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Richard J. DiPaolo, Ph.D.

 

Richard J. DiPaolo, Ph.D.
Associate Professor
Molecular Microbiology & Immunology
Saint Louis University School of Medicine

Education:
Post-Doctoral Fellowship: NIAID, National Institutes of Health
Ph.D: Washington University in Saint Louis, 2002
B.A.: University of Chicago, 1995

Doisy Research Center
1100 South Grand Blvd
Office 707/Lab 757
Saint Louis, MO 63104

Email: rdipaolo@slu.edu
Office Phone 314-977-8860
Laboratory    314-977-8861
FAX             314-977-8717

Richard J. DiPaolo, PhD.

Richard J. DiPaolo, Ph.D.

 

Research

There are more than 80 different autoimmune diseases that affect approximately 50 million people in the United States alone. Autoimmunity develops when the immune system, which normally protects the body from pathogens, instead attacks cells or tissues in the body. Juvenile diabetes, multiple sclerosis, rheumatoid arthritis, and lupus are a few examples of autoimmune diseases.

Regulatory T cells, or Tregs for short, play a critical role in preventing autoimmunity and regulating the immune system. The recent discovery of the immunosuppressive activities of Tregs has generated excitement because of the potential to manipulate their number and/or functions to treat disease. My laboratory has established mouse models of human diseases to examine whether antigen specific Tregs can be manipulated to suppress chronic inflammation. This research will provide valuable insight as to whether Tregs can be used to suppress the immune system in a specific manner, which will be useful in the development of new therapies for autoimmune diseases, and perhaps in other cases where immunosuppressive drugs are used, such as preventing organ rejection after transplantation.

Autoimmune Gastritis involves chronic inflammation mediated by the immune system attacking cells in the stomach. Like many other autoimmune diseases, autoreactive CD4+ T cells are important in the development of disease. Combinations of cellular and molecular assays are performed to understand how Tregs affect the various stages of disease.

Gastric Cancer is the second leading cause of cancer-related deaths in the world. We recently discovered that mice with autoimmune gastritis develop pre-cancerous lesions in the stomach with many similarities to disease in humans.  We are investigating strategies to manipulate the activities of Tregs to reduce the risk of gastric cancer.

Arthritis is an autoimmune disease that involves inflammation of one or more joints, which results in pain, swelling, stiffness, and limited movement.  We are using a mouse model of arthritis with many similarities to human disease to investigate whether Tregs can be used to suppress disease.  Our preliminary data suggest that cell-based therapy involving the transfer of antigen specific Tregs reduces joint inflammation and cartilage and bone destruction.  We are now investigating the cellular and molecular mechanisms used by Tregs to control joint inflammation.  This information is expected to lead to new strategies for treating arthritis.

Lab Members

Russ Kesman Long Nguyen Jeremy Herzog Tom Makhlouf

 

 

Publications

 

Nguyen TL, Makhlouf NT, Kesman RA, Anthony B, Teague RM, DiPaolo RJ. Antigen specific TGF-β-induced regulatory T cells suppress late stages of autoimmune gastritis. PLOS One, August 13, 2014. PMID: 25119105

 

Nguyen TL and DiPaolo R. A new mouse model of inflammation induced gastritis cancer. Oncoimmunology, October, 2013. PMID:24498543

 

Buchwald ZS, Kiesel JR, DiPaolo R, Yang C, Novack DV, Aurora R. Osteoclast-induced Foxp3+CD8+ T-Cells limit bone loss in mice. Bone, September2013. PMID: 23756229 

Nguyen, TL, Khurana, SS, Bellone, CJ, Capoccia, BJ, Sagartz, JE, Kesman, RA, Mills, JC, DiPaolo, RJ.  Autoimmune gastritis mediated by CD4+ T cells promotes the development of gastric cancer.  Cancer Research, 2013, Feb. 1. Epub ahead of print.  PMID:  23378345

Berrien-Elliott MM, Jackson SR, Meyer JM, Rouskey CJ, Nguyen TL, Yagita H, Greenberg P, DiPaolo RJ, Teague RM. Durable adoptive immunotherapy for leukemia produced by manipulation of multiple regulatory pathways of CD8+ T-cell tolerance.  Cancer Research, 2013; 73(2):605-16.PMID:  23188506

Li JY, Adams J, Calvi LM, Lane TF, DiPaolo R, Weitzmann MN, Pacifici R.  PTH expands short-term murine hemopoietic stem cells through T cells.   Blood. 2012 November 22;120(22):4352-62. PMID:  22955916

Buchwald, ZS, Kiesel, JR, DiPaolo, RJ, Pagadala MS, and Aurora, R.  Osteoclast activated FoxP3+ CD8+ T-cells suppress bone resorption.  PLoS ONE.  May 2012 7(6): e381990.  PMID:  22701612

Thanh-Long M. Nguyen, Nicole L. Sullivan, Mark Ebel, Ryan M. Teague, and Richard J. DiPaolo. Antigen-Specific TGF-β–Induced Regulatory T Cells Secrete Chemokines, Regulate T Cell Trafficking, and Suppress Ongoing Autoimmunity.  The Journal of Immunology, 2011 187:1745-1753.  PMID:  21746962

Huter EN, Stummvoll GH, DiPaolo RJ, Glass DD, Shevach EM.  Pre-differentiated Th1 and Th17 effector T cells in autoimmune gastritis: Ag-specific regulatory T cells are more potent suppressors than polyclonal regulatory T cells.  International Immunopharmacology, 2009 May;9(5):540-5. PMID: 19539565

DiPaolo RJand Shevach EM.  CD4+ T cell-development in a mouse expressing a transgenic TCR derived from a Treg.  The European Journal of Immunology, 39(1)234-40, Jan, 2009. PMID: 19065648

Huter EN, Stummvoll GH, DiPaolo RJ, Glass DD, Shevach EM.  Cutting Edge: Antigen specific TGF beta-induced T cells suppress Th17-mediated autoimmune disease.  The The Journal of Immunology, 181(12):8209-13, Dec 15, 2008.  PMID: 1905237

Levin D, DiPaolo RJ, Brinster C, Revilleza MJ, Boyd LF, Teyton L, Natarajan K, Mage MG, Shevach EM, Margulies DH.  Availability of autoantigenic epitopes controls the phenotype, severity, and penetrance in TCR Tg autoimmune gastritis. European Journal of Immunology, 38(12):3339-53, Dec 1, 2008.  PMID:  19039784

Shevach EM, Davidson TS, DiPaolo RJ, Andersson J. Role of TGF-beta in the induction of FoxP3 expression and T regulatory cell function. Journal of Clinical Immunology, 2008 Nov;28(6):640-6.  Pubmed abstract link: 18810612

Stummvoll GH, DiPaolo RJ, Huter EN, Davidson TS, Glass D, Ward JM, Shevach EM.  Th1, th2, and th17 effector T cell-induced autoimmune gastritis differs in pathological pattern and in susceptibility to suppression by regulatory T cells. The Journal of  Immunology, 2008 Aug 1;181(3):1908-16.  Pubmed Abstract link: 18641328

DiPaolo RJ, Brinster C, Davidson TS, Andersson J, Glass D and Shevach EM.  Autoantigen-Specific TGFbeta-Induced Foxp3+ Regulatory T Cells Prevent Autoimmunity by Inhibiting Dendritic Cells from Activating Autoreactive T Cells  The Journal of  Immunology 2007 179:4685-4693.  Pubmed Abstract link: 17878367

Davidson TS, DiPaolo RJ, Andersson J, Shevach EM. Cutting Edge: IL-2 is essential for TGF-beta-mediated induction of Foxp3+ T regulatory cells. The Journal of  Immunology, 2007 Apr 1;178(7):4022-6.  Pubmed Abstract link: 17371955

Zhao DM, Thornton AM, DiPaolo RJ, Shevach EM.  Activated CD4+CD25+ T cells selectively kill B lymphocytes.  Blood, 2006 May 15;107(10):3925-32.  Pubmed Abstract link: 16418326

DiPaolo RJ, Glass DD, Bijwaard KE, Shevach EM.  CD4+CD25+ T cells prevent the development of organ-specific autoimmune disease by inhibiting the differentiation of autoreactive effector T cells. The Journal of  Immunology, 2005 Dec 1;175(11):7135-42. Pubmed Abstract link: 16301616

Haeryfar SM, DiPaolo RJ, Tscharke DC, Bennink JR, Yewdell JW.  Regulatory T cells suppress CD8+ T cell responses induced by direct priming and cross-priming and moderate immunodominance disparities.  J Immunol. 2005 Mar 15;174(6):3344-51. Pubmed Abstract link: 15749866

Research Grants

ACTIVE

American Gastroenterological Association Pilot Research Award
Title: Determining the Effects of Gastritis on the Gastric Microbiome
Role: Principal Investigator
Period: 07/14 – 06/15

NIH-RO1 AR064821
Title: A Negative Feedback Loop Between Osteoclasts and CD8+ T cells
Role: Co-Investigator
Period: 04/14 – 03/19

American Cancer Society 22720-RSG-12-171-01-LIB
Title: The Regulation of Metaplasia in a Model of Autoimmune Gastritis
Role: Principal Investigator
Period: 07/12 – 06/16

NIH-RO1 AI098114-01
Title: T cell Activation by Immune Complexes and Complement in Autoimmunity
Role: Key Person
Period: 06/12 – 05/17

NIH-RO1 AR54625
Title: The role of PTH in T cell mediated bone metabolism
Role: Co-Investigator
Period: 09/12 – 08/17

Central Intelligence Agency HDTRA1-12C-0051
Title: Immunological Profiling to Distinguish Infection from Vaccination
Role: Co-Investigator
Period: 09/12 – 08/15

COMPLETED

Saint Louis University President's Research Fund
Title: A novel mouse model to measure vaccine specific T effector and T regulatory responses
Role: Principle Investigator
Period: 03/0/2013 – 07/30/2014

Washington University - Digestive Disease Research Core Center Grant (P30 DK52574)
Title: The Roles of IL-27/IL-35 in Inflammation Induced Gastric Epithelial Cell Changes
Role: Principle Investigator
Period: 05/01/2012 – 04/30/2013

Saint Louis University Medical School Seed Grant
Title: The Role of IL-35 in Treg-Mediated Suppression of Arthritis
Role: Principle Investigator
Period: 05/01/2011 – 05/30/2012

Arthritis National Research Foundation
Title: Adoptively Transferring GPI-specific Regulatory T Cells to Treat the Effector Phase of Arthritis
Role: Principle Investigator
Period: 06/01/2010 – 05/30/2011

Saint Louis University President's Research Award
Title: Large scale sequence analysis to determine the extent of overlap between T cell receptors expressed by T regulatory cells and non-regulatory cells.
Role: Principle Investigator
Period: 02/01/2010 – 02/20/2011

Arthritis National Research Foundation
Title: Adoptively Transferring GPI-specific Regulatory T Cells to Treat the Effector Phase of Arthritis
Role: Principle Investigator
Period: 06/01/2009 – 05/30/2010