Ka Bian, M.D., Ph.D.
Assistant Professor;
Center for Cell Signaling
phone 713.500.2469;
fax 713.500.2498
Ka.Bian@uth.tmc.edu
Dr. Bian obtained his MD degree from Zhejiang University School of Medicine in 1982 and worked as a physician (cardiovascular major) in both China and Japan. In 1990, he received his Ph.D in Medicine at National Shiga University of Medical Science, Japan where he was involved in multiple projects related to the treatment of vascular disease. He accumulated significant knowledge in vascular cell signaling and homeostasis of the vascular system through research in aspects of endothelium, smooth muscle and the perivascular nerve system of the vasculature. He has worked on identifying nitric oxide as a major neurotransmitter of perivascular nonadrenergic, noncholinergic (NANC) inhibitory nerves.
After pursuing postdoctoral training for vascular ion signaling with the patch-clamp in Providence Medical Center (Portland, Oregon), and with the apparatus that can simultaneously record the changes of calcium fluorescence signaling and vascular tone in the University of Texas Medical Branch in Galveston. His research resulted in a US patented technology of detecting extracellular calcium signaling by perivascular calcium sensing receptor which can be used for therapeutic regulation of vascular contractility.
During his term as a junior faculty member at the Department of Integrative Biology and Pharmacology at University of Texas Houston Medical School (1997), Dr. Bian further focused his efforts on the cellular signaling of nitric oxide/cGMP, a major player of various physiological and pathological activities. In 2007 he joined the Brown Foundation Institute of Molecular Medicine. He is also a faculty member of the Department of Integrative Biology and Pharmacology at the Medical School.
Inflammatory reaction has been linked to a wide variety of chronic pathological conditions including autoimmune disease and cancer. Current approaches to controlling inflammation are not always successful, making the need for new approaches urgent. Discovery of the NO related molecular mechanisms contributing to increased susceptibility to inflammatory lesions is the current goal of Dr. Bian’s research. His research has presented in areas including:
Nitrotyrosine (NO2-Tyr) – covalent modification of tyrosine residues of protein has been detected in various inflamed tissues which interrupt cellular signaling such as tyrosine phosphorylation. Over expressed iNOS resulting excessive production of NO which reacts with O2·- to form peroxynitrite (ONOO-)-classic pathway, and inflammatory accumulating myeloperoxidase (MPO) or other peroxidase – enzymatic pathway are two major elements for nitrating tyrosine. Dr. Bian’s study further revealed a non-enzymatic pathway: heme (Fe) catalyzed nitration, in which the formation of a Fe(IV) hypervalent compound may be essential. His group also addressed the H2O2 induced paracrine / autocrine signaling by oxidizing and nitrating its generator – SOD. Dr. Bian proposed a paradigm for a negative feedback mechanism of the metalloenzyme which is important for understanding the function of these enzymes under inflammatory reactions.
NO-Th2-immune diseases – The current epidemic of immune-mediated diseases may result from our loss of exposure to parasitic worms (hygiene hypothesis). Successfulness of clinical trails with helminths in treatment of (1) allergies; (2) inflammatory bowel diseases; and (3) autoimmunity (e.g. multiple sclerosis) is leading to novel therapies based on harmless organisms or their components. Dr. Bian’s research team has discovered a Trichinella spiralis-induced potent, selective and systemic iNOS down-regulation mechanism during the helminth-host interaction. The study has been selected as the Cover Story by PNAS and further elucidation of this pathway could lead to the development of new therapies for inflammatory conditions characterized by overproduction of NO, and also could provide more insight into the hygiene hypothesis that has been very influential in directing strategies to prevent immune-mediated diseases.
NO signaling-human cancer - The role of NO signaling in tumor biology have been extensively studied during the past two decades with puzzling information. Based on his research by using primary culture human cancer cell and isolated human cancer stem cell, Dr. Bian was able to form a new hypothesis which states the importance of NO / cGMP signaling in two separated categories: up-stream iNOS centered pathway is involved in the enhanced pro-inflammatory status that is key element for cancer micro-environment. Down-stream cGMP mediated pathway is responsible to proliferation, differentiation and self-renewal of cancer (stem) cells.
Selected Publications:
Bian K, Zhong M, Harari Y, Lai M, Weisbrodt N, Murad F. Helminth regulation of host IL-4Ralpha/Stat6 signaling: mechanism underlying NOS-2 inhibition by Trichinella spiralis.
Proc Natl Acad Sci U S A. 2005;102:3936-41.
Bian K, Gao Z, Weisbrodt N, Murad F. The nature of heme/iron-induced protein tyrosine nitration. Proc Natl Acad Sci U S A. 2003;100:5712-7.
Bian K, Harari Y, Zhong M, Lai M, Castro G, Weisbrodt N, Murad F. Down-regulation of inducible nitric-oxide synthase (NOS-2) during parasite-induced gut inflammation: a path to identify a selective NOS-2 inhibitor. Mol Pharmacol. 2001;59:939-47.