Literature DB >> 21952059

Going MAD: development of a "matrix academic division" to facilitate translating research to personalized medicine.

David C Whitcomb1.   

Abstract

Personalized medicine integrates an individual's genetic and other information for the prevention or treatment of complex disorders, and translational research seeks to identify those data most important to disease processes based on observations at the bench and the bedside. To understand complex disorders such as chronic pancreatitis, inflammatory bowel disease, liver cirrhosis, and other idiopathic chronic inflammatory diseases, physician-scientists must systematically collect data on relevant risks, clinical status, biomarkers, and outcomes. The author describes a "matrix academic division" (MAD), a highly effective academic program created at the University of Pittsburgh School of Medicine and the University of Pittsburgh Medical Center using translational research to rapidly develop personalized medicine for digestive diseases. MAD is designed to capture patient-specific data and biologic samples for analysis of steps in a complex process (reverse engineering), reconstructing the system conceptually and mathematically (disease modeling), and deciphering disease mechanism in individual patients to predict the effects of interventions (personalized medicine). MAD draws on the expertise of the medical school's and medical center's physician-scientists to translate essential disease information between the bed and the bench and to communicate with researchers from multiple domains, including epidemiology, genetics, cell biology, immunology, regenerative medicine, neuroscience, and oncology. The author illustrates this approach by describing its successful application to the reverse engineering of chronic pancreatitis.

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Year:  2011        PMID: 21952059      PMCID: PMC3210110          DOI: 10.1097/ACM.0b013e3182303d7a

Source DB:  PubMed          Journal:  Acad Med        ISSN: 1040-2446            Impact factor:   6.893


  20 in total

1.  Mutations in the gene encoding the serine protease inhibitor, Kazal type 1 are associated with chronic pancreatitis.

Authors:  H Witt; W Luck; H C Hennies; M Classen; A Kage; U Lass; O Landt; M Becker
Journal:  Nat Genet       Date:  2000-06       Impact factor: 38.330

2.  Combined bicarbonate conductance-impairing variants in CFTR and SPINK1 variants are associated with chronic pancreatitis in patients without cystic fibrosis.

Authors:  Alexander Schneider; Jessica Larusch; Xiumei Sun; Amy Aloe; Janette Lamb; Robert Hawes; Peter Cotton; Randall E Brand; Michelle A Anderson; Mary E Money; Peter A Banks; Michele D Lewis; John Baillie; Stuart Sherman; James Disario; Frank R Burton; Timothy B Gardner; Stephen T Amann; Andres Gelrud; Ryan George; Matthew J Rockacy; Sirvart Kassabian; Jeremy Martinson; Adam Slivka; Dhiraj Yadav; Nevin Oruc; M Michael Barmada; Raymond Frizzell; David C Whitcomb
Journal:  Gastroenterology       Date:  2010-10-25       Impact factor: 22.682

3.  Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene.

Authors:  D C Whitcomb; M C Gorry; R A Preston; W Furey; M J Sossenheimer; C D Ulrich; S P Martin; L K Gates; S T Amann; P P Toskes; R Liddle; K McGrath; G Uomo; J C Post; G D Ehrlich
Journal:  Nat Genet       Date:  1996-10       Impact factor: 38.330

Review 4.  Chronic pancreatitis.

Authors:  M L Steer; I Waxman; S Freedman
Journal:  N Engl J Med       Date:  1995-06-01       Impact factor: 91.245

5.  SPINK1/PSTI polymorphisms act as disease modifiers in familial and idiopathic chronic pancreatitis.

Authors:  R H Pfützer; M M Barmada; A P Brunskill; R Finch; P S Hart; J Neoptolemos; W F Furey; D C Whitcomb
Journal:  Gastroenterology       Date:  2000-09       Impact factor: 22.682

Review 6.  Chronic pancreatitis: diagnosis, classification, and new genetic developments.

Authors:  B Etemad; D C Whitcomb
Journal:  Gastroenterology       Date:  2001-02       Impact factor: 22.682

7.  Mutations of the cystic fibrosis gene in patients with chronic pancreatitis.

Authors:  N Sharer; M Schwarz; G Malone; A Howarth; J Painter; M Super; J Braganza
Journal:  N Engl J Med       Date:  1998-09-03       Impact factor: 91.245

8.  Translation of highly promising basic science research into clinical applications.

Authors:  Despina G Contopoulos-Ioannidis; Evangelia Ntzani; John P A Ioannidis
Journal:  Am J Med       Date:  2003-04-15       Impact factor: 4.965

9.  A mathematical model of the pancreatic duct cell generating high bicarbonate concentrations in pancreatic juice.

Authors:  David C Whitcomb; G Bard Ermentrout
Journal:  Pancreas       Date:  2004-08       Impact factor: 3.327

10.  Alcohol and smoking as risk factors in an epidemiology study of patients with chronic pancreatitis.

Authors:  Gregory A Coté; Dhiraj Yadav; Adam Slivka; Robert H Hawes; Michelle A Anderson; Frank R Burton; Randall E Brand; Peter A Banks; Michele D Lewis; James A Disario; Timothy B Gardner; Andres Gelrud; Stephen T Amann; John Baillie; Mary E Money; Michael O'Connell; David C Whitcomb; Stuart Sherman
Journal:  Clin Gastroenterol Hepatol       Date:  2010-10-26       Impact factor: 11.382

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  6 in total

Review 1.  What is personalized medicine and what should it replace?

Authors:  David C Whitcomb
Journal:  Nat Rev Gastroenterol Hepatol       Date:  2012-05-22       Impact factor: 46.802

2.  Innovation and hard work: The 2015 George E. Palade Medal Award Lecture.

Authors:  David C Whitcomb
Journal:  Pancreatology       Date:  2015-09-16       Impact factor: 3.996

Review 3.  Integrated Genomic Medicine: A Paradigm for Rare Diseases and Beyond.

Authors:  N J Schork; K Nazor
Journal:  Adv Genet       Date:  2017-07-25       Impact factor: 1.944

Review 4.  Genetics of alcoholic and nonalcoholic pancreatitis.

Authors:  David C Whitcomb
Journal:  Curr Opin Gastroenterol       Date:  2012-09       Impact factor: 3.287

5.  Framework for interpretation of genetic variations in pancreatitis patients.

Authors:  David C Whitcomb
Journal:  Front Physiol       Date:  2012-12-06       Impact factor: 4.566

6.  Primer on Precision Medicine for Complex Chronic Disorders.

Authors:  David C Whitcomb
Journal:  Clin Transl Gastroenterol       Date:  2019-07       Impact factor: 4.488

  6 in total

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