Cancer Biology : Careers
The mission of the Department of Cancer Biology is to build bridges and teams to drive the best ideas in basic and translational cancer biology and developmental therapeutics into accelerating improvements and landmark advances in the prevention, treatment, and cure of cancer.
Investigating Chromatin Dysregulation due to Aberrant Dioxygenase Function in Human Pathology
A postdoctoral fellowship position is available in Dr. Abhishek Chakraborty’s newly established laboratory in the Department of Cancer Biology at the Cleveland Clinic. The laboratory is part of Cleveland Clinic’s GU Malignancies Research Center and has close ties to both basic researchers as well as GU clinicians at the Cleveland Clinic and the broader Case Comprehensive Cancer Center.
The laboratory is interested in the relevance of oxygen- (and 2-oxo-glutarate) dependent dioxygenases in cellular physiology, particularly in oxygen sensing and human disease. The laboratory is especially interested in studying the oxygen-dependent JmjC histone demethylases (e.g. KDMs) to 1) fundamentally understand the regulation and biological importance of hypoxia-dependent changes in chromatin; and 2) exploit dioxygenase dysfunction to identify therapeutically targetable vulnerabilities in human cancer, particularly kidney cancer.
Two notable publications highlight our contributions in these areas. First, we discovered that the H3K27 histone demethylase UTX/KDM6A is a novel cellular oxygen sensor that directly links physiological oxygen availability to transcriptional readout. KDM6A function, therefore, governs critical oxygen-dependent biological programs, including the regulation of cell state [Chakraborty AA et al. Science. In Press]. Second, by studying the compensatory mechanisms that allow kidney cancer cells to survive even in the face of profound chromatin dysregulation, we identified the H3K27 histone methyltransferase EZH1 as a targetable dependency in kidney cancer [Chakraborty AA et al. Science Transl Med. 2017 (398). pii: eaal5272]. This work is now being developed to begin exploring the feasibility of clinically targeting EZH1 in kidney cancer patients.
In addition to these discoveries, the laboratory has recently uncovered that the chromatin dysfunction in kidney cancer routinely affects enhancer-dense genomic regions called “Super-enhancers”. In other biological contexts, including other cancers, Super-enhancers have been shown to mark some of the most important genes involved in determining cellular state. These findings have motivated studies in the Chakraborty laboratory to identify Super-enhancer targets whose function is essential for kidney cancer cells, with the hope that, in time, (some of) these candidates could be nominated as potential therapeutic targets in kidney cancer.
The major techniques/areas of interest in the laboratory are Biochemistry [Protein purification and Enzymatic Assays], Molecular Biology [Cloning, Western Blotting, etc], Proteomics, Cancer Biology [in vitro and in vivo tumor models], Cellular Metabolism [steady state and flux-balance analysis], Pharmacology [drug discovery and delivery], Genomic analysis [RNA-Seq and ChIP-Seq data], and Whole-genome and Custom (mini-pool)Genetic Screens [both positive selection (gain-of-function) and negative selection (loss-of-function) screens].
The ideal candidate would have a M.D., Ph.D., or M.D./Ph.D. degree with interests and expertise in one or more of these areas. A collaborative and collegial work ethic, a strong commitment to basic cancer research, and outstanding verbal and communication skills are all required.
The position will provide a unique and multidisciplinary exposure to chromatin function, tumor metabolism, molecular oncology, drug development, and clinical collaborations.
Candidates with an interest in the position should email their CV and contact information for 3 references to:
Abhishek A. Chakraborty, Ph.D.
GU Malignancies Research Center
Lerner Research Institute
Cleveland Clinic, OH
We are seeking a highly motivated postdoctoral fellow to join the Yu lab which focuses on cancer stem cell biology and mechanisms of radiation resistance at the Cleveland Clinic. Cancer stem cells play an important role in therapeutic resistance. Cancer stem cells reside in different niches including the perivascular and hypoxic niches. Our laboratory is interested in uncovering molecular mechanisms by which stemness in maintained in these different niches, with the long-term goal of targeting these pathways. We focus on glioblastoma, a primary brain tumor, and brain metastases. To this end, we utilize a combination of molecular biology and mouse modeling approaches. Because Dr. Yu is a physician-scientist, we aim to translate our research to the clinic. Applicants must have a PhD in cancer biology or related field and be highly motivated. For more information about our laboratory, please visit our website: http://www.lerner.ccf.org/stemcellbio/yu/. Interested applicants should send their application to email@example.com.
Postdoctoral Fellow position is available in the Cleveland Clinic Lerner Research Institute in the Department of Cancer Biology to investigate the DNA repair pathways in cancer development and cancer treatment.
We seek candidates with strong qualifications in the following areas: mammalian cell culture, molecular biology, biochemistry and mouse models.
Application Requirements: A Ph.D and/or M.D. with relevant research experience is required. Proficiency in spoken and written English is also required. Full applications should include curriculum vitae, expected availability date, a description of past research experience and accomplishments, and contact information for three references.
Please send applications and informal inquiries to Dr. Zihua Gong at firstname.lastname@example.org.
The Cleveland Clinic is one of the top five medical institutions in the United States (per US News and World Report Best Hospitals ranking), and the Lerner Research Institute is consistently ranked in the top ten in terms of NIH funding for Research Institutes.
Molecular Mechanisms and Translational Investigation of Advanced Prostate Cancer
A postdoctoral fellowship position supported by the National Institutes of Health and the Prostate Cancer Foundation are available in the laboratory of Dr. Nima Sharifi at the Cleveland Clinic.
Our laboratory is focused on metabolic and molecular mechanisms of androgen synthesis and androgen receptor (AR) gain-of-function that lead to resistance to hormonal therapy. Specific areas include:
1) Metabolic and genetic changes required for hormone therapy resistance in prostate cancer and tumor progression
2) Clinical validation in patients and clinical trials utilizing innovative approaches
3) Animal models of advanced prostate cancer for translational and therapeutic studies
4) Identifying targets for the development of new pharmacologic therapies
We discovered the first example of a gain-of-function in a steroid-synthesizing enzyme that enables prostate cancer resistance to hormonal therapy (Chang, et al. Cell. 2013 154(5):1074-1084) and that we have shown in a predictive biomarker of poor outcomes after hormonal therapy (Hearn, et al. Lancet Oncol. 2016 17(10):1435-44; Hearn, et al. JAMA Oncol. 2018 Apr 1;4(4):558-562). We are current evaluating this biomarker in a clinical trial and are pursuing similar mechanisms and developing new treatment modalities based on these discoveries.
We recently also discovered that abiraterone works by conversion to a more active steroidal metabolite (Li, et al. Nature. 2015 523(7560):347-51), that metabolism is pharmacologically modifiable to optimize therapy (Li, et al. Nature. 2016 533(7604):547-51), that this is a class effect of steroidal androgen synthesis inhibitors (Alyamani, et al. Cell Chemical Biology. 2017 24, 1-8, July 20) and genetic determination of metabolite generation (Alyamani, et al. J Clin Invest. 2018 Aug 1;128(8):3333-3340).
The position will provide a unique and multidisciplinary exposure to tumor metabolism, molecular oncology, drug development and clinical trials. Further details are available at the following link: https://www.lerner.ccf.org/cancerbio/sharifi/#lab
Candidates should hold a doctoral degree with a background in molecular biology, chemistry, metabolism or cancer biology. Candidates must have proficiency in verbal and written English. Candidates with an interest in the position should send their CV and contact information for 3 references to:
Nima Sharifi, M.D.
Kendrick Family Chair for Prostate Cancer Research