Research Fields
a) Scientific Research
Current research responsibility is as Director of the Gastric Pathobiology Research Group. This is a twenty to twenty-five member group variously studying pancreatic, gastric, ileal and colonic endocrine and biochemical phenomena in the gastrointestinal system. Persons involved are surgeons, PhDs, surgical residents, technicians and visiting scientists from different countries and institutions. The overall specific research areas are in brief as follows:
Pancreatitis:
Isolated pancreatic acini are utilized to provide a model for the study of intracellular zymogen activation. The methodology utilizes western blot techniques to identify active fragments. Immunogold electron microscopy is used to identify colocalization of enzymes in subcellular compartments.
Pepsinogen Secretion:
Isolated peptic cells are generated using elutriation centrifugation and nycodenz gradient systems. The mechanisms of exocytosis are studied with particular reference to identification of small GTP binding protein families and intracellular calcium flux. Characterization of CCK and gastrin type receptors is undertaken using peptide fragments and antagonists.
Parietal Cells:
Isolated parietal cells are studied with a view to identification of the subcellular mechanisms of secretion. This involves structural studies using confocal microscopy and biochemical cross-referencing using two dimensional gel separation of phosphorylated proteins. Specific identification of EGF and TGFa subcellular localization is the current primary goal.
Mastomys ECL Cells:
The histogenesis of the ECLoma tumor has been studied using cell culture and nude mice transfer. Western and northern blotting are used to demonstrate oncogene amplification. Secretion of tumor peptides and amines is assessed by HPLC and RIA methodology.
Intracellular pH Regulation:
The control of pH by specific related ion pumps is evaluated using isolated perfused gastric glands. This methodology involves fluorescent spectrophotometry and video enhanced isolated cell imagery. Calibration curves using Nigericin and cell loading with BCECF are components of the system.
b) Clinical Investigations
1. Minimally invasive surgery
2. Carcinoid tumors
3. Pancreatitis and neuroendocrine tumors of the pancreas
4. Peptic ulcer disease
c) Research Funding
Investigator |
Grant Title |
Agency |
Amount |
Dates |
I.M. Modlin |
Secretagogue Regulation of Protein Phosphorylation in Parietal Cells |
NIH |
$418,057 |
5/89-4/93 Complete |
J.R. Goldenring (IMM Co-Invest.) |
Cyclic AMP-Dependent Mediation of Parietal Cell Function |
NIH |
$371,912 |
4/91-3/96 Complete |
I.M. Modlin |
Pathophysiology of an Endocrine Tumor - A Peptic Ulcer Model |
VA |
$490,000 |
10/88-9/96 Complete |
G. Ballantyne (IMM Co-Invest.) |
Release of Peptide Tyrosine and Enteroglucagon from the colon |
VA |
$141,415 |
12/89-12/92 Complete |
M. Basson (IMM Co-Invest.) |
Growth Factor - Matrix Interaction in the Regulation of Enterocyte Migration |
Yale Univ. |
$7,000 |
12/90-11/91 Complete |
L. Tang (IMM Co-Invest.) |
Characterization of a Tubulovesicle-Associated 23 kDa GTP-Binding Protein from Rabbit Parietal Cell |
Yale Univ. |
$9,000 |
12/90-11/91 Complete |
M. Basson (IMM Co-Invest.) |
Control mechanisms for mammlian pepsinogen secretion |
NIH |
$35,300 |
7/91-6/92 Complete |
R. Powers (IMM Co-Invest.) |
Altered acinar cell function during acute pancreatitis |
NIH |
$186,032 |
8/88-7/93 Complete |
I.M. Modlin |
Research Training in Surgical Gastroenterology |
NIH |
$705,190 |
7/91-6/96 Complete |
F. Gorelick (IMM Co-Invest.) |
Intracellular Activation of Pancreatic Zymogens |
NIH |
$838,846 |
7/91-6/96 Complete |
C. Soroka (IMM Co-invest.) |
The cultured parietal cell: a model for membrane-cytoskeletal interactions |
VA |
$288,900 |
4/92-3/95 Complete |
S. Waisbren (IMM Co-Invest.) |
Intracellular pH regulation in perfused gastric glands |
NIH |
$29,500 |
7/91-6/92 Complete |
I.M. Modlin
|
Pathophysiology of an Endocrine Tumor – Gastric ECLoma Model |
VA |
$450,000 |
9/96-8/00 Complete |
J. Murren (IMM Co-Invest) |
Isotopic Therapy of SST expressing Neuroendocrine Tumors |
NCI |
$275,000 |
2/01-3/03 Active |
I.M. Modlin |
Molecular Strategies for Gastric Carcinoid Surgery |
NIH |
$650,000 |
8/03-7/05 Active |
I.M. Modlin |
Determination of the naive human EC cell transcriptome and identification of neoplastic genes in a novel small intestinal carcinoid cell line |
Yale Univ |
$10,000 |
1/06-12/06 |
I.M. Modlin (Mark Kidd Co-Invest) |
Molecular strategies to preemptively define gastrointestinal carcinoid surgery |
NIH |
$710,000 |
9/06-8/10 |