'Left'to'right: Carol Fierke, John Lowe, David Ginsburg, Alan
Saltiel, Gary Glick, Dan Klionsky (Not pictured, Rowena Matthews).
Photo by Gregory Fox, Courtesy of U-M.
*Click on photos for high resolution images.
A. Fierke Ph.D., Professor of Chemistry and Biological Chemistry.
A chemist who has spent her career working at the interface with
biology, Fierke studies enzymes, the chemical catalysts of living
systems. One focus of her current work is the ubiquitous metal zinc
and the role it plays in chemical catalysis and regulation. She
wants to understand how zinc levels are regulated and what functions
the metal plays in mammalian cells. New treatments to regulate zinc
concentrations may decrease neuron injury that occurs after stroke,
hemorrhage, seizures or brain trauma. Her lab is also investigating
an enzyme that puts fat-based "tags," much like mailing
labels, onto proteins to direct them from the cell’s interior
to its outer membrane. And she’s looking at enzymes that catalyze
key metabolic reactions in bacteria. Research in these areas may
point to new methods for interrupting the operation of cancer cells
and for developing new antibiotics.
Ginsburg, M.D., Warner-Lambert/Parke-Davis Professor of Medicine,
Professor of Genetics and Internal Medicine, Howard Hughes Investigator.
As a physician specializing in blood disorders and genetics, Ginsburg
studies the genetics and molecular biology of blood clotting. There
is a complex cascade of chemical signals that forms a clot quickly
to staunch bleeding from a wound, but these signals are also controlled
well enough that they don’t normally careen out of control
and create clots where they’d be damaging. "It’s
got to be just right," Ginsburg says. He is studying human
families with bleeding disorders like hemophilia and mice with genetic
"knockouts" to tease apart the complex interactions
of biomolecules that control the clotting response.
D. Glick, Ph.D., Werner E. Bachmann Collegiate Professor of Chemistry,
Professor of Biological Chemistry.
Glick is using the tools of synthetic chemistry to develop a deeper
understanding of cellular biology. One portion of his research is
looking at the structure, folding and dynamics of DNA and its messenger,
RNA. Related to this work is a project to explore immune system
proteins that bind to DNA in inflammatory diseases like systemic
lupus erythematosus and rheumatoid arthritis. This research has
led to the discovery of a new family of molecules with the promise
of being better treatments for lupus and related disorders. His
closest collaborations are with medical school faculty rather than
fellow chemists, and many of his graduate students are in a combined
MD/PhD program. Alan Saltiel calls him "a biologist’s
J. Klionsky, Ph.D., Professor of Molecular, Cellular and Developmental
Biology and Biological Chemistry.
Klionsky uses baker’s yeast as a model organism to study how
proteins are moved around the cell with great specificity, and how
the organelles, machines within the cell, develop and do their work.
Sorting the proteins out so that they go to the proper organelle
and do the right job is essential to the proper functioning of the
cell, but little is understood about it. Klionsky’s work also
explores "autophagy," the main protein disassembly and
recycling system inside the cell, and how it responds to starvation
conditions by cannibalizing parts of the cell. This work offers
intriguing clues into a variety of human diseases, including cancer,
cardiomyopathy (weakening and enlargement of the heart) and neurodegenerative
diseases like Alzheimer’s and Parkinson’s.
B. Lowe, M.D., Warner-Lambert/Parke-Davis Professor of Medicine,
Professor of Pathology and Howard Hughes Investigator.
As a post-doctoral fellow in pathology, Lowe became intrigued by
the complex carbohydrates that coat the outside of animal cells.
Although these sugar molecules are the cell's first line of interaction
with its environment, almost nothing was known at the time about
their functions. In two decades of subsequent work, Lowe and his
colleagues have isolated genes that control the assembly of complex
carbohydrates, and used these genes to uncover functions for these
molecules in the immune system. Working at the intersection of immunology
and carbohydrate biology, Lowe continues to explore complex carbohydrate
assembly and function using genetically altered mice, and cells
grown in the laboratory. His research is shedding light on cellular
signaling processes, and on inflammatory diseases like arthritis,
psoriasis and hardening of the arteries.
G. Matthews, Ph.D., G. Robert Greenberg Professor of Biological
Chemistry and Senior Research Scientist in the Biophysics Research
Division, Member of the National Academy of Sciences.
Ever since she was a Radcliffe undergrad working in the lab of a
future Nobel prizewinner, Matthews has studied the biochemicals
we call vitamins and their role in the chemical reactions of the
cell. A decade ago, her work crossed paths with findings from clinical
medicine that heart disease was linked to elevated blood levels
of an amino acid called homocysteine. Matthews’ work on riboflavin
and folic acid has helped determine how homocysteine levels can
be controlled, even in patients who have a genetic mutation that
could lead to harmful levels of the amino acid. Neural tube birth
defects are also linked to the function of folic acid. Matthew’s
work has contributed to the recommendation that all people
especially pregnant women should consume more folic acid.
Since folic acid supplements were recommended, blood levels of homocysteine
in Americans have fallen by an average of 20 percent, which may
lower the risk of heart disease.
R. Saltiel, Ph.D. , Director, Life Sciences Institute, John Jacob
Abel Collegiate Professor in the Life Sciences, and Professor of
Internal Medicine and Physiology.
Saltiel’s trailblazing work on the hormone Insulin and its
role in regulating cellular sugar levels has expanded into an investigation
of how cells send and receive signals. "Cell signaling encompasses
everything from the cell surface to the nucleus and everything in
between," Saltiel says. "It’s not new
it’s been hot for a long time but there’s so
much to learn." Saltiel’s laboratory has pioneered the
concept that cell signaling is confined to defined pathways within
the cell, adding another level of complexity to our understanding
of cellular regulation. A 1995 paper he co-authored on cellular
signaling remains the most cited paper from the Proceedings of the
National Academy of Sciences. (Citation rates are an indicator of
a paper’s significance.) Much of his career has been spent
in private-sector pharmaceutical work, most recently with Warner
Lambert/Parke-Davis in Ann Arbor. Saltiel joined the Institute in
March 2001 as its first faculty member.
Karl Leif Bates
Life Sciences Communications