Jack F. Shern, M.D.

Jack F. Shern, M.D.
Lasker Clinical Research Scholar

Dr. Jack Shern is a physician scientist within the Pediatric Oncology Branch. His research is focused on defining and developing precision therapies targeting the genetic mutations that drive tumorigenesis. Most recently, his efforts have turned towards using single cell sequencing to discover tumor subclonal populations that are responsible for relapse and refractory disease. He is actively engaged in the Children's Oncology Group, working on pediatric soft tissue sarcomas to investigate the utility of using mutational information as biomarkers for the diagnosis and management of pediatric rhabdomyosarcoma.

Areas of Expertise

1) rhabdomyosarcoma, 2) fusion oncogenes, 3) precision medicine, 4) whole genome
sequencing, 5) RNA sequencing, 6) epigenetics

Contact Info

Jack F. Shern, M.D.
Center for Cancer Research
National Cancer Institute
Building 10, Room 1-3750
Bethesda, MD 20892
Ph: 240-760-6201
Survival rates for childhood malignancies have been stagnant, in part due to a lack of a detailed understanding of the molecular mechanisms of action that drive these tumors. My group uses next generation genomic and molecular assays in an attempt to:

1. Detect and define the somatic lesions that drive tumorigenesis of rare and deadly pediatric tumors. In particular, we are interested in translocation events that produce fusion oncogenes of transcription factors. These events are the driving lesions in many of the difficult to treat pediatric sarcomas such as alveolar rhabdomyosarcoma and Ewing sarcoma. Interestingly, we have found that while these fusion oncogenes are often one of the few genetic rearrangements observed in within these tumors, they have profound effects on the transcriptional output of these cells.

2. Resolve underlying tumor heterogeneity and mechanisms of resistance that allow a tumor to progress or relapse after therapy. To accomplish this, we are using and developing novel droplet based methods to barcode and sequence and analyze the expression profile from thousands of cells in a single experiment.

3. Use high-throughput siRNA, small molecule and natural product drug screening to discover precision therapeutics designed to target a tumors underlying genetic or epigenetic drivers. The results of these studies are being rapidly translated into potential clinical trials within the Pediatric Oncology Branch.

NIH Scientific Focus Areas:
Cancer Biology, Cell Biology, Computational Biology, Genetics and Genomics, Molecular Biology and Biochemistry
View Dr. Shern's PubMed Summary

Selected Key Publications

  1. Libert D, Yuan CM, Masih KE, Galera P, Salem D, Shalabi H, Yates B, Delbrook C, Shern JF, Fry TJ, Khan J, Stetler-Stevenson M, Shah NN.
    Leukemia. [Epub ahead of print], 2020. [ Journal Article ]
  2. Gryder BE, Pomella S, Sayers C, Wu XS, Song Y, Chiarella AM, Bagchi S, Chou HC, Sinniah RS, Walton A, Wen X, Rota R, Hathaway NA, Zhao K, Chen J, Vakoc CR, Shern JF, Stanton BZ, Khan J.
    Nat Genet. 51(12): 1714-22, 2019. [ Journal Article ]
  3. Yeung C, Gibson AE, Issaq SH, Oshima N, Baumgart JT, Edessa LD, Rai G, Urban DJ, Johnson MS, Benavides GA, Squadrito GL, Yohe ME, Lei H, Eldridge S, Hamre J 3rd, Dowdy T, Ruiz-Rodado V, Lita A, Mendoza A, Shern JF, Larion M, Helman LJ, Stott GM, Krishna MC, Hall MD, Darley-Usmar V, Neckers LM, Heske CM.
    Cancer Res. 79(19): 5060-73, 2019. [ Journal Article ]
  4. Shalabi H, Kraft IL, Wang HW, Yuan CM, Yates B, Delbrook C, Zimbelman JD, Giller R, Stetler-Stevenson M, Jaffe ES, Lee DW, Shern JF, Fry TJ, Shah NN.
    Haematologica. 103(5): e215-e218, 2018. [ Journal Article ]
  5. Murgai M, Ju W, Eason M, Kline J, Beury DW, Kaczanowska S, Miettinen MM, Kruhlak M, Lei H, Shern JF, Cherepanova OA, Owens GK, Kaplan RN.
    Nat Med. 23(10): 1176-90, 2017. [ Journal Article ]
After completing undergraduate studies at the University of Notre Dame, South Bend, Indiana, Dr. John 'Jack' Shern received his M.D. from the Medical College of Georgia in 2007. This was followed by his pediatric internship and residency training at the University of Chicago Comer Children's hospital, which he completed in 2010. He then joined the combined Pediatric Hematology and Oncology Fellowship training program at the National Cancer Institute, Pediatric Oncology Branch (POB) and Johns Hopkins University. In his fellowship, Dr. Shern worked under the mentorship of Dr. Javed Khan in the Center for Cancer Research's Genetics Branch to use next generation sequencing to profile the somatic changes which drive multiple pediatric solid tumors. Dr. Shern was then an Assistant Clinical Investigator in the POB and became an NIH Lasker Investigator in 2018.
Name Position
Thomas Fountaine M.D. Clinical Fellow
Ira Kraft Special Volunteer
Haiyan Lei Ph.D. Bioinformatics Specialist (Contr.)
Carly Sayers Ph.D. Postdoctoral Fellow (CRTA)
Xiyuan Zhang Ph.D. Postdoctoral Fellow (Visiting)