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BIOMED Faculty Details: Uri Hershberg, Ph.D.
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Uri Hershberg, Ph.D.   [Details
Assistant Professor, School of Biomedical Engineering, Science & Health Systems
Office: Monell 102  Email:
Phone: 215.895.1698   Fax: 215.895.4983
Laboratory Web Page: Click Here to Visit Laboratory Web Page
Research Keywords:
Bioinformatics, immunology, neural computation, system biology, somatic selection, autoimmunity, genetic stability, germline diversity, dendritic cell, transcription elements, pathogens, computational and mathematical modeling, complex systems, cognition and inflammation.
Personal News:
Call for Students and Post-docs
We are looking for people who like to think about biology. Computational background a plus, but first of all we would love to hear your ideas and see if we can think of an interesting research project together.
There are several graduate student and post doc positions open, for questions or to apply email -
Uri Hershberg, PhD, is an Assistant Professor at the Drexel University School of Biomedical Engineering, Science and Health Systems and in the Department of Immunology and Microbiology at the Drexel University College of Medicine. He has a wide background in biology and computational methods. He was previously a Post Doc with Professor Mark Shlomchik, and then Associate Research Scientist with Professor Steven Kleinstein at the Yale School of Medicine. At Yale, Dr. Hershberg used computational tools to study the anti-viral response in dendritic cells and the dynamics of the B-cell repertoire in healthy and pathological immune responses. He was educated at the Hebrew University, where he received a PhD in Computational Biology at the Interdisciplinary Center for Neuronal Computation under the supervision of Professor Irun Cohen of the Department of Immunology at the Weizmann Institute and Professor Sorin Solomon of the Rakah Theoretical Physics Institute at the Hebrew University. His PhD titled "The Emergence of Meaning in Biological Systems" dealt with the ability of the T-cell repertoire in the immune system to defend from pathogens and maintain its diversity without attacking the body. Dr. Hershberg has published over 30 papers on topics related to B-cell, T-cell, and dendritic cell immunity, as well as the defining complex system criteria of cognitive perceptual systems, using the immune system as an example. He is on the editorial board of several publications and on the organizing committee of the International Conference on Artificial Immune Systems.
Ph.D. Computational Biology, Thesis: The Emergence of Meaning in Biological Systems. Interdisciplinary Center for Neural Computation (ICNC), Hebrew University of Jerusalem, Israel. 2005
M.Sc. Neural Computation, Hebrew University. 1999
B.Sc. Double major in Biology and Psychology. Cum laude. Hebrew University of Jerusalem, Israel. 1996
Active Research Projects:
In the lab we study how simple events at the molecular and cellular level of immune cell and pathogen interactions, lead to emergent phenomena of immune specificity and function in health and disease. We do this through the use of cutting edge systems biology and simulation techniques and by close collaboration with experimental laboratories. This close collaboration ensures that our research fits directly within reciprocal cycles of experiment, analysis, modeling and further experimental study. This, in turn, enables us to quickly move from basic (systems) biology questions to concrete biomedical findings.

Research Interests:

To study emergent multi-scale phenomena of the immune system the lab follows two main avenues of research:

(I) - How is a repertoire different than the sum of its parts – The B cell repertoire in health and disease:

Thanks to the diversity of the B cell repertoire the immune system can adapt to nearly any pathogen it encounters. This ability protects from recurrent infections, helps guard against rapidly mutating pathogens and is the basis for vaccines. Despite its importance the nature of this diversity and how it is generated remains unknown. The evolution of multivariate receptor repertoires and the selection of specific subsets, during the lifetime of the organism, cannot be understood at the level of a single cell. We will study this system by developing tools that allow us to analyze and visualize nucleotide and protein relationships at the level of the whole repertoire of cells. Using these tools we will identify how the B cell repertoire retains homeostasis while maintaining focus on specific epitopes.

(II) -What is the relationship of the timing of regulatory events and their causality?

Despite their central importance, the basic architecture and temporal dependencies underlying most eukaryotic gene programs are poorly understood. Such an understanding is essential if we wish to explain how cells integrate multiple stimuli using a limited vocabulary of signaling molecules, to create a vast multiplicity of behaviors. Using time-explicit models of regulatory cascades, we can start to define regulatory events underlying specific decision-points in cells undergoing short-term differentiation.
In the lab we use such tools to study dendritic cell (DC) differentiation in the antiviral response. Identifying for the first time the precise timing leading to a functioning anti-viral response. We will study the extent to which transcriptional regulation is reproducible in different types of responses and how this relates to disease outcome.
[*] Hershberg, U., Meng, W., Zhang, B., Haff, N., St Clair, E. W., Cohen, P. L., McNair, P. D., Li, L., Levesque, M. C., and Luning Prak, E. T. (2014) Persistence and selection of an expanded B cell clone in the setting of rituximab therapy for Sjogren's syndrome. Arthritis Research & Therapy 16, R51.

[*] Meng, W., Jayaraman, S., Bochao, Z., Schwartz, G. W., Daber, R., Hershberg, U., Garfall, A., Carlson, C. S., and Luning Prak, E. T. (2014) Trials and Tribulations with VH Replacement. Frontiers in Immunology 5.

[*] Goenka, R., Matthews, A. H., Zhang, B., O'Neill, P. J., Scholz, J. L., Migone, T.-S., Leonard, W. J., Stohl, W., Hershberg, U., and Cancro, M. P. (2014) Local BLyS production by T follicular cells mediates retention of high affinity B cells during affinity maturation. J Exp Med 211, 45-56.

[*] Schwartz, G. W., and Hershberg, U. (2013) Germline amino acid diversity in B cell receptors is a good predictor of somatic selection pressures. Frontiers in Immunology 4.

[*] Schwartz, G. W., and Hershberg, U. (2013) Conserved variation: identifying patterns of stability and variability in BCR and TCR V genes with different diversity and richness metrics. Phys Biol 10, 035005.

[*] Zaslavsky, E., Nudelman, G., Marquez, S., Hershberg, U., Hartmann, B. M., Thakar, J., Sealfon, S. C., and Kleinstein, S. H. (2013) Reconstruction of regulatory networks through temporal enrichment profiling and its application to H1N1 influenza viral infection. BMC Bioinformatics 14, S1.

[*] Reichenberger, E. R., Alexander, G. M., Perreault, M. J., Russell, J. A., Schwartzman, R. J., Hershberg, U.*, and Rosen, G.* (*the authors contributed equally) (2013) Establishing a relationship between bacteria in the human gut and Complex Regional Pain Syndrome. Brain, Behavior, and Immunity 29, 62-69.

[*] Uduman, M., Yaari, G., Hershberg, U., Stern, J. A., Shlomchik, M. J., and Kleinstein, S. H. (2011) Detecting selection in immunoglobulin sequences. Nucleic Acids Res. 39, W499-W504.

[*] Costa, K. D., Kleinstein, S. H., and Hershberg, U. (2011) Biomedical model fitting and error analysis. Science Signaling 4, tr9.

Zaslavsky, E*., Hershberg, U.*,(*These authors contributed equally), Seto, J., Pham, A.M., Marquez, S., Duke, J.L., Wetmur, J.G., tenOever, B.R., Sealfon, S.C. and Kleinstein, S.H. (2010) Antiviral response dictated by choreographed cascade of transcription factors , Journal of Immunology, Vol.184 issue 6 pp. 2908-17.

Anderson, S.M., Khalil, A., Uduman, M., Hershberg, U., Louzoun, Y., Haberman, A.M., Kleinstein, S.H., and Shlomchik M.J (2009) Taking advantage: Selection of high affinity B cells in the germinal center is controlled by death, not proliferation, Journal of Immunology Vol.183 issue 11 pp. 7314-25.

Herlands, R.A., Christensen, S. R., Sweet, R.A., Hershberg, U., and Shlomchik M,J. (2008) Antigen-driven activation of autoreactive B cells that is T cell-independent and TLR-dependent , Immunity Vol. 29 Issue 2 pp. 249-60.

Hershberg, U., Uduman, M., Shlomchik, M.J. and Kleinstein S.H. (2008) Improved methods for detecting selection by mutation analysis of Ig V region sequences, International Immunology Vol 20 issue 5 pp. 683-694, (Cover article).

Herlands, R.A., William, J., Hershberg, U. and Shlomchik M,J. (2007) Anti-chromatin antibodies drive in vivo antigen-specific activation and somatic hypermutation of Rheumatoid factor B cells at etrafollicular sites,European Journal of Immunology. Vol. 37 pp. 3339-51.

Hershberg, U. and Shlomchik, M. J. (2006) Differences in potential for amino acid change following mutation reveals distinct strategies for kappa and lambda light chain variation. PNAS Vol.103 No.43 pp. 15963-8.

Shalit, A., Erez, T., Deters, A., Hershberg, U., Shir, E. and Solomon, S. (2005) Postext - A mind for society. Lecture Notes in Computer Science: Adaptive Agents and Multi-Agent Systems Vol. 3394 pp. 24-40.

Adam, R., Hershberg, U., Schul, Y. and Solomon, S. (2004) Testing the Turing Test - Do men pass it? International Journal of Modern Physics C Vol.15 No.8 pp. 1041-1047.

Cohen, I. R., Hershberg, U. and Solomon, S. (2004) Antigen-Receptor degeneracy and immunological paradigms, Molecular Immunology Vol. 40 issue 14/15 pp. 993-996.

Hershberg, U. and Ninio, A. (2004) Optimal exemplar learning in cognitive systems, Cognitive Systems (ESSCS). Vol. 6 issue 2/3 pp. 181-188, special issue on the Multidisciplinary Aspects of Learning.

Hershberg U. (2003) Useful Examples and a new model of the immune system, Revue d'Intelligence Artificielle Vol. 17 No. 5/6 pp. 763-773, special issue - Regards croises sur l'analogie (Duvignau, K., Gasquet, O., Gaume, B. Ed.) Hermes Lavoisier.

Hershberg, U., Solomon, S. and Cohen, I. R. (2003) What is the basis of the immune system’s specificity?, Mathematical Modelling & Computing in Biology and Medicine, (V.Capasso Ed.), pp. 377-384, The MIRIAM Project Series, Progetto Leonardo, ESCULAPIO Pub. Co., Bologna, Italy.

Hershberg, U. (2002) Proposing a new focus for the study of natural and artificial cognitive systems, proceeding of the 2nd International Conference on Epigenetic Robotics pp.43-47.]

Hershberg, U. and Ninio, A. (2002) Cognitive systems and the special order of their environment, Res-systemica : European Systems Science Journal, Vol. 2, Special Issue: Proceedings of the 5th European Systems Science Congress, October 02, Crete. (

Hershberg, U., Louzoun, Y., Atlan, H. and Solomon, S. (2001) HIV time hierarchy: Winning the war while loosing all the battles, Physica A: Vol. 289 issue 1/2 pp.178-190, also placed on the net at (Nonlinear Sciences-Adaptation and Self Organizing Systems).

Hershberg, U. and Efroni, S. (2001) The immune system and other cognitive systems, Complexity, Vol. 6 issue 5 pp.14-21.
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