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Michael S. Lan, Ph.D.
- Professor, Department of Pediatrics
- Professor, Department of Genetics
Louisiana State University Health Sciences Center, New
Orleans
- Staff Scientist, Research Institute for Children,
Children’s Hospital, New Orleans
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| Curriculum
Vitae
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Research Projects
| Neuroendocrine
cell differentiation - We study a transcription factor,
INSM1/IA-1, in |
| pancreas and brain development.
INSM1 is a novel zinc-finger DNA-binding protein primarily
expressed in fetal pancreas, brain, and tumors of neuroendocrine
origin, but not in normal adult tissues. Functional analyses
revealed that INSM1 is a transcriptional repressor and its
DNA-binding domain recognizes 5’-flanking promoter region
of multiple target genes including |
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NeuroD/beta2, insulin, and INSM1 itself.
Global INSM1 gene deletion caused failure of beta cell development
suggesting that INSM1 is essential for pancreatic endocrine
cell. More experimental strategies are employed to elucidate
the biological function of INSM1.
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Developmental Regulation of
the Insulin Gene - In this proposal we aim to study:
1) Molecular mechanisms of how the transcriptional complex
contributes to the INSM1 repressor activity. The gain of function
experiment will be conducted using modified rat insulin I
promoter linked to the INSM1 cDNA. 2) We will test the effects
of loss of INSM1 expression specifically in beta cells. 3)
We will analyze an additional INSM1 binding site on the insulin
gene variable number of tandem repeates (INS-VNTR) region.
We will employ the biochemical methods and a unique dual reporter
transgenic animal model to study the mechanism of differential
allelic haplotype-dependent insulin expression levels. |
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Islet cell growth
and differentiation of fetal islet-like cell clusters (ICCs)
- We are interested in developing a culture system for pancreatic
stem cells to differentiate into the insulin producing cells.
We have found that stem cells derived from fetal pancreas
possess |
great potential
to proliferate and differentiate into islets as islet-like
cell clusters (ICCs). Efforts were placed on stimulating
ICCs to proliferate and differentiate into islets by growth
hormones and genetic engineered transcription factors into
precursor cells that could promote them to convert into
hormone producing endocrine cells.
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Promoter-Specific
Cancer Gene Therapy - Neuroendocrine tumor represents
a collection of rare kinds of tumors that predominantly
express INSM1 transcription factor. We studied the INSM1
promoter regulation in neuroendocrine tumors. Delivery of
a construct consists of INSM1 promoter linked to the HSV-tk
suicide gene into neuroendocrine tumor is capable of suppressing
the tumor growth after ganciclovir treatment. Currently,
new strategy is employed to enhance the INSM1 promoter activity
in neuroendocrine tumors. The modified INSM1 promoter could
be of great value for cancer gene therapy.
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Lan
Lab
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