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Ingolf Bach, Ph.D.

DERC - University of Massachusetts, Associate Professor
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Dr. Ingolf Bach’s interest in the molecular mechanisms has taken him from Paris, France where he received his PhD from the Pasteur Institute, to California for post-doctoral work, and back to his native Germany as a an Assistant Professor and Heisenberg Scholar at the Center for Molecular Neurobiology at the University of Hamburg. Today, he is with UMMS as a faculty member in the Program for Gene Function and Expression and the Program for Molecular Medicine.

Dr. Bach is specifically interested in the fundamental question of how protein complexes consisting of multiple proteins regulate basic biological processes such as embryogenesis and, when disturbed, cause cancer.  What led him to a diabetes-related research?
 
The Research:  Roles of Nuclear LIM Cofactors for Pancreas Development
To investigate certain molecular mechanisms, Dr. Bach uses the protein network around LIM domains as a model system.  LIM domains are protein structural domains, which mediate protein:protein interactions that are critical to cellular processes.  It is recognized that the insulin gene enhancer protein, Isl1, is a LIM homeodomain (LIM-HD) transcription factor that plays a crucial role in the development of insulin-producing beta (β) cells.  As Dr. Bach explains,

“Since diabetes mellitus results from a loss or dysfunction of the insulin-producing β cells in the pancreas, a central goal of diabetes research is to generate functional β cells that can be transplanted into patients.  As the LIM-HD protein network plays crucial roles for the development of β cells, the understanding of the molecular mechanisms that govern LIM-HD regulation in the developing pancreas will be crucial for a future successful production of β cells in vitro "

Little is known about how Isl1, as part of the LIM-HD protein network, is regulated during pancreas development and what genes it targets.  However, previously published results by Dr. Bach and colleagues (Gungor et al., 2007) show that LIM-HD cofactors CLIM and SSDP1 decisively regulate the biological activity of Isl1.
Dr. Bach’s lab have generated dominant-negative CLIM (DN-CLIM) and SSDP1 (DN-SSDP1) molecules which are then injected into developing zebrafish embryos.  These Hb9:GFP transgenic zebrafish express green fluorescent protein (GFP) in the developing pancreas and nervous system which can be observed.
Preliminary results showed that ectopic overexpression of DN-CLIM or DN-SSDP1 through mRNA microinjection prevents neuronal development by inhibition of specific LIM-HD proteins.  However, pancreas development was inhibited by overexpression of DN-CLIM,  but not by DN-SSDP1.  This indicates that in this tissue, Isl1 is regulated by a distinct mechanism(s).
Additional experiments are now focusing on using DN-CLIM to help identify LIM-HD target genes in the developing pancreas, shedding light on the mechanism(s) regulating Isl1.  Dr. Bach's hope is that
“...the results of this research will identify molecular networks and mechanisms that direct normal β-cell development, thus allowing us to generate functional β cells that can be transplanted into patients.”
And since β cells are the insulin producers within the pancreas, β-cell transplants are one encouraging area of research for diabetics.