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Lurie Cancer Center Member

Jonathan Licht

Jonathan Licht, MD

Academic Title:
Professor, Medicine, Hematology Oncology Division; Feinberg School of Medicine

Member of:
Cancer Cell Biology (CCB)
Hematologic Malignancies (HM)


View Publications Listing

Cancer-Focused Research:

The broad goal of my research program is to understand how mutations of transcriptional regulators may set up patterns of aberrant gene expression that yield cancer. By modeling the function of both the normal and mutated forms of these factors we hope to better understand the molecular basis of cancer and potentially identify new therapeutic targets and pathways in this disease.

1. The Sprouty Proteins: We identified Sprouty1 as a target of the WT1 tumor suppressor and over the past decade we have studied the genetic and biochemical functions of the Sprouty proteins. We found that Sprouty inhibits the activation of MAP kinase and represents a counter-regulatory signaling molecule that limits signaling through receptor tyrosine kinases. Current studies focus on knockouts of the Spry genes and the effects of these genes on animal development, suppression of tumors and signal transduction.

2. The Molecular Biology of Leukemia and Lymphoma: Our lab studies a variant form of acute promeylocytic leukemia, which is highly resistant to therapy. In this syndrome the retinoic acid receptor is linked to a protein known as PLZF, which in turn is a DNA-binding repressor of gene expression. PLZF is expressed in early hematopoietic cells and is a tumor suppressor. We found that the protein contains a conserved self-association and repression domain called the BTB/POZ domain. Working with colleagues we devised a peptide that inhibits the action of the BTB domain of the closely related BCL6 factor and are working towards therapeutic trials of this agent. We have also studied how gene expression changes in patients treated with therapies targeted to gene expression including combinations of DNA demethylating agents and histone deacetylase inhibitors.

3. The Molecular Basis of Multiple Myeloma: The MMSET (Multiple Myeloma Set Domain) gene was identified in the t(4;14) translocation, present in 15-20% of multiple myeloma. MMSET has proprieties of a transcriptional co-factor, including the ability to bind to sequence specific transcription factors, transcriptional co-factors and histone deacetylases. We are currently screening for agents that inhibit the histone methyl transferase activity of the MMSET protein that might represent novel therapeutic agents.

4. Molecular Basis of Myeloproliferative Neoplasm: These disorders characterized by an excess in blood cells are due in large part to the action of a constitutively active mutant form of the JAK2 kinase kinase. My laboratory is studying additional genetics changes that occur in MPN including other mutations, and dysregulation of mRNA and microRNAs. Most recently we have studied the biochemistry of the TET2 gene mutated in myeloproliferative neoplasm and other myeloid malignancies and showed that this protein catalyzes the conversion of 5 methylcytosine to 5 hydroxymethylcytosine.

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