Mingsheng Zhang

Research Interest

Autocrine signaling plays an important role in cell physiology. How the intracellular and extracellular signaling networks interact and respond to survival or death cues has not been systematically examined. Using the antibody arrays, I am going to explore how the autocrine signaling (about several hundred of cytokines) is regulated in mammalian cells after treatment of growth factors or death ligands. Selective perturbation of these pathways will generate valuable data to gain deeper insight of the makeup of these networks. Taking advantage of mathematical models established in the CDP program, which is largely based on the intracellular signaling, we are hoping to work out a universal model which takes into consideration cross talk of inside and outside signaling. Another interest of mine is to study the interaction of oxidative stress signaling and cell death. Under oxidative insults, cells invoke a spectrum of changes in the signaling networks and cell homeostasis. Depending on the cell type and type and dose of oxidative agents, the ultimate cell response could be proliferation, growth arrest, apoptosis or necrosis. I will study how the apoptosis pathway is regulated by the oxidative stress and how the apoptotic response is related to oxidative stress readouts, with the long term goal of illustrate overall picture of oxidative stress induced apoptosis.

Past experience

My undergraduate major is food science, with a curriculum of 70 percent of biology and 30 percent of engineering. After graduation in 1991, I went on to pursue my master degree studying biochemistry and physiology. With my master degree, I taught biochemistry in a pharmaceutical college for three years before I went to Beijing to start my Ph. D. study in 1997 in the Institute of Genetics of Chinese Academy of Sciences. There I got my Ph. D. in genetics, although my thesis mainly is about antibody engineering. I joined Dr. Phil Coffino lab at UCSF in 2001, focusing on the functional studies of the proteasomes. After that I became interested in system biology and moved in 2005 to MIT to join with Dr. Peter Sorger and study cell signaling pathways with systematical approaches.

Publications

1. Martin A. Hoyt, Mingsheng Zhang and Philip Coffino. Methods to assay ubiquitin-independent degradation of ornithine decarboxylase by proteasome. In Methods in Enzymology ( Deshaies R eds, to be published in 2005)

2. Rati Verma, Noel R. Peters, Mariapina D’ Onotrio, Gregory P. Tochtrop, Kathleen M.Sakamoto, Ranjani Varadan, Mingsheng Zhang, Philip Coffino, David Fushman, Raymond J. Deshaies, and Randall W. King. Ubistatins Inhibit Proteasome-dependent Degradation by Binding the Ubiquitin Chain. Science, 2004;306:117-120.

3. Mingsheng Zhang*, Alasdair I. MacDonald*, Martin A. Hoyt, and Philip Coffino Proteasomes Begin Ornithine Decarboxylase Digestion at the C Terminus J. Biol. Chem., 2004; 279: 20959 - 20965. (*, equal contribution)

4. Mingsheng Zhang and Philip Coffino Repeat Sequence of Epstein-Barr Virus-encoded Nuclear Antigen 1 Protein Interrupts Proteasome Substrate Processing J. Biol. Chem., 2004; 279: 8635 - 8641.

5. Mingsheng Zhang, Cecile M. Pickart, and Philip Coffino Determinants of proteasome recognition of ornithine decarboxylase, a ubiquitin-independent substrate EMBO J., 2003; 22: 1488 - 1496.

6. Martin A. Hoyt, Mingsheng Zhang, and Philip Coffino Ubiquitin-independent Mechanisms of Mouse Ornithine Decarboxylase Degradation Are Conserved between Mammalian and Fungal Cells J. Biol. Chem., 2003; 278: 12135 - 12143.