines, chemokines, adhesion molecules, and reactive oxygen and nitrogen species. Although, production and release of free radicals at the site of inflammation is helpful in eliminating invading pathogens, it can also damage healthy epithelial and stromal cells, which may lead to malignancy. Excessive lipid peroxidation, protein nitration, and DNA damage caused by free radicals can also activate several proto-oncogenes. The inflammatory link to carcinogenesis is supported by the fact that the NF-kB signaling pathway is dysregulated in a variety of human cancers. Several human lymphoid cancer cells are reported to have either mutations or amplifications of genes encoding NF-kB transcription factors. Constitutively active NF-kB is reported in many types of human tumors. In some cases, this is due to chronic stimulation of the IKK pathway, while in others the gene encoding IkBa is defective. Such constitutive nuclear NF-kB activity not only protects cancer cells from apoptotic cell death, but may also enhance their growth potential. Hence, designing anti-tumor agents to block NF-kB activity has great therapeutic value. This presentation will highlight some of the contemporary views linking chronic activation of NF-kB to tumorigenesis and link new research products developed by Merck Biosciences for investigating various signaling pathways involved in chronic inflammation and cancer.

Chandra Mohan received his PhD in 1976 from Bangalore University and did his post-doctoral work from 1977 to 1983 at the University of Southern California, School of Medicine.  From 1983 to 1993 he was an Assistant Professor of Pharmacology and Nutrition at the University of Southern California, Medical School in Los Angeles.  During this time he also served as an Associate Editor of the journal “Biochemical Medicine and Metabolic Biology.”  He joined Calbiochem (now EMD/Merck) in 1993 and is currently the Senior Director of Technical Services and Senior Technical Writer. His research interests include diabetes, biochemical basis of stress, inflammation, and the biology of aging.

 After the seminar, the representatives from Onwon (Geoffrey, Peter, Nelson and Frankie) had good discussions and follow-up with the researchers who attended.

GSK-3 seminar at Hong Kong University

Today, I accompanied the Onwon Trading Co. team to a seminar for researchers at the Research Centre of Heart, Brain, Hormone, and Healthy Aging of Hong Kong University.  The talk was given by Chandra Mohan, PhD of Merck Biosciences on the topic “Glycogen Synthase Kinase-3: Its Signaling Role in Development and Disease.”

To facilitate research and provide training opportunities, the Heart, Brain, Hormone & Healthy Aging Laboratory has been set up on the 5th Floor of the Laboratory Block, Faculty of Medicine Building, under the supervision of a laboratory committee, consisting of a Deputy Director and 3 Investigators.

After extensive consultation of Centre investigators, it was decided that the following 3 core facilities for Healthy Aging Research should be established within the Centre Laboratory.

1. Functional genomics: this will include facilities and expertise for understanding the gene function and dysfunction in aging-related diseases by making use of transgenic/knock-out mouse models generated by conventional and conditional approaches, siRNA (in vitro and in vivo), and global gene and protein expression (microarray and proteomics).
2. Biomarkers & phenotying: this will include the multiplex assays for inflammatory, oxidative and hormonal changes, as well as metabolic, haemodynamic and behavioral assessments.
3. Cell and tissue engineering: this will include human and mouse stem cell culture & differentiation, and recombinant viral vector generation.

Now, some highlights of Dr. Mohan’s talk on GSK-3.

Abnormalities in pathways that use GSK-3 as a regulator have been linked to several disease conditions. Hence, GSK-3 has emerged as a potential therapeutic target, particularly in non-insulin-dependent diabetes mellitus, Alzheimer’s disease, developmental disorders, and cancer. Several new GSK-3 inhibitors have recently been developed, most of which act in an ATP competitive manner. Inhibitors belonging to aloisines, the paullones, and the maleimide families have shown promise as therapeutic agents. Due to its involvement in multiple pathways, selectivity of GSK-3 inhibition is an important factor in the development of inhibitors for therapeutic applications.

“As we see people living longer,” said Dr. Mohan, “we see more and more dementia, which includes a loss of memory and loss of cognitive function.”

Alzheimer’s disease attacks specific neurons—the ones in areas of the brain that govern memory and cognitive capabilities. “What causes the loss of neurons is a fascinating field of research,” says Mohan. So far, scientists know of two processes involved in Alzheimer’s disease. For one thing, β:-amyloid proteins—just 40-42 amino acids long—get deposited between neurons in specific areas of the brain. Mohan says, “These peptides slow down the function of neurons and produce free radicals that lead to cell death.” In addition, too much phosphorylation of tau proteins destroys the function of microtubules, which inhibits intracellular processes, such as transporting mitochondria throughout a cell. Neurons die when they include overly phosphorylated tau proteins, which also arises in Alzheimer’s disease. “We have tried to concentrate on product lines in both these areas,” says Mohan. For example, Merck Biosciences carries a line of GSK-3 inhibitors. The GSK-3 enzyme causes phosphorylation. Mohan says, “GSK-3 is the most important enzyme. It is the most widely studied right now.”

Merck Biosciences carries antibodies against tau phosphorylation at specific amino acids: serine, threonine, and tyrosine.  You can take a brain section, use immunohistochemistry, and see where the phosphorylated tau was located.

Chandra Mohan received his PhD in 1976 from Bangalore University and did his post-doctoral work from 1977 to 1983 at the University of Southern California, School of Medicine.  From 1983 to 1993 he was an Assistant Professor of Pharmacology and Nutrition at the University of Southern California, Medical School in Los Angeles.  During this time he also served as an Associate Editor of the journal “Biochemical Medicine and Metabolic Biology.”  He joined Calbiochem (now EMD/Merck) in 1993 and is currently the Senior Director of Technical Services and Senior Technical Writer. His research interests include diabetes, biochemical basis of stress, inflammation, and the biology of aging.

After the seminar, our friends from Onwon (Geoffrey, Peter, Nelson and Frankie) had good discussions and follow-up with the researchers who attended.