Cancer Immunotherapy Position in Pediatric Oncology

A funded position is available to work on an innovative CANCER IMMUNOTHERAPY utilizing myeloid cells genetically programmed to generate pro-inflammatory tumor and lymph node macrophages and dendritic cells. This novel cell therapy has already proven successful in several murine models of cancer, and we now seek to further understand the mechanisms underlying slowing of tumor growth and to develop approaches for obtaining even stronger responses. Experience with cancer biology, immunology, molecular biology, and/or bioinformatics would be valuable.

Please submit a CV and names and contact information (email and phone numbers) for references to:
Alan D. Friedman, M.D., Professor, Pediatric Oncology
Johns Hopkins University School of Medicine
Cancer Research Building I, Room 253
1650 Orleans Street, Baltimore, MD 21231
E-mail: afriedm2@jhmi.edu

Macrophages can adopt a pro-inflammatory M1 phenotype capable of activating T cells to suppress tumor growth or, alternatively, a tumor-promoting M2 phenotype that inhibits T cell activation. NF-kB is a transcription factor favoring M1 gene expression. Multiple solid tumors grow slower in mice lacking the repressive NF-kB p50 subunit (e.g. Barberi T… Friedman AD. Cancer Immunol. Immunoth. 2018). To develop a way to translate these findings to patients that avoids also activating NF-kB in cancer cells, we conducted experiments in which we isolate immature myeloid cells from the bone marrow of mice lacking NF-kB p50; we find that intravenous injection of these cells, termed p50-IMC, slows the growth of prostate cancer, pancreatic cancer, neuroblastoma, and glioblastoma by increasing the number of activated tumor T cells (Suresh R… Friedman AD. J. Immunoth. Cancer 2020; Cui C… Friedman AD. Molec. Oncol. 2021; and unpublished).

Now we are pursuing efforts to further improve efficacy of murine p50-IMC in immune-competent mouse tumor models, e.g. by adding expression of chimeric antigen receptors (CARs) via viral transduction, which may favor p50-IMC tumor localization and may enhance phagocytosis of tumor cells and thereby antigen presentation, or by using CRISPR/Cas9 to edit additional genes in p50-IMC expected to further favor T cell activation. In addition, we are developing human p50-IMC for clinical application. The new post-doctoral fellow would contribute to these efforts while also helping us further characterize the cells that develop in vivo from p50-IMC and the gene expression changes present in these cells, e.g. using multi-parameter flow cytometry and immuno-histology, RNA-seq, ChIP-Seq, and ATAC-Seq.

The laboratory, located on the medical campus of Johns Hopkins University in the modern Cancer Research Building I, currently has one Research Associate and two post-doctoral fellows and employs cell culture, murine models, and methods of modern molecular and cell biology. I have had ongoing grant funding and have trained more than 30 graduate students and postdocs over the past 33 years. Many neighboring laboratories in the Cancer Center pursue related projects in cancer therapy, providing frequent opportunities for interaction, and excellent seminars in cancer biology occur frequently. The atmosphere in the laboratory is very friendly and supportive, and I as the PI often work in the laboratory and have frequent conversations with my lab members.

Johns Hopkins University is an equal opportunity employer and does not discriminate on the basis of gender, marital status, pregnancy, race, color, ethnicity, national origin, age, disability, religion, sexual orientation, gender identity or expression, veteran status, other legally protected characteristics or any other occupationally irrelevant criteria. The University promotes Affirmative Action for minorities, women, individuals who are disabled, and veterans. Johns Hopkins University is a drug-free, smoke-free workplace.