Penn Institute for Immunology
Perelman School of Medicine at the University of Pennsylvania
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Jonni S. Moore

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Professor of Pathology and Laboratory Medicine at the Hospital of the University of Pennsylvania
Department: Pathology and Laboratory Medicine
Graduate Group Affiliations

Contact information
220 and 297 John Morgan Building
3620 Hamilton Walk
Philadelphia, PA 19104
Office: (215) 898-6853
Fax: (215) 898-4227
Education:
B.A. (Biology)
University of Virginia, Charlottesville, 1972.
Ph.D. (Microbiology)
Thomas Jefferson University, Philadelphia, 1984.
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Description of Research Expertise

Research Summary

Research in our laboratory is focused on the contribution of failure of normal growth regulatory controls to the development of hematologic malignancies. Alterations in the balance of apoptosis and proliferation may lead to chronic leukemic states such as B cell chronic lymphocytic leukemia (B-CLL). Consistent genetic defects have been difficult to identify in B-CLL; hence our focus has been on alterations in cytokine networks which may affect the cellular environment of the malignant clone. We showed that TGFbeta, a potent immunosuppressive cytokine which can induce apoptosis and inhibit proliferation, is overproduced in mice and humans with B- CLL, but the leukemic B cells fail to respond to the apoptotic signals provided by TGFbeta. This defect in TGFbeta responsiveness is not due to a lack of expression of TGF receptors, but appears to be a failure in the signal transduction pathway for this cytokine. In addition to TGFbeta, we have investigated the role of T cell produced cytokines (IL4 and IFNg) in regulating the apoptotic process in CLL B cells.

We found a predominance of IFNg producing T cells in these patients as compared to normals, and that the leukemic B cells express higher levels of IFNg receptors. Interestingly, this cytokine has an extremely anti-apoptotic effect on the B cells. Thus, the leukemic B cell is producing a cytokine that can cause potent immunosuppression (and apoptosis) of other cells while being itself resistant and appears to be overly responsive to the anti-apoptotic effects of IFNg. Taken together, these aberrations could contribute to the survival and expansion of the malignant B cell. Current investigations are focused on the role of other cytokines in the control of hematologic malignancies, using both human and murine models, with the intent of identifying potent targets for therapy.

The laboratory is also involved in the development of new flow cytometric applications for research and clinical use. This includes basic and translational studies on applications for monitoring receptor/ligand binding, multiparameter functional studies, minimal residual disease detection, stem cell isolation and identification, and transplantation monitoring.

Current collaborators:
Peter Nowell, M.D. Pathology
Bruce Rosengard, M.D , Surgery
Alain Rook, M.D., Dermatology

Selected Publications

Kurtzman N, Zhang L, French B, Jonas R, Bantly A, Rogers WT, Moore JS, Rickels M, Mohler ER III: Personalized cytomic assessment of vascular health: Evaluation of the bascular health profile in diabetes mellitus. Cytometry Part B: Clinical Cytometry in press, 2013.

Mehta NN, Li RC, Takeshita J, Zhang L, VanVoorhees A, Rogers W, Wilcox M, Raper A, Moore J, Gelfand JM, Mohler ER: Elevated endothelial cell, platelet and T-cell micro particles in psoriasis may provide novel link to atherosclerosis free. Journal of the American College of Cardiology 59(13sI): E2055, 2012.

Mohler ER III, Zhang L, Medenilla E, Rogers W, French B, Bantly A, Moore JS, Huan Y, Murashima M, Berns JS: Effect of darbepoetin alfa on endothelial progenitor cells and vascular reactivity in chronic kidney disease. Vascular Medicine 16(13): 183-189, June 2011.

Baker JF, Zhang L, Imadojemu S, Sharpe A, Patil S, Moore JS, Mohler ER 3rd, Von Feldt J.: Circulating endothelial progenitor cells are reduced in SLE in the absence of coronary artery calcification. Rheumatol Int. January 2011.

Curtis AM, Zhang L, Medenilla E, Gui M, Wilkinson PF, Hu E, Giri J, Doraiswamy V, Gunda S, Burgert M, Moore JS, Edelberg JM, MohlerER III: Relationship of microparticles to progenitor cells as a measure of vascular health in a diabetic population. Cytometry Part B (Clinical Cytometry) 2010.

Jonni Moore and Mario Roederer: The Flow Cytometry Shared Resource Laboratory: Best Practices to Assure a High-Quality, Cost-Effective Partnership with Biomedical Research Laboratories. Cytometry Part A 75A(8): 643-649, August 2009.

Mohler, ER, Shi, YQ, Moore, J, Bantly, A, Hamamdzic, D, Yoder, M, Rader, DJ, Putt, M, Zhang, LF, Parmacek, M, Wilensky, RL: Diabetes Reduces Bone Marrow and Circulating Porcine Endothelial Progenitor Cells, an Effect Ameliorated by Atorvastatin and Independent of Cholesterol. Cytometry Part A 75A(1): 17-24, Jan 2009.

Milovanova T, Bhopale V, Sorokina E, Moore J, Hunt T, Hauer-Jensen M, Thom S.: Hyperbaric oxygen stimulates vasculogenic stem cell growth and differentiation in vivo. J Appl Physiol 106: 711-728, 2009.

Tatyana N. Milovanova, Veena M.Bhopale, Elena M. Sorokina, Jonni S. Moore, Thomas K. Hunt, Martin Hauer-Jensen, Omaida C. Velazquez, Stephen R. Thom: Lactate stimulates vasculogenic stem cells via the thioredoxin system and engages an autocrine activation loop involving hypoxia inducible factor-1. Mol. Cell. Biol. 28(30): 6248-6261, October 2008.

Wade T. Rogers, Alan R. Moser, Herbert A. Holyst, Andrew Bantly, Emile R. Mohler III, George Scangas, Jonni S. Moore: Cytometric Fingerpriniting: Quantitative Characterization of Multivariate Distributions. Cytometry Part A 73A: 430, May 2008.

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Last updated: 05/17/2013
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