Dr. Zhijian “James” Chen, professor of molecular biology and a Howard Hughes Medical Institute investigator at UT Southwestern Medical Center, studies the fundamental mechanisms cells employ to respond to viral infections. His discoveries not only are important for understanding immunity, but also relate to mechanisms involved in cancer.
Dr. Chen’s research focuses on the chemical signals cells use to convey information from their membranes to their interiors. His research on cell signaling has led to a revolutionary discovery about the protein ubiquitin, so named because it is ubiquitously, or universally, found in all cells.
Ubiquitin’s nickname is the “kiss of death” because its best-known role is to mark other proteins for destruction by the cell. But Dr. Chen and his research team identified another very different role for ubiquitin. They found that certain proteins in the cell, when tagged with ubiquitin, were activated instead of destroyed. Once turned on by this chemical tag, proteins send signals inside the cell that regulate immune response and cell growth, including abnormal growth associated with cancer.
“James Chen’s work has illuminated the ways in which animal cells defend against foreign stimuli,” said Dr. Eric Olson, chairman of molecular biology at UT Southwestern. “This work has not only provided important new insights into fundamental cellular processes but also has revealed new targets for drug development.”
Dr. Chen and his research team also made an important discovery about structures found in cells called mitochondria. For 50 years scientists have studied the mitochondrion’s function as a cell’s source of energy. Dr. Chen’s groundbreaking research has revealed that the mitochondria also help the body defend itself against viral infection.
Both of Dr. Chen’s discoveries are important for understanding the fundamental mechanisms of cancer and immunity, and they provide crucial insight into potential new methods to fight infection by common viruses such as hepatitis C, West Nile and influenza.
“What has set James apart from others has been his ability to simplify very complex biological processes and to re-create them in a test tube,” said Dr. Olson, who directs the Nancy B. and Jake L. Hamon Center for Basic Research in Cancer, and the Nearburg Family Center for Basic and Clinical Research in Pediatric Oncology. He also holds the Pogue Distinguished Chair in Research on Cardiac Birth Defects, the Robert A. Welch Distinguished Chair in Science, and the Annie and Willie Nelson Professorship in Stem Cell Research.
Dr. Chen’s discoveries have been widely recognized by the scientific community.
In February 2012 he received the National Academy of Sciences Award for Molecular Biology. In 2007 he received the Edith and Peter O’Donnell Award in Science from the Academy of Medicine, Engineering & Science of Texas. He also received the 2005 Norman Hackerman Award in Chemical Research from the Welch Foundation.
Dr. Chen received his Ph.D. in 1991 from the State University of New York at Buffalo and completed a postdoctoral fellowship at the Salk Institute for Biological Studies. He worked in industry before joining UT Southwestern in 1997. He holds the George L. MacGregor Distinguished Chair in Biomedical Science.
“James Chen is a superb biochemist, just second to none,” said Dr. Bruce Beutler, director of the newly formed Center for the Genetics of Host Defense. “And he happens to be very interested in host defense pathways. I envision we’ll have a lot of collaborations with him.”
Inside the human intestinal tract are 100 trillion microbes that live peacefully in concert with their hosts, aiding digestion and helping to deliver nutrients from ingested food. While most of these are beneficial, others can cause disease and illnesses such as food poisoning if they escape the gut and invade body tissues.
Dr. Lora Hooper is an associate professor of immunology and microbiology in the Cancer Immunobiology Center and an investigator with the Howard Hughes Medical Institute at UT Southwestern Medical Center. Her research is aimed at understanding the intricate ecosystem comprising the human gut and its plethora of naturally occurring, friendly bacteria, called commensals. Her research has shown, for example, that it may be possible to improve a person’s resistance to certain infections just by increasing the numbers of particular beneficial microbes in the intestines.
Dr. Hooper also has found that the cells lining the human gut provide a biochemical barrier that keeps bacteria – both the good and the bad types – in the right places. She and her colleagues showed for the first time how a protein produced by epithelial cells – those lining the gut – works to monitor the barrier. This defense mechanism prevents the naturally occurring bacteria from invading the wall of the intestine, where they can cause problems such as inflammatory bowel disease, or IBD.
In people with IBD – in which inflammation and the body’s response to it can result in painful ulcers and bloody diarrhea – the biochemical barrier is compromised and more bacteria come in contact with the intestinal lining. Dr. Hooper’s studies suggest new strategies for the prevention of IBD as well as for viral infections.
“Lora Hooper is at the forefront of studies of the interactions between intestinal bacteria and the host animal,” said Dr. Eric Olson, chairman of molecular biology at UT Southwestern and director of the Endowed Scholars Program in Medical Science.
“Using specially engineered germ-free mice, Lora’s laboratory has discovered a hidden biochemical dialog between intestinal bacteria and the immune system.”
Dr. Hooper joined the UT Southwestern faculty in 2003 as the Nancy Cain and Jeffrey A. Marcus Scholar in Medical Research, in Honor of Dr. Bill S. Vowell. She received her doctorate in molecular cell biology and biochemistry from Washington University in St. Louis. She holds the J. Wayne Streilein, M.D., Professorship in Immunology.
Dr. Bruce Beutler, director of the new Center for the Genetics of Host Defense at UT Southwestern, said Dr. Hooper’s research on intestinal homeostasis and immunological issues is an excellent example of the type of work that will complement the new research center.
“We know that there is awareness of these microbes, but usually there is a certain degree of quiescence to them,” Dr. Beutler said. “There are mechanisms in place so that on those occasions when microbes do cross the epithelial barrier, homeostasis is very quickly restored, injury in the epithelium is repaired, and the microbes that have gotten across are eliminated.
“All of this has to do with inflammatory bowel disease, and there definitely is a genetic component to this type of disease, which we are interested in studying.”
Dr. Sandra Schmid is an internationally acclaimed cell biologist who has made fundamental contributions to the understanding of endocytosis, the process by which cells internalize nutrients, signaling molecules and other proteins.
Dr. Schmid recently was recruited to the UT Southwestern Medical Center faculty as chairwoman of the Department of Cell Biology, and she holds the Cecil H. Green Distinguished Chair in Cellular and Molecular Biology. Her arrival comes at a time when her scientific expertise – and that of the faculty in the department she now leads – can greatly enhance research efforts in UT Southwestern’s new Center for the Genetics of Host Defense.
“We have such wonderful opportunities for collaboration at UT Southwestern,” said Dr. Bruce Beutler, director of the center. “I’m sure there will be researchers in the cell biology department who will be a good match to collaborate with us in the new center. I know, too, that Sandy has a way of spotting and encouraging such opportunities.”
Dr. Schmid’s research program employs sophisticated techniques to visualize how cell structures change during endocytosis and thus has direct applications for understanding immunity.
During endocytosis, a small piece of a cell’s membrane pinches off and fuses to another place in the cell, providing a means for transporting biochemical signals as well as a way for cells to communicate with each other and their surrounding environments. Endocytosis is essential not only for the efficient uptake of nutrients and growth hormones, for example, but also for the trafficking of biological agents involved in the immune system.
Building on an already strong foundation in UT South-western’s cell biology department, Dr. Schmid, like Dr. Beutler, said she anticipates recruiting new investigators and leveraging collaborative interactions with colleagues interested in biochemistry, biophysics, systems and stem cell biology, and human and mouse genetics to address complex problems related to physiology and disease.
“Revolutionary technologies in genetics and genomics can quickly link genotypes with specific diseases,” Dr. Schmid said. “To treat or prevent these diseases, one must determine how defective proteins cause them. Modern cell biology is essential for accomplishing this goal because it provides the tools to define protein function in the context of living cells, the fundamental unit of life.”
A Canadian by birth and a graduate of the University of British Columbia, Dr. Schmid earned her doctorate in biochemistry at Stanford University. Before coming to UT Southwestern, she was chairwoman of cell biology at the Scripps Research Institute in La Jolla, Calif., where she worked with Dr. Beutler for several years.
“Dr. Schmid’s outstanding abilities in both science and academic leadership will be of great benefit to UT South-western. Advanced cell biology techniques are essential to all modern basic and translational research activities,” said Dr. Gregory Fitz, executive vice president for academic affairs, provost and dean of UT Southwestern Medical School. “She and her colleagues will play pivotal roles in many important areas of science throughout our institution.”