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Joel L. Pomerantz Portrait

Joel L. Pomerantz
Associate Professor of Biological Chemistry
Johns Hopkins University School of Medicine

607 Broadway Research Building
733 N. Broadway
Baltimore, MD21205
Office Phone: 443-287-3100
Lab Phone: 443-287-3104
Fax: 443-287-3109
Email: joel.pomerantz@jhmi.edu
Lab Web Site

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Functional specificity and design of signal transduction pathways

Our laboratory studies the molecular machinery used by cells to interpret extracellular signals and transduce them to the nucleus to effect changes in gene expression. This process is of fundamental biological importance. The accurate response to extracellular signals results in a cell's decision to proliferate, differentiate, or die, and it is critical for normal development and physiology. The disregulation of this machinery underlies the unwarranted expansion or destruction of cell numbers that occurs in human diseases like cancer, autoimmunity, hyperinflammatory states, and neurodegenerative disease.

 

Currently, we study signaling pathways that are important in innate immunity, adaptive immunity, and in cancer, paying particular attention to pathways that regulate the activity of the pleiotropic transcription factor NF-kB. We are interested in these broad questions:

 

  • What are the biochemical mechanisms of signal transduction?
  • How is the input-output specificity determined so that each particular ligand or extracellular cue induces the appropriate cellular response?
  • How does the molecular specificity at the atomic level underlie biological specificity at the organismal level?
  • How are signaling pathways disregulated in human disease and can we use this knowledge to develop new therapeutics?
  • Can we use our understanding of signaling mechanisms to design novel, artificial signaling circuits for research and therapeutic purposes, for example, to control cell fate?

 

Examples of current projects:

 

The biochemistry of antigen receptor signaling in B and T lymphocytes.
The activation of NF-kB by antigen receptor engagement is a critical requirement for the activation of lymphocytes in the adaptive immune response. Using a novel expression cloning strategy designed to isolate molecules that signal to NF-kB in lymphocytes, we cloned CARD11, a multiprotein adaptor molecule and member of the MAGUK family of signaling proteins. We demonstrated that CARD11 plays a pathway-specific, factor-specific role in the activation of NF-kB downstream of T cell receptor signaling (Pomerantz, Denny, and Baltimore, 2002). We are currently investigating the biochemical mechanisms by which CARD11 transduces signals from the T cell receptor to NF-kB.

 

Expression cloning of signaling molecules that regulate NF-kB, NFAT, and other transcription factors.
We have used our expression cloning strategy (Pomerantz, Denny, and Baltimore, 2002) to clone several novel signaling molecules that signal the activation of the NF-kB or NFAT transcription factors. We will study their biological roles and characterize their mechanisms of action. We are also investigating whether our protocol is adaptable for the isolation of signaling molecules that regulate other transcription factors that influence the decision to proliferate, differentiate, or die, and that are disregulated in human disease.

 

Design of novel signal transduction pathways for cell engineering.
We are interested in testing our understanding of signal transduction by applying mechanistic insights toward the design of novel artificial cellular circuits. Our goal is to develop heterologous circuitry that would provide new tools for controlling gene expression to be used in biological research and to engineer cell fate decisions in novel therapeutic approaches.
Recent Publications

Chan, W., Schaeffer TB, Pomerantz JL.  A quantitative signaling screen identifies CARD 11 mutations in the CARD and LATCH domains tht induce Bc110 ubiquitination and human lymphoma cell survival. Mol Cell Biol. 2013. 33(2): 429-443.

Lamason, R.L., S.M. Lew, and J.L. Pomerantz. 2010. Transcriptional target-based expression cloning of immunoregulatory molecules. Immunol. Res. 47:172-178.
PubMed Reference

Lamason, R.L., R.R. McCully, S.M. Lew, and J.L. Pomerantz. 2010. Oncogenic CARD11 mutations induce hyperactive signaling by disrupting autoinhibition by the PKC-responsive inhibitory domain. Biochemistry 49:8240-8250.
PubMed Reference

Lamason, R.L., A. Kupfer, and J.L. Pomerantz. 2010. The dynamic distribution of CARD11 at the immunological synapse is regulated by the inhibitory kinesin GAKIN. Mol. Cell 40:798-809.
PubMed Reference

Yang, H.-C., L. Shen, R.F. Siliciano, and J.L. Pomerantz. 2009. Isolation of a cellular factor that can reactivate latent HIV-1 without T cell activation. Proc. Natl. Acad. Sci.USA, 106: 6321-6326.
PubMed Reference

McCully, R.R. and J.L. Pomerantz. 2008. The Protein Kinase C-responsive inhibitory domain of CARD11 functions in NF-κB activation to regulate the association of multiple signaling cofactors that differentially depend on Bcl10 and MALT1 for association. Molecular and Cellular Biology 28:5668-5686.
PubMed Reference

Sommer, K., B. Guo, J.L. Pomerantz, A.D. Bandaranayake, M.E. Moreno-Garcia, Y.L. Ovechkina, and D.J. Rawlings. 2005. Phosphorylation of the CARMA1 linker controls NF-kappaB activation. Immunity 23, 561-574.
PubMed Reference

Wurtz, N.R., J.L. Pomerantz, D. Baltimore, and P.B. Dervan. (2002) Inhibition of DNA binding by NF-kB with pyrrole-imidazole polyamides. Biochemistry, 41, 7604-7609.
PubMed Reference 

Pomerantz, J.L., and D. Baltimore. (2002) Two pathways to NF-kB. Mol. Cell, 10, 693-695.
PubMed Reference 

Pomerantz, J.L., E.M. Denny, and D. Baltimore. (2002) CARD11 mediates factor-specific activation of NF-kB by the T cell receptor complex. EMBO J., 21, 5184-5194.
PubMed Reference

Pomerantz, J.L. and D. Baltimore. (2000) Signal transduction � A cellular rescue team. Nature, 406, 26-29.
PubMed Reference

Pomerantz, J.L. and D. Baltimore. (1999) NF-kB activation by a signaling complex containing TRAF2, TANK, and TBK1, a novel IKK-related kinase. EMBO J., 18, 6694-6704.
PubMed Reference

Pomerantz, J.L., S.A. Wolfe, and C.O. Pabo. (1998) Structure-based design of a dimeric zinc finger protein. Biochemistry, 37, 965-970.
PubMed Reference

Kristie, T.M., J.L. Pomerantz, T.C. Twomey, S.A. Parent, And P.A. Sharp. (1995) The cellular C1 factor of the herpes simplex virus enhancer complex is a family of polypeptides. Journal of Biological Chemistry, 270, 4387-4394.
PubMed Reference 

Pomerantz, J.L., P.A. Sharp, and C.O. Pabo. (1995) Structure-based design of transcription factors. Science, 267, 93-96.
PubMed Reference 

Pomerantz, J.L., C.O. Pabo, and P.A. Sharp. (1995) Analysis of homeodomain function by structure-based design of a transcription factor. Proc. Natl. Acad. Sci.USA, 92, 9752-9756.
PubMed Reference

Pomerantz, J.L., and P.A. Sharp. (1994) Homeodomain determinants of major groove recognition. Biochemistry, 33, 10851-10858.
PubMed Reference

Pomerantz, J.L., T.M. Kristie, and P.A. Sharp. (1992) Recognition of the surface of a homeo domain protein. Genes & Development 6, 2047-2057.
PubMed Reference 

Pomerantz, J.L., F. Mauxion, M. Yoshida, W.C. Greene, and R. Sen. (1989) A second sequence element located 3' to the NF-kB binding site regulates IL-2 receptor-alpha gene induction. Journal of Immunology 143, 4275-4281.
PubMed Reference ​

Rothenberg, M.E., J.L. Pomerantz, W.F. Owen, Jr., S. Avraham, R.J. Soberman, K.F. Austen, and R.L. Stevens. (1988) Characterization of a human eosinophil proteoglycan, and augmentation of its biosynthesis and size by interleukin 3, interleukin 5, and granulocyte/macrophage colony stimulating factor. Journal of Biological Chemistry 263, 13901-13908.
PubMed Reference

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