.

Department of Pathology, Microbiology, and Immunology

 

 

Daniel J. Moore, M.D., Ph.D.

 

 

Assistant Professor

Dept. of Pediatrics
Ian Burr Division of Endocrinology and Diabetes

Dept. of Pathology, Microbiology and Immunology

 

 

Contact Information

 

 

Office Location:
11136 DOT

Phone: 615-322-7427
E-mail:
Daniel.moore@vanderbilt.edu

 

Campus Mail address:

Dept. of Pediatrics

11136 DOT (9170)

 

US Mailing address:
Vanderbilt University School of Medicine
Dept of Pediatrics, Pediatric Endocrinology Division

11136 DOT

Nashville, TN 37232-9170

 

 

 

Education

 

 

MD, University of Pennsylvania
PhD, University of Pennsylvania
AB, Harvard

 

 

Research Keywords

 

 

Autoimmunity Immune Tolerance transplantation biology Type 1 diabetes Allotransplantation Regulatory T cells Regulatory B cells Innate Immunity Inflammation

 

 

Research Description

 

 

Our research seeks to understand the cellular and molecular mechanisms that govern immune tolerance in order to prevent and reverse Type 1 Diabetes and enhance the success of organ transplantation. My graduate research as an MSTP student at Penn contributed to the understanding of the role played by B lymphocytes in the development of autoimmune disease. This research formed part of the foundation for current efforts to use B cell directed therapies to prevent diabetes, studies in which Vanderbilt is participating through the Type 1 Diabetes TrialNet and for which I participate as a co-investigator. We also previously extended these studies to demonstrate that B lymphocytes are absolutely required for some forms of transplantation tolerance induction in murine models. These studies suggest the presence of regulatory B cells which have yet to be defined. A main present focus of the lab, supported by an NIH K08 and other sources, is to understand how B lymphocytes regulate immune tolerance to transplants and how this cell type participates in broken tolerance in autoimmune disease such as Type 1 diabetes.

As part of a comprehensive program to understand immune regulation, we also actively investigate the mechanism of action of regulatory T lymphocytes which are critical for the prevention of autoimmune disease and for the establishment of transplantation tolerance. This research has revealed several new interactions required for the development and function of these cells and has identified inflammation as a factor that counter-regulates these regulatory cells. To overcome this newly identified obstacle to immune tolerance, I collaborate with Jacek Hawiger, M.D., Ph.D. and we have successfully applied a new kind of anti-inflammatory therapy to the prevention of diabetes in a pre-clinical model of disease (PLOS One, 2010).

My research has been funded by the National Institutes of Health, the American Diabetes Association, and the Juvenile Diabetes Research Foundation. I serve as a reviewer for the Journal of Immunology, Diabetes, the American Journal of Transplantation, and the Annals of the New York Academy of Science. Our research has been presented at the Scientific Sessions of the American Diabetes Association, the annual meeting of the Pediatric Academic Societies, and the American Transplant Congress. We have published in the Journal of Immunology, Diabetes, Transplantation International, the Journal of Autoimmunity, and Nature Medicine. Our research program has also been recognized by the Society for Pediatric Research with the 2007 House Officer Research Award and by Vanderbilt University with the David Karzon, Joe M. Strayhorn, Elliot V. Newman, and Vanderbilt Scholar in Diabetes Awards.

 

 

Clinical Research Description

 

 

Our laboratory, while focused on the basic science of autoimmunity and immune tolerance, constantly evaluates opportunities to translate our research into clinical application. These efforts include an interest in specifying the immunophenotype of individuals with autoimmunity and in identifying unique risk factors that predict autoimmune disease.

 

 

Publications

 

 

Wilson, CS, Elizer, SK, Marshall, AF, Stocks, BT, Moore, DJ. The Regulation of B Lymphocyte Responses to TLR Ligation During Diabetes Prevention in NOD Mice. J Diabetes, 2015

Sosenko, JM, Skyler, JS, DiMeglio, LA, Beam, CA, Krischer, JP, Greenbaum, CJ, Boulware, D, Rafkin, LE, Matheson, D, Herold, KC, Mahon, J, Palmer, JP, , , , . A new approach for diagnosing type 1 diabetes in autoantibody-positive individuals based on prediction and natural history. Diabetes Care, 38(2), 271-6, 2015

Zhao, G, Moore, DJ, Kim, JI, Lee, KM, O''Connor, M, Yang, M, Marshall, AF, Lei, J, Schuetz, C, Markmann, JF, Deng, S. An immunosufficient murine model for the study of human islets. Xenotransplantation, 2014

Elizer, SK, Marshall, AF, Moore, DJ. Dysregulation of T Lymphocyte Proliferative Responses in Autoimmunity. PLoS One, 9(8), e106347, 2014

DiGiandomenico, A, Veach, RA, Zienkiewicz, J, Moore, DJ, Wylezinski, LS, Hutchens, MA, Hawiger, J. The "Genomic Storm" Induced by Bacterial Endotoxin Is Calmed by a Nuclear Transport Modifier That Attenuates Localized and Systemic Inflammation. PLoS One, 9(10), e110183, 2014

Romano-Keeler, J, Moore, DJ, Wang, C, Brucker, RM, Fonnesbeck, C, Slaughter, JC, Li, H, Curran, DP, Meng, S, Correa, H, Lovvorn, HN, Tang, YW, Bordenstein, S, George, AL, Weitkamp, JH. Early life establishment of site-specific microbial communities in the gut. Gut Microbes, 5(2), 2014

Weitkamp, JH, Rosen, MJ, Zhao, Z, Koyama, T, Geem, D, Denning, TL, Rock, MT, Moore, DJ, Halpern, MD, Matta, P, Denning, PW. Small Intestinal Intraepithelial TCR????+ T Lymphocytes Are Present in the Premature Intestine but Selectively Reduced in Surgical Necrotizing Enterocolitis. PLoS One, 9(6), e99042, 2014

Liu, Y, Major, AS, Zienkiewicz, J, Gabriel, CL, Veach, RA, Moore, DJ, Collins, RD, Hawiger, J. Nuclear transport modulation reduces hypercholesterolemia, atherosclerosis, and Fatty liver. J Am Heart Assoc, 2(2), e000093, 2013

Gregory, JM, Moore, DJ, Simmons, JH. Type 1 diabetes mellitus. Pediatr Rev, 34(5), 203-15, 2013

The Effects of Inpatient Hybrid Closed-Loop Therapy Initiated Within 1 Week of Type 1 Diabetes Diagnosis Diabetes Research in Children Network (DirecNet) and Type 1 Diabetes TrialNet Study Groups (*). Diabetes Technol Ther, 15(5), 401-8, 2013

Sosenko, JM, Skyler, JS, Palmer, JP, Krischer, JP, Yu, L, Mahon, J, Beam, CA, Boulware, DC, Rafkin, L, Schatz, D, Eisenbarth, G, , , , . The prediction of type 1 diabetes by multiple autoantibody levels and their incorporation into an autoantibody risk score in relatives of type 1 diabetic patients. Diabetes Care, 36(9), 2615-20, 2013

Mouledoux, JH, Albers, EL, Lu, Z, Saville, BR, Moore, DJ, Dodd, DA. Clinical predictors of autoimmune and severe atopic disease in pediatric heart transplant recipients. Pediatr Transplant, 2013

Yeh, H, Moore, DJ, Markmann, JF, Kim, JI. Mechanisms of regulatory T cell counter-regulation by innate immunity. Transplant Rev (Orlando), 2013

Virostko, J, Radhika, A, Poffenberger, G, Dula, AN, Moore, DJ, Powers, AC. Bioluminescence Imaging Reveals Dynamics of Beta Cell Loss in the Non-Obese Diabetic (NOD) Mouse Model. PLoS One, 8(3), e57784, 2013

Sosenko, JM, Skyler, JS, Beam, CA, Krischer, JP, Greenbaum, CJ, Mahon, J, Rafkin, LE, Matheson, D, Herold, KC, Palmer, JP, , . Acceleration of the loss of the first-phase insulin response during the progression to type 1 diabetes in diabetes prevention trial-type 1 participants. Diabetes, 62(12), 4179-83, 2013

Engelhardt, BG, Jagasia, SM, Crowe, JE, Griffith, ML, Savani, BN, Kassim, AA, Lu, P, Weitkamp, JH, Moore, DJ, Yoder, SM, Rock, MT, Jagasia, M. Predicting post-transplant diabetes mellitus by regulatory T cell phenotype: implications for metabolic intervention to modulate alloreactivity. Blood, 2012

Weitkamp, JH, Koyama, T, Rock, MT, Correa, H, Goettel, JA, Matta, P, Oswald-Richter, K, Rosen, MJ, Engelhardt, BG, Moore, DJ, Polk, DB. Necrotising enterocolitis is characterised by disrupted immune regulation and diminished mucosal regulatory (FOXP3)/effector (CD4, CD8) T cell ratios. Gut, 2012

Lin, Q, Liu, Y, Moore, DJ, Elizer, SK, Veach, RA, Hawiger, J, Ruley, HE. Cutting Edge: The "Death" Adaptor CRADD/RAIDD Targets BCL10 and Suppresses Agonist-Induced Cytokine Expression in T Lymphocytes. J Immunol, 2012

Romano-Keeler, J, Weitkamp, JH, Moore, DJ. Regulatory properties of the intestinal microbiome effecting the development and treatment of diabetes. Curr Opin Endocrinol Diabetes Obes, 2012

Buscariollo, DL, Davidson, MA, Black, M, Russell, WE, Rothman, RL, Moore, DJ. Factors That Influence Parental Attitudes toward Enrollment in Type 1 Diabetes Trials. PLoS One, 7(8), e44341, 2012

Yu, L, Boulware, DC, Beam, CA, Hutton, JC, Wenzlau, JM, Greenbaum, CJ, Bingley, PJ, Krischer, JP, Sosenko, JM, Skyler, JS, Eisenbarth, GS, Mahon, JL, , . Zinc transporter-8 autoantibodies improve prediction of type 1 diabetes in relatives positive for the standard biochemical autoantibodies. Diabetes Care, 35(6), 1213-8, 2012

Shoemaker, AH, Zienkiewicz, J, Moore, DJ. Clinical assessment of HNF1A and GCK variants and identification of a novel mutation causing MODY2. Diabetes Res Clin Pract, 2012

Gregory, JM, Moore, DJ. Can technological solutions for diabetes replace islet cell function. Organogenesis, 7(1), 32-41, 2011

Mathew, RP, Moore, DJ. Autoimmune Alternating Hypo- and Hyperthyroidism in Children. Clin Pediatr (Phila), 50(11), 1040-4, 2011

Orban, T, Bundy, B, Becker, DJ, DiMeglio, LA, Gitelman, SE, Goland, R, Gottlieb, PA, Greenbaum, CJ, Marks, JB, Monzavi, R, Moran, A, Raskin, P, Rodriguez, H, Russell, WE, Schatz, D, Wherrett, D, Wilson, DM, Krischer, JP, Skyler, JS, , . Co-stimulation modulation with abatacept in patients with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled trial. Lancet, 378(9789), 412-9, 2011

Zhao, G, Moore, DJ, Kim, JI, Lee, KM, O''Connor, MR, Duff, PE, Yang, M, Lei, J, Markmann, JF, Deng, S. Inhibition of transplantation tolerance by immune senescence is reversed by endocrine modulation. Sci Transl Med, 3(87), 87ra52, 2011

Moore, DJ, Zienkiewicz, J, Kendall, PL, Liu, D, Liu, X, Veach, RA, Collins, RD, Hawiger, J. In vivo islet protection by a nuclear import inhibitor in a mouse model of type 1 diabetes. PLoS One, 5(10), e13235, 2010

Moore, DJ. Accounting for chance in the calculus of autoimmune disease. Med Hypotheses, 74(2), 289-93, 2010

Zhao, G, Moore, DJ, Lee, KM, Kim, JI, Duff, PE, O''Connor, MR, Hirohashi, T, Lei, J, Yang, M, Markmann, JF, Deng, S. An unexpected counter-regulatory role of IL-10 in B-lymphocyte-mediated transplantation tolerance. Am J Transplant, 10(4), 796-801, 2010

Kim, JI, Sonawane, SB, Lee, MK, Lee, SH, Duff, PE, Moore, DJ, O''Connor, MR, Lian, MM, Deng, S, Choi, Y, Yeh, H, Caton, AJ, Markmann, JF. Blockade of GITR-GITRL interaction maintains Treg function to prolong allograft survival. Eur J Immunol, 40(5), 1369-74, 2010

Kim, JI, Lee, MK, Moore, DJ, Sonawane, SB, Duff, PE, O''Connor, MR, Yeh, H, Lian, MM, Deng, S, Caton, AJ, Markmann, JF. Regulatory T-cell counter-regulation by innate immunity is a barrier to transplantation tolerance. Am J Transplant, 9(12), 2736-44, 2009

Kendall, PL, Moore, DJ, Hulbert, C, Hoek, KL, Khan, WN, Thomas, JW. Reduced diabetes in btk-deficient nonobese diabetic mice and restoration of diabetes with provision of an anti-insulin IgH chain transgene. J Immunol, 183(10), 6403-12, 2009

Moore, DJ, Gregory, JM, Kumah-Crystal, YA, Simmons, JH. Mitigating micro-and macro-vascular complications of diabetes beginning in adolescence. Vasc Health Risk Manag, 5, 1015-31, 2009

Sonawane, SB, Kim, JI, Lee, MK, Lee, SH, Duff, PE, Moore, DJ, Lian, MM, Deng, S, Choi, Y, Yeh, H, Caton, AJ, Markmann, JF. GITR Blockade Facilitates Treg Mediated Allograft Survival. Transplantation, 88(10), 1169-77, 2009

Huang, X, Moore, DJ, Mohiuddin, M, Lian, MM, Kim, JI, Sonawane, S, Wang, J, Gu, Y, Yeh, H, Markmann, JF, Deng, S. Inhibition of ICAM-1/LFA-1 interactions prevents B-cell-dependent anti-CD45RB-induced transplantation tolerance. Transplantation, 85(5), 675-80, 2008

Huang, X, Moore, DJ, Ketchum, RJ, Nunemaker, CS, Kovatchev, B, McCall, AL, Brayman, KL. Resolving the conundrum of islet transplantation by linking metabolic dysregulation, inflammation, and immune regulation. Endocr Rev, 29(5), 603-30, 2008

Porrett, PM, Lee, MK, Lian, MM, Wang, J, Caton, AJ, Deng, S, Markmann, JF, Moore, DJ. A direct comparison of rejection by CD8 and CD4 T cells in a transgenic model of allotransplantation. Arch Immunol Ther Exp (Warsz), 56(3), 193-200, 2007

Deng, S, Moore, DJ, Huang, X, Lian, MM, Mohiuddin, M, Velededeoglu, E, Lee, MK, Sonawane, S, Kim, J, Wang, J, Chen, H, Corfe, SA, Paige, C, Shlomchik, M, Caton, A, Markmann, JF. Cutting edge: transplant tolerance induced by anti-CD45RB requires B lymphocytes. J Immunol, 178(10), 6028-32, 2007

Moore, DJ, Kim, JI, Sonawane, S, Yeh, H, Deng, S, Lee, K, Markmann, JF. Progress toward antibody-induced transplantation tolerance. Crit Rev Immunol, 27(2), 167-218, 2007

Deng, S, Moore, DJ, Huang, X, Mohiuddin, M, Lee, MK, Velidedeoglu, E, Lian, MM, Chiaccio, M, Sonawane, S, Orlin, A, Wang, J, Chen, H, Caton, A, Zhong, R, Markmann, JF. Antibody-induced transplantation tolerance that is dependent on thymus-derived regulatory T cells. J Immunol, 176(5), 2799-807, 2006

Lee, MK, Moore, DJ, Chiaccio, M, Lian, MM, Deng, S, Mohiuddin, M, Huang, X, Koeberlein, B, Zakheim, A, Porrett, PM, Barker, CF, Caton, AJ, Markmann, JF. T-reg mediated suppression of the allograft response in the draining lymph node. Transplantation, 81(7), 1063-6, 2006

Moore, DJ, Markmann, JF, Deng, S. Avenues for immunomodulation and graft protection by gene therapy in transplantation. Transpl Int, 19(6), 435-45, 2006

Moore, DJ, Noorchashm, H, Lin, TH, Greeley, SA, Naji, A. NOD B-cells are insufficient to incite T-cell-mediated anti-islet autoimmunity. Diabetes, 54(7), 2019-25, 2005

Wilde, GE, Moore, DJ, Bellah, RD. Posttransplantation lymphoproliferative disorder in pediatric recipients of solid organ transplants: timing and location of disease. AJR Am J Roentgenol, 185(5), 1335-41, 2005

Moore, DJ, Huang, X, Lee, MK, Lian, MM, Chiaccio, M, Chen, H, Koeberlein, B, Zhong, R, Markmann, JF, Deng, S. Resistance to anti-CD45RB-induced tolerance in NOD mice: mechanisms involved. Transpl Int, 17(5), 261-9, 2004

Lee, MK, Moore, DJ, Jarrett, BP, Lian, MM, Deng, S, Huang, X, Markmann, JW, Chiaccio, M, Barker, CF, Caton, AJ, Markmann, JF. Promotion of allograft survival by CD4+CD25+ regulatory T cells: evidence for in vivo inhibition of effector cell proliferation. J Immunol, 172(11), 6539-44, 2004

Lee, MK, Moore, DJ, Markmann, JF. Regulatory CD4+CD25+T cells in prevention of allograft rejection. Front Biosci, 8, s968-81, 2003

Trani, J, Moore, DJ, Jarrett, BP, Markmann, JW, Lee, MK, Singer, A, Lian, MM, Tran, B, Caton, AJ, Markmann, JF. CD25+ immunoregulatory CD4 T cells mediate acquired central transplantation tolerance. J Immunol, 170(1), 279-86, 2003

Song, HK, Noorchashm, H, Lin, TH, Moore, DJ, Greeley, SA, Caton, AJ, Naji, A. Specialized CC-chemokine secretion by Th1 cells in destructive autoimmune myocarditis. J Autoimmun, 21(4), 295-303, 2003

Lee, MK, Huang, X, Jarrett, BP, Moore, DJ, Desai, NM, Moh Lian, M, Markmann, JW, Deng, S, Frank, A, Singer, A, Velidedeoglu, E, Caton, AJ, Markmann, AJ. Vulnerability of allografts to rejection by MHC class II-restricted T-cell receptor transgenic mice. Transplantation, 75(8), 1415-22, 2003

Velidedeoglu, E, Jarret, B, Lee, K, Moore, D, Huang, X, Deng, S, Lian, MM, Caton, A, Markmann, JF. Transgenic T cells persist in an adoptive transfer model of mouse liver transplantation tolerance. Transplant Proc, 34(8), 3342-4, 2002

Greeley, SA, Katsumata, M, Yu, L, Eisenbarth, GS, Moore, DJ, Goodarzi, H, Barker, CF, Naji, A, Noorchashm, H. Elimination of maternally transmitted autoantibodies prevents diabetes in nonobese diabetic mice. Nat Med, 8(4), 399-402, 2002

Kline, JB, Moore, DJ, Clevenger, CV. Activation and association of the Tec tyrosine kinase with the human prolactin receptor: mapping of a Tec/Vav1-receptor binding site. Mol Endocrinol, 15(5), 832-41, 2001

Greeley, SA, Moore, DJ, Noorchashm, H, Noto, LE, Rostami, SY, Schlachterman, A, Song, HK, Koeberlein, B, Barker, CF, Naji, A. Impaired activation of islet-reactive CD4 T cells in pancreatic lymph nodes of B cell-deficient nonobese diabetic mice. J Immunol, 167(8), 4351-7, 2001

Noorchashm, H, Moore, DJ, Noto, LE, Noorchashm, N, Reed, AJ, Reed, AL, Song, HK, Mozaffari, R, Jevnikar, AM, Barker, CF, Naji, A. Impaired CD4 T cell activation due to reliance upon B cell-mediated costimulation in nonobese diabetic (NOD) mice. J Immunol, 165(8), 4685-96, 2000

Shimada, H, Germana, S, Sonntag, KC, Banerjee, P, Moore, D, Sachs, DH, LeGuern, C. MHC class II alpha/beta heterodimeric cell surface molecules expressed from a single proviral genome. Hum Gene Ther, 10(14), 2397-405, 1999

Noorchashm, H, Moore, DJ, Lieu, YK, Noorchashm, N, Schlachterman, A, Song, HK, Barker, CF, Naji, A. Contribution of the innate immune system to autoimmune diabetes: a role for the CR1/CR2 complement receptors. Cell Immunol, 195(1), 75-9, 1999