Eischen Research

The primary focus of the Eischen lab is on identifying ways in which cancer cells survive and target these vulnerabilities.  Specifically, we want to know what are the genes, RNAs proteins, and pathways that contribute to cancer cell survival.  We also investigate novel compounds to target cancer cell vulnerabilites, particularly cancers that have high relapse rates and/or for which new treatments are needed.  We have studied for years the oncogenes Myc and Mdm2, the p53 tumor suppressor, and the BCL2 family of proteins.  More recently we have investigated the proteins in the DNA replications stress response.  B cell lymphomas are the cancer that we have almost 2 decades of experience studying, and multiple projects utilize this expertise.  However, we also study triple negative breast cancer, high grade serous ovarian cancer, and oral squamous cell carcinoma.  Research in the Eischen lab spans from basic science with and without mouse models through translational research with patient material and bioinformatics.

The first area of research focus is on the oncogene Myc. We study Myc and its roles in proliferation, transformation, tumor development, and tumor cell maintenance. A large part of studying Myc is centered on the apoptosis that it causes when overexpressed in normal, untransformed cells, and the transcription it induces to drive proliferation. Myc induces the p53 pathway and suppresses the expression of anti-apoptotic Bcl-2 family members to induce apoptosis in normal cells. Cancer cells acquire alterations that inactivate the ability of Myc to induce apoptosis and we have discovered targeted therapies that reverse one of the pathways. Moreover, Myc-induced transcription is still incompletely understood and currently not therapeutically targetable. We discovered a novel regulator of Myc called Mtbp and are studying its contribution to cancer and how it regulates Myc.   

The second area of research in the Eischen lab focuses on Mdm2.  We discovered that Mdm2 has p53-independent functions that contribute to tumorigenesis.  We determined that Mdm2 regulates double-strand DNA break repair through interaction with Nbs1, a component of the Mre11/Rad50//Nbs1 DNA repair complex. We observed that increased expression of Mdm2 induces genome instability and increases transformation through a mechanism that is independent of p53.  We recently discovered that cancer cells that have inactivated p53 still rely on Mdm2 for their continued survival. With a collaboration, we developed a targeted degrader against Mdm2 and showed that it effectively induces apoptosis in triple negative breast cancer.  This compound is being developed to one day be used to treat cancer patients.

The third area of research in the Eischen lab centers on DNA replicatation stress. There are many inducers of DNA replication stress, such as oncogenes, radiation, chemotherapy, aging, etc.  Cells have to mitigate this stress or suffer DNA damage and breaks that can lead to cell death or alterations that can lead to tumor development.