Postdoctoral Training Opportunity - RNA Binding Proteins, Histone Methyltransferases in Lung Cancer
Boumber Laboratory Overview
Do you have a background in molecular biochemical mechanisms including cancer signaling, RNA, cancer epigenetics or cancer biology? Are you interested in translational medicine? A postdoctoral fellowship position supported by the National Institutes of Health and Northwestern University is available in the laboratory of Dr. Yanis Boumber, a physician scientist at Northwestern University in Chicago. The laboratory focuses on mechanistic discovery to understand the role of RNA-binding proteins and histone-modifying enzymes in lung cancer.
Specific areas include:
- Since 2012, one major area of interest involves investigation of signaling pathways and biological processes controlled by RNA binding protein Musashi-2 (MSI2) in lung cancer and developing novel therapeutic approaches to target MSI2 in lung cancer. The laboratory uses in vitro models with inducible shRNA, transgenic Cre-Lox Kras-P53-Msi1/2 mouse model of lung cancer and lung cancer xenografts. In addition, they have partnered with Dr. John Karanicolas at Fox Chase Cancer Center in developing novel specific MSI2/1 inhibitors for lung cancer. Additional pilot projects that probe Musashi and other RBPs biology in lung cancer (upstream regulation of MSI2 expression, studies investigating MSI2-VEGFR2 axis, and evaluating other RBPs role in lung cancer) are also available.
- Since late 2018, the laboratory has been investigating the potential role of specific histone methyltransferases [HMTs] mutations impact in NSCLC, which will have translational implications and will improve their understanding of lung cancer biology. They use inducible in vitro CRISPR and shRNA regulated lung cancer models to investigate functional consequences of three specific HMT enzymes' loss. They are currently assessing whether depletion of three HMTs will affect cell growth and sensitize cells to specific drugs, and whether it affects downstream signaling and DNA repair for each of the enzymes. At a later phase of this project, they will evaluate the impact of the loss of select HMTs on downstream histone methylation in the genome using gene expression studies, and CHIP-Seq approach. Finally, the HMTs will be tested as biomarkers in the future active clinical trials, and they may develop new treatment modalities or clinical trials based on these discoveries in the future.
The most established research area of the laboratory is MSI2, which is an RNA-binding protein that regulates mRNA translation, and has previously been shown to have dysregulated function in leukemias. The laboratory recently identified MSI2 upregulation as common in the more metastatic cells derived from mice tumors and in lung cancer patient samples, and showed that loss of MSI2 decreased invasion and metastasis. MSI2 upregulates TGFβ and SMAD3 and suppresses claudins expression in lung cancer which contributes to metastatic lung cancer phenotype (Kudinov et al, PNAS, 2016, PMID: 27274057). They also recently reviewed the role of MSI2 in cancer (Clinical Cancer Research 2017, PMID: 28143872).
In the last 3 years, they identified MSI2 as a key regulator of EGFR protein expression at posttranscriptional level in lung cancer. RNA immunoprecipitation analysis demonstrated that MSI2 directly binds to EGFR mRNA, and sequence analysis predicted MSI2 binding sites in the murine and human EGFR mRNAs, which was confirmed by RNA-EMSA. MSI2 depletion selectively impaired cell proliferation in NSCLC cell lines with activating mutations of EGFR (EGFRmut). Depletion of MSI2 in combination with the EGFR inhibitors erlotinib and afatinib selectively reduced the growth of EGFRmut NSCLC cells and xenografts and indicated that targeting MSI2 may be of therapeutic value in lung cancer (Oncogenesis, under revision, 2020). In addition to work on MSI2 and ongoing work with HMTs, the laboratory, in collaboration with Golemis lab, was the first academic laboratory with access to the promising compound STA-12-8666 (now PEN-8666), a first-in-class member of a new class of HDC conjugate drugs platform. Based on their work with this highly promising compound, the laboratory demonstrated high preclinical activity and low toxicity profile in small cell lung cancer models (Clinical Cancer Research 2016, PMID: 27267850).
Qualifications and Application
This position will fit an individual with a strong interest in basic mechanistic discoveries in cancer research as well as translational applications of the findings, as this is a principal goal of Boumber Laboratory. The position will provide a unique and multidisciplinary exposure to cancer epigenetics and cancer biology at Northwestern University.
- The ideal candidate should have a PhD degree in molecular biology or cancer biology; MD degree with significant lab research experience is also acceptable;
- The candidate should be a team player since they will interact with other lab members and will supervise and train graduate students.
- The candidate should have the appropriate expertise in protein, DNA and RNA analysis, cell culture, preferably also with mouse work, shRNA/CRISPR, in vitro and in vivo drug studies; background in cancer epigenetics would be a plus.
- Knowledge of data analysis and bioinformatics analysis and paper writing experience would be helpful.
- The candidate should be highly proactive and driven.
- Good verbal and communication skills will be appreciated.
Yanis Boumber, M.D., Ph.D.
Robert H Lurie Comprehensive Cancer Center